1 100 6561 http://exhibits.library.stonybrook.edu/mfp/files/original/035fb0f29ed47985e9b4395a43cb14d0.pdf 4db2ed7f8f4aec275baaa2efc8c24ad0 PDF Text Text Seventy Years an Experimentalist in Neurology and Psychiatry Max Fink, M.D. Professor of Psychiatry and Neurology Emeritus, State University of New York at Stony Brook. First Publication in Archives: May 28, 2017 Updated April 18, 2021 11 Buttonfield Lane South Hadley, MA 01075 Tel. 631.637.1730 fink.max@gmail.com maxfink55@gmail.com max.fink@stonybrook.edu max.fink@stonybrookmedicine.edu max.fink@sunysb.edu max.fink@optimum.net Metrics: April 18, 2021 Pages: 100 Words: 38,107 The ultimate court of appeal is observation and experiment, and not authority. Thomas H. Huxley 1 �Introduction Inducing seizures to relieve severe behavior disorders-- electroshock, ECT -is a much prejudiced treatment that is undergoing a renaissance after eight decades of experience. Usage is increased to varying degrees worldwide. But raucous attacks by public critics and psychologists claiming treatments cause brain damage and memory losses are ever common. But assured safety and remarkable efficacy, even guides to specificity in illnesses, brings the intervention within a successful medical tent. Introduced for the relief of the imagined Kraepelinian diagnosis of schizophrenia, recent decades has defined catatonia (and its varieties of mutisms, manias, motor rigidities) and melancholia (depressive psychoses) as more specific systemic disorders that are rapidly and effectively relieved. How was the treatment discovered? And why was it rejected by the professions? Why the public stigma in the face of efficacy and specificity? How has the practice and the science of the treatment evolved? The author, well on his way for full training in conventional neurology and psychiatry is asked to oversee the seizure therapies in hospitalized severely psychiatric ill. He takes on the task of improving the science and increasing public and professional acceptance are highlighted in this personal story of an experimentalist physician. These pages cite my education as a physician with qualifications in neurology, psychiatry and psychoanalysis. From the beginning, I studied patients, their physiology and symptoms, and applied different interventions, often in a Random Controlled Trial. When I entered the profession, research studies in man was an accepted practice. In recent decades, bars to such studies have been increasingly applied, leading to focus on studies in animals and other surrogates. Over my professional career my interests focused on the treatment of induced seizures (electroshock, ECT), the effects of substances that altered brain functions (psychopharmacology, EEG), and the systemic behavior syndromes of catatonia and melancholia. The records of my studies are archived at the Stony Brook University Library. 1 2 �Contents Introduction for Readers Book One: Inducing Seizures as Treatments 2 Ending Insulin Coma Optimizing ECT Procedures The EEG as Index of Efficacy Modifying seizures: Muscle relaxants and sedatives Are subconvulsive treatments effective? Are chemical induced seizures as effective as electrical? Is Isoflurane anesthesia a replacement? Acetylcholine and Anticholinergic Drugs Neuropsychological Tests and EEG Slowing 9 11 13 15 16 17 17 18 The differences Electrode Placements make, Again Multiple ECT. MMECT ECT in Systemic Medical Illnesses Optimizing Treatments ECT in Schizophrenia Clozapine and ECT Seizures and Brain Fluphenazine CORE Study: ECT in Depressed Inpatients Persisting Stigma: Memory Loss and ECT 19 20 21 23 24 25 26 26 28 Creation of Induced Seizures as Therapy Immediate Rejection by the Profession First APA Task Force onECT Out-Patient ECT Commission Stigma persists: Public Joins Attack Church of Scientology and Malpractice Legal Suits Media Attacks: Madness with Jonathan Miller Active Defense: A Beautiful Mind 30 31 34 34 35 36 36 38 Book Two: After ECT Research Hiatus, Renewed Studies Book Three: Electroshock in the Public Eye 3 �Book Four: The Enigma: How do Seizures Affect Behavior? Seizures as systemic reflexes Neurophysiologic adaptive theory Cholinergic theory Neuroendocrine hypothesis Conferring in the search for mechanism 40 41 42 43 46 The Teaching Case Catatonia as a type of Schizophrenia? But Catatonia is not Schizophrenia In contrast, Catatonia is Treatable Is NMS a Form of Catatonia? The Drive to Official Definition Sedative Verification Test Many Faces of Catatonia Delirious mania Toxic serotonin syndrome Pervasive Refusal Syndrome Toxic encephalitis: NMDAR Receptor Self-injurious behavior in Autism DSM Classification Debates Catatonia Textbook, ACTA Supplement 50 51 52 53 54 56 56 57 57 59 59 60 62 62 64 What is next? Dexamethasons Suppression Test Melancholia Textbook, History 66 66 67 EEG Introduced to Hillside Hospital EEG in Psychopharmacology Grey Walter Analyzer Digital Computer analysis of EEG IBM 1800 analysis system Lessons learned: Putative Drugs Classified Association-Dissociation Controversy Pharmaco-EEG Paradigm 69 71 71 71 73 74 76 78 Book Five: The Road to Catatonia Book Six: Melancholia: Medical Model of Diagnosis Book Seven: Studies in Electroencephalography 4 �Book Eight: A Medical experimentalist is Created Medical School Experiences 1942-1945 Neurosyphilis and CSF Osteomyelitis, Barbiturates Interneship Penicillin in Empyema Residency Percutaneous Carotid Angiography Face-Hand Test 79 79 80 Early Life Family Affairs Dalliance with Psychoanalysis Military Career, Ship's Surgeon Perigrinations Books Published, Edited 85 87 87 89 93 93 Book Nine: Biography Appendices 81 82 83 94 5 �Book One: Inducing Seizures as Treatments My academic arc in electroconvulsive therapy began unexpectedly on January 2, 1952 as I enrolled for the fifth year of residency training in neurology and psychiatry at a hospital reputed to use classic psychoanalytic principles to treat hospitalized severely ill. I arrived on a clear winter day with another new recruit, to meet the Directors of this 170-bed multi-building Hillside Hospital caring for voluntary psychiatric in-patients, for up to a year, mainly at public cost. That morning I was assigned to the electroshock and insulin coma treatment services. In my previous years, I had no experience with either treatment. I received my M.D. degree from New York University School of Medicine on June 12, 1945, followed by nine-month interneship and 20 months service in the US Army Medical Corps. During the succeeding four years I studied in neurology and psychiatry residencies, attended a school of psychoanalysis, and sought a final year in psychoanalytic psychotherapy at an inpatient hospital in the Long Island farmland, with accredited training psychoanalysts on its faculty. I accompanied the Associate Medical director to a 2-story building that housed the electroconvulsive (ECT) treatment unit. One by one, five patients lying on a wheeled stretcher under sheet restraints were brought into a treatment room, a rubber bite-bloc placed between their teeth, two stimulating electrodes applied at the temples, protected by two aides, a seizure induced with currents delivered from a Medcraft alternating or a Reiter polyrhythm current device with the energy set according to estimates of what was needed to induce a full grand mal seizure. As the electric currents were applied, the neck and back arched, the body became rigid, followed by rhythmic muscle movements and breath holding. The patient became cyanotic with light blue lips. After a minute, the muscles relaxed, deep breathing followed, cyanosis waned, and color returned as the patient was moved to a recovery room, cared for by aides for 15 to 20 minutes until able to get off the stretcher and walk to the ward for shower, dressing and breakfast. Durations of the elicited seizures varied in length from 30 seconds to a few minutes, occasionally requiring termination by intravenous injections of amobarbital. Observing a full grand mal seizure in each patient jarred me. The previous week and for years before I had been taught by my neurologist teachers that seizures were dangerous to patients and must be stamped out. Every teacher had emphasized the need to fully inhibit seizures to avoid tooth, limb, and spine fractures, tongue-biting, confusion, injury from falls, and death. Much was made of the newly developed anticonvulsant phenytoin (Dilantin). 6 �And now, we were deliberately inducing grand mal seizures! This antithesis has plagued my professional life and the lives of neurologists who, to this day, are unable to accept the evidence that benefits in behavior accrue to repeated induced seizures in severely depressed, manic, catatonic, delirious, and psychotic patients. As I learned how to treat patients safely I realized the remarkable benefits of inducing seizures, and such treatments became an interest for the remainder of my professional life. After introduction to ECT that first morning, we crossed the hall to the insulin coma treatment unit, a well-lit air-conditioned suite with a large nursing staff. Filled with cries, coughs, grunts, and groans of patients in various stages of stupor, coma, drowsiness and confusion, and some suffering a seizure. They had come to the treatment unit in loose-fitting pajamas at 6 in the morning and had been injected subcutaneously or intravenously with measured doses of insulin. For the next three to five hours they were repeatedly tested for vigilance and response to commands as they lost consciousness; their tendon and pupillary reflexes disappeared, breathing became stertorous, and intense sweating soaked the bedsheets. After a measured hour, the stupors were ended by 10% glucose solution administered either by nasogastric tube or by intravenous injection. The change from unconsciousness to consciousness and to talking with the aides occurred rapidly, within 10 to 30 minutes. On awakening, each patient was taken to shower, dress, and within an hour was eating breakfast. Most were famished and ate everything put before them. Insulin coma treatments, like the ECT sessions at the time, were unsafe. Fractures of teeth and limbs occurred and confusion persisted for hours after treatment. During 1/5 of the ICT treatments, at least one unscheduled seizure emergency occurred each morning. For the patients who had shown little change in behavior during the course of insulin comas, seizures were induced electrically in the midst of the coma. This combination of ECT and coma was common for the severely psychotic patients, an implicit recognition that the seizure was the therapeutic feature of the coma treatments. Occasionally, consciousness did not return despite repeated doses of glucose. Stupor persisted with sweating, fever, elevated blood pressure, and rapid heart rates. We had no understanding of why a state of persistent coma occasionally occurred nor how to relieve it. Many experimental means were tried. Relief from the stupor occurred slowly over days of intensive nursing care. Two patients died in stuporous coma during the six years that I managed the service. By early afternoon, the ICT and ECT treated patients were in individual and group treatment sessions, participating in occupational activities, playing musical instruments and games, and meeting with relatives. I frequently tested their skills in chess and checkers, finding the skills of many better than my own despite their morning seizure or coma. It was remarkable to see a patient in coma, unresponsive 7 �to verbal, sensory, or painful stimulation and an hour later chatting with staff, drawing, and playing games. Older patients, though, were more often confused and fatigued, spending a good part of their post-treatment day in their rooms or their beds. For the next three months, I supervised both the ECT and ICT services, with ECT three times weekly and ICT every morning. My afternoons were spent in individual therapy sessions with patients, meeting families, attending staff conferences about individual patients and classes with attending physicians. By mid-year I had learned that ECT effectively reduced suicide thoughts, relieved negativism, aggression, depressed and manic moods. Of the hospital populations, the patients treated with electroshock improved the most. They became more cooperative and responsive, no longer expressing morbid thoughts and threats of self-harm, sleeping and eating better, and interacting more normally with their families, other patients, and staff. The outcomes with insulin coma were less well defined, and the risks much greater, but yet, greater percentages of patients so treated were rated improved than after psychotherapy. ECT treated patients typically improved rapidly; many returned home, with few transferred to the local Creedmoor State Hospital for lack of improvement. By contrast, few insulin coma treated patients returned home after a year's residence; most continued in chronic care. A 5-year follow-up study of 314 patients admitted to the hospital in 1950 reported a mean hospital duration for ECT-treated patients of 5.0 months, for psychotherapy-treated patients 6 months, and for ICT-treat patients 6.5 months. With ECT, 76% were rated as recovered or much improved compared to 53% for psychotherapy and 33% with ICT. Admittedly, the selection of treatments and the diagnostic labels were not random but dictated by the opinions and beliefs of the Attending physicians and by the preference for trials of psychotherapy before assignment for ECT or ICT. 2 The teachers used social and symptom guidelines for diagnosis and treatment. The younger, more literate, and better educated patients with phobias, obsessions, compulsive rituals, and anxiety states were assigned a diagnosis of psychoneurosis and valued as participants in psychotherapy; the more aggressive, over-active, and psychotic patients were labeled schizophrenic, with ICT or ECT the recommended treatments; while the elderly, poorly educated patients, often immigrants, were seen as depressed and referred for ECT. 8 �Ending Insulin Coma Therapy The introduction of Largactil (chlorpromazine) to Hillside Hospital in the fall of 1954 set in motion the demise of insulin coma therapy. Developed in France as a sedative, to reduce excitement and psychosis of the psychiatric ill, it first underwent safety and efficacy trials at various New York State hospitals. At an open meeting organized at Creedmoor State Hospital in Queens in 1954, I heard one researcher after another -- Herman Denber, Nathan S. Kline, Sidney Malitz, Sidney Merlis, Anthony Sainz, and John Whittier -- report reduced excitement, aggression, and mania, lesser disorders in thought, fewer injuries to patients and staff members, fewer fires set, fewer mattresses trashed, and fewer windows broken with chlorpromazine use. At the end of the sessions representatives of the Smith, Kline and French pharmaceutical company offered 25mg samples for clinical trials and I enrolled. As the dosing and risks of chlorpromazine were poorly known, the Hillside hospital administration decided that referrals for this experimental treatment were best prescribed and supervised by the ECT/ICT physicians. For the first trials we selected the most disturbed and least cooperative patients in one study unit. Patients became more responsive, less aggressive, less manic, and more cooperative. Soon, nurses from other units asked to enroll their patients. Initial reluctant staff attitudes changed quickly and our enthusiasm for chlorpromazine added to the voices encouraging its use from France and Canada. But soon one patient and then another developed jaundice. Other study centers reported similar toxicities. Our patients were examined for systemic liver disease, but no explanation for the jaundice was found. Our initial enthusiasm for chlorpromazine trials was inhibited, but the strength of the benefits encouraged continued trials. Within a year, such toxic reports became less frequent (there had been a contaminant in the initial batch, it turned out) and soon motor rigidity, tremors, and then tardive dyskinesia (delayed abnormal rhythmic movements of mouth, tongue and facial muscles) dominated discussions of its risks. These motor signs were the fore-runners of the Parkinsonism and tardive dyskinesia that are hallmarks of chronic chlorpromazine use. Similar motor effects were soon reported for successor neuroleptic drugs and motor inhibition became a marker of these agents. Decades later, the "atypical neuroleptics" were developed and promoted for their lesser motor effects with disregard for their lesser clinical efficacy. The NIMH-sponsored large clinical trial known as CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) undertaken in the 1990s randomly assigned ambulatory out-patients either to the atypical neuroleptics olanzapine, quetiapine, risperidone, ziprasidone or to the typical neuroleptic perphenazine. The atypicals did not match the beneficial effects or costeffectiveness of perphenazine. 9 �The EEG profile of chlorpromazine showed dose-related changes of reduced beta fast frequencies, increased theta slow frequencies, and occasional bursts of slow waves and spike activity. These rhythms heralded the seizures that became an acknowledged risk of the drug’s use. We had begun with 50mg doses but rapidly increased single dosing to 200mg and daily dosing to 1800mg. We learned that 1200 mg daily was effective and well tolerated in 80% of our subjects. These experiences led us to undertake two random controlled trials, one compared chlorpromazine to insulin coma and another comparing the effects of chlorpromazine, imipramine, and placebo in patients with a broad range of behaviors. The Random Controlled Trial: A compelling motive for the comparison of chlorpromazine and insulin coma was the risks posed by the high doses of insulin. Seizures occurred in more than 10% of the sessions, and delayed spontaneous (“tardive”) seizures often occurred late in the day or night, requiring additional intravenous or gavage dosing with glucose. For patients whose psychosis was responding slowly, electrically induced seizures were added at the height of the comas to augment the changes in behavior. A prolonged coma was a much feared risk, the patient not becoming alert and oriented for many hours despite extensive dosing with intravenous and gavaged glucose. Many explanations were considered and many interventions tested, but we did not find an effective treatment or method of prevention. We depended on intensive nursing care, repeated dosing with glucose, and monitoring until recovery. Two deaths in prolonged coma occurred in the five years that I supervised ICT, a 2% mortality rate. Sixty patients referred for ICT were randomized to receive either 50 insulin coma treatments or oral chlorpromazine (0.3 to 2.0 Gm/day; median 0.8 Gm/day) with both treatments given for a minimum of three months. Chlorpromazine treatment was as effective as insulin coma but with greater ease of use, greater patient comfort, lesser risks, and lesser expense— clearly favoring chlorpromazine as a replacement for ICT. More than half of each sample improved sufficiently to return to their homes. 3 These findings led to the closing of the Hillside Hospital's insulin coma unit in 1958, followed swiftly by the closing of other units throughout the nation. Within a decade the treatment had disappeared from American hospitals. A few units continued to treat patients with ICT as exemplified by the report that the 1994 Nobelist John Nash had received ICT in 1961 at Trenton State Hospital. 4 The treatment also persisted for decades in Russia and China, and was brought to Israel by Russian emigres. My review in 2003 of what was known about insulin coma treatment, the lesser efficacy of ICT in treating psychosis and its 10 �increased efficacy with augmented electrical seizures led me to conclude that the spontaneous random seizures were the basis for ICT’s reported efficacy in relieving psychosis. ICT, to the extent it had therapeutic value, was best considered a less efficient and more riskful form of induced seizure therapy. 5 Optimizing ECT Procedures The EEG as Index of Seizure Efficacy Since seizures were the core process in both ECT and ICT how can one record and understand the brain events that were central to the treatments? The answer seemed to lie in electroencephalography, but such was not available at the hospital. In 1771 the Bolognese physician Luigi Galvani had demonstrated that an electric stimulus caused a living frog muscle to twitch and contract. He observed electric currents from living muscles by the movements of a magnetized “galvanometer” needle. His experiments connected the newly discovered phenomena of electricity to living tissues. Similar reports by Giovanni Aldini and Benjamin Franklin strengthened the conviction of electricity in living tissues. 6 A century later, in 1875, the physiologist Richard Caton recorded electric oscillations from the exposed brain of a living animal, securing the connection between brain functions and electricity. But these currents were too small to be recorded through the skull and could only be demonstrated in an exposed brain. Then, in 1929 Hans Berger, a Jewish hospital psychiatrist in Jena Germany adapted the device that was developed to record the electrical activity of the heart to record electric oscillations from electrodes on the intact human scalp. Rhythms varied with changes in vigilance, sleep, body physiology, and the effects of systemic drugs. In his third report Berger described changes in the EEG under the influence of cocaine, scopolamine, morphine, chloroform, and sleep. The electrical changes associated with insulin-induced hypoglycemia (as in insulin coma therapy) and the chemical and electrical induction of seizures were next charted, as these treatments were increasingly applied in the severe mentally ill. Hillside Hospital lacked an EEG laboratory. I sought training in recording and interpreting the EEG at the Mount Sinai Hospital in New York City supported by a fellowship of the National Foundation for Infantile Paralysis. 7 By the end of 1953 an EEG technician had been trained, a laboratory established, and developed a protocol for the study of the changes in EEG associated with ECT. An application to the National Institute of Mental Health funded a five-year study under Grant MH-927 "Altered Brain Function Following Electroshock" in the summer of 1954. The support established a team of researchers to study the treatments. For the next 11 �decade, the physicians, psychologists, and technical staff were centered in a Department of Experimental Psychiatry. 8 The EEG brain rhythms in alert normal adults are filled with 8-to-12 Hz (alpha) frequencies with amplitudes of 40 to 80 microvolts (µv). Patterns vary with age, during day and night, and are altered by drugs and disease. After head injury and intracranial bleedings, the rhythms slow with increasing amounts of theta (4.5 -7 Hz) and delta (2-4 Hz) frequencies and the amplitudes increase from 50 µv often to 150 and 200 µv. As brain pathology improves, normal EEG rhythms return. During my EEG education I was shown records with high voltage slow waves with “spikes” appearing in one-to-three second bursts with longer runs of lower voltage slow waves as evidence of an epileptic seizure. We found similar records on inter-treatment days during the course of ECT. The pre-treatment records of our psychiatric ill did not differ from those of healthy individuals, with older patients showing slower rhythms than did the younger. In the minutes and first hours immediately after a seizure, EEG voltages increase, frequencies slow, and burst patterns appear. In ensuing days, the changes after each treatment persist for longer periods. After 4 to 10 treatments, slow waves persist throughout the day, then for many days and in some patients for weeks thereafter. It was technically unfeasible to record the actual seizure as our instruments became "blocked" by the electrical stimulus. 9 But we could examine the “interseizure” record, the changes in the resting EEG record on days between treatments. Brain electrical rhythms slowed and amplitudes increased during the ECT course. After treatment ends, more rhythmic, regularized alpha frequencies return. The changes induced induced by electricity and by the chemicals Metrazol or flurothyl are not distinguishable, arguing that the EEG records during treatment are related to the seizure and not to the seizure-inducing agent. We concluded that progressive slowing of inter-seizure frequencies was necessary for beneficial behavior effects. The patients whose inter-treatment rhythms changed very little did not recover from their illness. 10 Although it was customary to describe the rhythms in non-quantitative descriptive terms, I sought more reliable indices, measuring the frequencies and amplitudes by height and width of each wave, using calipers and ruler, one wave after another, in 10-second epochs , up to 60 seconds for each sample, with an average of 600 waves measured at baseline and 350 to 450 waves at the end of a course of treatment. By comparing numbers of treatments and degree of slowing for each patient, slowing occurred earlier and to a greater degree in patients exhibiting symptom relief than in the patients whose behavior changed slowly or failed to improve. EEG frequency slowing and amplitude increases became markers 12 �of the brain changes that underlie behavioral improvement. The rate and amount of change varied with electrical dosing and the number and frequency of treatments. We concluded that EEG change was necessary for the clinical changes to take place and marked the physiological changes that are the basis for the treatment response. This lesson became the critical observation of the ECT process and became the core of my studies to optimize and understand the convulsive therapy process. That the changes in EEG rhythms with ECT were similar to those in epilepsy and after head trauma was often used to justify an anti-ECT prejudice voiced by the public, by patients, and by psychiatrists and psychologists encouraging beliefs that seizures “damaged the brain.” We thought otherwise, concluding that the EEG changes induced by the seizures were necessary markers for the clinical benefits -without persistent EEG slowing, recovery of illness did not occur. The patients referred to hospital for ECT are very ill, unable to function at home or at work, sad and unhappy, expressing thoughts of suicide, strange ideation, and occasionally with aggressive manic behaviors. 11 Almost all have been treated by a cascade of medicines, psychotherapies, vacations, diets, and much else before the patient was exposed to electroshock, widely conceived as hazardous and life threatening. The patients met today’s diagnostic criteria for major depression, bipolar disorder, and schizophrenia. The quickest resolutions of illness occurred in the severely depressed, suicidal, catatonic, manic, melancholic, and delirious patients. The least benefits, were in the withdrawn, apathetic, poorly motivated, thought-disordered patients who today meet the criteria in the standard diagnostic system for schizophrenia or bipolar disorder. 12 Modifying Seizures: Muscle Relaxants and Sedatives Electroshock treatments were “unmodified” -- without sedation or muscle paralysis, allowing the full grand mal seizure to develop in each treatment. For anxious patients, amobarbital was injected to sedate and relax. We also interrupted the longer seizures by injections of amobarbital. The body movements, EEG seizure patterns, and changes in physiology are similar for each treatment. Indeed, the “seizure” has the same form and is readily recognizable in all mammals. It is an inherent pattern that occurs both spontaneously and when stimulated by electricity, by chemicals, and by disease. What is the function of such a universal response? In natural environments a seizure puts the subject at undue risk of predators and one would expect that after generations the behavior would be extinguished by natural selection. But the biology persists. Does the seizure serve a useful purpose? What is it? 13 Fractures of teeth, vertebrae, and long bones were unfortunately common. Many forms of physical restraint and chemical inhibition were tested. Curare, extracted from South American plants, prevented both the tonic (increased muscular tone, stiffening of the body muscles) and the clonic movements (rhythmic 13 �movements of the stiffened musces) of the seizure. 14 But curare was unstable. In some patients curare effectively blocked the motor movements and in others, the effects were small and a full seizure occurred. A dose on one occasion might effectively modify the seizure, but in the next, the same dose would fail to relax the patient. On occasion, paralysis persisted after the seizure and it was necessary to ventilate oxygen through a mask until natural breathing returned. We discontinued curare use and depended on sheet restraints alone to prevent fractures. Spine x-rays were taken in 50 patients before unmodified seizures and repeated in the week after the last treatment. In seventeen patients a compression fracture of lumbar vertebrae 4 or 5 or both was recorded. Surprisingly, these fractures elicited little complaint from the affected patients. Such compression fractures were accepted as a cost of the treatments. In the spring of 1953 a new synthetic muscle relaxant suxamethonium chloride (succinylcholine) was introduced. Limb paralysis occurred within 30 to 60 seconds of intravenous injection, dissipating within a few minutes of its application, making it an ideal agent for ECT. In our first experience we had not pre-sedated the patient, succinylcholine was injected, and when muscular twitchings (fasciculations) and a weakened knee jerk were seen, the seizure was induced. Tonic arching and clonic movements were much weakened. Spontaneous breathing returned quickly and the patient was moved to the recovery room. We injected our second patient, induced a seizure, and then we heard cries of “I cannot breathe, I cannot breathe” coming from the recovery room. Oxygen was administered by mask only to have the same experience with the next patient. Thereafter, we induced amnesia in every patient with amobarbital or thiopental before the succinylcholine injection. As more physicians studied this method of muscle relaxation, “modified ECT” was broadly accepted -- sedation by barbiturate, oxygenation by mask, injection of succinylcholine, and seizure induced when motor fasciculations and diminished ankle or knee jerk were recognized. Although my initial experience was in a hospital setting, most treatments were administered in office settings, such as in my office in Great Neck, where I treated patients in the early evening hours assisted by a nurse. “Modified ECT” raised questions. What was the role of the preliminary sedative -- to induce sleep, reduce anxiety, or block memory of the procedure? After the 1960s and 1970s, as “anesthesia” became the province of organized anesthesiologists, psychiatrists administering a sedative and the muscle relaxant were no longer tolerated, effectively ending ECT in independent psychiatrists' office settings. New sedation agents were studied. Benzodiazepines raised seizure thresholds, reducing treatment efficacy and outcomes. Methohexital offered short duration of action, safety and efficacy. New anesthetic agents – propofol, etomidate, 14 �ketamine, isoflurane –were tested. Propofol raised seizure thresholds, and the enthusiasm among some practitioners for minimal energies to induce seizures led to ineffective treatments and poor outcomes. Etomidate became fashionable for a time but the sedation was slow in onset and injection sites often became inflamed. Intramuscular ketamine usefully sedated excited delirious patients. An intramuscular injection in a patient restrained in bed would quickly sedate so that the patient could be moved to the treatment room and succinylcholine safely administered. By the 1980s “modified ECT” had become the universal standard, but not universal practice. In some countries, as in India, the expense of the additional chemicals and the belief in the need for an anesthesiologist led either to the inhibition of treatments or continued use of “unmodified” treatments. 15 Are Subconvulsive Treatments Effective? Were the benefits of electroshock and insulin coma inherent in the changes in physiology associated with seizures and coma or responses in the patient’s panic and fear? What was the role of electricity and the seizure? To address these questions, we induced sleep using amobarbital, muscle weakness by succinylcholine, and controlled the dosage of electricity at levels that did not induce a grand mal seizure. These methods reliably elicited “subconvulsive” non-seizure “sham treatments.” Of 24 patients in whom seizures were induced, 17 responded clinically and were discharged from the hospital; of 27 patients treated with subconvulsive sham currents, only 4 responded. Nineteen of the non-responders went on to convulsive treatments and 16 became responders. The EEG recordings of the subconvulsive treatments failed to show characteristic slowing. We confirmed that subconvulsive treatments were clinically ineffective and supported our belief that the therapeutic benefit was inherent in the seizure and not in the passage of electricity alone. 16 These findings ran parallel to those of a well-designed study conducted by George Ulett in St. Louis that also confirmed the seizure as essential to the treatment’s benefit. The results of our study were published in my 1979 textbook Convulsive Therapy. That year the British psychologist Timothy Crow challenged the profession to prove the need for the seizure. His challenge elicited multiple UK government supported studies presented in an all-UK conference in September 1979 in Leicester, and in a published appraisal edited by Robert L. Palmer. No study supported efficacy of non-convulsive treatments, reconfirming the critical role of the induced seizure. 17 15 �Are Chemical-induced Seizures as Effective as Electrical? In 1959 flurothyl (Indoklon), a new seizure-inducing chemical agent was proposed as a replacement for electrical induction. Hexaflurodiethyl ether, a volatile congener of the inhalant anesthetic diethylether, is both anesthetic and seizure-inducing. After a few inhalations the subject loses consciousness; additional breaths elicit a full grand mal seizure, usually within a few minutes. Four research teams – Joyce and Iver Small at University of Indiana, Albert Kurland at the Maryland Psychiatric Center, Björn Laurell in Sweden, and I and my associates at Hillside Hospital compared the effects of flurothyl and electrically induced seizures. Seizures were readily induced, with similar motor, seizure and interseizure EEG patterns. Both were clinically effective. Flurothyl seizures were of longer duration. Laurell reported lesser retrograde amnesia with flurothyl. In our study, 15 patients received unmodified flurothyl seizures and 12 unmodified ECT. The clinical benefits, behavior patterns, fracture rates, and degrees of EEG slowing were the same. For lack of an identifiable advantage over electricity, the induction of seizures by flurothyl fell by the wayside. The drug’s high cost and persisting ethereal aroma in the treatment room were deterrents. The smell was unpleasant, objected to by both patients and staff members. Further, the ease with which a seizure was induced frightened the professional staff as the treatment room soon was suffused with an ethereal aroma. Installing an in-wall exhaust air conditioner reduced the smell and mitigated the fears, but could not eliminate them. No advantage for flurothyl seizures was seen and we abandoned the method.18 Decades later, the pre-occupation with memory loss led to widespread reduction in treatment efficacy because many practitioners shifted to unilateral electrode placement, ultra-brief currents, and minimal dosing. Increasing reports of treatment failures sent me to re-assess the experience with flurothyl as a potential non-electricity seizure induction method. In the first quarter of the 21st Century, when repeated hospital site procedures for renal dialysis and chemotherapies and radiation for cancers are widely accepted, anesthesia sessions using flurothyl could well achieve the therapeutic advantages of induced seizures without the fright associated with electricity and the words “electric shock.” The review showed that flurothyl-induced seizures were clinically effective, that the effects on cognition and memory were less, encouraging a reassessment of flurothyl seizures. 19 Alas, I failed to entice any clinician to undertake such reassessment. 16 �Is Isoflurane anesthesia therapy a replacement for ECT? In the 1980s, Gerhard Langer and his colleague Greta Koinig in Vienna induced repeated sessions of isoflurane anesthesia in depressed patients believing such anesthesia sessions could replace ECT-induced seizures. Isoflurane is an inhalant anesthetic that quickly induces stupor, inhibition of EEG rhythms, and a flat-line EEG. Their report that six sessions on alternate days relieved severe depressive illness and was an effective replacement for ECT prompted my visit to the clinic in Vienna in 1983. I observed the feasibility of inducing isoelectric (“flatline”) EEG periods with the anesthetic and decided to replicate this experience. With the collaboration of Stony Brook anesthesiologists, isoflurane anesthesia sessions were undertaken in six patients who had been readmitted with recurrences of severe depression after earlier courses of ECT. In 21 of 26 anesthesia sessions, an isoelectric “flat-line” EEG lasting between 5 and 12 minutes was recorded. We did not observe reductions in depression rating scale scores, nor persistent changes on memory tests, nor characteristic changes in the inter-session EEG. After these failures, the patients were treated with conventional ECT with clinical recovery in five of the six. Isoflurane EEG suppression was deemed not an effective alternative for the seizures of ECT. 20 Periodically, this technology prompts interest and is re-evaluated. The studies have been poorly controlled and the reports convey authors’ enthusiasm without evidence of persisting behavioral or physiologic effects. Role of Acetylcholine: Anticholinergic Drugs and EEG and Behavior In the 1950s little was known of the physiology of the slow rhythms in EEG after induced seizures other than that their presence was necessary for clinical benefit. As the significance of EEG slow-wave activity was recognized, the chemistry of seizures was studied. George Ulett and LaVerne Johnson in St. Louis reported that anticholinergic atropine and atropine-like drugs blocked both post-seizure EEG slowing and the anticipated behavioral recovery after ECT. Herman Denber reported that injections of the chemical diethazine, another anticholinergic agent, reduced EEG slow wave activity after ECT. We replicated the finding for diethazine and also found that the antiparkinson agent procyclidine and various experimental anticholinergic drugs known as the JB-series also reduced post-ECT slow wave activity. When anti-cholinergic drugs were introduced late in the course of ECT, when mood and thought disorders were relieved, the EEG reversal was accompanied by behavioral worsening – patients no longer expressed denial language and increasingly complained of the recurrence of their symptoms. A day later, when EEG slow-wave activity had again returned, symptom relief was again expressed. We concluded that EEG slowing is a consequence of increased brain cholinergic 17 �activity. Puzzling over the brain effects of repeated seizures led me to consider a cholinergic hypothesis for the recovery with ECT. Free acetylcholine and acetylcholinesterases were elevated in the cerebrospinal fluid (CSF) of epileptic patients. CSF acetylcholine levels increased during ECT. In cats subjected to graduated head trauma, the amount of free acetylcholine and cholinesterases in the CSF increased with the severity of the trauma. I imagined that induced seizures, like cerebral trauma and epileptic seizures, altered cerebral permeability, increased free acetylcholine and cholinesterase levels in the brain, slowed EEG frequencies and increased amplitudes and rhythmic bursts. I pictured these biochemical changes as the basis for the behavioral effects we were seeing with ECT. 21 Study interest in acetylcholine waned as interest in brain neurotransmitters shifted to epinephrine, and then to dopamine and serotonin, as pharmacologists, excited by their ability to measure these neurotransmitters in animal brains tracked the effects of each of the new psychoactive moieties, that were then enthusiastically welcomed by clinicians and the public. At this juncture, half a century later, I find little interest in acetylcholine in clinical psychiatry or epilepsy. Neuropsychological Tests and EEG Slowing Immediately after a seizure, the patient awakens in confusion, poorly oriented as to location, date, or month, and often unable to recall the names of the attendant personnel. Commonly, the recovery is complete within an hour. The duration and severity of a patient’s errors vary with the number and frequency of seizures, the sedative and electricity doses, but most important is patient age -elderly patients are confused longer. With recovery to mental health, orientation normalizes and patients return to home, school and work. We tested the responses on the Face-Hand Test and found normal responses in the weeks after the last treatment. With increasing numbers of treatments, denial test scores and the changes with amobarbital paralleled scores on EEG measures, as earlier research had suggested. Persistence in denial was more often scored in older patients, in the less well-educated, and in immigrants with English as their second language. Scores on the Rorschach test were loosely correlated with the treatment outcomes but the specificity and predictability of the Rorschach criteria was low. Social attitude was tested by the 10-item California F-Scale, a measure of prejudice and authoritarianism that became of considerable interest in the wake of the NaziFascist eras. The patients with high authoritarianism scores were more likely to show benefits from ECT. 22 18 �Book Two: After an ECT Research Hiatus, Renewed studies During a four-year sojourn at the Missouri Institute of Psychiatry an ECT facility was not open to me -- psychopharmacology and quantitative EEG were the focus of our studies. Soon after I returned to New York in 1966 to direct studies of opioid abuse at Metropolitan Hospital, I received a letter from Richard Abrams, an Army medical officer scheduled to join the college medical residency program the following July, asking if I would meet him at a December conference of the ARNMD in New York City. He had compared the clinical benefits and changes on memory of ECT using non-dominant unilateral or bilateral electrode placements at a military hospital. He had administered seizures three times or five times weekly for 20 treatments in 10 subjects and reported no difference in efficacy nor in cognitive effects between treatments of the two electrode placements. He wanted to continue such studies and asked for my support and collaboration. I was still interested in understanding the mechanism of electroshock and agreed to support his studies. New York Medical College’s Department of Psychiatry lacked an ECT treatment unit at any of its clinical sites. The department chairman, Alfred Freedman, referred me to Lothar Kalinowsky, a member of the teaching faculty, who was treating his ECT patients at Gracie Square Hospital (GSH), a private hospital facility on East 76th Street in Manhattan. Kalinowsky was an early student of ECT, having witnessed its first applications in Rome in 1938 when he was studying with Ugo Cerletti and Luigi Bini, the developers of electroconvulsive therapy. He had published a leading textbook on the somatic therapies in 1946. He agreed to be a consultant to our work, arranged for GSH Medical Board approval of the study and for the collaboration by the clinicians who treated their patients in the hospital. Abrams and I asked: What is the optimal placement of electrodes in inducing seizures? We randomized patients to seizures induced either with non-dominant unilateral or with bitemporal electrode placements, measuring clinical, cognitive, and EEG changes at weekly intervals. And, could the treatment course be shortened by applying multiple treatments in one sitting? Recognizing that most patients recovered from a melancholic depression after 6 to 10 seizures, Paul Blachly, an Oregon physician, had reported that multiple seizures in one session were as effective as the same number of seizures spaced over many days. The Differences Electrode Placement Makes, Again 23 We tested 76 patients with a mean age of 63.4 years, 43 treated with bilateral and 33 with unilateral placements. By diagnosis, 60 patients were endogenous depressed and 16 reactive (neurotic) depressed. At the time, unilateral placement was considered less efficient in generating seizures and indeed some patients in the sample required additional seizures during their treatment course. 19 �We found bilateral ECT to be clinically more effective than unilateral ECT, with better and earlier outcomes regardless of age, number of treatments, or coincident medications. The memory tests during the treatment course changed less in the unilateral treated patients than the bilateral, varying with the task selected. On auditory tasks, the patients receiving bilateral treatments showed greater decrements than those receiving unilateral treatments; on a visual task, however, performance was unimpaired by either treatment. 24 EEG frequency slowing was greater after bilateral placement than after unilateral. An asymmetry was also observed in EEG slowing, accentuated on the right side with right unilateral electrode placement, and on the left side in bitemporal-treated patients. Although we did not understand the significance of either the degree of slowing nor the sidedness, these findings confirmed that the degree of EEG slowing was related to clinical outcome. The lesser EEG changes and asymmetry of unilateral ECT were signs of lesser physiologic changes--and lesser benefit compared to bilateral ECT. 25 Can Multiple ECT Treatments Per Session (MMECT) Shorten the Treatment Course? In 38 patients we applied either 4 or 6 seizures within a single anesthesia session. Different placements – bitemporal, non-dominant unilateral, or anterior frontal -- were tested. Only one patient achieved clinical remission after one session through bilateral electrodes, though we thought the benefits were accelerated in several others. The degree of EEG slowing was not enhanced, however, and the asymmetries were the same as we found in our single treatments. Post-ictal sleep among the MMECT patients was prolonged with greater disorientation and clouding of consciousness especially among the older patients. Neither we nor the experienced clinicians whose patients we treated were convinced that multiple treatments in a single session were an effective modification. We confirmed Richard Abrams’ experience that unilateral electrode placement could elicit effective relief with lesser effects on cognition, but at a price of lesser efficacy. Seizures induced through unilateral electrode placement, even with the maximal energies of alternating higher energy currents, were less effective than those developed through bilateral placements. The physicians at GSH, experienced practitioners with extensive clinical practices, were not surprised by our results. Many, including Renato Almansi, David Impastato, Lothar Kalinowsky, and William Karliner, were emigres from Europe who previously had each tested different electrode placements, electric currents, and dosing schedules and had concluded, based on their clinical experience, that unilateral placements were inefficient, requiring more seizures for relief and entailing higher early relapse rates. 20 �ECT in Systemic Medical Illnesses. In 1972 I accepted an appointment at the Stony Brook Medical School to teach psychopharmacology and develop an ECT Service at University Hospital. As the responsible clinician in the choice of treatments in an academic general hospital I explored ECT in patients with systemic medical disorders and psychiatric symptoms. We successfully treated mentally retarded adolescents, pregnant women, patients with brain tumors, brain aneurysms, cardiac pacemakers, malignant catatonia, anemia, Parkinsonism, delirium, and pseudodementia. ECT in Adolescents. ECT for children and adolescents was broadly interdicted by child psychiatrists as a matter of faith. They believed that ECT permanently damaged the developing brain. They did not ask for ECT consultations nor would they consider prescribing psychoactive drugs until the 1990s. Gabrielle Carlson, the Stony Brook Director of Child Psychiatry, would not allow her residents, many of whom had been trained in ECT while on the adult service, to consider ECT in any of their patients. The adult service, however, admitted adolescent patients over age 13. We successfully relieved adolescent patients in delirious mania, suicidal depression, malignant catatonia, and psychosis induced by LSD and cannabis. Young patients tolerated the treatments easily and the relief of psychosis was rapid with almost all returning home and to school. Mentally retarded patients are not protected from disorders in mood or psychosis by their condition, but when they suffer such illnesses, ECT is interdicted by beliefs that inducing seizures would further damage their brains. As our experience with adolescents became known, MR patients were referred for treatment and we described positive outcomes with remarkable improvements in their quality of life. A 14-yr-old mentally retarded boy with persistent self-injurious behavior (SIB), unresponsive to social and medication treatments was referred for treatment. He was admitted wearing helmet, glove, and camisole restraints to keep him from injuring his head, monitored by full-time aides for continuing protection. With parental consent a trial of ECT was begun. Within two weeks the restraints were no longer needed and he was allowed the freedom of the hospital unit. Over the next half year, continuation ECT sustained him in his community residence without the recurrence of his self-injurious repetitive behaviors. Decades later, Dirk Dhossche, a graduate of the Stony Brook University residency training programs and a participant in the catatonia studies, and Lee Wachtel, Director of the Neurobehavioral Unit of the Kennedy Krieger Institute of Johns Hopkins University, would identify SIB as a form of catatonia in autism, relieved by ECT. 26 ECT in Pregnancy. Many clinicians feared ECT during pregnancy, anticipating damage to the fetus by the electric currents and by the mother’s seizure, inducing miscarriage. But as fetal malformations were increasingly 21 �associated with psychoactive drug use during the first two trimesters of pregnancy, ECT was increasingly ventured. We simultaneously monitored the maternal and the fetal heart rates during each treatment. As the seizure in the mother unfolded, we could hear the rapid increase in her heart rate from 70 bpm to the 110s while that of the fetus ran at its own steady rapid rate of 110 to 130 bpm. The fetal heart rate did not increase during the seizure, showing only a small transient increase during the post-seizure recovery. After more than a dozen such monitored seizures, we no longer requested fetal monitoring and routinely accepted pregnant psychotic patients for ECT. We learned how to treat patients in each pregnancy trimester and optimally position a large pregnancy for proper oxygenation and anesthesia. The benefits of ECT were not limited by pregnancy and is now an accepted treatment. Pseudodementia. Confused elderly patients with poor memory, poor orientation, and poor self-care are considered demented and commonly labeled to be suffering Alzheimer’s disease. In some patients, however, the behavior is not the result of a structural brain defect but the consequence of a melancholic depressive illness labelled "pseudodementia." Both the mood disorder and the dementia signs disappear with effective antidepressant treatments. All patients admitted to my psychiatric ward suffering “dementia” were carefully evaluated and many treated for melancholia. This lesson was brought home to me by a 58-yr-old depressed, often mute, staring, and posturing woman who had been diagnosed as suffering from Alzheimer’s disease at two prior hospital centers. For eight years she had been continuously cared for in her home by her husband and daughters. When Helen was admitted to University Hospital with acute pneumonia, she was confused, disoriented, and depressed. A trial of antidepressant medications offered temporary relief but a full course of ECT resolved her dementia. She returned home to care for herself and her family. She relapsed, however, and monthly continuation ECT sustained her for years. Each relapse was marked by mutism, staring and repetitive picking at pictures and wall signs. When these symptoms were recognized as signs of catatonia, treatment with lorazepam extended the periods of her relief and only occasionally was ECT required. She lived for another decade, caring for her home and family, and taking part in community affairs. 27 As we could not distinguish pseudodementia from a structural dementia by our examinations, we offered medications, especially the older tricyclic antidepressants, finding good relief in about a quarter of the trials. An 85-year-old man with a 2-year progression of dementia requiring continuous nursing care was admitted for evaluation. Among the test findings he exhibited a positive dexamethasone suppression test consistent with melancholic depression. ECT was offered and accepted. Within three weeks he became oriented and able to care for himself. Continuation treatment with imipramine sustained his benefit and on one clinic visit he appeared well-dressed, accompanied by a well-dressed mature woman, declaring that they were to be married that week. 22 �Sadly, in the ensuing years since I left active service the prejudice against ECT is so strong that my recommendation among consultations for senile dementia were frequently rejected. The risks of ECT and of tricyclic antidepressants are small compared to the potential gain to a more normal mature independent life. Delirium. Many psychiatric consultations in a general hospital are to evaluate delirium, the common confusional and disoriented syndrome associated with systemic diseases, trauma, anesthesia, and surgery. After successfully relieving patients in delirious mania with ECT, we successfully treated deliria in post-surgical patients, those with abnormal systemic hormonal and fluid balances, and in alcohol withdrawal. We often found signs of catatonia in delirious patients, justifying the recommendations for ECT or high doses of benzodiazepines. Systemic medical risks. Many authors ascribe undue risks for ECT in patients with systemic illnesses. Brain lesions, tumors, and vascular abnormalities are considered “absolute contraindications” for ECT on the fear that the seizure would increase cerebrospinal fluid (CSF) pressures leading to cerebellar herniation and death. But the CSF pressures do not rise during our modified treatments. We reported safe treatment in a patient with a growing meningioma and in another patient with a large arteriovenous malformation. 28 Treatment of mentally ill patients in atrial fibrillation found conversion to normal sinus rhythm to occur and led us to recommend ECT with anticoagulation treatment as safe. 29 Optimizing Treatments. Anesthetics. After the hiatus from the ECT studies at Hillside Hospital in the 1950s, we again evaluated ways to optimize our treatments. The sedation and amnesia associated with the anesthetics etomidate, propofol, and ketamine, which were similar to that of methohexital, sometimes proved valuable. We again found a special use for ketamine in delirious patients – an intramuscular injection sedated a very disturbed patient within a few minutes, allowing us to move the patient from the ward room to the treatment room, and successful treatments followed without need for additional anesthesia. The induced seizures were more robust and their durations longer with ketamine. Neither etomidate nor propofol offered better amnesia than methohexital. Propofol raised seizure thresholds and shortened the duration of seizures. In elderly patients its use elicited seizures of poor quality. The rise in threshold associated with propofol is useful, however, in treating adolescents since their seizures are often prolonged even at minimal electrical dosing. Seizure durations. We studied the varying durations of monitored seizures by EEG, heart rate, and motor movements. In such recordings EEG durations were generally greater than 40 seconds, and arbitrarily considered “prolonged” when 23 �greater than 180 seconds. We often used intravenous diazepam to end seizures that ran over 150 seconds. Measured durations of EEG were longer than that of the motor seizure and both were commonly longer than the duration of the heart rate increase. We augmented seizure duration by injections of theophylline and caffeine. Although both agents lengthened seizure durations, such use had no observable benefit in treatment outcome and we discarded their use. How best to select energy to induce an optimal seizure? Concern for the cognitive side effects led to popular use of ever lower energies, just sufficient to elicit a motor seizure, often measured as 10 to 30 seconds. Were these seizures “adequate” for clinical benefit? We evaluated our recordings and identified a pattern of a slow build-up of amplitudes, onset of slow wave bursts mixed with spike activity, sudden ending in an electrically silent period. Seizures less than 40 seconds did not show these characteristics. For a number of years, clinicians were confused about seizure duration and efficacy. Some considered a series of short seizures, with added durations greater than 25 seconds “adequate” but such short seizures were clearly ineffective. Adequate seizures are best defined when greater than 40 seconds in duration with the full elicited EEG pattern. ECT in schizophrenia. The role of ECT in treating schizophrenia is confusing. Early I used the guidelines for diagnosis that labeled patients who were persistently psychotic, with language and speech abnormalities, episodic excitement and aggressive behavior as meeting the Kraepelinian criteria for schizophrenia that were adopted in the official American Psychiatric Association DSM classifications. We had no test to identify or verify such diagnoses so the treated patients were highly varied in their syndromes. The report of the 1978 APA Task Force on ECT offered little guidance, citing promising reports from clinicians with wide experience and the failure of organized clinical trials. I was invited to write several reviews on the role of ECT in schizophrenia, each time offering ambivalent opinions in the report. 30 No consensus could be reached because the diagnosis of schizophrenia was itself ambiguous, not distinguishing among long-term, chronic hospitalized patients and short-term acutely ill in ambulatory settings. The types of schizophrenia identified as paranoid, disorganized, undefined, and residual (each best viewed as variations of “hebephrenia”) were unresponsive to ECT. The single form of schizophrenia that was responsive was the catatonic. But as described later, this form was erroneously identified as schizophrenia, and is best appreciated as a uniquely identifiable, verifiable and treatable disorder. The presence of mood disorder in conjunction with schizophrenia confuses the matter. A melancholic psychotic illness is difficult to distinguish from schizophrenia and the insecurity is commonly arbitrated with the label of “schizoaffective” illness. Except for neurosyphilis, some hormone and vitamin deficiencies, 24 �catatonia and melancholia, all other psychiatric diagnoses are “in the eye of the beholder” and are not test verifiable. By contrast, the diagnoses of systemic medical illnesses have come to depend more and more on verification tests. The “medical model of diagnosis” is rejected in psychiatry – indeed the DSM classifications, including the DSM-5 of 2013 specify that no tests are known and none are applicable and that the diagnoses are best made by the association of symptoms recorded in interviews, illness course, and family associations. In studies of catatonia and melancholia, my associates and I, however, have argued that the search for verification tests is essential to the development of a psychiatric science. 31 Clozapine and ECT. A patient’s slow responses to chlorpromazine or fluphenazine is often augmented by concurrent ECT. When clozapine was first tested for the relief of psychosis, it was associated with an acute blood dyscrasia and withdrawn from the formulary. At the behest of clinicians who believed they saw unique beneficial properties in its use, however, prescription of clozapine was reinstated, but limited to patients who had failed at least two prior medication trials and whose serum clozapine levels could be tested weekly. We did not see a particular clinical benefit for clozapine alone in our patients. When we augmented clozapine treatment with ECT, the augmentation was occasionally useful. Such combined treatments was encouraged , however, by the EEG of clozapine. With clinical doses the EEG pattern becomes filled with bursts of slow waves, and the risk of overt seizures at high dosages. Such physiologic effects justified a clinical trial. We treated psychotic patients with clozapine and then, when the results were poor, augmented the treatment with ECT. We thought the synergy of the two treatments might be clinically useful and considered a proper clinical trial. The faculty at Hillside Hospital had supported clozapine use in therapyresistant psychotic patients. Many patients, however, were poor clozapine responders and they constituted a large population in their clinic. After I resumed an affiliation with Hillside Hospital in 1997 for the CORE studies I raised the question of augmenting clozapine with ECT. I obtained financial support from NIMH for a random-assignment study of ECT in clozapine-treatment failures. Half the patients who had not responded to at least eight weeks of serum-level monitored clozapine treatment continued with ECT augmentation and half continued clozapine alone. A 40% reduction in PANSS positive symptom scores without change in negative symptoms was recorded in about half the patients. What was missing in this study was treatment by ECT alone after withdrawal of clozapine. Intensive statistical manipulation of the ratings found minimal statistical advantages. 32 25 �Brain concentrations of fluphenazine. Was the increase in response of patients whose neuroleptic treatment was augmented by ECT seizures due to elevated brain concentrations of the neuroleptic agent? Studies by Tom Bolwig of Copenhagen had reported an increase in permeability of the blood-brain barrier after induced seizures in rats and in humans. We measured the brain concentrations of fluphenazine in rats treated with electroconvulsive shock but were unable to record a difference. 33 The CORE Study of ECT in Depressed Inpatients. In 1992 the psychologist Harold Sackeim of Columbia University applied for NIMH support for a multi-site study of continuation medications – placebo, nortriptyline, and the combination nortriptyline and lithium -- after ECT (using unilateral electrode placements) among unipolar major depressed patients. The NIMH consultants reviewing the application asked why he did not consider continuation ECT instead of placebo, since high relapse rates with no continuation medication were well documented. He demurred insisting on the placebo treatment arm. The reviewers, however, were unwilling to support such a study of continuation medications alone. The chairman Jonathan O. Cole argued for support, however, agreed to by the members provided a parallel study could be developed comparing continuation ECT with continuation medication of combined lithium and nortriptyline. With Cole’s encouragement I enticed Charles Kellner (Medical University, Charleston SC), Teresa Rummans (Mayo Clinic, Rochester MN) and John Rush (University of Texas, Dallas TX) to collaborate in a multisite collaborative study with the criteria for selection of patients, outcome evaluations, and combined medications identical to the Columbia University Consortium study. The single distinction was the CORE use of bilateral electrode placements at a minimum of 1.5 times the measured seizure threshold while the Columbia group used unilateral electrode placements with dosing set at 1.5 to 2.5 times the measured seizure threshold in their treatments. Patients meeting the clinical criteria for unipolar depressed patients were to be identified by an interview with a trained social worker using questions from a standard behavior rating scale. Initially, patients labeled bipolar depressed were excluded from the study, although many were treated with the same protocol after rejection from the study. The outcomes of the two subtypes did not differ, so we designed a second study treating both unipolar and bipolar depressed patients randomly assigned to bitemporal, bifrontal, and right unilateral placements. Both CORE studies were funded in 1997 by NIMH. 34 In Columbia’s CUC study the six-month relapse rates were much as anticipated: 80% for placebo, 62% for nortriptyline alone, and 36% for the 26 �combined lithium and nortriptyline. In the CORE study, the relapse rate for lithiumnortriptyline was 39%. With Continuation-ECT 32% relapsed, 22% dropped out of the study, and 46% continued in 6-month remission. We were disappointed with these ECT results and realized that the C-ECT treatment schedule had been arbitrarily set, less effective than what clinicians reported as necessary in ambulatory treatment schedules. When patients relapsed and we were able to induce seizures on clinical criteria alone, almost all patients sustained their remission with ECT as needed, like the treatment of diabetes or heart failure. To sustain an ECT benefit we needed to be flexible and introduce treatments when symptoms recurred. This lesson had been learned by practitioners in the early decades of ECT practice; and summarized in the review by the 1996 ACT ECT Task Force. (We foolishly erred in the CORE study based on our desire to be comparable to the CUC study.) 35 Much was learned, however. Seizures induced with unilateral electrode placements (RUL) are inherently inefficient. The lesser immediate (and transient) memory-loss effects associated with a unilateral electrode are a poor justification for outcome inefficiencies and the increase in the number of seizures and anesthesia sessions. The benefits of bifrontal ECT are slightly inferior to bitemporal ECT but can be justified by their ease of application. ECT is as effective in patients with bipolar depression as in unipolar. The common belief that ECT is less effective in bipolar depressed patients is false, a consequence I believe of the pharmaceutical industry’s marketing drive to establish a place for inefficient “mood stabilizers” and anticonvulsants separate from the prescription of lithium and antidepressants in psychiatric disorders, and the unwillingness of research leaders to recognize ECT as effective and safe. ECT rapidly reduces suicide preoccupations in melancholic and delusional depressive illnesses. In the more severely ill, those with high ratings on suicide assessment (item 3) in the HAMD24 rating scale, the suicidal self assessments were reduced 60% with six treatments within two weeks, justifying ECT as the primary treatment in patients who require special protections for suicide risk. Delusions in depressed patients identify a population of ECT-responsive patients. In the 1970s, Alexander Glassman and his colleagues at Columbia University reported that delusional depression did not respond to blood-level, monitored imipramine treatment. They did respond to ECT, however. While the overall ECT remission rate for the major depressed in the CORE study was 84%, the rate among the psychotic depressed patients was much higher, at 95%. The common policy of first treating psychotic depressed patients with medications, especially the use of less effective serotonin targeted antidepressants, with or without atypical antipsychotic drugs, cannot be justified. Like the use of RUL treatments, the insistence that psychotic depressed patients be subjected to one or two medication trials before ECT is questionable in its efficacy and its ethics. 27 �The Persisting Stigma: Memory Loss and ECT The argument that memory loss is a critical risk in all induced seizure treatments persists, however, encouraged by the constant singing of a “memory loss” mantra by psychologists and by some in the laity. At this writing, more than half a century after the initial studies, the use of unilateral electrode placement persists despite compelling evidence of its lesser efficacy in the studies sponsored in the UK in the 1960s and the more extensive NIMH-supported studies by the Columbia University Consortium (CUC) and the 4-hospital Consortium for ECT (CORE) that clearly showed that seizures induced through unilateral electrodes were clinically less effective, lowered recovery rates by 40% and increased the mean number of treatment sessions from 7 to 10.5. 36 Physicians are applying unilateral electrode placements knowingly offering patients lesser effective treatments that increase risks of treatment failure and higher relapse rates. What is the impact of ECT on memory? Patients who come to this treatment are severely ill, often with long periods of poor self-care, poor sleep, weight loss, and preoccupation with the self, the body’s discomforts, and little attention to work or family. They are then advised that they will need anesthesia, and electricity will course through their heads. They are warned, verified by the consent that they (and often members of their family) are asked to read and sign that explicitly states that they may lose memory, become confused and disoriented. They are then given a chemical intravenously that puts them to sleep, electrodes are pasted on the head, and a grand mal seizure is induced. Every seizure disrupts the brain’s physiology and chemistry. Awakening is slow, with confusion and disorientation persisting for some minutes in all subjects, much longer in the elderly and brain compromised. Most patients since the 1960s have first been treated with brain toxins – every “psychoactive” pill, whether antidepressant, anxiolytic, or neuroleptic or whether the alcohols, marijuanas, opioids or sedatives that are publicly attractive -- induces persistent changes in the brain’s electrophysiology that is measurable by the EEG. Responses to questions in the first hours after a treatment are slow, deliberate, and confused. And, it is fashionable nowadays, and surely by the psychologists and nurses who test for memory effects, to fire questions, one after another before treatment and again as soon as the patient’s eyes are open. Where are you? What is my name? What is your name? Where do you live? How much is 23 times 11? What is today’s date? 28 �And on, and on. When tests are repeated after many hours, the answers are slow but now correct. But after a series of treatments the errors may persist for days, especially in the elderly and in the chronically ill who have been the most brain-altered by an extensive potpourri of medicines. When specific neuropsychological tests are presented before treatment and again a week, a month, and 6 months after the last treatment, the recovery of cognitive functions is progressive so that in time the recovered patient functions as well, often better than during the illness. In batteries of more than 20 tests, psychologists have generally found that the normal functions have returned with only personal memories still offering errors. Of course, psychologists have prominently carried the “memory loss, memory loss” mantra against ECT by attention to these singular test data, not relating their test measures to the clinical changes and benefits in the patients. I have repeated psychological testing in all my ECT studies, at Hillside (twice), New York Medical College, and Stony Brook. I am often surprised by the quick return of functions with recovery after the illness. In the elderly I am not surprised by the patients who, in the hours after a treatment, speak poorly, recognize a relative hesitantly, and soil themselves. For the many who recover, these deficits disappear, and they return to pre-illness activities. Patients and family members are satisfied; so much so, that they insist on ECT when the illness recurs. Slow recovery is common in the repair of any illness. Think of the pains and discomforts in the long rehabilitations after a fracture, after major surgery, after acute trauma. The recovery after electroshock is the same slow and repair quality of major surgery. Shouting “memory loss, memory loss” is the same as shouting “painful walking, painful walking” after hip surgery. What is to be made of the anti-ECT positions of psychologists, psychiatrists and psychotherapists? The slander that infected ECT from the immediate post World War II period persists and frightens practitioners so that they do not realize that by offering inadequate treatments they are encouraging ongoing negative attitudes. The enthusiasm of the ECT practitioners for non-seizure treatments and the scalp tickling of the “brain stimulation” movements (encouraged by payments by sponsoring industrial companies) thrives on the falsehood that these treatments “do not affect memory." My personal experience lead me to conclude that memory effects are transient and no more limiting than the pains and blood loss after surgery. The most realistic and best documented reviews of the cognitive data are to be found in Richard Abrams’ textbook. 37 29 �Book Three: Electroshock in the Public Eye Creation of Induced Seizures as Therapy Was the mark of Cain that prejudices the use of inducing seizures to relieve emotional illnesses deserved? The carnage of the First World War released inhuman attitudes and tolerance, even enthusiasm, for attacks on human bodies in the name of treating the severe psychiatric ill. Prolonged sleep for days on end was accompanied by pneumonia and death; comas and seizures induced by insulin led to prolonged coma and death; lobotomy, especially the ice-pick variety, was associated with seizures, hemiplegia, and death. Skills in neurosurgery encouraged open brain surgery and electrode placement and stimulation by deep brain stimulation, leaving many with permanent brain lesions. Although electroshock had none of these risks, it was lumped together since the practitioners of one were called upon for all. The first inductions of seizures by chemicals did not go well. Ladislas Meduna, at a state hospital in Budapest, induced seizures by injecting the irritant camphor-in-oil into patient muscles. Few injections resulted in a seizure, all were painful and irritated the tissues. He next tested the intravenous chemical pentylenetetrazol (Metrazol), which, although more efficient, failed often enough that patients became extremely anxious, frightened, and refused further treatment after experiencing panic induced by a partial seizure. Despite panic and pain, the occasional fracture, the immediate confusion, the relief occasioned by many of the first patients encouraged its continued use. In his review of his experience, Meduna reported half his patients improved sufficiently to leave the hospital. 38 In May 1938 two Roman physicians, Luigi Bini and Ugo Cerletti, devised a more assured and less frightening method using electricity that quickly replaced chemical inductions and has since become the principal method of inducing seizures worldwide. Although the inductions were still frightening to both patients and clinicians, they aroused little public concern. They were better accepted within medical practice, and less feared than insulin-induced comas, prolonged sleep, or leucotomy. The names “electroshock” and “shock therapy” added to public concerns but did not stop the practice. That the treatment relieved the suicidal depressed, the hopelessly psychotic, and the uncontrollable manic encouraged widespread use in the world’s sanitaria and physicians’ offices. This success occurred at the time when the leaders of psychiatry were enthusiastically following the flag of psychoanalysis, promising cures for the psychiatric ill after months and years of “talk therapy” catering to the walking wounded. Psychiatric leaders committed themselves to the psychology of the mind, separate from the functions of the body and the brain. Every report of relief of an emotional disorder by fits and the repeated highlight of another Freudian therapy had failed or required a new therapist stimulated defensive attacks by psychiatry’s leaders that electroshock did not help the patient 30 �“understand or resolve his conflicts.” The benefits of inducing seizures were considered transient and, furthermore, damaging to the brain and antithetic to psychoanalysis since seizures extinguished personal memories. ECT Immediately Rejected By the Profession Immediately after the end of World War II, American psychiatric leaders formed a select political society, the Group for the Advancement of Psychiatry, that issued its first broadside on “Shock Therapy” on September 15, 1947. The handbill complained that electroshock’s widespread use in office practices offered only temporary relief. The benefit was considered inferior to the psychoanalytic understanding of life’s experiences and the resolution of conflicts that were the basis for a patient’s distress. I had studied psychodynamic theory at New York’s William Alanson White Institute and had undertaken a personal analysis for five years. I saw no challenge to a “biological explanation” of a patient’s history and symptoms and the reality that “somatic” treatments relieved my patients. No matter how I presented my experiences of rapid relief induced by repeated seizures, I was met by disbelief. In the 1970s romanticizing Freud became fashionable for Hollywood and Broadway, accompanied by images of Frankenstein’s monster, the electrified man, as the frightening alternative. Public reports of an excessive use of ECT in children in Massachusetts in 1970 sharpened the attacks. State legislators frantically proposed laws to prohibit ECT. Milton Greenblatt, the director of the state’s mental health program, argued that legislative restrictions would interfere with accepted medical practice and negotiated the tabling of the proposed legislative bills until the actual experiences could be studied. He commissioned a survey of ECT in Massachusetts to be conducted by Fred H. Frankel, Professor of Psychiatry at Boston’s Beth Israel Hospital and an expert in hypnosis treatments. The 1973 review of practices in Massachusetts did find hospitals where ECT use was excessive, seizure inductions haphazard, and medical care facilities inadequate. Greenblatt issued medical guidelines to standardize ECT practice. His report and the regulations satisfied both legislature leaders and the practitioners, markedly improving clinical practice, becoming a national model for treatment facilities. The resolution encouraged a broader acceptance of the treatment and a reference source for establishing treatment facilities. First American Psychiatric Association ECT Task Force (1975) Early in my career in psychiatry, at annual meetings of the American Psychiatric Association (APA) I joined the Section on Brain Function & Behavior where ongoing arguments on how to optimize ECT were active. Discussions on ECT were also featured as clinicians assembled annually at the Electroshock Research Association, Society of Biological Psychiatry, and similar associations dedicated to lobotomy, insulin coma, and carbon dioxide therapy. When Milton Greenblatt 31 �deflected the drive of the Massachusetts legislature in 1970 to interdict the use of ECT, he organized the survey of ECT and also asked me to edit a special number of his journal Seminars in Psychiatry on the scientific status of ECT. 39 Legislative restrictions against the use of ECT and lobotomy with specific interdiction in persons under age 18 surfaced again in 1972, this time in California. In response, psychiatrists led by Dr. Gary Aden applied for court relief from legislative interference in accepted medical practice. The court agreed that the legislative restrictions of medical practice were unacceptable. The legislature responded by using the state’s power to monitor health and safety to limit the number and frequency of treatments, restrict guidelines for consent, require extensive reporting of treatments, and prohibit its use in persons under the age of 18. The regulations forced many patients in need of treatment to go out of state as California physicians abandoned the treatment. These regulations are still in effect in 2021 and severely limit ECT use, especially in adolescents. The same restrictions were adopted in Texas in 1993 and in other states to a lesser degree. Requests for professional support by California psychiatrists led the American Psychiatric Association to establish a Task Force on ECT in 1975, and appointed Fred Frankel of Boston as its chairman. I was an appointed member. The report published in May 1978 described whom to treat, how to assure safe procedures and effective treatments, and discussed concerns about cognition and memory and how to minimize these effects. A query about ECT practices had been sent to 20% of the Association’s membership. Responses were received from 75% of those canvassed. Was ECT an appropriate treatment for any of 11 different psychiatric diagnoses? The responses showed widespread confusion as to whom to treat. ECT was considered useful for patients with major depression (86%), less so for manic excitement (42%), and marginally for schizophrenia (25%). About 22% of the responding practitioners had used or recommended ECT in the prior 6 months. Featured in this confusion was the inadequacy of the official psychiatric classification schemes, their use providing poor descriptions and inadequate diagnoses and not assuring optimized treatment plans. The Task Force members were experienced in clinical care and most procedural questions were readily resolved. A thorny issue was endorsement of treatments using unilateral electrode placement. At a committee vote, I and another clinician member could not recommend the use of unilateral placement, arguing that its inefficacy necessarily led to increased numbers of seizures with attendant anesthesia risks, lengthened hospital stays, higher costs, and potential for increased morbidity. The reported lesser effect on cognition was transient, not justifying the inefficacy of the treatments and prolongation of illness. 32 �When the Task Force report was submitted to the APA Board of Trustees for publication under its imprimatur, the policy leaders insisted nevertheless that the unilateral form of treatment be endorsed (along with the bilateral), to support the practices and beliefs of some members. How best to assure consent? Patients referred for ECT are severely ill, depressed, psychotic, delirious, and suicidal, often mute and negativistic, raising questions as to their competency to understand the risks and benefits of proposed treatments and to consent freely. Can a patient so ill as to be referred for seizure therapy properly evaluate the risks of memory losses described by psychologists and in the public press? Medical practice treats patients by voluntary consent, the patient appearing at the physician’s office and choosing whether to follow the physician’s prescriptions. Can the same rules apply for electroshock? The Task Force members recommended a lengthy printed description of the procedure with detailed risks to be read by and to each patient, to be signed voluntarily, and properly witnessed. The form would name the treating personnel, and specify the maximum number of treatments under the consent. I was conflicted in this discussion. My father was a general medical practitioner; I had seen his interactions with patients and their families, and how they respected him and readily accepted his recommendations, including his insistence for an independent second opinion in complex diagnoses. I experienced the same deference when I took over his practice during his holidays and again when I opened a community office in Great Neck for consultations in neurology and psychiatry. In the Task Force discussions, I was one of two physicians who, at first, did not see the need for a written “contract”, but agreed before submission to the APA. ECT was viewed as a surgical procedure (since it uses anesthesia) with a potential for harm that must be specifically consented to by the patient. Patient autonomy would be respected by describing the anticipated benefits and risks before treatment and treating only those who voluntarily agreed. Further protection was to be achieved by a family member also reading the descriptions, discussing the procedures and risks, and witnessing the patient’s signature. Exceptions to voluntary consent were recommended for those with mental deficiency or dementia. These were considered to be the family and community responsibility. State-mandated procedures for judicial authorization for treatment on an incompetent patient’s behalf were supported by the task force. The recommendation of a signed, voluntary consent for treatment was the main benefit of the Task Force Report. The text was considered an “official” action of a national association and served as a guide for the opening of new ECT treatment centers throughout the nation in the post-1978 years. I was often invited to visit 33 �and organize new treatment units based on the Task Force Report. The recommended procedures were sufficiently conservative to be widely adopted. The Task Force report was distributed at the May 1978 APA annual meeting in Miami with each task force member presenting an aspect of the report to a large audience. I was the spokesperson for the technical recommendations. The report was generally accepted and praised. The concept of a written consent was argued but accepted. The note accepting treatments through unilateral placements, however, met strong protests from practitioners, notably New York’s Lothar Kalinowsky. Much of his criticism was directed at me as the spokesperson. The practitioners, themselves extremely well experienced with bilateral and unilateral electrode placements, argued that treatments through unilateral electrode placements were so inefficient as to put patients at risk of prolonged illness and suicide, poor outcomes, longer courses of treatments, and higher relapse rates. Out-Patient ECT: Association for Convulsive Therapy Commission Post-World War II, ECT patients had been increasingly treated as outpatients in doctor’s offices, both for their treatment courses and continuation treatments. But as ECT in the 1980s demanded collaboration of a qualified anesthesiologist, ECT became a hospital-based procedure. The prescription of a fixed number of treatments, usually 6 to 10, became commonplace. Such courses had been sufficient with the high energy, bilateral placement seizure inductions favored by the early office practitioners and those treating patients at Gracie Square Hospital. When patients showed signs of relapse, ambulatory continuation treatments were readily undertaken. During the 1970s, with repeated public and professional attacks on ECT, physicians often negotiated a fixed number of treatments for a course. The idea that the length and frequency of an ECT course could be prescribed in advance, even agreed to in the patient-signed consent, was widely accepted as recommended by the ECT Task Force of the American Psychiatric Association in its 1978 report. The treatment image became one of a specifically effective treatment, much like a prescribed antibiotic for an infection. But ECT treatment for depression or mania or even catatonia is more like that of insulin for diabetes: an acute fixed schedule is prescribed and is immediately effective but open-ended continuation dosing is necessary for sustained relief. When ECT was re-introduced in the 1980s, many clinicians thought that psychoactive medications would sustain ECT relief. After a course of ECT patients were prescribed psychoactive medications, often in unique combinations of polypharmacy, and while success was common, relapse became an increasing burden. In 1987, Thomas Aronson and colleagues from the Stony Brook out-patient treatment facility reported greater than 50% relapse rates within 6 months for my ECT-treated delusional depressed patients regardless of continued medications. I 34 �was chagrined and saw the need for continuation ECT. Our ECT Service treated patients three days a week, so we set aside one day (and later two) for out-patient treatments. We no longer asked patients to consent to a fixed number of treatments but asked their consent for continued observation and treatment “as needed” beginning as in-patients and continuing in our ECT out-patient clinic for six or more months. How best to prescribe and manage continuation treatments was widely discussed in the journal Convulsive Therapy and at meetings of the Association for Convulsive Therapy (ACT). That Association established a Task Force that surveyed usage, evaluated risks, and recommended guidelines, publishing their conclusions in 1996. I chaired the group and published a report that became a guide for continuation treatments. 40 The Stigma Persists: The Public Joins the Attack The popularity of psychotherapy and psychotropic drugs in the 1960s led to a sharp decline in ECT use. But as medication treatments increasingly failed and families asked what else could be done, ECT use resurfaced. The shadow of lobotomy and patient and psychologists' complaints of memory loss encouraged persistent attacks against ECT, and as these became more strident, my public support for the procedure brought me much public criticism. Burton Roueche’s exaggerated description of a government economist’s memory loss in the 1974 New Yorker article “All About Eve” brought Marilyn Rice to public attention. She instituted a malpractice suit against the psychiatrist who administered the treatments complaining that she had not been warned that her memory would be affected and that she would be unable to work. 41 She went on to develop and lead the public action group Committee for Truth in Psychiatry that launched further attacks on ECT. She frequently appeared at public forums to challenge ECT use, proclaiming her persisting loss of memories. (The Court supported the physician defendant.) After Marilyn Rice died in 1992 the Committee for Truth in Psychiatry was led by Linda Andre, who made the same claims after her treatment course following a suicide attempt by drug overdose. She was a vivacious, well-spoken, and attractively dressed woman who attended public meetings and paid particular attention to meetings in which I presented my work. She challenged speakers and attended the 1992 international ECT meeting in Graz, Austria to voice her opposition to the treatment. The international audience was surprised by her personal attacks. She attended my public lectures and protested my presentations at annual Continuing Medical Education psychiatry training sessions in various cities. On one occasion, when the floor was opened to questions, she attacked me as dishonest and paid to lie about the effects of ECT. She walked up to the podium offering me a tray containing a pig’s head surrounded by dollar bills. 35 �Church of Scientology and Malpractice Legal Suits In the 1960s, the national political and social movement of Scientology led by the futurist Ron Hubbard opportunistically attacked psychiatry with special attention to the prescription of psychotropic drugs in children and adolescents and the brain effects of ECT and lobotomy. The members and their children demonstrated with shouts and anti-ECT posters in the halls and at entrances to American Psychiatric Association meetings and other sessions at which ECT was discussed. On occasions when its members arranged for complaints to be aired on TV talk shows, I was asked to defend the treatment but refused to take part. The hosts delighted in challenging professionals on their incomes and on the damage that had been done to the patients who complained bitterly about memory losses. Yet, many patients spoke well, encouraged by the host whose mission was to support the “poor” patient and to castigate physicians for damaging patient’s brains. The Church of Scientology also encouraged and financed malpractice suits against practitioners, asserting that patients had lost memories of long periods of their lives, particularly the most personal family memories. I appeared as a witness for the defense on numerous occasions with Peter Breggin, John Friedberg, and Harold Sackeim as expert witnesses for the plaintiffs. The cases were weak and my defense of the practitioners was successful in every instance except that of Peggy Salters in South Carolina in 2005. She had been given ECT as an outpatient with 13 treatments in 19 days. The physician deemed the patient suicidal, but failed to offer her hospital protection. She complained that her memory was so damaged that she could no longer work. While I did not believe that the patient had suffered compensible damage, the physicians had not followed standard practice in protecting the suicidal patient nor in justifying almost daily treatments. I deem the judgment for the patient correct. Media Attacks: BBC-PBS Madness with Jonathan Miller. In 1990 I received a call from a London TV production company asking if I would help with the presentation of convulsive therapy in a planned 5-hour BBC/PBS documentary on the history of treatments of the mentally ill to be titled Museums of Madness. The producer, Jonathan Miller, had impressive qualifications as a Cambridge University graduate in neurology and the son of a psychiatrist. He had acted in the original cast of the successful Broadway play Beyond the Fringe (1960-64), directed performances in theatre and opera, and written and directed a popular 13-hour BBC production The Body in Question (1979). While playing on Broadway he attended Saturday morning Grand Rounds in Neurology at the Neurological Institute with H. Houston Merritt. 36 �I met with Miller and Grace Kitto of Brook Productions and agreed to their filming of my patients and the treatment procedures at University Hospital. I arranged that they return again three weeks after the first filming to record the patient’s progress and that I see the frames of my patients before they were aired. For filming on May 17, 1990 I selected patients with different diagnoses who were early in their course of treatment. SK, an 18-year old delusional psychotic man who had been in repeated treatments for more than two years; EF, a 60-year old psychotic depressed woman who was posturing, repetitive in speech, and unable to care for herself; ET, a melancholic depressed woman with a history of mania and excitement; and JF, an elderly man who had been depressed, lost much weight, and careless in his self-care. Appropriate consent for filming was obtained for each patient. The filming of interviews and treatments went smoothly. The team returned three weeks later for follow-up filming. Patient SK was better oriented, EF answered questions without repetitive speech or acts, ET smiled and was friendly and better oriented, while JF assured us that while he could not recall why he was being treated, he felt well and was ready to go home. Asked about memory, he thought that his memory was as good as it ever was. The treatments were not painful at all, he said, and surely less uncomfortable than seeing the dentist. On October 15, 1990 on my way back from meetings in Berlin, I visited the Brook Production Studios in London to review the print. The presentation of the patients and the treatment were very well done and I was pleased. My concept of neuroendocrine dysfunction as the basis for the disorders that are relieved by seizures was well presented. Many months later, when the series was aired in the U.S., Miller’s voice-over set a very different tone: ‘The administration of an electric shock through the skull is a comparatively crude assault on the brain. ‘. . . as machines were invented to whirl, swirl, shock, rock, and douche the patient back to sanity, the sick brain was treated to a series of traumatic assaults presumably in the hope that its distorted parts would be jolted into place. ‘. . . the treatments resulted in violent convulsions with serious bruising . . . fractures of limbs and spine . . . and other atrocious consequences. ‘. . . despite its understandably sinister reputation, ECT, Metrazole and insulin have much more in common with the whirling chairs and rotating cradles which they superseded, in that they were addressed to the brain as if it were a single undifferentiated organ.” 37 �Miller’s failure to find a positive thread in the histories presented by the patients left many viewers with a bad taste, and the series was not presented again. In a recent biography of Miller, the author Kate Bassett makes much of Miller’s conflicts with his father, a leading forensic psychiatrist, as the basis for his negative attitude to medicine. Whether this relationship contributed to his views of psychiatry or not, he was among many creative writers who saw psychotherapy and psychoanalysis favorably, indulged by themselves, friends and family members, seeing electroshock treatments as hazardous, ineffective, and not acceptable in their social class. An Active Defense: A Beautiful Mind: The Nobelist John Nash and Insulin Coma. A call from the biographer Sylvia Nasar in 2001 asking whether I had experience with insulin coma therapy made me aware of the life history of John Nash, the 1994 Nobelist in Economics. A brilliant mathematician, Nash had successfully completed his doctorate at Princeton University, publishing a thesis on game theory that was reputed to revolutionize economics. While teaching at MIT in May 1959 he became delusional, overactive, impulsive, and fearful, meeting criteria for delirious mania. He was treated in Boston’s McLean Hospital by psychotherapy and chlorpromazine. Aware that his statements led to his incarceration he hid his beliefs and was discharged to the community. He left his teaching position and returned to Princeton. The paranoid psychosis persisted and he fled to Europe and sought to give up his American citizenship. Returning to Princeton in 1971 floridly delusional, he was admitted to Trenton State Hospital. His Princeton colleagues implored the Medical Director that Nash was a potential Nobelist and warranted the most effective treatment. Insulin coma treatment, although discarded elsewhere, was still in use. It was the most heavily staffed service, and in response to his colleagues’ pleas, Nash was assigned for treatment in that unit. He responded by relief of his overt delusions but the director suggested the follow-up treatment be ECT. Nash’s wife and colleagues refused that “brain-damaging treatment” and he was continued on medication with chlorpromazine. Nash did not recover and did not return to productive work; he remained cared for by his wife and attended lectures at Princeton. Nasar’s biography A Beautiful Mind was to be the basis of a Hollywood film and she wanted advice on the actual experience of the treatments that Nash had been given. I described my experience at Hillside Hospital, noted that seizures occurred in more than 10% of the coma sessions. The film highlighted the seizure, and I was pleased by the portrayal of the illness and the treatment in the film. I reviewed my experience with insulin coma and concluded again that the central therapeutic events were the incidental seizures, not the coma or an effect of insulin, or any other aspect of the treatment. Like injections with camphor and 38 �Metrazol, insulin coma was best viewed as an inefficient form of induced seizure therapy. As the originator of ICT, Manfred Sakel insisted that the comas selectively destroyed sick brain cells leaving only healthy cells. He argued that the seizures were incidental, irrelevant side-effects. But experienced clinicians welcomed the seizures and often added ECT during coma sessions for the poorly responsive. I realized that the efficacy of insulin coma therapy lay in the occasional grand mal seizure, that ICT is best seen as an imperfect form of induced seizure therapy. 42 39 �Book Four: The Enigma: How Do Seizures Alter Behavior? Seizures are Inherent Reflexes Grand mal seizures are patterned reflexes seen in our species, indeed in all mammals. Seizures that occur spontaneously constitute the debilitating disease of epilepsy. Ladislas Meduna’s 1934 discovery that inducing seizures in the psychiatric ill relieved both abnormal thoughts and the peculiar and repetitive motor behaviors of schizophrenia was a remarkable and still unheralded discovery in the history of medicine. By 1938 electric currents had been shown to immediately induce a seizure with minimal pain and less risk than Meduna’s chemical methods, and the electrical induction of seizures -- electroshock -- quickly became a widely accepted treatment of the psychiatric ill. The induction of a bilateral grand mal brain seizure is the central therapeutic event. A patterned EEG of a minimum duration of 30-40 seconds is the principal marker of an adequate treatment. An increase in hypothalamic-pituitary hormones in the blood and cerebrospinal fluid is another marker. No characteristic of the induction stimulus itself, whether chemical or electrical, is essential for clinical benefits. Attempts to treat patients by subconvulsive electric or magnetic currents or by non-seizure inducing anesthesia (isoflurane) dosing have been unsuccessful in eliciting behavioral benefits. Although many patients report immediate changes in mood, motor activity, and thought, repeated seizures over many days or weeks are typically necessary for lasting clinical benefits. Attempts to sustain the clinical benefits by psychotropic drugs are occasionally successful, but for persistent benefits repeated seizures are best. How do seizures alter behaviors? We do not know. My thinking on this question has evolved over the years. Early in my career and with the hubris of the novice I combined physiological and psychological features in “a unified theory of the action of physiodynamic theories.” That construct was re-labeled the neurophysiologic-adaptive view a few years later. I argued that the changes in behavior, toward greater denial of illness, was facilitated by altered brain physiology. 43 My studies with anticholinergic compounds showed me that drugs that inhibit brain acetylcholine reversed the mood benefits of ECT. The elevated levels of brain acetylcholine associated with recovery in mood and thought seemed sufficient to justify what in 1962 I described as a cholinergic theory. I argued that seizures increased the brain levels of acetylcholine and cholinesterases, and that these changes altered neuroendocrine functions, mainly of the hypothalamic-pituitaryadrenal and hypothalamic-pituitary-thyroid axes. This hypothesis was consistent 40 �with the ongoing enthusiasm for changes in the brain transmitters that were thought the basis for the changes in behavior associated with psychotropic drugs. As chemist’s skills improved and concentrations of endocrine hormones in the blood could be measured, my interest focused on vegetative signs in psychiatric illnesses. Attention to the TSH hormone response to TRH and abnormal thyroid physiology was quickly followed by interest in adrenal hormones and the dexamethasone suppression test in depressive illness. Not only were thyroid and cortisol abnormalities markers in the psychiatric ill, the abnormalities normalized with effective treatments. I sought to confirm these reports in our patients treated with ECT at the Northport Veterans Administration hospital in Eastern Long Island. When Jan-Otto Ottosson also saw merit in a neuroendocrine image of ECT, we formulated a neuroendocrine theory that we published in 1980.44 After forty years, I believe this theory remains the most viable explanation for the efficacy of induced seizures in patients ill with melancholia. While this theory may not be applicable to the benefits in other psychiatric illnesses, it is a pointer that warrants greater study. The Theories The behavior changes induced in the psychiatric ill by the bizarre technology of repeatedly inducing grand mal seizures is puzzling and has encouraged a plethora of theories, some based on brain and body physiology and chemistry, and some on magical thinking. My ruminations and their origins have evolved with my experience. Neurophysiologic-adaptive theory. At Bellevue Hospital in the 1940s my teachers were much interested in anosognosia, the failure of awareness or the active denial of a deficit in motor functions (as in post-stroke) or denial of sensory loss (as in denial of blindness), as I described in Chapter 1. Special attention was paid to how humans perceived multiple stimulations as when two pinpricks or finger strokes were simultaneously applied to different body parts. Even in patients with brain functions compromised by trauma, age, infection or tumor, a single sensory stimulus may be readily perceived but the perception of two simultaneous stimuli varies with the subject’s alertness and vigilance. The errors are evidence of compromised brain functions, of the syndrome loosely described as the “organic mental syndrome.” After head injury, stroke, brain tumor, aging, infection or repeated seizures, only one stimulus is reported (extinction), or the second stimulus is perceived at another body site (displacement), or pointed into space before them (exosomesthesia). Under the influence of injected amobarbital, perception errors and the expression of denial language increase. These reports became the basis for the Face-Hand Test. During the course of electroshock, errors increased with numbers of treatments. The greater the degree of EEG change, the greater the perceptual errors. Among the scientists at Bellevue, Edwin Weinstein, Louis Linn, and Robert 41 �Kahn proposed “denial” as the mechanism for the relief afforded depressed patients by electroshock. They catalogued a “language of denial” making it possible to score the number of denial terms in an interview transcript. When amobarbital was injected at a fixed concentration and a specified rate, the number of expressed denial terms increased, especially in brain compromised patients. I studied the expression of denial during ECT by weekly amobarbital and EEG tests and recording patient responses. As EEG slow wave activity increased with more seizures, so did expressions of denial in those patients who showed the greatest relief of depressed mood., I adopted this explanation of the changes in behavior during ECT as an increase in denial. Depressed patients commonly complained of insomnia, anorexia, fatigue, weakness, and loss of interest in daily activities. After treatment, the complaints are relieved and when asked what is wrong, they deny their earlier complaints. Since the connection between denial and improvement had been proposed by my teachers, and as EEG and sedation tests verified their proposition, I adopted denial as an explanation. 45 I did not seek greater understanding of physiology until years later. Such an explanation was applicable in the patients with melancholic and psychotic depression, but was not relevant for the response of those in delirious states, catatonia, mania, or psychosis. These states are marked by disorientation and confusion, mutism and negatism, hyperactivity and disorders in thought that needed broader explanations than the simplistic denial of symptoms. Their responses required another explanation. Cholinergic theory. My interest in the effects of psychoactive drugs on the EEG led me to study the effect of drugs on the ECT process. A colleague, Herman Denber, interested me in studying the behavioral effects of diethazine, an experimental anticholinergic drug that blocked acetylcholine stimulation. The chemical was a new moiety created in industry with the hope that it might have clinically favorable psychoactive properties. He was unable to identify a clinical benefit, reporting that patients became more disorganized and irritable. I tested diethazine to our improving ECT patients, those with signs of denial and recovery from a depressive state and with high degrees of EEG slowing. The slow waves were blocked and the records became filled with low voltage fast rhythms. Patients became irritable, anxious, agitated and again depressed, a reversion to their pretreatment states. We inferred that the relief of depressed mood with ECT was related to increased levels of acetylcholine in the brain. George Ulett and his colleagues at Washington University had administered atropine, a potent anticholinergic drug, during the ECT treatment course and reported that it blocked EEG slow waves and elicited pre-treatment behaviors in the patients. Similar reversal of mood was also reported after injections of the experimental anticholinergic JB-329 (Ditran) and its congeners, supporting the connection between brain cholinergic levels and mood. 42 �Much interest was shown in acetylcholine in neuroscience research in the 1950s. Free acetylcholine and acetylcholinesterases were elevated in the cerebrospinal fluid (CSF) of epileptic patients. CSF acetylcholine levels increased during ECT. In cats subjected to graduated head trauma, the amount of free acetylcholine and cholinesterases in the CSF increased with the severity of the trauma. Again, hubris allowed me to picture the physiologic consequences of induced seizures as similar to those of head trauma. 46 I imagined that induced seizures, like cerebral trauma and epileptic seizures, altered cerebral permeability increasing free acetylcholine and cholinesterase levels in the brain, slow EEG frequencies and increase amplitudes and rhythmic bursts. I pictured these biochemical changes as the basis for the behavioral effects we were seeing with ECT. My focus on acetylcholine as the critical agent in treatment followed the happenstance finding that anticholinergic agents reversed the seizure-induced EEG and behavioral changes. But study interest in acetylcholine waned as interest in brain neurotransmitters shifted to epinephrine, and then to dopamine and serotonin, as pharmacologists, excited by their ability to measure these neurotransmitters in animal brains tracked the effects of each of the new psychoactive moieties, that were then enthusiastically welcomed by clinicians and the public. At this juncture, half a century later, I find little interest in acetylcholine in clinical psychiatry or epilepsy. The Neuroendocrine Hypothesis. When I was asked in 1977 to supervise an acute treatment unit and its ECT facility at the Veterans Administration hospital in Northport, much academic interest was being shown in brain peptide hormones in the psychiatric ill, particularly those of the thyroid, adrenal, and pituitary glands. The Nobel Prize for Medicine that year was awarded for the demonstration of peptide hormones in the brain and for the radioimmune assay that measured their presence. Hormone changes in our patients became measurable by thyroid and adrenal function tests. These glands are instrumental in maintaining the daily wakefulness cycle, the response to fear and stress, and monitoring sleep and other bodily functions. The TRH stimulation test, the release of TSH to an intravenous bolus of TRH, was blunted in a quarter of the severely depressed patients. After a course of ECT, we did not find the changes in TRH levels that we had hoped would help us decide whether the treatment course was successful. Cortisol derived from the adrenal gland was a useful marker. Serum cortisol levels were unusually elevated in institutionalized depressed patients, an observation in the 1970s that led an Australian psychiatric team under Brian Davies and Bernard Carroll to study cortisol functions in their patients. They developed the dexamethasone suppression test (DST) as a measure of adrenal function. Their reports are filled with extensive observations of hormone functions and psychiatric 43 �illness but the note that particularly stimulated my interest was their experience with ECT in melancholia. In five melancholic patients the cortisol measures were deemed abnormal (elevated and not suppressed by the steroid dexamethasone) before treatment. After ECT the clinical features of melancholia remitted and the cortisol measures normalized. Then two of the patients relapsed, again exhibiting signs of melancholia with abnormal cortisol functions. Second courses of ECT resolved the clinical illness, again normalizing the cortisol measures. Carroll described an additional seven patients in whom treatments had not resolved the depressive illness nor normalized the DST. The test, it seemed, was a marker of illness severity and of treatment response. At the Northport hospital a research fellow Yiannis Papakostas confirmed the relationship between severity of depression, abnormal DST, and the response to ECT that Carroll had described. The test was difficult to perform and the end-point criteria needed more careful study, but the changes in the neuroendocrine tests with improvement in melancholia led to more detailed studies of the response to ECT. Seizures, both in epileptic fits and in those induced in ECT, released the pituitary adrenocorticotrophic hormones (ACTH) and prolactin into the CSF and blood. By 1978 attention was directed to the association of the contributions to behavior of the products of the hypothalamus, pituitary and adrenal glands, (HPA axis) in melancholic depression and the response to ECT. At the 1978 New Orleans NIMH Conference on ECT, I described my experience with the DST, supporting Bernard Carroll’s experience. At the same conference Jan-Otto Ottosson independently supported the same endocrine findings. Melancholic psychotic patients have abnormalities in functions of the HPA endocrines, and these return to normal after recovery. I described a “neuroendocrine” hypothesis for ECT in Convulsive Therapy: Theory and Practice and cited what was known of the process: “A theory of convulsive therapy must account for the significance of the seizure but disregard the mode of induction, the direct actions of currents, and the distinctions caused by various electrode placements. It must consider the difference in response among patients with diverse psychopathologies and the time, measured in days, needed for a favorable outcome. Biochemical explanations must relate to changes in the brain rather than in the blood, urine or other tissues. Psychological, personality, and linguistic considerations may affect the behavioral response and should be considered, but these are probably not central to the antidepressant efficacy of induced convulsions.” And I described the hypothesis thus: 44 �“Hypothalamic dysfunction is a core process in endogenous depressive psychosis. Convulsive therapy alters hypothalamic activity both by direct stimulation of hypothalamic cells and by increasing the functional neurotransmitter activity in the brain, thereby releasing substances, probably peptide hormones, that alter the vegetative functions of the body and the endocrine glands. Specific substances are released that modify mood and the behaviors associated with mood disturbances. The biochemical events that precede and accompany the seizure are the trigger for increased neurohumoral activity. In ECT, the direct stimulation of electric currents augment but are not necessary for the effects on hypothalamic functions.” The mechanism was envisioned for patients with psychotic depression in whom the efficacy of ECT was well grounded, inducing remission in more than 90% of the cases. In the same chapter I discussed the evidence for ECT’s effect on mania, catatonia, and schizophrenia. While the treatments were successful in mania and catatonia, we lacked studies of endocrine changes to support a connection similar to that with melancholia. In schizophrenia the efficacy of ECT was insecure, being successful in acute illnesses and in catatonia, but ineffective in the more common chronic ill with the hebephrenic forms of the illness. In the 1980s I attempted a study of peptides in the cerebrospinal fluid during ECT. Of nine patients with psychotic depression referred for ECT with mean scores on the Hamilton Depression Rating Scale greater than 25, eight were nonsuppressors on the DST. I collected their lumbar CSF before ECT and then after treatments number 6, 10, 12 and 14. The samples were collected within one day after a treatment, and in five patients additional treatments were deemed necessary. The frozen samples were shipped to Charles Nemeroff and Garth Bissette at Duke University and to Huda Akil at the University of Michigan for analyses for the peptides of the corticotrophin-releasing factor, somatostatin, and beta-endorphin. The samples showed significant falls in levels of corticotrophin releasing factor and ß-endorphin but a non-significant rise in somatostatin. 47 The findings were not encouraging to the neuroendocrine hypothesis. While the hypothesis could be erroneous, our actual procedures did not meet the more optimal criteria that would be used today. We made arbitrary choices in our treatment mode. We used unilateral electrode placement with EEG monitoring of seizure duration, selected sampling in mid-course of treatment, with varying resolution of the illness and the DST, and were only able to test for a limited number of peptides. The study demonstrated the complexity of studies of the ECT mechanism. While I was interested in proceeding further, I lacked facilities for chemistry. Instead, I was in a position to pay more attention to the clinical questions of the ECT process that became the CORE studies undertaken between 1993 and 2005. 45 �Conferring in the Search for the Mechanism Believing that it must be possible to understand the relief of certain psychiatric illnesses by inducing seizures, I have participated and encouraged discussions of possible mechanisms throughout my working life. Surely the extensive experience that inducing seizures improves the behaviors and the lives of many severe mentally ill must be a challenge in present day biology. What follows is a chronological account of moments in this endeavor. 1972. The first encouragement came in convincing a committee at the NIMH to support a symposium on ECT mechanism. The committee asked two leading neurobiologists, Seymour Kety and James McGaugh, to join me in organizing a 1972 meeting in San Juan, Puerto Rico, titled Psychobiology of Convulsive Therapy. Attention was focused at the meeting on the neurophysiology of seizures, the role of changes in cognition, and the neurochemistry of catecholamines. 48 The panelists dedemed persistent changes in EEG recordings essential to the behavior changes in the therapy. In the absence of persistent EEG changes, only weak and transient behavior effects occurred. Changes in memory were not essential to the behavior benefits. The complaints of loss of recent memories were side-effects of the electricity, the anesthetics, and the seizure. The changes were not central to the effects of seizures on mood and thought. Much interest was shown in newly discovered brain neurotransmitters that “explained” the effects of psychoactive drugs on brain functions and behavior. Changes in the neurotransmitters were considered an explanation of the behavioral effects of repeated induced seizures as well. Seymour Kety cautioned, however, that “. . . there is no dearth of demonstrable biochemical changes which are associated with electroconvulsive shock. Indeed, the difficulty lies not in demonstrating such changes, but in differentiating between those which are more fundamental and those that are clearly secondary, and also in attempting to discern which of the changes may be related to the important antidepressive or amnestic effects and which are quite irrelevant to these.” In the 49 years since that meeting, the ECT literature has been filled with correlations of brain and systemic increases of many biochemical and behavior measures. But no study has offered a consistent association between neurotransmitter functions and changes in mood and thought, either for induced seizures or for any of the many psychoactive pills. 46 �1978. Continuing interest in ECT encouraged NIMH leaders to organize a larger conference in February 1978 in New Orleans on “Efficacy and Impact” with a larger panel of clinicians and scientists. In the six years since the San Juan Conference interests had broadened to the safety of regressive ECT (intensive daily treatments that were applied in chronic psychotic patients), the efficacy of different electrode placements, changes in electric currents from alternating to brief pulse currents, the clinical usefulness in patients with mania and schizophrenia, and the relation to endocrine measures. At this conference I became aware that Jan-Otto Ottosson had also been stimulated to examine the changes in neuroendocrine measures, and we joined in publishing the neuroendocrine hypothesis for the mechanism of induced seizures in Psychiatry Research in 1980. I was so impressed with the relation of neuroendocrine changes to behavior that in writing my 1979 textbook Convulsive Therapy: Theory and Practice, I credited the neuroendocrine explanation for ECT as the most viable. 1985. The hostility and controversies about ECT encouraged the NIMH to hold a public Consensus Conference in October 1985. Although the panelists included experienced practitioners, greater attention was paid to the critical opinions and biases of lay and professional critics. The discussions were raucous and were accompanied by shouting and hostility. The published reviews added little to either the clinical or the mechanism interests, reflecting the continuing rejection of and prejudice against the treatment in the public and the professions. 1986. Motivated by the circus of the Consensus Conference, Sidney Malitz and Harold Sackeim organized a conference at the New York Academy of Sciences in 1986. The presentations covered the broad issues of clinical efficacy varying with diagnosis, results of biochemical, neurophysiologic, neuroendocrinologic, and psychologic changes during the course of treatments, and mechanisms of action. Jan-Otto Ottosson detailed the essential characteristics of an effective seizure and treatment course; Bernard Lerer and Baruch Shapira looked at the impact of seizures on neurotransmitters; and Robert Post and his NIH colleagues discussed the anticonvulsant effects of seizures. They saw the anticonvulsant effects in mania in the therapeutic stream, endorsing anticonvulsant medicines to treat manic behaviors. Harold Sackeim and colleagues reported a rise in seizure thresholds during the course of ECT treatments, arguing that the benefits of induced seizures were in the anticonvulsant effects. Pierre Flor-Henry focused attention on the theoretic lateralized changes in the non-dominant hemisphere as the basis for the behavior change with seizures. These proposed mechanisms were no more exciting than the presentations a decade earlier in the San Juan conference, and they stimulated little further study. 1989. Still hoping that invited discussions might encourage study, and as Editor of the journal Convulsive Therapy, I asked Harold Sackeim to invite authors with an interest in the mechanism to write reviews for a special number of volume 5. An impediment to formulating a single hypothesis is the efficacy of induced seizures across the broad spectrum of psychiatric disorders. Surely, no single 47 �mechanism can explain the diverse effects in melancholia, mania, catatonia, delirium, and Parkinsonism. The same hurdles were described by Pesach Lichtenberg and Bernard Lerer and by Sukdeb Mukherjee in discussing the relief of mania. In a reprise of the debates on the merits of unilateral electrode placements, Richard Abrams challenged the reported advantage for treatments induced in the right hemisphere rather than the left, raising the importance of the details in any induced seizure study seeking to understand mechanism. Charles Nemeroff and I, in the midst of our collaborative studies of peptides in CSF, asked whether we anticipated higher or lower levels of peptides as the basis for melancholic depression and relief by ECT. We favored the image of lower levels of peptides active in maintaining normal mood and suggested that the seizures might release an active peptide that we named antidepressin. Our optimism in picturing an additional peptide was generated by the increasing number of substances that were being publicly characterized as altering mood, alertness, and cognition in the psychiatric ill. But, nothing has come of it, another nagging consequence of my not having developed skills in biochemistry. 1992. In editing a second edition of his textbook Abrams repeated the diversity argument that the efficacy of induced seizures over many illnesses made theorizing not particularly useful until a better understanding of psychiatric illness emerged. He saw our understanding as similar to that of the peoples in the 18th Century picturing burning as a process involving the imaginary substance phlogiston. He concluded that we await the intervention of a modern Anton Lavoisier, the French scientist who discovered oxygen, 20% of the air we breathe and the basis for burning substances by their combination. 1998. The continuing challenge of mechanism led Charles Kellner, the succeeding editor of Convulsive Therapy, to ask Bernard Lerer to invite opinions on what was learned about the neurobiology of seizures. Lerer again complained of the difficulty of seeking a single mechanism for a procedure with such a broad effect among many disorders. Reviews by John Mann and Ron Duman were no more useful. Nor was an explanation based on the anticonvulsant actions of seizures. Studies of the brain neurotrophic factor, neuropeptides, TRH and related peptides, and neuropeptide Y each fell to the criticism by Kety that the broad effects of seizures on many brain chemicals made it unlikely that changes in any single measure would be relevant to the mechanism. At best, any single measure would be a marker of the breadth of the changes induced in brain biology. 2014. The present editor of the Journal of ECT, Vaughn McCall organized another review of mechanisms. He asked Pascal Sienaert to organize the reports that were published in June 2014. Each survey considered the main measurable consequences of seizures – changes in the EEG and psychological tests, neurotransmitters, neuroendocrines, and immune and cardiovascular systems. I chose to remind readers that the central event was the seizure and not in any aspect of electricity, by noting the equivalent efficacy and consequences of flurothyl induced seizures to those induced electrically. 48 �Roger Haskett of the University of Pittsburgh discussed the neuroendocrine hypothesis. Haskett had studied cortisol in melancholia and ECT in collaboration with Bernard Carroll when both were at the University of Michigan in the 1980s. In retrospect, the discovery of the changes in human behavior by repeated inductions of seizures is a remarkable page in the history of medicine. As I read the invited articles on mechanism submitted to JECT in 2014, I do not see a better explanation than that of the impact of seizures on the hypothalamic-pituitaryadrenal and hypothalamic-pituitary-thyroid systems. 49 �Book Five: The Road to Catatonia During my days in medical school and residency training I assume I observed catatonic patients. Indeed I recall walking through hospital wards, dressed in the short white coat of the student, with two 500 mg vials of Amytal sodium in one pocket, a metal autoclave box containing a sterile syringe and needles, a tourniquet and bottled water in the other, to sedate the excited and the manic and to relax and obtain the cooperation of the negativistic and the mute. But during the decades of clinical practice as a research physician in New York and St. Louis hospitals, I cannot recall recognizing catatonia as a distinct syndrome. In my research positions, I had little front-line responsibility to examine and treat the acutely ill. It was during my visit to the Bakirköy Hospital in Istanbul in 1965 that I saw nude women, standing in rigid Christ-like postures in hospital windows and rows of posturing men as we went through the wards. Catatonia is a systemic disorder of acute onset with mutism, posturing, rigidity, and stupor, and at other times as intense excitement and delirium. Patients remained ill for months and years filling long-stay hospital wards. Now, we have the technical means and the skill to recognize and treat these patients successfully and rapidly. Turan Itil, my research colleague at the MIP in St Louis, and I were visiting the Istanbul Bakirköy hospital to supervise a study of a new neuroleptic, butaperazine. Our arrival was welcomed by a patient band, colorfully dressed in 19th Century Turkish pantaloons and multicolored shirts, beating drums and cymbals, and playing the baglama string instruments -- an image of a mental hospital before the psychopharmacology era. My enduring interest in catatonia was aroused in 1980, when I became responsible for supervising the care of acutely ill patients and teaching students on the in-patient unit at University Hospital at Stony Brook. My experience with a fully restrained delirious woman and the resolution of her illness excited my interest.. The Teaching Case On a morning in the Fall of 1987 I was teaching an expert class in ECT when a patient from the medical service was referred for evaluation. A class of five graduate physicians saw a restless, delirious and febrile 25-year-old woman in fourlimb restraints, nasogastric and urinary catheters and intravenous fluids running. When alert, she was negativistic, posturing, rhythmically thrashing, alternating mute and screaming. She was suffering the systemic disease of lupus erythematosus, an acute autoimmune disease, being treated with intravenous methylprednisone for the lupus and sedated with haloperidol and lorazepam. An EEG had shown seizure-like activity and phenytoin was prescribed to block spontaneous seizures. She was in an acute manic and catatonic delirium. 50 �Was she a candidate for ECT? The physicians, influenced by the severity of her systemic illness, the restraints, parenteral feeding, and manifest weight loss, thought not, that the treatment was likely to do her more harm. They demurred even after I described the rapid relief with ECT in three patients with the same psychiatric complications of lupus that had earlier been reported by Samuel Guze at Washington University. Contrary to the class opinion, the severity of her excited illness supported treatment with ECT since the treatment was remarkably safe even in the most systemically ill patients. With consent of her family and her physicians, a course of ECT was begun on hospital day 28. Within 10 days and 7 treatments the delirium was relieved, restraints were lifted and cooperation improved. But family and physician fears and prejudices against continuing ECT forced me to stop her treatment, a decision that I strongly objected. She regressed rapidly, again required restraints, and her family now pleaded for further treatment. A second ECT series from days 68 to 90 resolved her catatonic illness. By day 100 she was discharged with medical relief of lupus and without signs of catatonia or delirium, to remain well and report the care of her family at one-year examination. The severity and life-threatening nature of her illness, the rapid resolution with ECT, and my realization of her behaviors as “catatonia” intrigued me. Gregory Fricchione, then chief of Stony Brook’s Consultation and Liaison Service and very experienced with catatonia, having developed lorazepam treatment while studying at Boston’s Massachusetts General Hospital, had referred her for ECT after failed treatment with high doses of lorazepam. For the next few years we studied catatonia together. I became fascinated with the remarkable change from a delirious and moribund woman to a recovering mother with relief of a syndrome that I had hardly studied. I became interested in the story – how catatonia was discovered and described in Germany in 1874, how another German psychiatrist incorporated catatonia in his concept of schizophrenia that prevented much progress in its study. Catatonia as a Type of Schizophrenia In 1874 Karl Kahlbaum, the director of a private sanitarium in Görlitz, Germany, clustered peculiar motor behaviors of some of his patients into a single syndrome of “Die Katatonie.” In a rich text of 26 clinical vignettes, he clustered mutism, immobility, negativism, posturing, staring, grimacing, stereotypy, mannerisms, and several other motor signs as a single syndrome. The underlying illnesses that brought the patients for hospital care varied, with 12 patients severely depressed, nine suffering from seizure disorders, three with neurosyphilis, and two with tuberculosis. In a poignant final chapter of his book, Kahlbaum sadly notes that he could offer no useful treatment except to hope for spontaneous remission, which actually did occur in some cases. Death was all too common. 49 51 �By 1899 Emil Kraepelin, the German psychopathologist, teacher, and author of numerous textbooks, having recognized the same signs, published dramatic photographs of posturing and grimacing patients. He observed his chronic mentally ill patients for many years and characterized two principal syndromes. The patients with delusions, language difficulties, and hallucinations that began during adolescence and progressed to dementia were suffering from dementia praecox. Those with depressed moods alternating with mania suffered from manic-depressive illness. Catatonia was seen in both groups. In later editions of his textbooks, Kraepelin described catatonia as a marker of dementia praecox. This association of catatonia with dementia praecox was accepted by the Swiss psychiatrist Eugen Bleuler who renamed the illness as schizophrenia. His approach was based on the beliefs of psychoanalysis, seeing catatonic symptoms as accessory manifestations of Freudian complexes, thereby marginalizing their importance in the diagnosis of schizophrenia for generations of psychiatrists, sidestepping the analysis of psychiatric nosology and obscuring efforts to conceptualize catatonia. When official classifications of psychiatric disorders by the American Psychiatric Association emerged in the 1950s, schizophrenia, catatonic type was the singular recognition for catatonia. This characterization dominated the psychiatric classifications during all of the 20th Century. It was this association that I was taught. But Catatonia Is Not Schizophrenia Awareness that catatonia was not limited to patients with schizophrenia came slowly. By 1973, after examining the records of 2500 hospitalized patients with extended follow-up at the University of Iowa, James Morrison reported that 10% met criteria for catatonia at their index admissions. Re-examination of the records of those patients at a later date found 40% had, at some point, recovered completely after treatment with sedative hypnotics or ECT. Morrison argued that these recovered patients could not be examples of schizophrenia, a disorder for which treatments, at best, reduced the severity of symptoms but did not relieve the illness. A year later Richard Abrams and Michael Alan Taylor, two students from my classes at New York Medical College, identified 55 patients with one or more catatonia signs admitted to two wards at New York City’s Metropolitan Hospital over a 14-month observation period. Only four patients among these satisfied the research diagnostic criteria for schizophrenia, while more than two-thirds met the criteria for affective disorders, usually mania. They reported the salutary effects of treatments and a factor analysis of the data identified two factors, one associated with mania and good outcome with treatment. 52 �That same year, Alan Gelenberg in Boston described eight patients who became toxic and febrile with severe Parkinsonian motor signs after receiving high potency neuroleptic drugs. He cited the cases as instances of “the catatonic syndrome.” In 1980, Stanley Caroff in Philadelphia, after describing 60 reported cases of neurotoxic responses to neuroleptic drugs, labeled an acute onset lethal catatonia syndrome with fever, autonomic instability, altered consciousness, stupor, and the rigidity and posturing signs of catatonia as the “neuroleptic malignant syndrome” (NMS), a label that was widely adopted. He ascribed the syndrome to excessive dopamine blockade and prescribed dopamine agonists such as bromocriptine. In time we learned that these treatments were ineffective, and they were replaced by lorazepam and ECT, the effective catatonia treatments today. In Contrast to Schizophrenia, Catatonia is Treatable. In 1930 William Bleckwenn, an American physician in Wisconsin, reported that catatonia could be relieved by injections of 2.0 or more grams of amobarbital (Amytal). Mute, staring, stuporous and posturing patients responded to injections by speaking, answering questions, and self-feeding. These changes were reported and also shown in a black-and-white film that was instrumental in launching the practice I was taught. A second effective treatment of catatonia, inducing grand mal seizures, came de novo into the world on January 2, 1934 when Ladislas Meduna, a Hungarian neuropsychiatrist, injected camphor-in-oil into the buttocks of chronic psychiatric ill at the Lipótmezó sanitarium in Budapest. By happenstance, the majority of his patients exhibited the negativism, mutism, and motor abnormalities -- now considered signs of catatonia -- that were then considered signs of schizophrenia. His method of induction was inefficient, however, eliciting a seizure in only one third of the subjects. Behaviors changed little but the few that did improve sufficiently impressed him to continue. Later that year he used a better method of intravenous injections of pentylenetetrazol (Metrazol), which elicited fuller and more reliable seizures. The changes in behavior were so remarkable that he reported his cases in 1935 and again a year later at a meeting in Switzerland that canvassed experiences in new treatments of psychosis from 22 countries, setting the stage for worldwide interest in seizures as therapy. Three years later he published his experience with 110 patients, reporting relief in more than half, especially among those acutely ill with catatonia. A year after that, the Italian physicians Ugo Cerletti and Luigi Bini demonstrated the same relief-inducing seizures using electricity rather than chemical injections. These treatments were remarkably successful in relieving 53 �catatonia, so much so, that once clinicians caught on, it was possible for a neurologist in 1981 to ask decades later, “Where have all the catatonics gone?” Is NMS a Form of Catatonia? Recognition of the neuroleptic malignant syndrome came slowly into professional awareness. The occasional sudden death of a psychotic patient treated with chlorpromazine or other potent neuroleptic drugs raised little intellectual interest until the Caroff report appeared. After reading his description we at Stony Brook recognized three patients treated with neuroleptics who met his criteria for NMS. Repetitive motor movements, mutism, posturing, and negativism marked each story. We discontinued neuroleptic medications and, following Caroff’s guide, prescribed bromocriptine. One patient responded slowly, but two did not. ECT brought quick relief. Although my curiosity about catatonia was not aroused until we treated the woman in delirious mania described earlier, we did find other cases of NMS. 50 At the height of the summer of 1976, a 23-year old agitated and aggressive psychotic man under my care at the Central Islip Psychiatric Center was refusing food and fluids and required restraint and sedation. Intramuscular haloperidol was administered. The ward was incredibly hot, he became dehydrated, febrile, suffered a seizure, became stuporous, and died within 12 hours. Neither physical nor psychological post-mortem reviews suggested a compelling reason. In retrospect, his acute death was an unrecognized example of NMS, the toxic syndrome associated with haloperidol that was waiting to be discovered. Another example of NMS was the death of Libby Zion, an 18-year-old college student being treated for depressed mood with phenelzine. In the summer of 1984 she was admitted to New York Hospital febrile, agitated, and disoriented with abnormal motor movements. Meperidine was administered, her agitation worsened and parenteral haloperidol was added. Now in stupor, her temperature quickly rose to 107oF and she died. Her family sued the hospital for malpractice and in 1993 I was asked to review the records as an expert witness in the hospital’s defense. The many initial diagnoses did not consider NMS, but by the time of the legal case her experience was recognized as an example of neuroleptic-induced malignant catatonia. As NMS became increasingly recognized, various treatments were tested. By 1983 Gregory Fricchione described four cases in which high doses of lorazepam and withdrawal of the neuroleptic relieved the syndrome. Case reports of lethal catatonia secondary to neuroleptic use followed quickly, each affirming the connection and citing relief with cessation of neuroleptic use and treatment with benzodiazepines and ECT. The significant connection between malignant catatonia and prior experience of catatonia was made by Denise White of South Africa who described five patients in whom the catatonia signs preceded the administration of a neuroleptic. In a second report a year later catatonia was presented as a precursor 54 �to the malignant state, raising the question as to whether the neuroleptic malignant syndrome, malignant catatonia, and the non-malignant forms of catatonia were manifestations of the same psychopathology. The acceptance of NMS as a form of catatonia was slow, inhibited by the different treatments offered. Stanley Caroff and his colleagues believed that NMS resulted from the neuroleptic inhibition of dopamine activity and focused treatment with dopamine agonists bromocriptine and amantadine. Because the fever, muscle rigidity, and weakness simulated malignant hyperthermia, they augmented treatment with the muscle relaxant dantrolene. Despite poor responses and continuing deaths, many authors applied this prescription. An international debate ensued, carried on for more than two decades, whether NMS was best considered an abnormality of dopamine metabolism and treated with dopamine agonists or malignant catatonia and treated with benzodiazepines and ECT. The debate argued at meetings of psychiatric societies and in the literature with Stanley Caroff, Gregory Fricchione, Steven Mann, Patricia Rosebush, Theresa Rummans, Michael Taylor, Gabor Ungvari, Denise White, and myself as the protagonists. The debates strengthened my interest in catatonia, as I viewed NMS as a form of malignant catatonia. Essential to the different views was the failure to recognize the signs of catatonia. For many observers the essence of NMS was the fever, autonomic instability, and muscle rigidity, encouraging belief in an overlap with malignant hyperthermia. Interest in catatonia was minimal, blocked by the prevailing belief that catatonia was schizophrenia, despite the reality that few NMS patients met the criteria for the thought disorder, impaired speech, delusions, and hallucinations that characterized schizophrenia. Further, treatments of NMS-classified patients with barbiturates and benzodiazepines were considered to risk tolerance development and dependence, beliefs that were substantiated by the FDA’s restricted prescribing rules. Dosing was limited to a few milligrams of lorazepam, inadequate for the relief of catatonia. Few hospitals had ECT treatment units so clinicians could not prescribe this treatment--but all could prescribe dopamine agonists and dantrolene. Then, in 1990, Michael Taylor presented a detailed argument distinguishing catatonia from schizophrenia in a historical and clinical review of its 100-year history. He described both retarded and excited forms of catatonia and detailed effective treatments with barbiturates, benzodiazepines, and ECT. He connected the motor signs to the pathophysiology of the frontal lobes, presenting catatonia as an entity of many causes and many forms, thus challenging its consideration solely as a form of schizophrenia. 51 Simultaneously, the neurologist Daniel Rogers from the Burden Neurological Hospital in Bristol, England presented a similar challenge. Of the100 chronic schizophrenic ill he had examined, many exhibited catatonia and Parkinsonism. Their presentations, though, were similar to those that had occurred during the 1918 encephalitis epidemic, indicating that catatonia was not confined to 55 �schizophrenia. He described a systematic examination and a rating scale to identify catatonia, defining catatonia within neurology practice. 52 Both Taylor and Rogers questioned the Kraepelinian dictum that catatonia was a form of schizophrenia. Their doubts were consistent with my own that catatonia was not a marker of schizophrenia. That led me to argue for an independent status for catatonia in the illness classifications. The Drive to Official Definition. Was catatonia a singular identifiable disorder with common characteristics and homogeneous pathophysiology, or a galaxy of psychiatric aberrations with different pathologies? The 1980 DSM-III identified catatonia by the presence of at least one of the five signs of stupor, negativism, rigidity, excitement, or posturing. My Stony Brook colleagues culled the more detailed descriptions of catatonia signs by Kahlbaum, Kraepelin, Taylor, Rogers, Rosebush, and Lohr and Wisniewski to develop a 23-item list of identifiable signs scored on a 3-point scale and described a systematic examination that could be used to derive a diagnosis. Using that rating scale in 1994-95 we examined every patient admitted to our ward for catatonia signs. In potential catatonia cases, prescribed neuroleptics were quickly withdrawn, the effect of a single dose of intravenous lorazepam or diazepam was tested, and the patients treated with high doses of diazepam or lorazepam or with ECT. We next surveyed all patients admitted to the Psychiatric Service and the Psychiatric Emergency Room of University Hospital during a 6month period using our rating scale. Of 215 patients examined, 9% had two or more signs of catatonia. In the next year, of 470 patients examined we admitted 28 patients with four or more signs of catatonia to the in-patient service of University Hospital. Of these, 15 were affectively ill, 4 psychotic, 3 with NMS, and 6 with various systemic medical illnesses. A review of the University Hospital records for the 5-year period beginning in 1985 with discharge diagnoses of schizophrenia, catatonic type (DSM 295.2) identified 43 charts. Of these, seven patients were also charted or discharged as affective disorder, five as organic affective disorder, and seven as schizophrenia. Eleven had been treated with ECT, with full relief in eight, confirming again the remarkable efficacy of seizures to relieve catatonia. The Sedative Verification Test Could the relief of catatonia’s signs with intravenous lorazepam confirm the diagnosis? Since William Bleckwenn had rapidly resolved catatonia with injections of amobarbital, intravenous amobarbital had been widely used to gain speech for the mute, encourage feeding and toiletting in the negativistic, quiet the aggressive, 56 �and arouse the stuporous. In 1983 Gregory Fricchione recommended that amobarbital be replaced by lorazepam and that the reduction of catatonia signs be considered a verifying test for catatonia. As verification of catatonia in patients with 2 or more catatonia signs for 24 hours or longer, we adopted the criterion of a 50% reduction in the catatonia rating scale score, if it occurred within 10 minutes of the intravenous administrations of 1 to 2 mg lorazepam. The prescription of 3 mg/day of lorazepam, increased rapidly by 3 mg increments to 30 mg/day became our treatment protocol. Of 28 patients identified with catatonia signs, 23 recovered with lorazepam dosing alone, 5 did not. Of the four who consented to ECT, three recovered with 2 to 3 treatments, while one required 11 treatments. This experience was published in 1996 and the protocol became our standard diagnostic and treatment procedure; within a few years these methods were widely adopted and central to the recommendations of the textbook of catatonia that Taylor and I published in 2003. 53 The Many Faces of Catatonia. Beginning with our recognition of NMS, Michael Taylor and I soon accepted other syndromes such as delirious mania, toxic serotonin syndrome, pervasive refusal syndrome, NDMAR encephalitis, Self-Injurious Behaviors in adolescents, and several other labeled syndromes that exhibited multiple signs of catatonia that were relieved by known treatments. We thought that the syndromes must have a common pathophysiology since the signs were overlapping and the same treatments were effective. Delirious mania. Catatonia is recognized in a sedated form of stupor, mutism, posturing, and negativism. It also is recognized in an excited, manic state. Catatonia is more often recognized among manic patients than among those with depressive moods or psychosis. Among the patients admitted to our psychiatric facility so excited and overactive as to require physical restraint, we increasingly recognized the signs of catatonia. Some vacillated between aggressive screaming and posturing mutely, with peculiar repetitive movements. Others were febrile, hypertensive and tachycardic. Some were delirious, all were confused and poorly oriented. Many had been treated with haloperidol or other high potency neuroleptics precipitating the malignant febrile form of illness. Some had seized and anticonvulsants had been prescribed. Many patients required four-limb restraints or were maintained in a padded isolation room. We withheld neuroleptics, prescribed high doses of parenteral benzodiazepines, and were often able to minimize the excitement. But the severity of the fever often forced more immediate treatment with ECT. Daily ECT found relief of excitement, delirium, and fever had occurred by the third day in almost every case. 57 �Taking patients who are suffering a malignant systemic illness and subjecting them to the risks of anesthesia and induced seizures is counter-intuitive. But the fatality rate of febrile catatonia and the life-saving quality of daily ECT was demonstrated in 1952 by Otto Arnold and H. Stepan. They had treated 18 patients in their first clinic in 1947/48 with delayed treatments and 16 in their second 1949/50 with prompt treatments. Of the 18, 15 died and 3 survived; of the 16, 13 survived and 3 died, The lesson of daily or multiple seizures was learned, and I applied their experience on numerous occasions . The Stony Brook hospital unit consists of rooms around a circular core. From the entrance to the ward it is possible to see the doors to 3 to 5 rooms. I often came to the ward by 7 am, seeing a chair outside a room, with an aide watching the patient inside. These were the patients under 1:1 observation and care, often the most delirious and excited, or late adolescents with self-injurious behaviors. A 29year-old HIV infected man had become severely depressed, suicidal, and delirious, refusing his HIV medications. In the ER, he was injected with haloperidol, became agitated and febrile. On the ward he was in 4-limb restraints, 1:1 observation, and parenteral fluids. After increased dosing with lorazepam with little response, we induced his first seizure. That afternoon he was out of restraints, only to relapse slowly. His temperature elevated and treatments were repeated on each of the next two days, with complete relief, cooperation and full self-care. A 20-year-old college student was admitted in delirious excitement. After 4 daily ECT sessions he was discharged to continue out-patient ECT for a total of 10 treatments. He completed his college courses. A 25-year-old musician in delirious mania was relieved by 5 daily ECT sessions, fully recovered by a full course of 12 treatments. Four years later, he was re-admitted after returning from an overseas working trip during which he had become exhausted. Again, daily ECT relieved the syndrome and he remained well. In a review of the hospital records I found 9 additional patients with delirium, mania, and signs of catatonia who had responded well to ECT. These experiences encouraged additional treatment of non-manic delirious patients and led me to recommend that ECT was an effective treatment for delirium, regardless of cause. An interesting misconception developed in the 1980s as the label “bipolar disorder” was popularized as a diagnosis after its delineation in DSM-IV. Depressed patients with a single manic episode in their history were labeled as suffering from bipolar disorder, neglecting possible catatonic features. The treatments for bipolar disorder span the breadth of the pharmacy, applying atypical antipsychotics, mood stabilizers, lithium, anticonvulsants, anxiolytics, sedatives, and antidepressants in complex combinations with notoriously poor outcomes. As excited patients are forcefully restrained, treated with haloperidol and other potent neuroleptics, they rapidly develop seizures, fever, become mute, refuse fluids and food, become dehydrated and die, sometimes with fever and inanition or by improper tube 58 �feeding. Recognizing catatonia in severely manic and delirious patients and offering catatonia treatments is an unheralded aspect of the understanding of mania. But delirious mania is still not recognized in the revised nomenclature of DSM-5 published in 2013. In his critique What Psychiatry Left Out of DSM-5, the historian Edward Shorter identifies delirious mania as just one of many illnesses that are not recognized. 54 Michael Taylor makes the same observation in his personal history as researcher and clinician titled Hippocrates Cried. 55 Toxic serotonin syndrome. A 59-year-old married woman was admitted to University Hospital with a long history of treatment for mood disorder. Her most recent prescription had been the sedative trazodone at bedtime. She developed urinary incontinence and the serotonergic agent nortriptyline was prescribed. Within five hours after a single 25 mg dose, she became fearful, tremulous, sweating, tachycardic, hypertensive, incontinent of urine with explosive diarrhea. Four days later, she exhibited seizure-like movements of her extremities and lost consciousness. At the psychiatric emergency room she was mute, rigid, tremulous, tachycardic, sweating, and hypertensive. The examination was consistent with NMS and lorazepam [1mg q6h] was prescribed, relieving the motor and vegetative signs within two days. She remained depressed and retarded, however, and responded well to ECT with lorazepam as continuation treatment. She had not been exposed to neuroleptic agents as her husband, a high school biology teacher insisted, showing his daily record of her symptoms and all administered medications. Toxic serotonin syndrome (TSS) is an acute change in mental status with systemic signs following the addition or increase in dose of a known serotonergic agent to an established psychoactive medication regimen. No effective treatment is known other than withdrawal of the precipitating medications and supportive care. The overlap in signs of toxic serotonin syndrome with NMS, and the successful response to catatonia treatments, argues that toxic serotonin syndrome is best considered and treated as a form of malignant catatonia. Pervasive refusal syndrome. A syndrome described in the UK in 1991 meets our criteria for catatonia and represents another face of the syndrome. Four British girls between the ages of 9 and 14 suffered “a profound and pervasive refusal to eat, drink, walk, talk or care of themselves in any way over a period of several months.” They required nasogastric tube feeding and spent such prolonged periods in bed that they “occasionally requiring manipulations of the joints under general anesthetic to prevent contractures.” After extended hospital care and family and individual psychotherapies they eventually recovered. A report of an 8-year old girl who stopped eating and drinking after a viral infection and who was hospitalized for more than a year before being returned to her family in partial remission was brought to my attention by Donald Klein; did she meet our criteria for catatonia, he wondered. We agreed and asked the report’s authors whether not testing and treating for catatonia was unethical. The authors 59 �offered a complex rejoinder without explaining the failure to apply proper tests. A decade later I was consulted by the Irish child psychiatrist Fiona McNicholas about an 11-year old prepubertal girl who developed symptoms of asthma, abdominal pain, and insomnia. She refused to attend school or to eat or drink, became withdrawn and mute, and required nasogastric feeding and hospital care. After many months, a video of her behavior was sent to me. Mutism, negativism, and posturing confirmed catatonia. Lorazepam testing and treatment was recommended. The parents refused medication treatments but participated in family therapy. At first the girl took part but in time she refused. After 18 months of hospital care, as the date for her scheduled return home was imminent, she began to speak, eat and care for herself. Over the next six years she completed her schooling and went on to University. These cases are labeled “pervasive refusal syndrome.” Less than 30 additional cases are cited in the literature, with a 3:1 ratio of girls to boys. Each reported case required prolonged hospital care. Similar cases are labeled “elective” or “selective mutism.” The patients meet criteria for catatonia but it remains difficult for many physicians to consider catatonia except in the shadow of schizophrenia. The tragedy in each case is the availability of effective treatments and the clinicians’ refusal to offer a proper diagnosis and effective care. Recent descriptions of a “Resignation Syndrome” among Syrian refugees in Sweden and a “Nodding Syndrome” among children in the wars in Uganda find behaviors of withdrawal, mutism, loss of self-care, failure to feed that clearly mimic catatonia mutisms. Both these syndromes should be considered forms of catatonia. Such recognition would offer effective relief and bring these syndromes under the catatonia umbrella. Anti-N-Methyl-D-Aspartate Receptor Encephalitis. A 2008 case report in the New England Journal of Medicine describes a 26-year-old woman admitted for headache, behavioral changes, abnormal movements, and mutism of seven weeks’ duration. After extensive laboratory examinations a serum anti-NMDAR encephalitis test was reported positive, supporting the presence of an autoimmune disease. Throughout her illness she had been somnolent, mute, and negativistic, with repetitive movements of her arms and mouth, but these were not recognized nor treated as catatonia. An ovarian teratoma was found, surgically removed under anesthesia, and the encephalitis syndrome resolved within a day. Was the removal of the tumor or was the anesthesia the therapeutic agent? The rapidity of the resolution and her course favor the probability that catatonia was relieved by the anesthesia. Another report described a 16-year-old boy with protracted stupor, psychomotor retardation, mutism, posturing, stereotypical movement, refusal to eat and drink, and episodic agitation. A positive blood test supported an anti-NMDAR diagnosis. The presence of catatonia was not recognized and no consideration given 60 �to its treatments. Instead, haloperidol and other antipsychotic agents were prescribed worsening the symptoms. After seven months of nursing care the illness abated. The experience was trumpeted as a clinical lesson in the American Journal of Psychiatry despite the failure to recognize catatonia or to consider its treatment. The signs of catatonia were commonly described in a 2008 report of 100 cases of encephalitis with positive NMDAR serum tests, but neither catatonia nor its treatments were discussed. Case reports now dot the literature with most patients being female and with resolution after resection of ovarian teratomas when found. But the syndrome is also reported in males. Limbic encephalitis is an acute autoimmune neurological disorder first described in the 1960s as a ‘paraneoplastic condition’ – self-poisoning systemic changes induced by tumors. More than 80 different autoimmune disorders are described in the medical literature. The pathophysiology is poorly understood and the treatments are empiric and of limited efficacy. The diagnosis of anti-NMDAR encephalitis depends on a positive serum or cerebrospinal fluid antibody test. The recommended treatments are tumor resection when found and non-specific immunotherapy (corticosteroids, intravenous immunoglobulin or plasma exchange) or immunotherapy medications (cyclophosphamide or rituximab). These treatments have not been demonstrated to be effective and are associated with prolonged illness. My appreciation is that these patients have a systemic illness of acute onset, with a positive chemical test, with a high incidence of tumor, and frequently expressed as catatonia. These characteristics assure the syndrome's definition within the medical model. Treatments for catatonia, when applied, have successfully relieved the illness. A heightened enthusiasm for this diagnosis is reflected in an editorial in the British Journal of Psychiatry in April 2012 calling for laboratory tests for antiNMDAR encephalitis in “all individuals with a first presentation of psychosis, or people with psychosis and features of autonomic disturbance, movement disorder, disorientation, seizures, hyponatraemia or rapid deterioration . . . with the possibility of antibody-mediated encephalitis in mind.” The recommendation continues: “This assessment should include, as a minimum, a neurological and cognitive examination and early serum testing for antibodies against the NMDA receptor and voltage-gated potassium channel. All patients testing positive for these serum antibodies should be referred to neurological centres with expertise in managing these cases.” The enthusiasm for this diagnosis is also illustrated by the rapidly increasing case-report literature. The initial references to anti-NMDAR encephalitis cited in Medline are in 2007. By July 2014, the number had increased to 230 citations. and by February 2021 increased to 1588 with 83 with catatonia, and 19 with the catatonia treated with ECT. 61 �As with patients with pervasive refusal syndrome, recognizing catatonia in anti-NMDAR encephalitis offers effective treatment. It is reasonable to consider catatonia in the differential diagnosis and offer its tests and effective treatments but this is still too seldom done. Self-injurious behaviors in mental retardation and autism. Patients identified in the past as suffering from mental retardation are now often discussed as examples of autism or autism spectrum disorders. Many exhibit persistent repetitive movements, often screaming and hitting themselves. Such self-injurious behaviors cause much damage. Restraints, antipsychotic medications, and deconditioning procedures are poorly effective. Courses of ECT, however, markedly reduce the repetitive behaviors and many young patients have been returned to home and community. They do require continuation ECT, however. A benefit of the success of these treatments has encouraged broader acceptance of ECT among child and adolescent psychiatrists. Other repetitive behaviors in children and adolescents are recognized as obsessive compulsive disorder (OCD) and Gilles de la Tourette syndrome (GTS). These are commonplace among adolescents labeled as suffering autism or autism spectrum disorders. A 2014 report describes an 18-year-old man with a 8-year history of progressively severe GTS that responded rapidly to ECT. The scientific literature is speckled with incidental relief of GTS and OCD with ECT that encourages a more inclusive application of catatonia criteria to these syndromes with the application of catatonia treatments. The DSM Classification Debates: Where Should Catatonia be Classified? The initial classification of psychiatric disorders published by the American Psychiatric Association in 1952 was revised in 1968 and again in 1980. In each version catatonia was singularly recognized as schizophrenia, catatonic type (295.2), making catatonia signs markers of this broad class of psychosis and neglecting evidence of catatonia among other disorders. The catatonia-is-schizophrenia equation led physicians to prescribe neuroleptic drugs whenever catatonia signs were recognized. Such treatments were not only unhelpful, but they often precipitated a malignant neurotoxic state, worsening the illness, and causing death. Only when the clinician distinguished the signs of catatonia were the patients appropriately treated with barbiturates, benzodiazepines, and ECT. Taylor and I argued that it was necessary to divorce Kraepelin’s marriage of catatonia to schizophrenia and to recognize catatonia as a distinct, independent syndrome warranting a home of its own.56 The 1994 revision (DSM-IV) retained the five types of schizophrenia and added the independent class of “catatonia secondary to a general medical condition” (293.89). I was pleased that an independent syndrome was recognized and hoped that such a designation would increase its recognition and encourage the 62 �prescription of effective treatments. Indeed, over the next two decades, recognition of catatonia increased and reports of malignant catatonia declined. Another DSM revision was planned in 2008 with catatonia assigned for consideration in the Psychosis Work Group. By this time an extensive literature supporting catatonia as an independent entity had developed and a consortium of catatonia scholars that I led asked that the catatonia type of schizophrenia (295.2) be deleted and that catatonia be designated by a single code as a distinct, definable, and treatable syndrome. The publication of DSM-5 in May 2013 deleted the class of schizophrenia, catatonic type (295.2); continued the class of catatonia secondary to a systemic medical condition (293.89); offered a class of “unspecified catatonia” (781.89); and included a “catatonia specifier,” coded as xxx.x5, for ten principal disorders including depression, bipolar disorder, and schizophrenia types. (A specifier is a label added to a primary diagnosis to indicate a subtype of the primary diagnosis. It avoids a decision about which aspect of the behavior, the psychosis or the catatonia, is the verifiable diagnosis.) The divorce of catatonia from schizophrenia has led many psychiatrists to an earlier prescription of effective treatments, lowering rates of chronic illness and death. Many variants of catatonia with unique effective treatments are now recognized. Once considered rare, catatonia is now reported in about 10% of the populations admitted to psychiatric hospital units, assuring earlier recognition and more effective treatments. During these recent DSM deliberations the initial debates occurred between classical scholars represented by Gabor Ungvari and the catatonia scholars beginning with the work of Michael Taylor and Richard Abrams in 1970s. Ungvari supported the Kraepelin image of catatonia as the abnormal motor signs found among patients with chronic psychosis. He had treated hospitalized long-term Chinese ill in Hong Kong with lorazepam and saw little benefit, but he had not tested the benefits of ECT. Modern scholars, however, are recognizing catatonia in acute treatment hospitals, finding many cases that meet the Kahlbaum criteria for catatonia. When Kraepelin identified catatonia in his chronically ill patients, he assumed that he was describing the same syndrome. The experience of the DSM-I to DSM-III classifiers was with similar chronic hospitalized ill since their office practices of psychotherapy did not accept catatonic patients – those with mutism, negativism, and posturing, for example. By the time of DSM-IV’s publication in 1994, however, some scholars had identified the catatonia described by Kahlbaum. Their experiences led to the addition of the special class of “catatonia secondary to a medical condition.” The connection of the catatonia scholars to the Psychosis Work Group was through Stephan Heckers, the chairman of Psychiatry at Vanderbilt University. That he accepted our picture of catatonia as an independent treatable syndrome is seen in his retrospective review published at the beginning of 2015. After examining 339 hospital charts, two or more signs of catatonia were recorded in 300 patients with 63 �232 validated by positive relief with lorazepam treatment or ECT. The mean lorazepam dose was 6 mg/day with 84% responding. ECT was applied in 20% with 42 of 45 (93%) responding. Publication of a Catatonia Textbook and an ACTA Supplement Taylor and I decided to summarize our experience with catatonia and published Catatonia: A Clinician’s Guide to Diagnosis and Treatment, a 256-page text in 2003. At the same time we presented our experience in a review in the American Journal of Psychiatry. We are clinicians, not laboratory scientists. We identify illnesses, use verifying tests, and explore effective treatments. We recognize that inducing seizures is a most remarkable and unique discovery in medicine, one that has been unfairly stigmatized by the professions of psychiatry, neurology, and psychology, as well as by the public. The science is poorly taught in medical schools and psychiatric residencies, many of which have no facility for its use, thereby denying relief to many of the mentally ill who they serve. Since that publication we have explored catatonia further. A decade later it seemed timely to bring our knowledge up-to-date and I published a review as a supplement to the Acta Psychiatrica Scandinavica. It is a biography of the syndrome, how it was developed, its early exploration, the incorporation in schizophrenia, and its rediscovery as a definable distinct entity. The essay reviews the arguments about its classification, and the new forms that are recognized. It also discusses an interesting association with animal tonic immobility, a defense described in prey animals. Many catatonia signs – stupor, mutism, posturing, repetitive behaviors – are characterisic of animals when they find a predator in their neighborhood, and I suggest that catatonia is a relic of human biologic history. Subsequently, I have argued that catatonia is an atavism, a relic of the past when Homo sapiens was both predator and prey, with the defenses of flight, fight, and dissimulation that are retained today. How is catatonia best recognized and what is its place in the medical world? We soon came to see it as a behavior syndrome, severe and occasionally fatal but treatable, so much so that its resolution left no residual marks. Edward Shorter and I discussed these many aspects of the syndrome and in the fall of 2016 resolved to write its history. We organized our thoughts and decided that we could best assess the syndrome as an atavism, a relic of the primitive stages of animal development when fears encouraged defenses of freeze, flight, or fight. We formulated these thoughts in an essay asking "Does persisting fear sustain catatonia?" in the Acta Psychiatrica Scandinavica in 2017. 57 A proposal for a volume by Shorter and myself was accepted by the Oxford University Press, and in July 2, 2018 the first copies of A Madness of Fear: A History 64 �of Catatonia with the deep blue cover image of Caravaggio's Medusa were published. The text describes the 150 year story of a systemic medical syndrome, the successful application of the Hunterian model of the identification of a systemic illness. It joins neurosyphilis and melancholia as among the few behavior disorders that is identifiable, verifiable and successfully treatable. 65 �Book Six: Melancholia and the Medical Model of Diagnosis After publishing our text on Catatonia in 2003, MickeyTaylor and our wives Ellen and Martha met for a celebratory lunch in Chicago. "Well, what is next?" We agreed that Melancholia was a discussable syndrome -- multiple forms were widely recognized, each responsive to the tricyclic imipramine and to ECT, and a verification test in the dexamethasone suppression test had been described. Melancholia syndrome met our criteria for a medical diagnostic syndrome, parallel to our image of the catatonia syndrome, and we both had successfully treated melancholic patients. 58 Like catatonia, melancholia is not recognized as a clinical entity in any of the American Psychiatric Association Diagnostic and Statitical Manuals, although it is widely described in the clinical literature. Melancholia is accepted as a descriptor or modifier for DSM diagnoses, not as a distinct identifiable entity, not accorded a specific code. As a consequence its study is not well defined, not recognized in the citation indices, and is poorly studied; it is buried in the Major Depressive Disorder and Bipolar Disorder categories. The parallel with the catatonia story is uncanny. 59 During my Hillside Hospital experience, the treatment of severely depressed patients, suicidal, anorexic, insomniac, mute and stuporous, with ECT was remarkably effective. Often, inducing seizures daily resulted in complete relief in 24 days, with suicide risk, appetite, insomnia and withdrawal fully relieved. In our RCT study of chlorpromazine and imipramine, we identified a population of psychotic depressed patients that responded to both agents. 60 In my days in Missouri, we often identified melancholic patients but their diagnosis and treatment was of no particular interest. In our studies of ECT at Gracie Square, the clinicians recommended psychotic depressed, postpartum and partum depressed for treatment without our particular attention to their identification. The Dexamethasone Suppression Test: By the 1960s, chemists had reported serum cortisol measures to be elevated in melancholic patients. By 1972, the Australians Davies, Carroll and Mobray reported that a straighforward test, the Dexamethasone Suppression Test (DST) was a marker of severe psychotic depressive illness. Diurnal serum cortisol levels were elevated, and administration of the steroid dexamethasone failed to suppress the elevated levels. One report by Bernhard Carroll intrigued me. Five severely ill melancholic patients with abnormal DST responded clinically to courses of ECT; their DST normalized. Two relapsed, again with abnormal DST tests; re-treatment with ECT resulted in clinical improvement, again with normalization of the DST. 61 Was the DST a marker of melancholia and predictor of the response to ECT? 66 �I had been asked to supervise a psychiatric unit at the Long Island Northport VA in 1972. I organized clinical trials of a potential psdychotropic drug flutroline, which we found clinically ineffective. In 1968, the Fellow supervising treatments Yiannis Papakostas, accepted the tasks of developing the chemical tests for cortisol and TSH testing patients before and during the course of ECT.62 Of 20 unipolar melancholic patients, 16 exhibited abnormal DST. Of the 14 treated with ECT, all test normalized with recovery. These findings stimulated interest in cortisol as a test of a specific form of depressive illness. Over the next few years, numerous reports associating the DST and depressive disorders, some finding a close association with severe depression and psychosis, others finding poor relations. The APA TAsk Force on Laboratory tests concluded that the test was not useful in identifying major depressive illness. 63 As I and Bernard Carroll noted, a laboratory test with high specificity for melancholic depression was applied to a broad class of "major depressive illness" that included neurotic and characterological depressions, those unhappy with their social status and lives. The patients with positive DST tests were the severely ill, often suicidal, unresponsive to psychological therapies, but responsive to the more effective antidepressant tricyclic medications and ECT. Never the less, the DST was rejected as a test of a specific form of depressive illness; each variation of the DSM (-III, IV, 5) discarded all laboratory tests for the diagnosis of any of its hundreds of described conditions. Earlier I described my development of the CORE collaborative studies of depressed patients treated with bitemporal ECT with continuation treatments either lithium and nortriptyline or ECT. The study was an excellent opportunity to test the DST and severe depressive illness, but the NIMH committee and managers reviewing the study budget, rejected funding for the DST, justified by the APA Task Force report. Never the less, we examined the rating scales of our depressed patients for evidence of the loss of pleasure in all, or almost all, activities or lack of reactivity to usually pleasant stimuli at baseline. Of 489 patients in the CORE study, 311 (63.6%) met criteria for melancholic features. The overall remission rate was 68.1%, with higher rates (78.7%) for those who did not meet the melancholia specifier criteria and 62.1% of (or more) of six cited vegetative signs of melancholia. The specifier is added on the basis those with melancholia specifier (42). We concluded that the approximation of "melancholia" in our patients was a poor substitute for the DST.64 After our meeting in Chicago, a flurry of letters, interim reports, literature searches, led to our publication in the Spring 2006 by Cambridge University Press of our melancholia textbook. 65 We described the century-old experience, defined the syndrome by psychopathology and laboratory tests, treatments by medication and ECT, and argued for its recognition as a distinct entity in psychiatric classifications. The book was well presented but was priced very high, the advertising minimal, and the distribution disappointing. 67 �Increasing interest in melancholia led to an international conference in Copenhagen of authors who had studied melancholia, also in 2006.66 By the conference end, melancholia was defined as an identifiable mental illness, the DST was agreed as a defining test, and ECT as a definitive treatment. The argument for a unique identity among behavior illnesses was again made. Discussions with members of the DSM-5 panel for depressive illnesses were strongly made, but again ignored in DSM-5 in 2013. Disappointed with our failure to convince clinicians about the unique qualities of melancholia, both Taylor, in his book Hippocrates Cried 67, and I, joining with Edward Shorter, described the story in Endocrine Psychiatr that we published in 2010.68 At this editing in March 2021, melancholia iremains buried among the diverse illnesses coded as major depression and bipolar depression. Like catatonia, the illness needs efforts to identify its biology, to bring it out of its burial, much as was successfully done for catatonia. 68 �Book Seven: Studies in Electroencephalography (EEG) EEG Introduced to Hillside Hospital 1953 Electrical rhythms from the intact human scalp were first described in 1929 by Hans Berger, a German psychiatrist. Within two years, in his third report, he described the changes associated with morphine, scopolamine, and other psychoactive drugs. Spontaneous seizures and the rhythms of the inter-seizure EEG in epilepsy were next described. Would EEG recordings distinguish effective from ineffective treatments in the induced seizures of ECT? Could the EEG identify a successful course of treatment? Were the seizures induced by pentylenetetrazol the same as those induced by electricity or by insulin? While I had seen electroencephalograms of patients as a medical student and a resident at Bellevue Hospital, I had no technical experience with the procedure. Reports of recordings during epileptic seizures induced by Metrazol, the chemical used by Meduna to induce seizures in schizophrenic patients, had dotted the literature since 1938 followed by similar descriptions for insulin coma and for ECT. During each procedure EEG frequencies slowed, amplitudes increased, and sharp, spike-like waves appeared. Missed and partial seizures induced little or no change in the EEG. Greater slowing of frequencies and increases in the duration and amplitudes of slow waves and spike activity marked more intense seizures. The altered rhythms persisted for weeks and, in a few patients, for months after the treatment course ended. I sought training in recording and interpreting the EEG. As my residency at Hillside was to be completed in December 1952, I applied for a fellowship at the Mount Sinai Hospital in New York City beginning January 1953. (By this time, too, after five and half years of postgraduate medical training I opened a private-practice community office in neurology and psychiatry, which I did in the summer of 1953 in Great Neck, Long Island. ) With Hans Strauss and Mortimer Ostow I learned how to apply scalp electrodes, maintain the EEG recorders, and interpret the records. The Medical Director Joseph S.A. Miller, established an EEG Service with a Grass electroencephalograph purchased with a $5,000 grant from the Dazian Foundation obtained by Dr. Israel Strauss, the Founder of the Hospital. By the end of 1953 I had appointed and trained an EEG technician and developed a protocol for the study of the changes in EEG associated with ECT. An application to NIMH funded a five-year study under Grant MH-927 "Altered Brain Function Following Electroshock" in the summer of 1954. Hans Berger had recorded rhythmic frequencies of 4 to 16 Hz. The more common 8-12 Hz waves were labeled alpha waves, the faster (>13 Hz) as beta, and the slower labeled as theta (4.0-7.5 Hz) and delta (<4.0 Hz) waves. 69 �At first the changes were measured from baseline crossing to baseline crossing by a ruler to estimate mean frequencies. The peak amplitudes were measured for each wave using calipers. In our first study of the changes after induced seizures, the technician Hannah Mosquera and I measured the height and width of each wave in 10-second epochs for 60 to 120 seconds in artifact-free samples for each weekly recording. We scored the records as low, medium and high degree changes. As the recordings were done weekly, we had six to eight records for each subject. Progressive slowing of frequencies and increased amplitudes marked treatment courses. In later records, bursts of slow waves with sharp spike activity were seen. The best clinical recoveries occurred in patients with high degrees of slowing and amplitude increases and we concluded that the EEG changes were necessary for the recovery of the patients. EEG recording became the center of my research interest, studying changes during the hospital course of patients treated with ECT and ICT. We were unable to record the actual seizure as our instruments were "blocked" by the electrical stimulus. But we could examine the interseizure record. Treatments were given on Mondays, Wednesdays, and Fridays with EEG recordings done on a regular schedule for each patient on Tuesdays or Thursdays. These records showed varying degrees of progressive slowing with increasing numbers of treatments. The grand mal seizure was the central feature for changes in behavior and the beneficial behavior effects. With increasing numbers of seizures the EEG rhythms slowed and the amplitudes increased. The patients whose inter-treatment rhythms changed very little did not recover from their illness. Those with greater degrees of slowing had the better clinical evaluations. The development of slow rhythms and higher amplitudes were markers associated with recovery. Necessary, but not sufficient. Some patients with these rhythms did not show beneficial behavior changes. At the time, we were treating a wide range of illnesses. Many would meet criteria for major depression, bipolar disorder, and schizophrenia in modern classifications. The schizophrenic patients, except those with the catatonic form of the illness, showed the least benefit with treatment. The specificity of seizure effects depended on psychopathology. Diagnosis became a critical process by which patients with high likelihood of benefit could be selected for treatment. For the next four decades I reported on the EEG effects of ECT and ICT; then the changes accompanying many new psychoactive drugs introduced after 1954. I developed methods to quantify EEG changes using digital computer methods; classified psychoactive drugs by their EEG characteristics; and developed and defended the contentious concept of the "Association of EEG and behavior with psychoactive drugs in man." 69 70 �EEG in Psychopharmacology By 1954, the first clinical tests of chlorpromazine found it to be very effective in reducing aggression, excitement, and paranoid thoughts. The EEG profile of chlorpromazine differed from amobarbital and ECT. Imipramine (Tofranil, IMI), our next new agent, was also distinguishable from chlorpromazine. Were these differences related to their differing behavior effects? And how were the changes related to behavior changes? While the changes in EEG during ECT were easily seen and readily measured by ruler and calipers, the changes accompanying the chemical agents were more subtle, the changes much smaller. We looked for a more sensitive quantitative measuring instrument and EEG quantification became an interest. The Grey Walter Frequency Analyzer. During World War II the English physiologist Grey Walter at the Burden Neurological Institute developed an electronic frequency analyzer to measure the degree of EEG slowing to assess the severity of head trauma. A single channel record, electronically filtered to minimize movement artefacts, was sent through a bank of 24 electronic filters, each tuned to respond to individual energies from 3 Hz to 33 Hz. The premise of its military medical use was that increases in slow-waves were signs of brain dysfunction following trauma. In 1957, George Ulett at Washington University described his use of a Grey Walter device to measure the effects of atropine and scopolamine on the postseizure EEG. He quantified the changes in brain electrical energy as mm pen deflections within each frequency band and reported that both anticholinergic chemicals reduced the percentage time and the magnitude of high amplitude EEG slow waves induced by seizures. I visited Ulett in St Louis and was impressed that the device did measure the drug-induced EEG changes. I received funding from NIMH and Ulett built a device for my studies at Hillside. We obtained the instrument in the autumn of 1959 and used it in various studies, most prominently in the CPZ-IMI-PLO random assignment study. While CPZ enhanced the amplitudes and slowed the frequencies, imipramine increased the percent time of fast frequencies, distinguishing the brain effects of each agent. EEG Analysis by Digital Computer. In 1960, at the dedication of the Brain Research Institute at UCLA, scientists from the Massachusetts Institute of Technology presented the analysis of a short EEG segment using digital computer programs. Ten seconds of analog electrical activity were digitized and then measured by two statistical programs labeled power spectral density and period analysis. 71 �The Walter analyzer was inherently unstable and sensitive to room temperature. It required daily calibration. I was impressed that digital computer analyses would be within the future for the analysis of psychoactive drug effects. Central to my move to St. Louis was my request for funding to explore digital computer analysis methods for medication studies. In early 1963 I approached the computer center at Washington University to establish a laboratory for EEG analysis at the Missouri Institute of Psychiatry. Donald M. Shapiro, a doctoral candidate in digital computer processing, agreed to develop the computer programs. In the autumn of 1964 an IBM 1710 digital computer system with a central processor based on the IBM 1620 was installed at the MIP. Over the next few years Shapiro developed signal processing programs to record EEG on digital tape, filter electrical noise, digitize the analog measurements, file the numeric values in the computer memory, and keypunch the data on Hollerith cards for statistical analysis. After examining different analysis programs, we concluded that the baseline cross and power spectral analysis gave us the best measures of medication effects. Some years later, we compared the relative merits of these analysis methods, concluding that the methods offered useful analogous measurements. IBM-1800 Analysis System: In 1966 I moved to New York Medical College to study opioids and their antagonists, hashish, and marijuana, and to renew my studies of ECT. Donald Shapiro joined me, and in 1967, with NIMH funding we leased an IBM-1800 computer system that he programmed to quantify taperecorded EEG records. The programs for both power spectral density (Fourier) and period baseline cross analyses were developed and applied. This system was complex and while more stable than the Grey Walter frequency analyzer, also required constant maintenance. Yet, we were enabled to quantify the EEG changes, identify drug-related patterns, predict their clinical uses, suggest effective dosage ranges, and relate the EEG changes to behavior. We also measured the time course of single dose effects and related them to drug and metabolite plasma levels. Following the introduction of chlorpromazine, then its congeners, and then different agents related to imipramine, came a flood of putative psychoactive drugs from industry laboratories. Psychopharmacologists were busy testing their effects on physiology and behavior in animal species. How to find new chemical entities with defined behavioral effects in man became researchable and fundable questions. Testing drugs in mice and rats identified animal toxicity. Phase-1 human toxicity trials in volunteers guided clinical use and safety. But what measures could be markers for antipsychotic, antidepressant, or anxiolytic potential? While a broad science of animal pharmacology catalogued the physiologic and behavioral effects of known psychoactive agents, did such studies predict the effects of new agents in man and in patients with different behaviors? 72 �Pharmacologists developed simple motor tests in animals responding to known chemicals, and then brought to human trial those agents that matched the pre-clinical response profiles of known drugs. Scientists at each pharmaceutical company tested their chemicals in rabbits, mice, rats, cats, guinea pigs, and occasionally in monkeys and chimpanzees. But their predictions did poorly when tested in the clinic. Although proposed agents matched known active agents in the pre-clinical animal trials, many failed in the clinic. Human trials became necessary to identify the association between the tests in animals and in man. Clinicians in the NIMH supported ECDEU program studied different physiology measures as markers for the effects in patients. In the Hillside CPZ-IMI-PLO trial, we had distinguished the EEG, physiologic, psychologic and behavioral effects of the active agents, seeing each as profiles of the classes of antipsychotic and antidepressant agents. We tested amobarbital and amphetamine, then the new compounds megimide and fenfluramine. The novel anticholinergic diethazine very rapidly desynchronized the slow waves developed during ECT. Study of this compound and other experimental anticholinegic drugs led to our hypothesis of a cholinergic basis for the clinical effects of induced seizures. Soon, the flood of psychoactive agents that were being prescribed in diverse patterns to our hospitalized psychiatric patients elicited complex baseline EEG patterns. The effects of each agent persisted for days and weeks, absorbed in body tissues and slowly leached out and metabolized in time. Each exposure altered the brain patterns in complex, difficult to define, ways. We could no longer find “a clean head” in which to measure a new agent’s EEG effect. We sought to test agents in prisoners, and came into conflict with changing concepts of ethics in human research. Prisoners were not “free agents” and, although we were careful to assure that their participation had only a monetary award and no change in their civil penalty, we were discouraged from such use. In New York we studied new drugs in healthy male volunteers, paying for their hourly participation, and found such trials useful to identify the central effects of new entities. The digital computer system offered quantitative measures of frequency and amplitude changes with each agent. We developed EEG criteria for antipsychotic, antidepressant, stimulant, and sedative drugs using the effects of chlorpromazine, imipramine, amobarbital, and amphetamine as guides. We also identified patterns for hallucinogens (LSD, mescaline), deliriants (atropine, scopolamine, diethazine), opioids (heroin, methadone, levomethadyl), their antagonists (naloxone, cyclazocine), marijuana, hashish and Δ-9-tetrahydrocannabinol, and a miscellany of agents with reported behavioral effects including phenytoin, aspirin, diphenhydramine, and novel peptides. Numerous world laboratories studied the EEG effects of psychoactive agents and with the leadership of the German scientists an International Pharmaco-EEG Society (IPEG) was formed and met every two years. The behavioral and 73 �physiologic effects were defined in patient and volunteer trials. Many consulted with industry pharmacologists and offered identifications of clinical activity that was inconsistent with the predictions of drug effects in animal studies. While the human studies were more reliable and predictive of the clinical activity of the compounds, these were expensive, time consuming, and difficult to fund and carry out. The association of EEG and human behavior was discussed at the 1966 meeting of the CINP, in a symposium on "Anticholinergic Drugs and Brain Functions in Animals and Man." The dissociation between predictions of behavior effects in animals and man was not resolved. 70 As new entities were created in industry laboratories increased emphasis on the absence of side effects resulted in compounds sent to the clinic with decreasing efficacy. These were identified as selective serotonin and norepinephrine reuptake inhibitors and the atypical antipsychotics. At clinical dosing and in volunteer trials, the impact on EEG were hardly measurable. We were unable to identify patterns the we had established for different behavioraltering agents. Our methodology was criticized as failed, and discarded. But over the past three decades, the benefits of these new agents were increasingly not distinguishable from placebo comparators. Not understanding the role of brain change measurable by EEG in man has resulted in a worldwide flood of ineffective medications. Psychopharmacology Lessons Learned by Pharmaco-EEG Over the three decades of activity, we profiled agents that were clinically active and some marketed, measured the relative potency and dosage ranges of sedative and stimulant drugs to guide clinical use, examined the psychoactive properties of agents in the search for a new useful chemical core, and agents that showed little promise that were abandoned. In some instances the EEG profile was instrumental in predicting effective clinical uses and dosage ranges and targeting marketing applications. Doxepin (Sinequan). Based on its chemistry and its effects in animal tests Pfizer pharmacologists recommended this tetracyclic compound for clinical trials as an anxiolytic. After a year in clinical trials with a lack of an observable benefit in anxious patients, investigators met at the company’s offices in Groton, CT to review the experience. A pall hung over the discussions until three investigators, Turan Itil, Herman Denber and I offered understanding from our EEG studies. We had failed to find the patterns of anxiolytic drugs, but did see changes similar to those of the antidepressant imipramine. We recommended doxepin be tested in depressed patients. Guided by our findings, doxepin was was quickly reported effective in depressed patients. It was successfully marketed as an antidepressant. Mianserin (Tolvon, GB-94) was developed by the Dutch company Organon and recommended for a use in treating migraine. The research director, Theodor (Jack) Vossenaar, sent the compound for EEG assessment to Turan Itil in St. Louis 74 �who reported its EEG profile to be most similar to that of amitriptyline. Because the pharmacologists considered the finding inconsistent with their experience as a serotonin and histamine antagonist, Vossenaar asked me to replicate the EEG study. I quickly confirmed Itil’s finding and the subsequent clinical testing and marketing in Europe and Asia as an antidepressant was medically and economically successful. I became invested in the EEG-mianserin story and presented the findings in many venues. Mirtazapine, 6-azamianserin. chemically related to mianserin, is a racemic mixture. In preclinical chemical and animal studies, the dextro-enantiomer was reported to be active and the laevo-enantiomer inactive. We examined the EEG profiles of both enantiomers and found no difference between them in the magnitude of the EEG changes with a pattern most similar to that of mianserin. Clinical trials for each enantiomer found both to be clinically effective although neither differed from placebo at the tested doses. The racemic mixture was successfully marketed as the antidepressant Remeron in the1990’s. Flutroline. Pharmacologic studies in dogs reported that a single 1-mg dose of flutroline inhibited the vomiting induced by apomorphine for as long as one week. Extrapolated to man, pharmacologists enthused that flutroline would be an ideal antipsychotic, requiring a single oral dose each week, pictured as the “Saturday night pill.” In our clinical trials in actively psychotic patients we failed to elicit an antipsychotic effect, even at multiple and higher dosing schedules than initially recommended. EEG measures in our volunteers also failed to show a measurable change. The preclinical prediction of small doses being effective for days or weeks was untenable and studies of the drug ended. Aspirin, Anticonvulsants, Antihistamines. We looked at commonly marketed agents with reputed behavioral effects seeking potential alternative clinical uses in their EEG profiles. Acetylsalicylic acid (Aspirin) was reported to be soporific at its common dosing of two tablets each at .0325 Gm. We tested single doses of 0.65, 1.95 and 3.6 Gm in healthy adult men. The two higher doses elicited quantitative EEG, symptom effects, and cognitive functions characteristic of soporifics. Doses of 0.65 Gm were similar in direction and pattern but failed tests of significance. We sought to measure the basis for reports of changes in mood with the anticonvulsant phenytoin, finding the EEG patterns to mimic those of antidepressant drugs. The dosages for clinical benefit were high, so high as to risk toxicity. In an enthusiasm for peptides following the identification of euphoriant effects of beta-endorphin, we examined the effects of the peptides ACTH4-10 and desTyr-gamma-endorphin. We could not elicit systematic EEG changes at the dosages and the parenteral routes that we were advised to use based on pre-clinical trials. 75 �The sedative effects of antihistaminic agents were well documented. Diphenhydramine and terfenadine elicited soporific, not antidepressant or anxiolytic patterns, and were not tested further. Opioids and Cannabis. The same principles of EEG study of new agents were applied to opioids and their antagonists, and hashish, marijuana and THC-∆-9. We defined the EEG and behavior profiles of the compounds and measured the speed with which the antagonists blocked the effects of heroin and levomethadyl. In studies of marijuana and hashish the behavior and EEG effects were consistent with THC-∆-9 content. The Association/Dissociation EEG and Behavior Controversy. Industry searches for new agents with potential for human benefit are commonly based on similarities in chemical structure and observations in animal trials. Early in our EEG studies, beginning with chlorpromazine and imipramine, our descriptions of the effects in patients and normal volunteers differed from the reports of EEG studies in animals. At meetings of EEG and biological psychiatry societies, both Turan Itil and I were often criticized for reporting effects on behaviors and EEG that differed from those reported in the animal trials that had preceded our human studies. Changes in the resting alert EEG in patients and healthy volunteers had elicited drug specific changes in frequency and amplitudes that we related to their clinical effects. During the course of ECT, EEG frequencies slowed and amplitudes increased. During the ECT course some agents increased and others inhibited slowing, some increased fast frequencies, and some altered amplitudes. The post-ECT EEG became a sensitive index of brain function that varied in response to the chemistry of the tested medication. These studies had been done at Hillside Hospital in the 1950s. Diethazine had been a new agent with well-defined anticholinergic properties that we administered to our patients during an ECT course. In postseizure recordings with slowed EEG frequencies and increased amplitudes, intravenous diethazine sharply and quickly reduced amplitudes and increased the mean frequencies. The patients became agitated, depressed, and reported their preECT symptoms. We inferred that seizures liberated free acetylcholine in brain and CSF and increased concentration of brain cholinesterases. These observations led me to suggest a cholinergic explanation of the ECT mechanism. Replications of the same effect with Ditran and experimental anticholinergic drugs of the JB series assured us of this pharmacology. When we measured the EEG effects of imipramine in our patients, in volunteers and in ECT patients, we found the same changes as we had seen with the anticholinergic agents. We inferred that imipramine blocked free brain acetylcholine, a finding that was inconsistent with its inferred pharmacology. 76 �At a Montreal conference in 1969, my suggestion of imipramine’s anticholinergic activity was criticized since such effects had not been observed in animals. The pharmacologists insisted that imipramine lacked such effects. In time the anticholinergic effects of imipramine were increasingly recognized. The anticholinergic properties were even flouted as riskful by marketeers seeking to replace imipramine with newer agents. The next year, at the World Congress of Psychiatry also in Montreal, nine investigators from Europe and the United States, described their experiences with new psychoactive agents on the EEG and behavior. EEG changes characterized the qualities of psychoactive drugs – the defined changes predicted the behavior effects, and their absence identified clinically ineffective agents or ineffective dosing. Itil, I, and an increasing number of electroencephalographers studied druginduced changes in human volunteers. As we described drug-related patterns that were clinically confirmed, greater interest in human screening of new clinical entities developed world-wide. The study program that began at Hillside Hospital, flourished at my laboratories in St Louis and New York. Many industrial pharmacologic laboratories established animal testing centers using implanted electrodes in diverse animal species. When pharmacologists assayed the EEG effects of putative and established agents in rats, mice, rabbits, cats and dogs, results differed from parallel findings in human studies. The principal argument was made by Abraham Wikler who tested morphine, atropine, n-allylnormorphine and mescaline in dogs in slings. The animal EEG recordings showed sleep patterns; yet, their legs and eyes were moving rapidly. He concluded that there was a dissociation between the induced behaviors and the EEG effects. His inference was supported by pharmacologists studying other animal species. At an international conference of the CINP in Washington DC in 1968, the issue of pharmacologic “association” or “dissociation” was debated and resolved by acknowledgement that the systemic and brain pharmacology of animals are not identical to that of man. Indeed, an agent showing similar effects in an animal species and in man is a happenstance that cannot be predicted in advance. Preclinical studies in mice, rats, cats and dogs studies do not reliably predict drug effects in humans. We had our own experience with the differences between the behavioral effects of drugs in animals and in man in St. Louis in the mid-1960s. Sam Gershon had trained in Australia and studied lithium in the treatment of mania. On the advice of Jonathan O. Cole, I invited him to join the MIP staff as pharmacologist. He brought an interest in the actions of acetylcholine, studying the anticholinergic drug Ditran and the cholinomimetic agent tetrahydroaminoacridine (THA). He developed animal testing facilities and appointed a team of collaborating pharmacologists and technicians. 77 �His animal of interest was the beagle dog. One occasion, when Gershon was away from the Institute, the administrator asked me to approve the purchase of six setter dogs as replacements for unavailable beagles from the animal breeder. The price for the setters would be the same. Not knowing of any difference between the species, thinking “a dog is a dog,” I approved the purchase. A few weeks later, Gershon complained that his anticholinergic drug experiments with setters failed to elicit the behaviors that were readily elicited in beagles. That the pharmacologic sensitivities varied among dog types as well as among animal species supported my argument that human trials were essential to understanding psychoactive drug effects. The Pharmaco-EEG Paradigm Whether the EEG and behavior of psychoactive drugs are “associated” and predictable in man as we maintained or were “dissociated” as pharmacologists asserted, clarified the pharmaco-EEG paradigm in clinical studies. Today’s search for new psychoactive agents is rooted in the happenstance that chlorpromazine was a powerful sedative agent especially in paranoid, aggressive, hostile, and manic patients. Similarly, the antidepressant relief accorded by imipramine encouraged its trials in melancholic psychotic patients. These experiences invigorated a massive industrial investment, mainly in animal studies, with lesser expenditures in the clinics. Much energy is being spent to find the effects of the agents on the brain’s neurohumoral and neuroendocrine chemistry. Psychoactive substances alter behavior to the extent that they change brain chemistry. The pharmaco-EEG paradigm offers quantitative measures of these chemical changes that relate to their behavior effects. We are able to predict the behaviors of psychosis, depression, or anxiety, elicit a delirium or reduce a manic episode, from the EEG changes. Failure to alter the EEG means that the agent has little effect on behavior, that it is behaviorally inert, and best marketed as a placebo. Human studies are expensive and the science of pharmaco-EEG failed its promise and is no longer supported either in research laboratories or in individual patient care in clinics. Sadly, the same questions are now being asked in human studies using the present-day fashionable brain imaging methods with emphasis on concepts of connectivity and the size of brain nuclei. It is difficult to see such measures that are momentary images and not continuous as having more promise than that of pharmaco-EEG, which readily permits continuing assessments over time. Sadly, pharmaco-EEG in managing individual patients and in predicting the effects of chemical agents and physical treatments is a discarded science. 71 78 �Book Eight: A Medical Experimentalist is Created Medical School Experiences 1942-1945 My letter of admission to New York University College of Medicine arrived on December 6, 1941, the day before the Japanese attack on Pearl Harbor and the entry of the nation into war. That Sunday I was accompanying my father on a house call, listening to radio news, when the attack was announced. My parents had actively encouraged the emigration of friends and classmates from Vienna, acting as surety for their transitions to America. They had avidly followed the news of the war in Europe and were particularly agitated by the Nazi murders of Jews. I began a three-year intensive medical school training program at New York City’s Bellevue Hospital in June 1942. We were sent to Fort Dix in New Jersey for a week’s military orientation and returned to classes as soldiers dressed as Privates First Class in the U.S. Army. The war had called many experienced faculty members to military duty offering students unusual opportunities for hands-on medical experiences and responsibility for medical and surgical procedures far beyond our knowledge and experience. I vaguely remember the anatomy and chemistry lessons of the first year. The cadaver was an elderly, skinny woman. My teammates were Felix Wroblewski, who later did medical research at the Rockefeller Institute and Luther Cloud, an officer in an insurance firm. Neuroanatomy was taught by Wendell Krieg, who asked each student to make paper mache crossection models of the human brain. These models were supplemented by brain slices preserved in formaldehyde in crocks that allowed us to map the brain’s nuclei. Neurosyphilis and Cerebrospinal Fluid: Clinical teaching began in the second year and in an assignment to the syphilis clinics I was taught by Bernhard Dattner, a 1938 émigré from Vienna. He had studied under Julius Wagner-Jauregg, the 1927 Nobel Prize winner in Medicine for his report that malaria-induced fevers relieved one third of patients of active neurosyphilis. While at Vienna's Allgemeines Krankenhaus, the number of white cells and levels of protein in the cerebrospinal fluid (CSF) were highest in the actively ill, making CSF examination indices of the severity of the illness and guides to treatment. Withdrawal of cerebrospinal fluid by lumbar punctures between Lumbar- 3 and Lumbar-4 vertebrae are often followed by headache. To reduce this incidence Dattner obtained the CSF from the 4th ventricle by an occipital puncture to the cisterna magna. For the next month I monitored the progress of the patients by CSF measures obtained by ventricular taps. I assumed that it was a customary procedure, despite the risk of penetrating ("pithing") the brain stem. The procedure is now considered too riskful to be considered even by experienced neurologists. 79 �Neurosyphilis is a late development in the life course of syphilitic disease, appearing years after the original infection. The symptoms develop slowly, making difficult an accurate diagnosis with its devastating consequences in personal life and the risks of the toxic treatments of mercury and arsenic. A principal sign of the disease is pupillary irregularity and failure to narrow with a light stimulus (the Argyll-Robertson pupil). When mental and neurologic symptoms appear, this sign is present in less than 60% of known ill. Dattner argued that white cell counts and the concentration of protein in the CSF offered better and more reliable criteria of the severity and activity of the disease. The presence of cells, elevated protein and positive colloidal gold reaction tests were the guide to fever treatments. The CSF changes normalized in the patients who responded to the fever therapies. While syphilitic patients were treated with arsenical preparations, the more actively ill were also subjected to malarial or “sweat box” fevers. Patients remained seated for hours in a box heated by lightbulbs with only their heads exposed. The treatments were severely debilitating and assuring hydration and monitoring body temperatures was one of my responsibilities. Follow-up studies did show improvements in serological and CSF tests and some relief in psychiatric symptoms. I was astonished by what patients were willing to suffer on the promise of cure. During my schooling in 1943, Bellevue Hospital’s R-S buildings were filled with more than 200 patients with syphilitic disorders. Six years later in 1949 when I returned as a resident in neurology, 2/3 the beds no longer served these disorders, the remarkable impact of penicillin therapy. In later years, when I applied novel treatments for psychiatric ill, I sought similar test guides to treatment outcomes – as in the Face-Hand Test, the amobarbital denial test, and the high levels of slow wave and spike activity in the interseizure EEG as measures of progress in ECT. Later I was fascinated by the dexamethasone suppression tests in melancholia and the lorazepam response test in catatonia. Personally Experiencing Psychoactive Drug Effects. Student training in pharmacology included individual experiences with medications administered to and by fellow students – morphine, scopolamine, atropine, vasodilators, nitrous oxide, amobarbital, and amphetamine are those that I recall. Doses were pharmacologically active and our observations were recorded. Blood samples were taken and nasogastric tubes passed. The hilarity induced by nitrous oxide inhalation and the pleasant feelings associated with barbiturates made some of us look forward to these classes. For others, the unpleasant experiences with scopolamine and morphine drove them from the laboratory. 72 Osteomyelitis. Among children, infections of fractured bones required intensive care. Débridement (surgically removing dead and infected tissues) was followed by repeated flushing with warm saline and dressings to keep the wounds clean to encourage healing. Plaster casts restrained the movement of limbs. In my 80 �junior year during the rotation in pediatric surgery I debrided children’s wounds. An ongoing research study applied live maggots to the open wound to clear the pus and dead tissues. I cleansed bone fragments and tissue debris, washed wounds with sterile saline solutions, created a plaster protective shell to immobilize the limb, and applied live maggots for days at a time. Maggots digested pus and wound debris, allowing surgical repair of the skin and bone. This usage disappeared with the introduction of antibiotics but references now appear from time to time citing maggot therapy in resistant infections. Barbiturates. During a rotation on the active psychiatric service at Bellevue Psychiatric Hospital in my senior year I was taught to use amobarbital (Amytal Sodium) to control agitated and aggressive behaviors. It also relieved catatonic refusal of food, mutism, and posturing. I do not recall the use in stuporous catatonic patients, a use that became a central interest four decades later. InterneshipTraining 1945-6 My first Random Controlled Trial; Penicillin in Empyema My medical internship continued the same ‘hands-on’ experiences. During a rotation on the pulmonary medicine service, patients with pleural cavity infections (empyema) filled the beds. Every other day I introduced a large 18-guage trocar between the ribs into the pleural space, removed pus, and washed out the pleural space with warm saline. An ongoing experiment washed the pleural space with either sulfadiazine or an experimental substance “x” with patients randomly assigned by the odd or even final number of their chart record. Supplies of “x” were locked in a safe in the hospital director’s office. Withdrawn samples were carefully recorded according to the patient's chart number. Within a few weeks the superiority of substance “x” became apparent, even to a neophyte physician – thick pleural fluid thinned rapidly from yellow putrescent pus to pink serous to clear fluid; fever curves flattened, pain and apathy disappeared, and appetite and activity improved, all within 10 days of administration. A young febrile Hispanic woman with empyema was admitted with her nursing infant. The random medication assignment was for sulfadiazine Assuring myself of the ethics of the switch for a nursing mother, I administered “compound x” and did so daily. When the empyema rapidly cleared, the Attending physician Dr. Eli Rubin was puzzled. Checking the records he noted the switch and in anger, marched me to the Medical Director’s office and ordered my suspension from the internship. I had broken two rules, direct orders of an Attending physician and the research protocol. Cooler heads prevailed a few days later and I was re-instated but the lesson of adherence to research assignment was learned. (Compound “x” was penicillin.) 81 �Work schedules were exhausting, with 48 hours on call frequent, with learning from an Attending physicians who supervised each patient’s care was payment for the exhausting hours. The neurologist Nathan Savitsky visited his patients at 7:30 each morning, inviting any interne to join. He was a dynamic and knowledgeable teacher, citing the literature much as Google or Wikipedia provide today. I joined him often and soon I was called to attend the autopsies of patients we had examined together. The logic of the symptoms and course of illness and the demonstrated neuropathology was impressive. Residency Training: 1948-1952 New Science of Percutaneous Carotid Angiography As the new hire at Montefiore Hospital’s residency in July 1948, I was first assigned to the neurosurgery rotation. As a student assistant during brain surgery with Dr. Leo Davidoff, the hours standing as a masked assistant in one place without voice or movement were enervating, and I escaped to the clinic as quickly as I could. The technology of percutaneous carotid angiography had just been perfected and the neurosurgical residents taught me how to insert the needle into the carotid artery by touch, rapidly inject radio-opaque dye, and call for three x-ray images at 2second intervals. I became skilled in identifying the signs of meningioma, glioblastoma, subdural hematoma, arterial aneurysm, and arterial blockage. In pneumoencephalography air is injected into the cerebrospinal canal and ventricles through a needle puncture between lumbar vertebrae 4 and 5. The air fills the ventricles outlining the spaces showing any abnormal images. I became skilled in obtaining cerebrospinal fluid and used the technique in later studies. The films showed tumors, bleedings, and encephalopathies, directing neurosurgical intervention when appropriate. 73 Montefiore Hospital was a museum of chronic neurological disorders under study for decades. The film library included examples of classic syndromes of abnormal motor movements and seizures that I viewed to properly label peculiar repetitive movements. I have no recollection of experience with psychiatric patients. In July 1949 I continued training at Bellevue Hospital, first as resident in neurology and then in psychiatry. Percutaneous carotid angiography had not been introduced to the hospital so I brought this new technique to the Neurology Service. After obtaining permission from Prof E. D. Friedman to develop such tests, a fellow resident Joseph Stein and I built a film holder for multiple images and collaborated with radiologists to organize a service. The first films of a subdural hematoma showed the blood vessels, displaced by a dark mass, clearly outlining the lesion and its effects, encouraging surgical relief. Over the next year, we did 102 procedures, 82 �reporting a high diagnostic success rate and a 5% morbidity rate. Studies of the CSF showed no persistent abnormalities as a result of these tests. After one such procedure, a young man lay in bed, alert, relaxed, staring into space. Asked what he was seeing and pointing to objects in the room, he pleasantly confabulated responses of imaginary objects. He had developed an acute syndrome of visual neglect and denial of blindness known as the Anton Syndrome. After a few days of nursing care his condition resolved. My teachers interpreted the phenomenon as an interaction between the physical changes induced by the injection and the psychological “defense mechanism of denial” based on psychoanalytic philosophy. It was a lesson in applied psychodynamic philosophy to psychopathology. Other clinical experiences were as intriguing. The popular folk singer Lead Belly -- Huddie Ledbetter -- was admitted with advanced amyotrophic lateral sclerosis. No effective treatment was known but my teachers thought the disease resulted from neurotoxicity caused by the passage of toxins through the bloodbrain-barrier to progressively destroy neurons. Animal studies had shown that the transmission of proteins through the barrier could be inhibited by infusions of large molecule dyes such a trypan red. Lacking any effective treatment, daily infusions of 1% trypan red in saline were administered. Lead Belly was a very black man and after a week of perfusions, his sclera, palms, and soles of his feet became brilliant red. He died in December 1949. Double Simultaneous Stimulation: The Face-Hand Test Two teachers, Morris B. Bender and Edwin A. Weinstein encouraged my interest in clinical research during my neurology residency at Bellevue Hospital. While in the Naval medical service Bender, a clinician trained with the neurologists Israel Wechsler and Israel Strauss at Mt Sinai Hospital, became interested in the phenomenon of visual extinction on double simultaneous stimulation in a sailor with a parieto-occipital shrapnel wound. The interaction of simultaneous administered stimuli delineated sensory lesions better than single stimulation. Following professorial tradition he called me and my colleague Martin A. Green to his office, handing each a stack of 3x5 inch blank white cards, telling us to survey the responses of patients to simultaneous tactile stimulations of the face and hands – first in our patients on the Neurology wards, and then on the Psychiatry wards. When we had a hundred such records he asked that we find 100 normal children, then he sent us to Letchworth Village in Thiells, Rockland County to examine an equal number of mental retardates. Applying pin pricks or finger touches simultaneously to both cheeks or hands were correctly perceived by normal adults. But in patients with diverse brain dysfunction and diminished vigilance, as after head trauma, structural brain damage with bleeding, tumor, or stroke, one stimulus was reported and the other was not, even though the sensation of each single stimulus was readily perceived (extinction). 83 �At times the patients mislocated one of the stimuli on their body (displacement) and occasionally insisting that the stimulus was applied to space in front of them (exosomesthesia). These phenomena were not explicable by classical neuroanatomy. The phenomena had been conspicuous in soldiers with severe head injuries and we reported the same phenomena in patients with abnormal brain syndromes, publishing reports on the Face-Hand Test (FHT) as a measure of gross brain dysfunction, the organic mental syndrome. Similar test abnormalities were demonstrated in normal children under the age of 6, and in patients with mental retardation with low mental age scores on Stanford Binet tests. The positive FHT was a rapid estimate of mental age, normalizing at age 6. Impaired brain functions in the elderly were demonstrated in those with impaired orientation and memory. Intravenous injections of amobarbital increased omissions and displacements. Sensory errors increased during the course of electroshock therapy (when slow waves in the EEG became prominent after 3 to 9 seizures) when brain functions were altered. In later experiments carefully measured sensory stimuli demonstrated extinction as sensitive to the stimulus strength as well as the state of vigilance. For a time the FHT was widely recommended as a “soft neurological sign” of brain abnormality but seems no longer to be so used. 84 �Book Nine: Personal Biography I was born in Vienna on January 16, 1923, the same year that my father Julius Fink graduated from the University of Vienna Medical School. He had special training in the new science of radiology and took an externship in medicine and radiology at the Bergen County Hospital in New Jersey. My mother Broniaslawa Lowenthal (Bronia, Bronka) had been a medical student at the University of Vienna. She was much courted and married Julius on March 12, 1922, in her third year of training. I was born within a year. My mother cared for me in Vienna while my father worked in New Jersey. My mother and I sailed from Bremen on the SS George Washington on October 17, 1924 arriving in New York on October 24, shepherded under the watchful eye of her younger brother Adolf Lowenthal, who had been sent by the family from New York. A Greek scholar Lazaros Triarhou published a report on the faculty and students at the Wagner-Jauregg clinic in Vienna when W-J received the Nobel Prize in 1927. A class picture shows the faculty and cites 6 women graduates who went on to careers in neurology and psychiatry. He portrays two graduates, Alexandra Adler and Edith Klemperer, who were consultants during my residency days at Bellevue and my work at Hillside. Thinking of their education, I realized that they were students in Vienna in early 1920s, likely classmates of my mother Bronia, who left her education because of pregnancy. She tried to return to medicine in 1950, was not accepted, and graduated the Columbia University School of Social Work in 1953. In the picture, Josef Gerstmann, Bernhard Dattner, and Paul Schilder appear, scholars who taught at Bellevue New York University during my schooling. Dattner was particularly instrumental in developing my interest in tests and diagnosis. In our family setting, I always “knew” that I would become a physician. Admission to medical school in the U.S. was limited by the publicly acknowledged quotas for Jews, and to successfully gain admission one needed to be “in the top of the class.” My elementary and high school classes were at PS 77 and James Monroe High School in the Bronx, a few streets from my father’s office at 1201 Elder Avenue. My high school teachers, sympathetic to my goal and recognizing the problems in college and medical school admission, encouraged me to be a leader of the Arista Club, to publish articles in the German-language magazine Plaudermäulchen, and to be the Manager of the football team, gaining my athletic “M” at graduation. I graduated from high school in January 1939 at age 16 and enrolled at the New York University College campus at University Heights of the Bronx for its Feb/Sep program. In 1942, at age 19, I began medical school at NYU School of Medicine. The demands of WW II collapsed our training period to 3 years, and I graduated on June 12, 1945 at age 22, the youngest member of my class. 85 �My medical experience began in my father’s office, developing x-ray films, clinical tests of blood and urine, and answering the telephone when he was out of his office. He was a general medical practitioner in a free-standing office equipped for clinical laboratory tests of blood and urine, x-ray, fluoroscopy, and electrocardiography. He trudged to house-calls at all hours of day or night, in all weathers. He was a model for my brother and me, both selecting medical careers. My schooling emphasized an experimental, “hands-on” approach beginning in college where teachers answered questions by suggesting experiments. When I entered my junior college class, I volunteered for the project to count the numbers of mitoses in the neural ependymal layer of the 48-72 hour developing chick, to answer the question how the diurnal light-dark cycle impacted the growth rate. Other students had measured the mitoses in the 24 to 48 hour and 72 to 96 hour cycles. (As I recall, the light cycle did not affect the rates of mitoses.) During medical schooling I lived at home in the Bronx, about an hour’s subway trip. Although school began at 0900, the Army rules insisted that we be present for roll call each morning at 0730. Such was not easy during the winter and I soon was reprimanded for lateness and ordered to guard duty as punishment. Students had some holiday time and on June 6, 1944 – D-Day - I and fellow classmates were camping on Big Burnt Island in Lake George to hear the shouts and waving paddles announcing the invasion as classmates canoed back from Lake George Village. I came of age in America during the war years of the 1940s and 1950s, and for seven decades I have been a treating clinician and researcher, caring for neurologic and psychiatric ill. For many decades, the mentally ill had been warehoused in large sanitaria far from city centers, at least until the seizure therapies, electroshock and insulin coma, were introduced in the 1930s slowing the growth of mental hospital populations from the peak in 1955 at 560,000 patient beds to 170,000 in 2014 in the United States. The efficacy and the mystery of these treatments, inducing grand mal seizures, became my lifelong challenge. The treatment methods, however, were highly controversial in the public and within the profession. For my interest I was often berated and have thought that a less hostile life might have been preferred. The 1950s and 1960s brought new psychoactive medicines that changed brain chemistry and physiology, with resultant improvements in behavior, encouraging a massive deinstitutionalization, pushing tens of thousands of the severe psychiatric ill to leave U.S. hospitals and live at home, or on the streets, in jails, in flophouses, or in and out of community hospitals. Identifying the benefits and developing treatment protocols for these new medicines became a professional challenge. As the effects of the new agents were measurable in the electrical 86 �readings of the scalp recorded electroencephalogram (EEG) patterns, and the digital computer revolution offered means to quantify these effects, the new science of pharmaco-EEG occupied 35 years of my research life. My interest in the effects of psychoactive medications on the human brain included active studies of the opioids and cannabis that were interdicted by governments as addicting and life-threatening. In my later years I actively led an effort to rescue the disorder of catatonia from its entombment within the poorly understood concept of schizophrenia and show it as an independent, identifiable, verifiable, and fully treatable syndrome. Bringing it out of its closet encouraged worldwide recognition and improved diagnosis and effective care. Catatonia is unique among the behavior disorders in having two effective treatments and a useful verification test, which makes each recognition of the syndrome life-saving. The arc of my professional career runs from a childhood in the Bronx, medical school in New York City, a decade organizing Hillside Hospital’s research facilities, a brief stint to establish a Psychiatric Research Institute in Missouri, back to New York for a continuing academic career in different hospitals, then spending 35 years teaching psychiatry at the State University of Stony Brook. After meeting requirements for professional certification in neurology, psychiatry, and psychoanalysis, I spent my years as an experimentalist researcher and teacher. Family Affairs. I married Martha Pearl Gross, a graduate of Barnard College on September 11, 1949. We had met when I returned from a trip as the ship's surgeon on the Grace Line's Santa Monica in March 1948. Martha was dockside awaiting her parents who had been passengers on the cruise to Barranquilla and Cartagena. Her father was ill with amyotrophic lateral sclerosis, and as the ship's surgeon I was called for his care. After I called on her parents at their home in Great Neck, we dated and married after her graduation in June. I continued my training at Bellevue and in May 1951 our son Jonathan was born. We had an apartment at 404 East 54 Street in NYC. When I continued my training at Hillside, we moved to Martha's parents' home in Great Neck, about 10 minutes from Hillside. Our son, Jonathan was born on May 2, 1951, our daughter Rachel September 29, 1956, and our daughter Linda June 3, 1958.. In early 1953 we bought a home in Russell Gardens at 11 Wensley Drive. Dalliance with Psychoanalysis: School and Personal Analysis My interest in psychoanalysis developed during my classes in Texas in 1946. The enthusiasm for Freudian psychodynamic theory and practice rapidly infected American psychiatric teaching and practice. Beliefs that Freudian images explained the behaviors of the psychiatric ill and also offered effective treatment, personal understanding, and clinical relief flashed through clinical psychology, psychiatry, and popular culture in the theatre, film, and education. As a military 87 �veteran, I was entitled to educational training supported by the GI Bill and like many peers, I decided to attend an analytic training program. The New York Psychoanalytic Institute and Columbia University programs required full-time attendance and clinic care of psychiatric patients but the William Alanson White Institute organized its classes during evenings and week-ends. I enrolled for their psychoanalytic course for physicians not for any faith in their beliefs but to continue my neurology training. I began a personal analysis with a WAW graduate Dr. Joseph Miller, meeting for one hour three times a week for the next five years. The WAW did not see merit in the “Freudian couch” approach so the discussion was face-to-face. A psychological assessment by Dr. Ralph Crowley directed the early discussions. School classes were small with Clara Thompson, Ralph Crowley, Frieda FrommReichman, and Janet and David Rioch among my teachers. David Rioch offered elective classes in neurophysiology and brain function that were held on Saturdays in Washington, D.C. We read the writings of Sigmund Freud, Karen Horney, Erich Fromm, and Harry Stack Sullivan, emphasizing the social aspects of interpersonal interactions rather than the classical studies of the unconscious and psychological defenses. I completed the school’s requirements for a Certificate for Physicians in 1953. During my residency at Hillside, my supervisor was Sidney Tarachow, a teaching psychoanalyst from the Columbia University School of Psychoanalysis. He enquired whether the presence of one or two parents during childhood influenced the expression of a psychoneurosis. Did the absence of one parent by death, separation or divorce early in childhood encourage the expression of an obsessivecompulsive neurosis while the childhood presence of two parents was associated with a hysterical neurosis? It was a testable question. I examined the hospital records for those diagnosed with a psychoneurosis, abstracted the family history and evaluated the patient's main symptoms. We identified patients with dominating obsessive or hysterical symptoms and found 50 records with sufficient data for study. We did not find a difference in family histories to support the hypothesis. 74 Another study also failed to support the psychodynamic suggestion that homosexuality was a root of paranoia. I was assigned the care of a 26-year-old Jewish married man with severe panic episodes. The faculty diagnosis varied between a neurosis with homosexual panic and paranoid schizophrenia. Supporting the diagnosis of schizophrenia were his fantasies of aggression and the paranoid imagery on his Rorschach Test responses. I presented his story to an audience of psychoanalytic teachers. The discussion was robust in interpretations but inconclusive as to diagnosis and treatment options. The proceedings were published. Re-reading this report after 60 years showed the many changes in our diagnostic styles, the rejection of homosexuality as a disease, the present tolerance of American society of homosexuality as a life-style, and the awareness that our later experience with medications would offer patients effective treatment with imipramine. 88 �Neither the teachings of Freudian scholars at Hillside Hospital nor the social psychological principles of the Sullivanian scholars at the William Alanson White Institute impressed me as useful therapies. Nor did I have the patience to indulge hour after hour, month after month, listening to a patient’s anxieties, social difficulties, moods and fantasies. In time, my interests shifted and by 1958 I decided to close my private office and devote my life to a medical research career. Military career and travels as ship’s surgeon My active military service as medical officer began in April 1946. After two weeks of field training I was assigned to a regimental field station in Camp Campbell, Kentucky, managing morning sick-call and incidental accidents and injuries. That winter I received orders to attend the Army School of Military Neuropsychiatry at Fort Sam Houston in Texas for a 4-month intensive program in neurological and psychiatric examinations, management of traumatic injuries and combat stress reactions, psychodynamic principles, and lectures on ECT, insulin coma, and lobotomy. Many instructors were imbued with the fervor of psychoanalysis, promising cures for the most severe mental disorders. We were enthralled and so enthused that many of us sought psychoanalytic training when we returned to civilian life. After completing basic military training I was assigned to Kentucky’s Fort Knox Station Hospital as Chief of Psychiatry. Three wards of 30 patients each included a range of severely ill psychotic patients, some undergoing insulin coma and some ECT. The nurses and technicians were competent and experienced, more so than I, and my responsibilities of supervision were light. The nearest medical school was in Louisville, about an hour away. I attended weekly Grand Rounds in Neurology with Ephraim Roseman and took a course in the Rorschach test procedures with Arthur Benton. The war against Japan ended with the atomic bomb in August 1945, saving the lives of many thousands of American soldiers as well as of many Japanese. By 1946 President Truman, faced with the costs of a very large active military service, ordered the summary discharge of thousands of soldiers on duty. As a member of an Officer's Board to decide on the qualifications for soldiers desiring to remain in the post-war career Army and as the panel psychiatrist I used interpretations of the Rorschach Test in the recommendation for discharge or retention. My comments had little influence on the Boards’ decisions, as only the longest serving and meritawarded soldiers were recommended for retention. At the end of November 1947 my service was suddenly ended after 20 months active duty. I had enrolled for residency training in neuropsychiatry at the Montefiore Hospital with H. Houston Merritt for July 1948. The tantalizing question became whether to advance my medical training experience to January or to spend the six89 �month gift of freedom elsewhere. After the continuing years of schooling and military service the glamour and challenge of a position as ship’s surgeon led me to Grace Line’s Hudson River Pier 57. A position was open on the S.S. Santa Maria, a C-2 freighter with 52 passengers, leaving five days later to the west coast of South America, with stops at ports in Columbia, Peru, and Chile. The duties of the ship’s surgeon were "sick call" sessions twice a day, writing health status reports of passengers and crew on entry to ports, examination of food storage areas and freezers for vermin, and accompanying port health inspectors as they surveyed the ship in each port. It was possible to visit port cities during one to two days of loading and unloading cargo. I visited the local mental hospital in Lima where Honorio Delgado, a leader in psychoanalysis, cared for the severe mentally ill. He encouraged patient art. Although the hospital was more like a prison with stone palettes, iron rings in the walls to attach restraints, patient drawings and paintings adorned the walls of the wards. These paintings were fore-runners of the enthusiasms for “Outsider Art” in the 1970s. After two 5-week voyages to Valparaiso, I signed on the Santa Monica for a 3week cruise to Cartajena and Barranquilla on the north coast of Colombia. My final trip was on the American Export Lines Marine Perch, a large C-4 passenger ship that served as troop carrier during the war and as refugee ship after the war. We traveled to Palermo (Sicily), Naples (Italy), and Valleta (Malta). The ship had a large medical complement and the work was easy. In Naples, I hired a taxi for a 28-hour trip to tour Rome visiting the Roman ruins during the night. When we landed in Malta, I visited the port and soon I had a following of young boys and girls, pointing to my white uniform and especially my white shoes. When I enquired as the cause of the hilarity at a silver shop managed by a Jewish owner he pointed to the almost universal black clothes of women and men, honoring the dead. “I must be rich, very rich, to wear white shoes.” Peregrinations In 1962, I was invited to direct a new research institute, the Missouri Institute of Psychiatry on the grounds of the St. Louis State Hospital, with an academic affiliation as Research Professor at Washington University School of Medicine. We found a home in the Lake Forest suburb, and our children were soon registered in the community schools. When our youngest child, Linda was schooled daily, Martha enrolled at Washington University for an M.A. in Education, which led to her lifelong elementary school teaching career. We adjusted to a new community even though warnings of religious intolerance appeared early. When we were looking for a home, I asked George Ulett, 90 �the head of the State mental health services who invited me, where he lived. “In Ladue,” continuing with the advice, “You would not be happy there.” I did not catch the warning but we soon experienced the strong smells of anti-semitism and nativism that pervaded the St. Louis communities, the state, and even the hospital government during our stay. My appointment to the MIP was announced as “Austrian Heads Institute.” Two years later the Missouri State legislature failed to renew the biennium funding for the Institute, and I and the other scientists fled. I found a position at the New York Medical College to lead the opioid detoxification center at New York City’s Metropolitan Hospital beginning in July 1966. Martha and I found a home in Great Neck and enrolled our children in community schools. Martha began teaching students at the elementary school in Port Washington and then in Great Neck schools. I set up my computer center to analyze EEG at the Psychiatry Department offices on East 102nd Street, developed an ECT study at Gracie Square Hospital, and obtained a Federal contract to study the systemic effects of hashish in users in Athens, Greece. I had exceptional students in Richard Abrams, Michael Taylor, and Robert Levine and was fortunate in the collaboration of Rhea Dornbush, Jan Volavka, Jiri Roubicek, and Donald Shapiro. In July 1969 Herman Denber, the director of psychiatric research at Manhattan State Hospital, invited me to join him on a single-engine Cessna 172 flight that he piloted over the Hudson Valley and the New York harbor. It was a day of brilliant sunshine and I decided to learn to pilot a small plane. A flying school was still active at LaGuardia Airport and I began my flying lessons on July 4, 1969. I soloed Nov 13, 1969. For the next few years I leased airplanes at Long Island’s Republic and Westchester airports. I piloted Jonathan’s move to Colby College in Maine and flew to professional meetings. A transcontinental trip in May 1970 from Westchester Airport, through Tulsa, then the next day on the southern route to San Diego and San Francisco with Herman Denber to attend the APA meetings. Interested in leasing a summer home in the Adirondacks in May 1972 Martha and our daughters flew to Lake Placid. My last flights as pilot were in June 1973. In 1972 a new medical school was established 40 miles East of Great Neck at Stony Brook, Long Island. Chairman of Psychiatry Stanley Yolles invited me to join his faculty to lead research in psychopharmacology and ECT. I gladly accepted to avoid the hassles of travel to New York City and the social and political hostilities of the addiction community and the city leaders. For the first few years I taught students and residents at the Central Islip Psychiatric Center and the Veteran’s Hospital in Northport. With the opening of University Hospital in 1980 I organized my teaching, EEG, and ECT studies at that facility. Martha and I bought a home in Nissequogue on the Stony Brook harbor in 1980. By that time our children had each graduated with doctoral degrees in the 91 �sciences and had begun their academic careers. Jonathan’s degree from Stanford University led to a post-doc in volcanology and an academic career at Arizona State University in Tempe. Rachel graduated in marine biology from Cornell and Duke Universities and then taught at Mt Holyoke College in Massachusetts. Linda received her undergraduate degree from Amherst College, among the first women after the college became co-ed, and her doctorate in entomology at University of Florida in Gainesville. She began a teaching career at Sweet Briar College in Virginia. Each married at our Nissequogue home and soon the family grew with four grandchildren. My research work was well supported by NIMH and private foundations and I led a consortium to study continuation treatments after successful ECT in depressed patients. (The CORE studies.) For various administrative reasons I was unable to carry out my portion of the NIMH funded collaborative study at Stony Brook and I moved the project to Hillside Hospital, a return for me after 35 years. For the next decade I supervised this study, developed others, and continued teaching. In 2005, at the age of 82, I left the study group at Hillside and retired to my home to pursue writing. Since 1999 I have wrtitten articles and books with Michael Taylor, Jan-Otto Ottosson, Edward Shorter, and multiple colleagues on convulsive therapy, catatonia, ethics, and melancholia. I also continued to lecture and attend national and international meetings until 2019. Martha died suddenly on March 31, 2016. I remained at my Long Island home spending my time writing. By 2018, I established a second home in South Hadley, Massachusetts with my daughter Rachel. In June 2019 I sold my Long Island home and moved to Rachel's home in South Hadley, Massachusetts. 92 �Books Authored by Max Fink Electroencephalography in Human Psychopharmacology. EEG Journal, Supplement 23, 1964. NY: Elsevier. Convulsive Therapy: Theory and Practice. NY Raven Press, 1979. ELECTROSHOCK: Restoring the Mind. Oxford U Press, New York, 157 pp., 1999. Electroshock: Healing Mental Illness. NY: Oxford U Press. 2002. Ehics in Electroconvulsive Therapy. NY: Routledge. 2004. (Ottosson J-O, Fink M.) Catatonia: A Clinician's Guide to Diagnosis and Treatment. Cambridge UK: Cambridge U Press, 2003 (Fink M, Taylor MA.) Rediscovering Catatonia: The Biography of a Treatable Syndrome. Acta psychiatr Scand. 127: Supplement 441;1-50, 2013. The Madness of Fear: A History of Catatonia. NY: Oxford University Press, 2018. (Shorter E, Fink M.) Melancholia:The Diagnosis, Pathophysiology, and Treatment of Depressive Illness. Cambridge UK: Cambridge University Press, 2006. (Taylor MA, Fink M,) Endocrine Psychiatry: Solving the Riddle of Melancholia. NY: Oxford U Press. (Shorter E, Fink M.), 2010. Edited Books: Fink M. (Ed.) Convulsive Therapy. Seminars in Psychiatry. Grune & Stratton, 1972. Fink M, Kety S, McGaugh J, Williams T. (Eds): Psychobiology of Convulsive Therapy. Washington, DC, V.H. Winston and Sons 1974. Bradley P, Fink M. (Eds): Anticholinergic Drugs and Brain Functions in Animals and Man, P. Bradley and M. Fink (eds.), Progress in Brain Research, Vol. 28, Elsevier, 1968. Dornbush RL, Freedman AM, Fink M., Chronic Cannabis Use.. Annals N.Y. Academy of Sciences, 282: 430 pp., 1976. Stefanis C, Dornbush RL, Fink M. Hashish: A Study of Long-Term Use (eds.). New York, Raven Press, 181 pp, 1977. 93 �1 2 3 4 5 6 7 8 Archives: When the historians Edward Shorter and David Healy visited my home in 2006 to examine my files and books for their history of the shock therapies, they were impressed by the extent of the files and asked what I planned to do with them.1 They encouraged their being publicly archived. The Stony Brook University Library archivist Kristen Nyitray examined and agreed to archive the collection. These files are established as the Max Fink Archives in the Special Collections at the Main Library of Stony Brook University. I also deposited my library; these books are indexed in the University files and in WorldCat. Contact: Kristen J. Nyitray, Head, Special Collections and University Archives, University Archivist, Associate Librarian, Stony Brook University. < kristen.nyitray@stonybrook.edu> t: 631.632.7119 / f: 631.632.1829 Rachlin HL, Goldman GS, Gurvitz M, Lurie A, Rachlin L. Follow-up study of 317 patients discharged from Hillside Hospital in 1950. J Hillside Hosp 1956; 5:17-40. Fink M Shaw R, Gross G, Coleman FS. Comparative study of chlorpromazine and insulin coma in the therapy of psychosis. J. Amer. Med. Ass., 1958; 166: 18461850 Sylvia Nasar's biography A Beautiful Mind was filmed; I was the consultant to the producers in the making of the film. Discussed in Book Three. Fink M. A Beautiful Mind and insulin coma: social constraints on psychiatric diagnosis and treatment. Harvard Review of Psychiatry 11: 284-290, 2003. Fink M, Bolwig T. Electrotherapy of melancholia: The pioneering contributions of Benjamin Franklin and Giovanni Aldini. J ECT 2009; 25:15-18. Beginning January 1953 with Hans Strauss and Mortimer Ostow I learned how to apply scalp electrodes, maintain the EEG recorders, and interpret the records. The Medical Director Joseph S. A. Miller, purchased a Grass electroencephalograph with a $5,000 grant from the Dazian Foundation obtained by Dr. Israel Strauss, the Founder of the Hospital. In the 10 years of its existence, Ira Belmont, Martin A. Green, John C. Kramer, Max Pollack, Eric Karp, Donald F. Klein, Abraham Kaplan, Arthur Willner, Karl Andermann, Joseph Jaffe, Hyman Korin, George Krauthamer, Nathaniel Siegel, Henry J. Lefkowits, Harold Esecover, and Barre Alan, collaborated in the studies. Arnold G. Blumberg of the Medical Department was an active collaborator.. 94 �9 By 1977 in USA, Paul Blachly created an ECT stimulating device using brief pulse stimuli that recorded the EEG of the seizure. His device, labeled MECTA, has been widely adopted. The technology became world standard. 10 11 12 13 14 15 16 17 18 Fink M, Kahn RL, Green M. Experimental studies of the electroshock process. Dis. Nerv. Syst., 19: 113-118, 1958. In the last two decades, ECT has been denigrated as a "neurostimulation." Since neurostimulation devices are applied in neurotic depressed and character disordered subjects, increased outpatient usage has changed the character of modern treatment to encompass low energy, short seizure, RUL placement treatments that fail to influence severely ill, but act mainly as placebo psychotherapiess similar to the weakened SSRI, SNRI antidepressants and atypical neuroleptics that dominate outpatient care since the 1990s. Fink M, Taylor MA, Shorter E, Vaidya NA. The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition. Acta Psychiatr Scand 2010; 122: 173-183. The question is the basis for the neuroendocrine hypothesis of ECT, that the seizure pattern is based on systematic changes sensed by pathology in the organism that can be redressed, much as a sneeze or a cough clears physical passages. Bennett, A.E. The introduction of curare into clinical medicine.Present and potential usefulness. Am Sci 46; 34:434-431. While on a lecture tour in 5 cities in India in 1991, the first question at each site was my attitude to the use of unmodified ECT, inducing seizures without sedation and motor relaxation. When I expressed my experience, recalling the benefits of my first experiences at Hillside in 1952, I opined "unmodified ECT is better than no ECT." The audience applauded. The argument persisted for many years as the cost of the agents and the fee of the anesthesiologist surpassed the reimbursements for the ECT procedure. When the anti-psychiatry cries of psychologists became strident again in 2020s, with claims that ECT had not been properly tested in an RCT with sham ECT. The sham-ECT study data was republished in 2001 in JECT. Palmer RL. Electroconvulsive Therapy: An Appraisal. NY: Oxford U Press, 1981 Fink M, Kahn RL, Karp E, Pollack MA, Green MA, Alan B, Lefkowitz HJ. Inhalantinduced convulsions. Arch. Gen. Psychiat., 4: 259-266,1961. 95 �19 20 21 22 23 24 25 26 27 28 29 Cooper K, Fink M. The chemical induction of seizures in psychiatric therapy: Were flurothyl (Indoklon) and pentylenetetrazol (Metrazol) abandoned prematurely? J Clinical Psychopharmacology. 2014; 34(5):602-7. Fink M, Greenberg LB, Gage J, Vikun S. Isoflurane anesthesia therapy: A replacement for ECT in depressive disorders? Convulsive Ther 1987; 3: 269277. Fink M. Cholinergic aspects of convulsive therapy. J. Nerv. Ment. Dis., 1966; 142: 475-484. The results are widely published by Robert Kahn, Max Pollack, and Ira Belmont. The results are summarized in Convulsive Therapy: Theory and Practice, NY: Raven Press, 1979. We received four-year funding from NIMH for the project. After we introduced the study to the GSH practitioners, many agreed to cooperate and to let us treat their patients according to our protocols. They endorsed their patients’ cooperation for EEG and psychological tests. Aside from Richard Abrams and myself, our study collaborators were Jan Volavka, Jiri Roubicek, Rhea Dornbush, and Stanley Feldstein from the Biological Psychiatry Research division of the New York Medical College. This is my second study reporting the greater efficacy of seizures induced by bilateral electrode placements. The CORE study replicated again. Fink M, Abrams R, Volavka J, Roubicek J, Dornbush R. Lateralized EEG changes after unilateral and bilateral electroconvulsive therapy. Dis. Nerv. Syst., 31 (11) Suppl.: 28-33, 1970. Wachtel LE, Dhossche DM. Self-injury in autism as an alternative sign of catatonia: implications for convulsive therapy. Med Hypotheses 2010; 75(1):111-4. Bright-Long L, Fink M. Reversible dementia and affective disorder: The Rip van Winkle Syndrome. Convulsive Ther 1993; 9: 209-16. Greenberg LB, Mofson R, Fink M. Prospective electroconvulsive therapy in delusional depressed patient with a frontal meningioma. Br J Psychiatry 1988; 153: 105-107. Petrides G, Fink M. Atrial fibrillation, anticoagulation, and electroconvulsive therapy. Convulsive Ther. 1996; 12: 91-98 96 �30 31 32 33 34 35 36 Fink M. Is EST a useful therapy of schizophrenia? In J.P. Brady and H.K.H. Brodie (eds.): Controversy in Psychiatry. Philadelphia, W.B. Saunders Co., 183-193, 1978. Fink M. EST and other somatic therapies of schizophrenia. In L. Bellak (ed.): Disorders of the Schizophrenic Syndrome. Basic Books, New York, 353-363, 1979. Fink M., Sackeim HA. Convulsive therapy for schizophrenia? Schizophrenia Bull. 1996; 221: 27-39 Fink M, Taylor M.A. The medical evidence-based model to identify psychiatric syndromes: Return to a classical paradigm. Acta Psychiatr Scand 2008; 87: 81-84 . I did not believe that ECT augmentation of clozapine in clozapine non-responders was effective. When George Petrides, with the encouragement of John Kane to publish a "positive" report, I withdrew my association. Augmentation by ECT of fluphenazine and chlorpromazine treatment in psychosis are better documented. Greenberg LB, Zervas I, Suckow RF, Cooper T, Jandorf L, Fink M. Rat brain concentration of fluphenazine during a course of electroconvulsive shock. Convulsive Ther 1990; 6: 273-9. I moved the study site to Hillside Hospital with George Petrides as Principal Investigator. Fink M. What was learned: Studies by the Consortium for Research in ECT (CORE) 1997-2011. Acta Psychiatrica Scand. 129: 417-426, 2014. Fink M, Taylor MA. Electroconvulsive therapy: Evidence and challenges. JAMA 2007; 298: 330-332 . R. Electroconvulsive Therapy. Edition IV. NY: Oxford University Press, 2002. 37Abrams 38 39 40 Meduna L: Die Konvulsionstherapie der Schizophrenie. Halle Germany, Karl Marhold, 1937. Fink M. (Ed.): Convulsive Therapy (ed.). Seminars in Psychiatry 4: 1. Grune & Stratton, Inc., New York, 70 pp. Fink M, Abrams R, Bailine S, Jaffe R. Ambulatory electroconvulsive therapy. Ta force report of the association for convulsive therapy. Convulsive Ther. 1996; 12: 42-55. 97 �41 42 43 44 45 46 47 Fink M. Complaints of loss of personal memory after electroconvulsive therapy: Evidence of a somatoform disorder. Psychosomatics 2007; 48:290=293. Fink M. A Beautiful Mind and insulin coma: social constraints on psychiatric diagnosis and treatment. Harvard Review of Psychiatry 2003; 11: 284-290. Fink M. A unified theory of the action of physiodynamic therapies. J. Hillside Hosp.,1957; 6: 197-206. Fink M, Ottosson J-O. A theory of convulsive therapy in endogenous depression: Significance of hypothalamic functions. Psychiatry Research 2: 49-61, 1980. Fink M. The mode of action of convulsive therapy: the neurophysiologic-adaptive view. J. Neuropsychiat., 3: 231-233.1962. Fink M. Cholinergic aspects of convulsive therapy. J. Nerv. Ment. Dis., 1966; 142: 475-484. Nemeroff C, Bissette G, Akil H, Fink M. Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy. Corticotrophinreleasing factor, beta endorphin and somatostatin. Br J Psychiatry 1991; 158: 59-63. 48 49 50 51 52 53 Fink M, Kety S, McGaugh J, Williams T. (Eds): Psychobiology of Convulsive Therapy. Washington, DC, V.H. Winston and Sons Kahlbaum KL. Die Katatonie oder das Spannungsirresein: eine klinische Form psychischer Krankheit. Berlin: Verlag August Hirshwald, 1874. Greenberg LB, Gujavarty K. The neuroleptic malignant syndrome: Review and report of three cases. Comprehens Psychiatry 1985; 26:63–70. Taylor MA. Catatonia: A review of a behavioral neurologic syndrome. Neuropsychiatry, Neuropsychology Behavioral Neurology. 1990; 3(1):48-72. Rogers D. Motor disorder in psychiatry. Chichester UK: John Wiley & Sons, 1992. Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia: I: rating scale and standardized examination. Acta psychiatr. Scand 1996; 93 (2): 129-36. Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia: II. Treatment with lorazepam and electroconvulsive therapy . Acta Psychiatr. Scand 1996; 93 ( 2):137-43. 54 Shorter E. What Psychiatry Left Out of DSM-5. NY: Taylor & Francis, 2015. 98 �55 56 57 58 59 60 61 62 63 64 65 Taylor MA. Hippocrates Cried: The Decline of American Psychiatry. NY: Oxford U Press, 2013. Taylor M, Fink M. Fink Catatonia in psychiatric classification: A home of its own. Am J Psychiatry 2003; 160: 1233-1241. Fink M, Shorter E. Does persisting fear sustain catatonia? Acta Psychiatr Scand 2017; Nov; 136(5):441-444. Our experience together had been at New York Medical College during his residency training and when he and his colleague Richard Abrams joined the Stony Brook University faculty. Clinicians versed in ECT see the rapid response of catatonia and melancholia, in their varied forms, to repeated induced seizures. The DSM commissioners, all five teams from 1952 to 2013, lacked members with experience in ECT. Many were known opinion leaders and paid consultants to industry, with ambulatory office practices and little experience with the severely ill, so had no experience with the many forms of catatonia and melancholia. Further, in the decades from 1980 to 2013, they were paid well as industry consultants to support the new agents, the SSRI, SNRI, and atypical neuroleptics, and reject the tricyclic antidepressants (imipramine, amitriptyline) and the typical neuroleptics (chlorpromazine, fluphenazine) as toxic. Fink M, Klein DF, Kramer J. Clinical efficacy of Chlorpromazine-Procyclidine combination, Imipramine and placebo in depressive disorders. Psychopharmacolgia (Berl.), 7: 27- 36. Davies BJ, Carroll BJ, Mowbray RM: Depressive Illness: Some Research Studies. Springfield, IL: C. C Thomas, 1972. Papakostas Y, Fink M, Lee J, Irwin P, Johnson L. Neuroendocrine measures in psychiatric patients: Course and Outcome with ECT. Psychiatry Res 1981;4: 55-64. Glassman A. APA Task Force on Laboratory Tests in Psychiatry: The Dexamethasone Suppression Test in Psychiatry. Am J Psychiatry 1987;144:1253-1262 Fink M, Rush J, Knapp R, et al. DSM melancholic features are unreliable predictors of ECT response: A CORE Publication. JECT 2007; 23(3): 139-146. Taylor MA, Fink M. Melancholia: The Diagnosis, Pathophysiology, and Treatment of Depressive Illness. NY: Cambridge University Press, 2006. 99 �66 67 68 69 70 71 72 73 74 Bolwig T, Shorter E. Melancholia: Beyond DSM, Beyond Neurotransmitters. Acta Psychiatrica Scandinavica Supplement 433; 115:1-183, 2007. Participants included, in addition to the Editors, Gordon Parker, Michael Taylor, William Coryell, Athanasios Koukopoulos, Donald Klein, Bernard Carroll, Jules Angst, Walter Brown, Max Fink. Taylor M. Hippocrates Cried. The Decline of American Psychiatry. NY: Oxford University Press, 2013. Shorter E, Fink M. Endocrine Psychiatry: Solving the Riddle of Melancholia. NY: Oxford University Press, 2010. Bradley P, Fink M. (Eds): Anticholinergic Drugs and Brain Functions in Animals and Man. Progress in Brain Research, Vol. 28, Elsevier, 1968. Fink M. EEG classification of psychoactive compounds in man: review and theory of behavioral associations. Psychopharmacology: A Review of Progress, 19571967: D. Efron, J. Cole, J. Levine and J.B. Wittenborn (eds.): U.S. Govt. Printing Office, Washington, DC, pp. 497-507. Fink M. Remembering: the forgotten neuroscience of pharmaco-EEG. Acta Psychiatr Scand 2010; 121: 161-73. In my schooling, self-administration of trial medication was accepted as part of my educational experience. By 1980s, a change had occurred among students. When teaching psychopharmacology I offered self-exposures to various psychoactive medications,many of which I had experienced. The students refused, and I was admonished by the Dean that such teaching was not acceptable. As the death of President Kennedy was announced over the hospital radio, I was in the r-ray suite, inserting a needle in a patient's spinal canal for a PEG. Dr. Tarachow presented these findings at a meeting of the American Psychoanalytic Association in New York in 1953. I was denied admission to the meeting as I had not graduated from an accredited psychoanalytic institute. 100 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Biographical Files Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource 70 Years an Experimentalist in Neurology and Psychiatry Subject The topic of the resource <a title="Autobiography" href="http://id.loc.gov/authorities/subjects/sh85010050" target="_blank" rel="noreferrer noopener">Autobiography</a>, <a title="Psychiatry" href="http://id.loc.gov/authorities/subjects/sh85108381" target="_blank" rel="noreferrer noopener">Psychiatry</a>, <a title="Neurosciences" href="http://id.loc.gov/authorities/subjects/sh91006099" target="_blank" rel="noreferrer noopener">Neurosciences</a>, <a title="Neurology" href="http://id.loc.gov/authorities/subjects/sh85091139" target="_blank" rel="noreferrer noopener">Neurology</a> Description An account of the resource Unpublished autobiographical account written by Dr. Max Fink, M.D. Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank" rel="noreferrer noopener">Fink, Max, 1923-</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Date A point or period of time associated with an event in the lifecycle of the resource 2021-04-18 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank" rel="noreferrer noopener">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Relation A related resource The Max Fink Collection Type The nature or genre of the resource text Identifier An unambiguous reference to the resource within a given context mfp_experimentalist_20210418 Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Biographical http://exhibits.library.stonybrook.edu/mfp/files/original/491a406bfc36b0865ea98089beb94eec.pdf 8b176841a98af4f8f1d1cc5a94eac7a1 PDF Text Text MAX FINK, M.D. 11 Buttonfield Lane South Hadley, MA 01075 Cell: 631.637.1730 fink.max@gmail.com maxfink55@gmail.com PRESENT APPOINTMENT Professor of Psychiatry and Neurology, Stony Brook University 1972-1997 Professor Emeritus 1997CERTIFICATIONS Diplomate, National Board of Medical Examiners 1946 Diplomate, American Board of Psychiatry and Neurology Certified in Neurology Certified in Psychiatry 1952 1954 William Alanson White Institute of Psychoanalysis Certificate in Psychoanalysis for Physicians License, Practice of Medicine and Surgery New York Missouri 1953 1946 1962 EDUCATION University College, University Heights Campus New York University, B.A. cum laude, Honors in Biology 1939-1942 New York University College of Medicine, M.D. 1942-1945 William Alan White Institute for Psychoanalysis Certificate in psychoanalysis for physicians 1948-1953 Morrisania City Hospital, Rotating Internship July 1945-April 1946 Montefiore Hospital, Residency in Neuropsychiatry July 1948-June 1949 Bellevue Psychiatric Hospital, Residencies in Neurology and Psychiatry July 1949-December 1951 Hillside Hospital, Resident in Psychiatry January 1952-December 1952 Mount Sinai and Hillside Hospitals, Fellow in Neuropsychiatry; National Foundation for Infantile Paralysis (also January 1951-December 1951) January 1953-December 1953 �ACADEMIC and RESEARCH AWARDS C. Charles Burlingame Award, Lecture, Institute for Living, CT 2019 Thomas William Salmon Award and Medal, New York Academy of Medicine 2011 Honorary Member, Associazione Italiana per la Terapia Elettroconvulsivante (AITEC) 2006 Honorary Member, European Forum for Electroconvulsive Therapy (EFFECT) 2006 Honorary Fellow, International Pharmaco-EEG Society (IPEG) 2000 Fellow, Association for Convulsive Therapy 2000 Arrigo Prize for Lifetime Achievement in Neurophysiology, University of Pavia 1998 Lifetime Achievement Award, Society of Biological Psychiatry 1996 Lifetime Achievement Award, Psychiatric Times and CME, Inc. 1995 Gold Medal Award of the Society of Biological Psychiatry 1988 Laszlo Meduna Prize of the Hungarian National Institute for Nervous and Mental Diseases 1986 Taylor Manor Hospital Psychiatric Award 1983 Anna Moniker Foundation Prize for Contributions to the Study of Endogenous Depression 1979 Samuel W. Hamilton Award, American Psychopathological Association 1974 Alpha Omega Alpha, New York University 1973 A.E. Bennett Psychiatric Research Award, Society of Biological Psychiatry 1958 Electroshock Research Association Award 1956 Elected Phi Beta Kappa and Alpha Pi Christopher Coates Biology Prize Phi Lambda Upsilon Chemistry Prize, New York University 1939-1942 2 �TEACHING AWARDS “Teacher of the Year,” Department of Psychiatry Stony Brook University 1992, 1993, 1996 MEMBERSHIPS Distinguished Life Fellow American Psychiatric Association (APA) Secretary, Chairman, section on Brain Function and Behavior Member, Task Force on Electroconvulsive Therapy Nassau Neuropsychiatric Society Suffolk County District Branch 1957, 1958, 1962 1975-1978, 1988-1990 1954-1962 (President, 1959) 1973- Fellow New York Academy of Medicine American College of Neuropsychopharmacology (ACNP) Association for Convulsive Therapy International -Pharmaco-EEG (IPEG) Vice President Councillor Honorary Fellow 1981-1984 1986-1990 2000 Senior Member Society of Biological Psychiatry 1960 Member American Psychopathological Association Secretary Vice President President-Elect President 1968-1971 1971-1972 1972-1973 1973-1974 Association for Convulsive Therapy Chairman, Task Force on Ambulatory ECT 1995 Collegium Internationale Neuro-Psychopharmacologicum (CINP) 1960 Deutsche EEG Gesellschaft 1962 International Brain Research Organization (IBRO) 1964 International Society for Psychoneuroendocrinology 1964 Instituto de Psiquatria y Psicologia de Montevideo 1964 World Federation of Societies of Biological Psychiatry Chairman, Task Force on ECT 2002-2005 3 �EDITORIAL APPOINTMENTS Founding Editor, Convulsive Therapy, 1984-1994 Editorial Board, 1995Contributing Editor Comprehensive Psychiatry (1972-2000) Currents Developments in Psychopharmacology Directions in Psychopharmacology Journal of Clinical Psychiatry (1980-1999) Neuropsychiatry, Neuropsychology & Behavioral Neurology (1988-2003) Neuropsychology (Associate Editor, Pharmaco-EEG, 1983-1997) Pharmacopsychiatry Psychiatric Journal, University of Ottawa (1980-1992) Clinical Pharmacology & Therapeutics (1977-1981) Psychopharmacologia (1975-1978) Sleep &Wakefulness (1978-1981) PRIOR APPOINTMENTS Academic Assistant in Neurology, New York University 1952-1954 Research Professor of Psychiatry, Washington University 1962-1966 Professor of Psychiatry, University of Missouri 1963-1966 Visiting Professor University of Istanbul National Institute of Neurology of Mexico University of California at Irvine Organon Special Visiting Lectureship, Netherlands 1968, 1969 1969 1976 1988 Honorary Member, Societe Royale de Medecine Mentale de Belgique 1969 Professor of Psychiatry, Albert Einstein College of Medicine 1998-2005 4 �Hospital Staff Neurologist, Long Island Jewish Hospital Associate Attending Neurologist, North Shore Hospital 1954-1959 1954-1962 Supervising Psychiatrist; Director of Research Director, Department of Experimental Psychiatry Hillside Hospital, Glen Oaks, NY 1954-1962 Director, Missouri Institute of Psychiatry, St. Louis, MO 1962-1966 Director, Division of Biological Psychiatry, NY Medical College 1966-1973 Attending Psychiatrist Metropolitan Medical Center Flower & Fifth Avenue Hospitals Bird S. Coler Hospital University Hospital, Stony Brook University 1965-1973 1966-1973 1966-1973 1980-1997 Consulting Psychiatrist Grasslands Hospital Central Islip Psychiatric Center V.A. Hospital, Northport, NY 1971-1973 1974-1979 1972-1981 Director, Division of Clinical Sciences Long Island Research Institute 1976-1983 Attending Psychiatrist, Department of Psychiatry Long Island Jewish Hillside Hospital 1981-2005 CONSULTANT Committee on Clinical Drug Evaluation Psychopharmacology Service Center, NIMH 1962-1965 Division of Mental Diseases of the State of Missouri 1962-1966 VA-NIMH-SAODAP Collaborative Studies in Opiate Dependence 1972-1974 Bureau of Drugs, Food & Drug Administration 1970-1973 American Psychiatric Association Task Force on ECT 1975-1978 V.A. Merit Review Board on Behavioral Sciences 1977-1980 German BGA Commission of Pharmaco-EEG 1980-1981 NIMH Committee on Collaborative ECT Project 1980-1982 5 �National Academy of Sciences, National Research Council Committee on Toxicology: Committee on Anticholinergic Drugs Panel 1981-1982 U.S. Army Workshop on the Feasibility of Using Incapacitating Agents Against Terrorists 1986 American Psychiatric Association Task Force on Electroconvulsive Therapy 1988-1990 MILITARY SERVICE Captain, U.S. Army Medical Corps. School of Military Neuropsychiatry, Fort Sam Houston Chief, NP Clinical Service, Fort Knox Station Hospital 1946-1947 PRIVATE PRACTICE Ship Surgeon Grace Line American Export Line 1947-1948 1948 Neurology and Psychiatry 275 Middle Neck Road, Great Neck, NY 1954-1958 6 �PUBLICATIONS 1950 1. Subdural hematoma developing during hospitalization. Amer. J. Psychiat.,107: 381-383 (with M. Green). 2a. Patterns in perception of simultaneous tests of face and hand. Trans. Amer. Neurol. Ass., 75: 250 (with M.B. Bender and M. Green). (abstract). 1951 2b. …ibid., Arch. Neurol. Psychiat. (Chic.), 66: 355-362. 1952 3. The face-hand test as a diagnostic sign of organic mental syndrome. Neurology (Minneap.), 2: 46-58 (with M.B. Bender and M. Green). 4. Tactile perceptual tests in the differential diagnosis of psychiatric disorders. J. Hillside Hosp., 1: 21-31 (with M.B. Bender). 5. A clinical evaluation of carotid angiography. Contin Neurol. (Basel), 12: 181-195 (with J.M. Stein). 6a. Exosomesthesia, or displacement of cutaneous sensation into extra-personal space. Trans. Amer. Neurol. Ass., 77: 260-262 (with M.F. Shapiro and M.B. Bender). (abstract). 6b. …ibid., Arch. Neurol. Psychiat. (Chic.), 68: 481-490. 7a. Order of dominance in cutaneous perception. Trans. Amer. Neurol. Ass., 77: 238-240 (with M.B. Bender and M. Green). (abstract). 7b. Patterns of perceptual organization with simultaneous stimuli. Arch. Neurol. Psychiat. (Chic.), 72: 233255 (with M.B. Bender and M. Green), 1954. 1953 8. Perception of simultaneous tactile stimuli in normal children. Neurology (Minneap.), 3: 27-34 (with M. B. Bender). 9. Perception of simultaneous tactile stimuli by mentally defective subjects. J. Nerv. Ment. Dis., 117: 43-49 (with M.B. Bender and M. Green). 10. Spinal fluid findings following cerebral angiography. Neurology (Minneap.), 3: 137 (with J.M. Stein). 11. A statistical study of a psychoanalytic hypothesis: absence of a parent as a specific factor determining choice of neurosis. J. Hillside Hosp., 2: 67-71 (with S. Tarachow). 7 �12. Effects of intravenous barbiturate on perception. Trans. Amer. Neurol. Ass., 78: 244-245 (with M.B. Bender, P. Bergman, and M. Nathanson). (abstract). 13. Homosexuality with panic and paranoid states case report. J. Hillside Hosp., 2: 164-190. 1954 14. Standardization of the face-hand test. Neurology (Minneap.), 4: 211-217 (with M. Green). 1955 15. The “Amytal test” in patients with mental illness. J. Hillside Hosp., 4: 3-13 (with R.L. Kahn and E.A. Weinstein). 16. Delusional reduplication of parts of body after insulin coma therapy. J. Hillside Hosp., 4: 134-147 (with R.L. Kahn and D. Graubert). 1956 17. Relation of Amobarbital test to clinical improvement in electroshock. Arch. Neurol. Psychiat. (Chic.), 76: 23-29 (with R.L. Kahn and E.A. Weinstein). 18. Evaluation of high dose reserpine therapy for the relief of anxiety. J. Hillside Hosp., 5: 67-77 (with M. Wachspress, A.G. Blumberg, and J.S.A. Miller). 19. Relation of Changes in Memory and Learning to Improvement in Electroshock. Confin. Neurol. (Basel), 16: 88-96 (with H. Korin and S. Kwalwasser). 20. Denial of blindness following cerebral angiography. J. Hillside Hosp., 5: 238-245. 21a. Quantitative studies of slow wave activity following electroshock. Electroenceph. Clin. Neurophysiol., 8: 158 with R.L. Kahn). (abstract). 21b. Relation of EEG delta activity to behavioral response in electroshock: quantitative serial studies. Arch. Neurol. Psychiat. (Chic.), 78: 516-525, 1957 (with R.L. Kahn). 1957 22a. EEG and clinical response to Megimide. Electroenceph. Clin. Neurophysiol., 9: 180 (with M. Green). (abstract). 22b. Clinical and electroencephalographic effects of Megimide in patients without cerebral disease. Neurology (Minneap), 8: 682-685 (with M. Green). 23. A unified theory of the action of physiodynamic therapies. J. Hillside Hosp., 6: 197-206. 24. Perception of embedded figures after induced altered brain function. American Psychologist, 12: 361 (with R.L. Kahn). 25. Social factors in selection of therapy in a voluntary mental hospital. J. Hillside Hosp., 6: 216-228 (with R.L. Kahn and M. Pollack). 8 �26. Role of stimulus intensity in perception of simultaneous cutaneous electrical stimuli. J. Hillside Hosp., 6: 241-250 (with H. Korin). Added 2/25/17 Soviet Medical Advances: Importance of making literature available to American scientists. New York Times Letters, 15 Nov 1957, pg 26. 1958 27. Changes in language during electroshock therapy. In P.H. Hoch and J. Zubin (eds.), Psychopathology of Communication. Grune and Stratton, New York, 1958: 126-139 (with R.L. Kahn). 28. Lateral gaze nystagmus as an index of the sedation threshold. Electroenceph. Clin. Neurophysiol., 10: 162-163. 29a. Effects of Diethazine on EEG and significance for theory of convulsive therapy. Electroenceph. Clin. Neurophysiol. 10: 207-208. (abstract). 29b. Effect of anticholinergic agent, Diethazine, on EEG and behavior: significance for theory of convulsive therapy. Arch. Neurol. Psychiat. (Chic.), 80: 380-387. 29c. ..ibid., In J.H. Masserman (ed.), Biological Psychiatry. Grune and Stratton, New York, 1959, 1: 184-194. 30. Experimental studies of the electroshock process. Dis. Nerv. Syst., 19: 113-118 (with R.L. Kahn and M. Green). 31. Comparative study of Chlorpromazine and insulin coma in the therapy of psychosis. J. Amer. Med. Ass., 166: 1846-1850 (with R. Shaw, G. Gross, and F.S. Coleman). 32. Electroencephalographic correlates of the electroshock process. Dis. Nerv.Syst., 19: 227 (with M. Green). (abstract). 33a. Experimental studies of convulsive and drug therapies in psychiatry: theoretical implications. Arch. Neurol. Psychiat. (Chic.), 80: 733-734 (with R.L. Kahn and M.A. Green). (abstract). 33b. Alteration of brain function in therapy. In N.S. Kline (ed.), Psychopharmacology Frontiers. Little, Brown & Co., Boston, 1959: 325-332. 34a. Effect of anticholinergic compounds on post-convulsive electroencephalogram and behavior. Electroenceph. Clin. Neurophysiol.,10: 776. (abstract). 34b. Effect of anticholinergic compounds on post-convulsive electroencephalogram and behavior of psychiatric patients. Electroenceph. Clin. Neurophysiol., 1960, 12: 359-369. 1959 35. Effects of diffuse altered brain function on perception. In Proc. XV Int. Congr. Psychol. North Holland, Amsterdam: 238-239 (with R.L. Kahn and H. Korin). (abstract). 36. Psychological factors affecting individual differences in behavioral response to convulsive therapy. J. Nerv. Ment. Dis., 128: 243-248 (with R.L. Kahn and M. Pollack). 9 �37a. Significance of EEG pattern changes in psychopharmacology. Electroenceph. Clin. Neurophysiol., 11: 398. (abstract) . 37b. EEG and behavioral effects of psychopharmacologic agents. In P. B. Bradley, P. Deniker, and C. Radouco-Thomas (eds.), Neuro-Psychopharmacology. Elsevier, Amsterdam, 1959, 1: 441-446. 38a. Electroencephalographic and behavioral effects of Tofranil. Canad. Psychiat. Assoc. J., 4 Suppl.: 166171. 38b. …ibid., Electroenceph. Clin. Neurophysiol., 1960, 12: 243-244. (abstract). 39. Relation of tests of altered brain function to behavioral change following induced convulsions. In L. van Bogaert and J. Radermecker (eds.), First International Congress of Neurological Sciences. Pergamon Press, London, 1959, 3: 613-619 (with R.L. Kahn and H. Korin). 40. The Role of set in the perception of simultaneous tactile stimuli. Amer. J. Psychol., 72: 384-392 (with H. Korin). 41. Personality factors in behavioral responses to electroshock therapy. J. Neuropsychiat., 1: 45-49 (with R.L. Kahn). 42. Sociopsychologic aspects of psychiatric treatment in a voluntary mental hospital: duration of hospitalization, discharge ratings and diagnosis. Arch. Gen. Psychiat., 1: 565-574 (with R.L. Kahn and M. Pollack). 1960 43. Efficacy of divided and single dose schedules in insulin coma therapy. Amer. J. Psychiat., 116: 839-840 (with A.G. Blumberg and P. Laderman). 44. Changes in verbal transactions with induced altered brain function. J. Nerv. Ment. Dis., 130: 235-239 (with J. Jaffe and R.L. Kahn). 45. Drug induced changes in interview patterns: linguistic and neurophysiologic indices. In G.J. Sarwer-Foner (ed.), The Dynamics of Psychiatric Drug Therapy. C.C. Thomas, Springfield, IL, 1960: 29-44 (with J. Jaffe and R.L. Kahn). 46. Social attitude California F Scale and convulsive therapy. J. Nerv. Ment. Dis., 130: 187-192 (with R.L. Kahn and M. Pollack). 47. Figure-ground discrimination after induced altered brain function. Arch. Neurol. (Chic.), 2: 547-551 (with R.L. Kahn and M. Pollack). 48. Prognostic value of Rorschach criteria in clinical response to convulsive therapy. J. Neuropsychiat., 1: 242-245 (with R.L. Kahn). 1961 49. Modification of psychotherapeutic transactions by altered brain function. Amer. J. Psychother., 15: 46-55 (with J. Jaffe, H. Esecover, R.L. Kahn). 10 �50. Neuropsychologic response patterns of some psychotropic drugs. In E. Rothlin (ed.), Neuropsychopharmacology. Elsevier, Amsterdam, 1961, 2: 381-384 (with M. Pollack, E. Karp, G. Krauthamer, and D.F. Klein). 51. …ibid., Problems of antagonists to psychotropic drugs, 30-32. 52. Inhalant-induced convulsions. Arch. Gen. Psychiat., 4: 259-266 (with R.L. Kahn, E. Karp, M. Pollack, M.A. Green, B. Alan, H.J. Lefkowits). 53. Behavioral patterns in convulsive therapy. Arch. Gen. Psychiat., 5: 30-36 (with R.L. Kahn). 54. Sociopsychological characteristics of patients who refuse convulsive therapy. J. Nerv. Ment. Dis., 132: l53-l57 (with M. Pollack). 55. EEG techniques in study of psychotropic drugs. Acta of the Internationat. Meeting on the Techniques for the Study of Psychotropic Drugs, Bologna, 1960. Societa Tipografica Modenese, Modena, 1961: 3pp. 56. Withdrawal symptoms following discontinuation of Imipramine therapy. Amer. J. Psychiat., 118: 549-550 (with J.C. Kramer and D.F. Klein). 57. Experimental psychiatric research at Hillside: review and prospect. J. Hillside Hosp., 10: 159-169. 58. Prediction of individual patient response to convulsive therapy. VA Cooperative Chemotherapy Studies in Psychiatry, 6: 317-324. 59. Social aspects of psychiatric treatment in three hospitals: methodological problems. VA Cooperative Studies in Psychiatry, 6: 202-206 (with M. Pollack, N. Siegel, and R.L. Kahn). 59b. Sociopsychological aspects of psychiatric treatment in three voluntary hospitals. A.M.A. Arch. Gen. Psychiat., 14: 20-25 (with R.L. Kahn and N. Siegel). 60. Quantitative electroencephalography and human psychopharmacology: I. Frequency spectra and drug action. Med. Exp. (Basel), 5: 364-369. 1962 61. The critical flicker frequency and EEG alpha: a reliability study. Electroenceph. Clin. Neurophysiol., 14: 60-63 (with E. Karp and M. Pollack). 62. The mode of action of convulsive therapy: the neurophysiologic-adaptive view. J. Neuropsychiat., 3: 231-233. 63. Disordered perception of simultaneous stimulation of face and hand: a review and theory. In J. Wortis (ed.), Biological Psychiatry. Plenum Press, Inc., New York, 1962, 4: 362-369 (with M. Pollack). 64. Tachistoscopic perception after induced altered brain function: influence of mental set. J. Nerv. Ment. Dis., 134: 422-430 (with M. Pollack, R.L. Kahn, and E. Karp). 65. Motivation for psychotherapy. Comprehens. Psychiat., 3: 170-173 (with N. Siegel). 66. Psychiatric reaction patterns to Imipramine (Tofranil). Amer. J. Psychiat., 119: 432-438 11 �(with D.F. Klein). 67. Behavioral reaction patterns with Phenothiazines. Arch. Gen. Psychiat., 7: 449-459 (with D.F. Klein). 68. The disposition of applications for psychotherapy in an out-patient clinic. Social-Casework, 43: 545-547 (with N. Siegel). 69. Social class, diagnosis, and treatment in three psychiatric hospitals. Social-Problems, 10: 191-196 (with N. Siegel, R.L. Kahn, and M. Pollack). 70. Imipramine as an adjunct to Phenothiazine therapy. Comprehens. Psychiat., 3: 377-380 (with J.C. Kramer and D.F. Klein). 1963 71. EEG and human psychopharmacology. Abstracts of Proceedings of Symposium at Third World Congress of Psychiatry, Montreal, 1961). Electroenceph. Clin. Neurophysiol., 15: 133-137. 72. Multiple item factors as change measures in psychopharmacology. Psychopharmacologia (Berl.), 4: 4352 (with D.F. Klein). 73. Quantitative electroencephalography in human psychopharmacology II: drug patterns. In G. Glaser (ed.), EEG and Behavior. Basic Books, Inc., New York, 177-197. 74. Effects of Imipramine and Chlorpromazine on perceptual analytic ability, perceptual responsivity and memory as revealed in Rorschach responses. J. Nerv. Ment. Dis., 137: 42-50 (with I. Belmont, M. Pollack, and A. Willner). 1964 75. A selected bibliography of electroencephalography in human psychopharmacology, 1951-1962. Electroenceph. Clin. Neurophysiol., Suppl. 23, 68 pp. 76. Comparative study of period analysis and frequency analysis of the electroencephalogram. Electroenceph. Clin. Neurophysiol., 17: 454-455. (with N. Burch). (abstract). 77. Comparative studies of Chlorpromazine and Imipramine I: drug discrimination patterns. In P.B. Bradley, F. Flugel, and P.H. Hoch (eds.), Neuro-Psychopharmacology. Elsevier, Amsterdam, 3: 370-372 (with M. Pollack, D.F. Klein, A.G. Blumberg, I. Belmont, E. Karp, J.C. Kramer, and A. Willner). 78. Comparative studies of Chlorpromazine and Imipramine II: psychological performance profiles. In P.B. Bradley, F. Flugel, and P.H. Hoch (eds.), Neuro-Psychopharmacology. Elsevier, Amsterdam, 3: 373376 (with M. Pollack, E. Karp, I. Belmont and A. Willner). 79. Digital computer analysis of EEG using an IBM 1710 system. Electroenceph. Clin. Neurophysiol., 17: 712 (with D. Shapiro, D. Bridger and T. Itil). (abstract). 1965 80. Clinical efficacy of Chlorpromazine-Procyclidine combination, Imipramine and placebo in depressive disorders. Psychopharmacolgia (Berl.), 7: 27-36 (with D.F. Klein and J. Kramer). 12 �81. Imipramine-induced behavioral disorganization in schizophrenic patients: physiological and psychological correlates. In J. Wortis (ed.), Biological Psychiatry. Plenum Press, Inc., New York, 7: 53-6l (with M. Pollack, D.F. Klein, A. Willner, and A.G. Blumberg). 82a. EEG analyses by digital computer, I: development of IBM 1710 System. Electroenceph. Clin. Neurophysiol., 18: 520 (with T. Itil, D. Shapiro, and D. Bridger). (abstract). 82b. EEG analyses by digital computer, II: relation of pentothal induced changes to resting pattern. Electroenceph. Clin. Neurophysiol., 18: 520-21 (with T. Itil). (abstract). 83. Quantitative EEG and human psychopharmacology, III: changes on acute and chronic administration of Chlorpromazine, Imipramine and placebo saline. In W. P. Wilson: Applications of Electroencephalography in Psychiatry. Duke University Press, Durham, North Carolina, 226-240. 84. Clinical neurophysiology. In D. Bente and P. Bradley (eds.), Neuro-Psychopharmacology, Elsevier, Amsterdam, 4: 64-69. 1966 85. Klinische Untersuchungen und quantitative EEG-daten bei experimentellen Psychosen. ArzneimittelForsch., 16: 237-240 (with T. Itil). 86. Die Anwendung von Digital-Computer Methoden in der Psychopharmakologie. Arzneimittel-Forsch., 16: 297-299 (with T. Itil and D. Shapiro). 87. Trifluperidol in the treatment of psychosis. observations suggestive of anticholinergic activity at higher dosages. J. New Drugs, 6: 174-181 (with A. Don, M. Stallings, T. Itil and J.M. Holden). 88. Cholinergic mechanisms in mental illness: anticholinergic hallucinogens. In J. Wortis (ed.), Recent Advances in Biological Psychiatry, Plenum Press, Inc., N.Y., 8: 115-119. 89. …ibid., Drug induced or spontaneous psychopathological changes and the relationship to quantitative electroencephalography, 8: 303 (with T. Itil and A. Keskiner). (abstract). 90. …ibid., Classification of psychosis by quantitative EEG measures, 8: 305-312 (with T. Itil and D. Clyde). 91. Cholinergic aspects of convulsive therapy. J. Nerv. Ment. Dis., 142: 475-484. 92. The question of dissociation of EEG and behavior with anticholinergic agents. Electroenceph. Clin. Neurophsiol., 21: 41 (with T. Itil). (abstract). 93. Prolonged adverse reactions to LSD in psychotic subjects. Arch. Gen. Psychiat., 142: 450-454 (with J. Simeon, W. Haque, and T. Itil) 94. Behavior and quantitative EEG changes induced by hallucinogenic drugs. Proc. XVIII Int. Cong. Psychol., (Moscow) I: 224 (with T. Itil). (abstract). 95. Anticholinergic drug induced delirium experimental modification, quantitative EEG and behavioral correlations. J. Nerv. Ment. Dis., 143: 492-507 (with T. Itil). 96. Therapeutic studies in therapy resistant schizophrenic patients. Comprehens. Psychiat., 7: 488-493 13 �(with T. Itil and A. Keskiner). 14 �1967 97. Clinical trial of Navane Thiothixene in schizophrenia. Curr. Ther. Res., 9: 10-16. (with J. Simeon, A. Keskiner, D. Ponce, T. Itil). 98. Clinical laboratory test standards in new drug trials. J. Clin. Pharmacol. and New Drugs, 7: 1-8. (with J. M. Holden, T. Itil, J. Simeon). 99. Organic treatment of schizophrenia. In Textbook of Psychiatry, A.M. Freedman and H. Kaplan (eds.). Williams and Wilkins, Baltimore, pp. 661-664 (with T. Itil). 100a. …ibid., Computers and psychiatry, Chapter 5.2, pp. 232-238. 100b. …ibid., Human Behavior: Biological, Psychological, and Sociological, A.M. Freedman and H. Kaplan (eds.), Atheneum, 1972, 450-460. 101a. Quantitative analysis of the electroencephalogram by digital computer methods. III. Applications to psychopharmacology. VII IBM Medical Symposium, Poughkeepsie, IBM Press, pp. 263-290. 101b . …ibid., Computers and Electronic Devices in Psychiatry, N.S. Kline and E. Laska (eds.), Grune and Stratton, 109-123, 1968 (with D.M. Shapiro, C. Hickman and T. Itil). 102. Through a mirror darkly. Review of Psychopathology of Perception. P.H. Hoch and J. Zubin (eds.), N.Y., Grune and Stratton. Contemp. Psychol., 11: 536-538. 103. Altered sensitivity to centrally active drugs following lobotomy. In. J. Wortis (ed.), Biological Psychiatry, Plenum Press, Inc. N.Y., 9: 157-170 (with T. Itil, J. Holden, A. Keskiner). 104. Effect of Sulthiame in schizophrenic patients. Proc. First Init. Cong. Acad. Psychosom. Med., E. Dunlop (ed.) pp. 185-194, Amsterdam, Excerpta Med. Fdn. (with T. Itil, A. Keskiner). 105. Digital computer analysis of the human EEG in psychiatric research. Comprehens. Psychiat., 8: 521-538 (with T. Itil and D. Shapiro). 106a. EEG and behavioral aspects of the interaction of anticholinergic hallucinogens with centrally active compounds. Anticholinergic Drugs and Brain Functions in Animals and Man, P. Bradley and M. Fink (eds.), Elsevier, Amsterdam, pp. 149-168 (with T. Itil). 106b. Anticholinergic hallucinogens and their interaction with centrally active drugs. Neuropsychopharmacology, H.Brill (ed.), Excerpta Medica, Amsterdam, pp. 381 (with T. Itil). 107. Anticholinergic drugs and brain function in animals and man. Neuro-psychopharmacology, H. Brill (ed.), Excerpta Medica, Elsevier, Amsterdam, pp. 374-390. 108. Treatment of chronic psychotic patients with combined medications. Neuropsychopharmacology, H. Brill (ed.), Excerpta Medica, Amsterdam, pp. 1016-1020 (with T. Itil, J. Holden, D. Shapiro, A. Keskiner). 109. EEG Patterns with combined drug treatments in psychotic patients. Turk J. Electroenceph. Clin. Neurophysiol, 1: 1-9 (with T. Itil, G. Ulett). 15 �110. Anticholinergic Drugs and Brain Functions in Animals and Man, P. Bradley and M. Fink (eds.), Progress in Brain Research, Vol. 28, Elsevier, Amsterdam, pp. 375, 1968. 111. Brain, behavior and anticholinergic drugs. Anticholinergic Drugs, and Brain Functions in Animals and Man, P. Bradley and M. Fink (eds.), Elsevier, Amsterdam, pp. xii-xvi. 112. Quantitative EEG: A new dimension in psychopharmacology. Proceedings IV World Congress Psychiat., Excerpta Med. Fdn., Amsterdam, pp. 338-339. 113a. The differentiation of tranquillizers by quantitative EEG. Electroenceph. Clin. Neurophysiol. 24 (with T. Itil, D. Shapiro, C. Hickman, and N. Kiremitci). (abstract). 113b. 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Clinical electroencephalography and echoencephalography, 59-62 (with C.P. Panayiotopoulos, J. Volavka, C. Stefanis). 262. …ibid., Acute EEG effects of cannabis preparations in long-term users, 79-90 (with J. Volavka, C.P. Panayiotopoulos). 263. …ibid., Study of long-term hashish users in Greece: Summary and Discussion,151-158. 264. Book review: Marihuana Chemistry, Biochemistry, and Cellular Effects. G.C. Nahas, W.D.M. Paton, and J.E. Idanpaan-Heikkila (eds.). New York, Springer-Verlag, 1976. Quart. Rev. Biol. 52: 236. 265. Quantitative EEG analysis and psychopharmacology. In Remond, A. (ed.): EEG Informatics. A Didactic Review of Methods and Applications of EEG Data Processing. Amsterdam, Elsevier, 301-308. 266. EEG, blood level, and behavioral effects of the antidepressant Mianserin (Org GB 94). Psychopharmacologia 54: 249-254 (with P. Irwin, M. Gastpar, and H. de Ridder). 267. Myths of “shock therapy.” Amer. J. Psychiat. 134: 991-996. 1978 268. Comments on report by P. Simon. In P. Deniker, C. Radouco-Thomas, and A. Villeneuve (eds.): Neuropsychopharmacology. Oxford England, Pergamon Press, 215-217. 269. Psychoactive drugs and the waking EEG. In M.A. Lipton, A. DiMascio, and K.F. Killam (eds.): Psychopharmacology: A Generation of Progress. New York, Raven Press, 691-698. 270. EEG response strategies in psychiatric diagnosis. In Spitzer, R. and D.F. Klein (eds.): Critical Issues in Psychiatric Diagnosis. New York, Raven Press, 253-263. 271. EEG study of Mianserin (GB-94) in depressed patients. Brit. J. Clin. Pharmacol. 5 Supplement (1): 43S49S (with P. Irwin). 26 �272. Sieben jahre klinische erfahrung mit opiat-antagonisten bei Opiatabhangigkeit. In W.F. Biniek (ed.): Drogenabhangigkeit. Darmstadt, Wissenschaftliche Buchgesellschaft, 422-431. 273. Efficacy and safety of induced seizures (EST) in man. Comprehens. Psychiat. 19: 1-18. 274. ECT in metropolitan New York hospitals: A survey of practice 1975-1976. Amer. J. Psychiat. 135: 479482 (with G.M. Asnis, S. Saferstein). 275. Is EST a useful therapy of schizophrenia? In J.P. Brady and H.K.H. Brodie (eds.): Controversy in Psychiatry. Philadelphia, W.B. Saunders Co., 183-193. 276. Electroshock therapy: myths and realities. Hosp. Pract. 13: 77-82. 277. EEG and psychopharmacology. In Cobb, W.A. and van Duijn, H. (eds.): Contemporary Clinical Neurophysiology Suppl. 34, Electroenceph. Clin. Neurophysiol. 45: 41-56. 278. Book review: Neuropeptide Influences in the Brain and Behavior. Adv. Biochem. Pharmacol. 17: L.H. Miller, C.A. Sandman and A.J. Kastin (eds.), New York, Raven Press, 298 pp, 1977. Quart. Rev. Biol. 53: 195. 279. Book review: Psychopharmacology. A Biochemical and Behavioral Approach. L.S. Seiden and L.A. Dykstra (eds.), New York, Van Nostrand Co., 451 pp., 1977. Quart. Rev. Biol. 53: 196. 280. Book review: Psychotherapeutic Drugs. Part 1: Principles. Part 2: Applications. E. Usdin and I.S. Forrest (eds.), New York, Marcel Dekker, 698+699 pp., 1976. Quart. Rev. Biol. 53: 210-211. 281. Book review: Hemi-Inattention and Hemisphere Specialization. E.A. Weinstein and R.P. Friedland (eds.), New York, Raven Press, 156 pp., 1977. Quart. Rev. Biol. 53: 211. 1979 282a. Convulsive Therapy: Theory and Practice. New York, Raven Press, 308 pp. 282b. Convulsive Therapy: Theory and Practice. Published in Japanese translation, Tokyo, Seiwa Shoten, 394 pp., 1980. 283. Mania and electroseizure therapy (EST). In Shopsin, B. (ed.): Manic Illness. New York, Raven Press, 219-228. 284. A history of convulsive therapy. Psych. Jrl. Univ. Ottawa Fac. Med. 4: 105 - 110. 285. Efficacy of ECT. Lancet 2: 1303 -1304. (letter). 286. EST and other somatic therapies of schizophrenia. In L. Bellak (ed.): Disorders of the Schizophrenic Syndrome. Basic Books, New York, 353-363. 287. CNS effects of the antihistamines, Diphenhydramine and Terfenadine RMI-9918. Pharmakopsych. Neuro-Psychopharmakologie 12: 35, 44 (with P. Irwin). 288a. Phenytoin: EEG effects and plasma levels in volunteers. Therap. Drug Monitoring 1: 93-104 (with P. Irwin, W. Sannita, Y. Papakostas, M.A. Green). 27 �288b. EEG study of phenytoin in normal volunteers at non-toxic doses. Electroenceph. Clin. Neurophysiol. 49: 83 (abstract). 289a. EEG profile studies of clozapine in volunteers and psychiatric patients. Pharmakopsych. Neuro-Psychopharmakologie 12: 184-190 (with P. Irwin and P. Weinhold). 289b. EEG effects of clozapine: Association or dissociation of EEG and behavior? NeuroPsychopharmacology. Oxford, Pergamon, 363-369. (abstract). 290. Anxiety, anxiolytics and the human EEG. In w. Fann, I. Karacen, A. Pokorny, and R.L. Williams, (eds.): Phenomenology and Treatment of Anxiety. New York, Spectrum Publications, 237-250. 291. Neurobiology Group Report, Dahlem Conference. In K.S. Fu and T. Pavlidis (eds.): Biomedical Pattern Recognition and Image Processing. Life Sciences Research Report 15. Verlag Chemie, Basel, 364-394 (with D.B. Cooper, M. Abeles, G. Bodenstein, et al.). 292. Normal prolactin responses in tardive dyskinesia. Psychopharmacology 66: 247-250 (with G.M. Asnis, E.J. Sachar, G. Langer, F.S. Halpern). 293. Book review: Contemporary Research in Behavioral Pharmacology. D.E. Blackman and D.J. Sanger (eds.), New York, Plenum Press, 506 pp., 1978. Quart. Rev. Biol. 54:118-119. 294. Book review: The Endorphins. Adv. Biochem. Pharmacol. 18. E. Costa and M. Trabucchi (eds.), New York, Raven Press, 379 pp., 1978. Quart. Rev. Biol. 54: 119. 295. Book review: Rational Anti-epileptic Drugs Therapy. P.J.M. Guelen and E. van der Kleijn. Amsterdam, Elsevier/North Holland. Trends in Neurosciences 2: 492-494. 296. Book review: Psychotropic Drugs: A Guide for the Practitioner. H.M. van Praag, New York, Brunner/Maxel, 1978. Comprehens. Psychiat. 20 :494-495. 1980 297a. A neuroendocrine theory of convulsive therapy. Point of view. Trends in Neurosciences 3: 25-27. 297b. …ibid. Nervenheilkunde 1: 26-29, 1982. 297c. Convulsive therapy and depression: A neurohumoral and neuroendocrine theory. In Saletu, B. (ed.): Neuro-Psychopharmacology. Oxford, Pergamon, 41-44. (abstract). 297d. A theory of convulsive therapy in endogenous depression: Significance of hypothalamic functions. Psychiatry Research 2: 49-61 (with J.O. Ottosson), 298. Convulsive therapy and endogenous depression. Pharmakopsychiat. 13: 49-54. 299. Neuroendocrinology and ECT: A review of recent developments. Comprehens. Psychiat. 21: 450-459. 300. ECT, mood and hormones. In D. de Wied and P. A. van Keup (eds.): Hormones and the Brain. MTP Press, Lancaster, England, 253-262. 301. Convulsive and drug therapies of depression. Ann. Rev. Med. 32: 405-412. 28 �302a. Neuroendocrine measures in psychiatric patients: Course and outcome with ECT. Psychiatry Research 4: 55-64 (with Y. Papakostas, J. Lee, P. Irwin, L. Johnson). 302b. Dexamethasone suppression test and outcome with ECT. In C. Perris, G. Struwe, and B. Jansson (eds.): Biological Psychiatry 1981. 1075-1078, 1981. 303. Random thoughts about ECT. (editorial). Am. J. Psychiat. 138: 484-485. 1981 304. Toward a rational theory of behavior. Career Directions 7: 2-12. 305. An objective classification of psychoactive drugs. Prog. Neuro-Psychopharm. 4: 495-502. 306. EEG and behavioral profile of flutroline (CP-36,584), a novel antipsychotic drug. Psychopharmacology 72: 67-71 (with Peter Irwin). 307. EEG and behavioral effects of pirenzepine in normal volunteers. Scand. Jrl. Gastroenterol. 15 Supplement 66: 39-46 (with Peter Irwin). 308. Classification of psychotropic drugs: Quantitative EEG analysis in man. In van Praag, H.M., Lader, M.H., Rafaelson, O.J. and Sachar, E.J. (eds.): Handbook of Biological Psychiatry. Volume VI. Marcel Dekker, New York, 309-326. 309. The significance of quantitative pharmaco-electroencephalography in establishing dose-time relations and its impact on clinical pharmacology: Critical review and perspectives. Psychopharm. Bull. 17:94. (abstract). 310a. Lateral cerebral differences in psychotropic drug effects. Psychopharm. Bull.17:98. (abstract). (with Peter Irwin). 310b. Do psychoactive drugs affect the EEG from the cerebral hemispheres differently? In C. Perris, D. Kemali and L. Vacca (eds.): Electroneurophysiology and Psychopathology. S. Karger, Basel, Adv. Biol. Psychiat 6: 121-125 (with P. Irwin). 311a. Critical flicker-fusion frequency, EEG, and psychoactive drugs. Psychopharm. Bull. 17: 103. (abstract). (with P. Irwin). 311b. EEG, CFF and behavior. Pharmakopsychiatria 15: 36-38, 1982 (with P. Irwin). 312. A single measure of EEG spectral differences with heuristic value in assessing drug effect. Electroenceph. Clin. Neurophysiol. 51: 32P (abstract). (with P. Irwin). 313. CNS effects of clonidine in normal volunteers. Psychopharm. Bulletin. 17: 16-17 (with P. Irwin). 314. Pharmaco-EEG and bioequivalence: A practical methodology for psychoactive drugs. Psychopharm. Bulletin 17: 120-121. 315. Pharmacoelectroencephalographic study of brotizolam, a novel hypnotic. Clin. Pharm. Therap. 30: 336342 (with P. Irwin). 29 �316. EEG and behavioral effects of aspirin in asymptomatic volunteers. In C. Perris, G. Struwe, and B. Jansson (eds.): Biological Psychiatry 1981, Elsevier, Amsterdam, 227-229 (with P. Irwin) 317. Clinical trials with des-Tyr-gamma-Endorphin GK-78. In C. Perris, G. Struwe, and B. Jansson (eds.): Biological Psychiatry 1981, Elsevier, Amsterdam, 398-401 (with Y. Papakostas, J. Lee, T. Meehan, L. Johnson). 318. Book review: The Psychosurgery Debate. E. S. Valenstein (ed.). W.H. Freeman & Co., San Francisco, 1980. Amer. J. Psychiat. 138: 408-409. 319a. Book review: Divergent Views in Psychiatry. M. Dongier and E. D. Wittkower (eds.). Harper & Row, Hagerstown, MD, 1981. Am. J. Psychiat. 138: 1641. 319b. Divergent views of divergent views: Dr. Fink replies. (letter). Am. J. Psychiat. 139: 1219-1220, 1982. 320. Book review: Neural Peptides and Neuronal Communication. E. Costa and M. Trabucchi (eds.). Raven Press, New York, 1980. Quart. Rev. Biol. 56: 98. 321. Book review: Differential Psychopharmacology of Anxiolytics and Sedatives. J. R. Boissier (ed.). S. Karger, Basel, 1979. J. Nerv. Ment. Dis. 169: 469-470. 322. Book review: The Psychodynamic Approach to Drug Therapy. M. Ostow (ed.). Van Nostrand, Reinhold, New York, 1980. Science Books and Films 16: 209. 323. Book review: Law and Ethics in the Practice of Psychiatry. C.K. Hofling (ed.). Brunner/Mazel, 1981. Science Books and Films 17: 64-65. 1982 324. Mianserin. In H. Lehmann (ed.): Non-MAOI and Non-Tricyclic Antidepressants. S. Karger, Basel. Mod. Probl. Pharmacopsychiat. 18: 70-101 (with R. Pinder). 325. Quantitative pharmaco-EEG to establish dose-time relations in clinical pharmacology. In W.M. Herrmann (ed.): Electroencephalography in Drug Research. Gustav Fischer, Stuttgart, 17-22. 326a. Guidelines for pharmaco-EEG studies in man. Pharmacopsychiat. 15:107-108 (with G. Stille, W.M. Herrmann, D. Bente, T.M. Itil, W.P. Koella, S. Kubicki, H. Kunkel, J. Kugler, M. Matejcek. and Petsche, H.). 326b. …ibid., Empfehlungen für pharmakoelektroenzephalographische Untersuchungen am Menschen. EEGEMG 13: 1-2. 327. Anticholinergic drugs and the EEG. In Committee on Toxicology, National Academy of Sciences. Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents: I: Anticholinesterases and Anticholinergics. National Academy Press, Washington, DC, June 1-8. 328. Neurophysiologic methods to establish antidepressant activity. Neurophysiologische Methoden zum Nachweis antidepressiver Wirkung. Arzneimittelforschung 32: 857-859. 329. CNS effects of acetylsalicylic acid Aspirin (with P. Irwin). Clin. Pharm. Therap. 32: 362-365. 30 �330a. Pharmaco-EEG study of 6-azamianserin ORG-3770: Dissociation of EEG and pharmacologic predictors of antidepressant activity (with P. Irwin). Psychopharmacology 78: 44-48. 330b. …ibid., Psychopharm. Bull. 19: 96, 1983. 331. Blood levels and quantitative EEG response to CNS-active drugs: Retrospective observations. Electroenceph. Clin. Neurophysiol. Suppl. 36: 447-452 (with P. Irwin). 332. Predictors of outcome in convulsive therapy. Psychopharm. Bull. 18: 50-57. 333. Convulsive therapy: A risk-benefit analysis. Psychopharm. Bull. 18: 110-116. 334. Placebo-controlled studies of ECT. Br. J. Psychiat. 141: 213-214. (letter). 335. Neuroendocrine aspects of convulsive therapy. In R. Abrams and W. Essman (eds.): Electroconvulsive Therapy: Biological Foundations and Clinical Applications. Spectrum Publications, New York, 187-198. 336a. Monitoring the duration of ECT seizures: ‘Cuff’ and EEG methods compared (with L. Johnson). Arch Gen. Psychiat. 39:1189-1191. 336b. EEG monitoring of ECT preferred to cuff method. Reply. Am. J. Psychiat. 140: 1649, 1983. 336c. ECT Seizure Monitoring. Arch. Gen. Psychiat.: 106-107, 1984 (with L. Johnson). (letter). 337. The enigma of convulsive therapy: An effective, safe and controversial treatment. In J.O. Cavenar and H.K.H. Brodie (eds.): Critical Problems in Psychiatry. J. B. Lippincott, Philadelphia, 203-219. 338. ECT in the elderly. In C. Eisdorfer and W.E. Fann (eds.): Treatment of Psychopathology in the Aging. Springer Publishing Co., New York, Chapter 7, 97-111. 339. ECT in anxiety: An appraisal. Am. J. Psychother. 36: 371-378. 340. The present status of electroconvulsive therapy. Directions in Psychiatry. Hatherleigh Co. Ltd., New York, 35:1-8. 341. Book reviews: ECT in Great Britain. J. Pippard and L. Ellam: Electroconvulsive Treatment in Great Britain, 1980. Gaskell, London, 162 pp., 1981; and R. L. Palmer (ed.): Electroconvulsive Therapy: An Appraisal. Oxford, New York 316 pp., 1981. Am. J. Psychiat. 139:958-959. 342. Book review: Drug Development Research. H. Lal and S. Fielding (eds.). A.R. Liss, New York. Quart. Rev. Biol. 57: 234. 1983 343. Guidelines for electroconvulsive therapy in the elderly. In T. Crook and G. D. Cohen (eds.): Physicians’ Guide to the Diagnosis and Treatment of Depression in the Elderly. Mark Powley Associates, New York, VI: 55-60. 344. Missed seizures and the bilateral-unilateral electroconvulsive therapy controversy. Am. J. Psychiat. 140: 198-199. (editorial). 345. Bias against ECT: again. Contemp. Psychol. 28: 246-247. (letter). 31 �346. Antidepressant effects of electroconvulsive therapy. Br. Med. J. 286:1744 1745. (letter). 347. Electroshock and Berkeley: II. Biol. Psychiat. 18: 610-613. (editorial). 348. ECT and depression: What have we learned? In F.J Ayd, I.J. Taylor, and B.T. Taylor (eds.): Affective Disorders Reassessed: 1983. Ayd Medical Communications, Baltimore, pp. 56-72. 349. Pharmacoelectroencephalography. Neuropsychobiol. 9: 45-46. (editorial). (with D. Bente and H. Kunkel). 350. Book review: The Unfathomed Mind: A Handbook of Unusual Mental Phenomena. W.R. Corliss. Glen Arm, MD, 754 pp., 1981. Science Books and Films 18: 242. 351. Book review: Neurobiology. G. M. Shepherd. Oxford University Press, NY, 611 pp., 1983. Science Books and Films 19: 83. 352. Book reviews: Advances in Biochemical Pharmacology. Vol. 31. Typical and Atypical Antidepressants: Molecular Mechanisms. Vol. 32: Clinical Practice. E. Costa and G. Racagni (eds.). Raven Press, N.Y. 391 pp. and 400 pp., 1982. Non-Tricyclic and Non-Monoamine Oxidase Inhibitors. H.E. Lehmann (ed.). S. Karger, Basel, 1982. Quart Rev. Biol. 58: 300-301. 1984 353. Theories of the antidepressant efficacy of convulsive therapy ECT. In R.M. Post and J.C. Ballenger (eds.): Neurobiology of Manic Depressive Illness. Williams & Wilkins, Baltimore, 721-730. 354. Theories of convulsive therapy: A neuroendocrine hypothesis. In B. Lerer, R.Weiner, and R.H. Belmaker (eds.): ECT: Basic Mechanisms. John Libbey &. Co., London, pp. 115-123. 355a. Convulsive therapy: Fifty years of controversy. Clin. Neuropharmacol. 7. Supplement 1: 8-9 (abstract). 355b. Meduna and the origins of convulsive therapy. Am. J. Psychiat. 141: 1034-1041. 356. Neuroendocrine aspects of the relief of melancholia by induced seizures ECT. In E. Usdin, M. Asberg, L. Bertilsson, and F. Sjoqvist (eds.): Frontiers in Biochemical and Pharmacological Research in Depression. Adv. Biochem. Psychopharm. 39: 345-357. 357. Pharmaco-EEG effects of antihypertensive agents. Clin. Neuropharmacol. 7 Supplement 1: 119 (abstract). 358. Familiarization session and the placebo control in EEG studies of drug effects. Neuropsychobiology. 10: 173-177 (with P. Irwin). 359. ECT: For whom is it justified? J. Clin. Psychopharmacol. 4: 303-304 (editorial). 360. The present status of unilateral ECT: Some recommendations. Jrl. Affective Dis. 7: 245-247 (editorial). (with R. Abrams). 361. Book review: L.B. Kalinowsky, H. Hippius, and H.E. Klein. Biological Treatments in Psychiatry. Grune & Stratton, New York, 424 pp., 1982. Compr. Psychiatr. 25: 126-127. 32 �362. Book reviews: Vaillant, G. E. The Natural History of Alcoholism. Harvard Univ. Press, Cambridge, MA, 359 pp., 1983; B. Tabakoff, P.B. Sutker, and C.L. Randall (eds.): Medical and Social Aspects of Alcohol Abuse. Plenum Press, New York, 403 pp., 1983; R.G. Smart, F.B. Glaser, Y. Israel, H. Kalant, R.E. Popham, and W. Schmidt (eds.): Research Advances in Alcohol and Drug Problems vol. 7, Plenum Press, New York, 472 pp., 1983. Quart. Rev. Biol. 59: 369-370. 363. Book review: P. Carlton. A Primer of Behavioral Pharmacology. W. H. Freeman & Co., 301 pp., 1983. Quart. Rev. Biol. 59: 511-512. 1985 364. Pharmaco-electroencephalography: A note on its history. Neuropsychobiology. 1984; 12: 173-178. 365. Convulsive Therapy. Convulsive Ther. 1985; 1: 1-3. (editorial). 366. Reducing memory loss in electroconvulsive therapy. Convulsive Ther. 1985; 1: 77-80. (editorial). 367. A ‘gratuitous’ conclusion on ECT. Am J Psychiatry 1985; 142: 1129. (letter). 368. Anesthesia in electroconvulsive therapy. Convulsive Ther. 1985; 1: 155-157. (editorial). 369. Convulsive therapy: Fifty years of progress. Convulsive Ther. 1985; 1: 204- 216. 370. The ethics of placebo. In L. White, B. Tursky, G.E. Schwartz (eds.): Placebo: Theory, Research and Mechanisms. Guilford Press, New York, 1985; 423-430. 371. Anesthesia in ECT. J Clin Psychopharmacol. 1985; 5: 312. (letter). 372. MAOI, anesthesia, and ECT. J Clin Psychopharmacol 1985; 5: 313. (with K. Freese). 373. National Institutes of Health Consensus Conference on ECT. Convulsive Ther. 1985; 1: 231-233. (editorial). 374. Pharmaco-EEG as a method to assess bioequivalence of CNS active substances in man. Integrative Psychiatry 1985; 3 Supplement: 12S-19S. 375. Summary. Integrative Psychiatry 1985; 3 (Supplement): 92s-93s (with L. Hollister). 376. Book review. E.A. Turner. Surgery of the Mind. Carmen Press, Birmingham UK, 238 pp., 1982. In Am J Psychiatry 1985; 142: 374-375. 377. Book review. M. Fraser. ECT: A Clinical Guide. John Wiley, New York, 134 pp., 1982. In Convulsive Ther 1985; 1: 66-67. 378. Book review. N.S. Endler. Holiday of Darkness: A Psychologist’s Personal Journey Out of Depression. Wiley-Interscience, New York, 169 pp., 1982. In Convulsive Ther. 1985; 1: 140-142. 33 �379. Book reviews: L. Kalinowsky, H. Hippius, H.E. Klein. Biological Treatments in Psychiatry. Grune & Stratton, New York, 424 pp., 1982; R. Abrams, W.B. Essman (eds.): Electroconvulsive Therapy: Biological Foundations and Clinical Applications. Spectrum Publications, New York, 270 pp., 1982. In Convulsive Ther. 1985; 1: 222-223. 380. Book review: S.E. Luria. A Slot Machine, A Broken Test Tube. Harper & Row, New York, 230 pp., 1984. In Am J Psychiatry 1985; 142: 1210-1211. 381. Book review: G.G. Nahas. Marijuana in Science and Medicine. Raven Press, New York, 312 pp., 1984. In Quart Rev Biol. 1985; 60: 551-552. 382. Book review: R.G. Smart et al. (eds.): Research Advances in Alcohol and Drug Problems. Vol 8. Plenum Press, New York, 333 pp. In Quart Rev Bioi 1985; 60: 552. 385a. Historical Article: Autobiography of L. J. Meduna. Convuls Ther. 1985; 1(1): 43-57. 1986 383. Neuroendocrine predictors of ECT outcome: DST and prolactin. Annals New York Academy Sci 1986; 462: 30-36. 384. Convulsive therapy today: A decade of increased understanding and acceptance. Psychiatry Letter 1986; 4: 7-12. 385b. Autobiography of L.J. Meduna. Ideggyogyaszati szemle 1986; 39: 225-34. (article in Hungarian). 386. Electroconvulsive therapy today. Currents 1986; 5: 5-12. (interview). 387. Convulsive therapy and epilepsy research. In M.R. Trimble and E.H. Reynolds (eds.): What is Epilepsy? The Clinical and Scientific Basis of Epilepsy. Churchill Livingstone, Edinburgh, 1986, 217-228. 388. Serial dexamethasone suppression tests in ECT. Clin Neuropharm 1986; 9: Suppl. 4: 444-446 (with K. Gujavarty K, L. Greenberg). (abstract). 389. Multi-lead EEG dynamic mapping during ECT. Clin Neuropharm 1986; 9: Suppl. 4: 536-537 (with M. Fink, L. Greenberg, K. Gujavarty). (abstract). 390. Convulsive therapy: How it evolved. Psychopharm Bull 1986; 22: 357-459. 391. A new evaluation of convulsive therapy: The Ontario report. Convulsive Ther 1986; 2: 73-76 (editorial). 392. Training in ECT. Convulsive Ther 1986; 2: 227-230. (editorial). 393. Book review: J. Winson. Brain and Psyche: The Biology of the Unconscious. New York, Doubleday, 1985, 300 pp. In Science Books and Films 1986; 21: 157. 394. Book review: D.C. Horwell (ed.): Drugs in the Central Nervous System Disorders. New York, Marcel Dekker Inc. 1985, 354 pp. In Quart Rev Biol 1986; 61: 146. 34 �1987 395. Serial dexamethasone suppression tests and clinical outcome in ECT. Convulsive Ther 1987; 3: 111-120 (with L. Greenberg, K. Gujavarty). 396. Electroconvulsive therapy and neuroleptic medication in the treatment of therapy resistant positivesymptom psychosis. Convulsive Ther 1987; 3: 185-195 (with K. Gujavarty, L. Greenberg). 397. Isoflurane anesthesia therapy: A replacement for ECT in depressive disorders? Convulsive Ther 1987; 3: 269-277 (with L.B. Greenberg, J. Gage, S. Vikun). 398. Update on ECT. Psychiatric Annals 1987; 17: 47-53 (interview). 399. Convulsive therapy in affective disorders: A decade of understanding and acceptance. In H. Meltzer (ed.): Psychopharmacology: A Third Generation of Progress. Raven Press, New York, 1987, Chap 108: 1071-1076. 400. ECT: A last resort treatment for resistant depression? In J. Zohar, R. Belmaker (eds.): Treating Resistant Depression. PMA Publishing Co, New York, Chap 9: 163-173. 401. Convulsive therapy. In G Adelman (ed.): Encyclopedia of Neuroscience. Birkhuser, Boston, 1987, 277278. 402. Neuroendocrine aspects of convulsive therapy: Review of recent developments. In C.B. Nemeroff, P.T Loosen (eds.): Handbook of Clinical Psychoneuroendocrinology. Guilford Press, New York, 1987, Chapter 11: 255-265. 403. New technology in convulsive therapy: A challenge in training. Am J Psychiatry 1987; 144: 1195-1196 (editorial). 404. Neuropsychiatry and behavioral neurology. Convulsive Ther 1987; 3: 91-92 (editorial). 405. Is ECT usage decreasing? Convulsive Ther 1987; 3: 171-173. (editorial). 406. Maintenance ECT and affective disorders. Convulsive Ther 1987; 3: 249-250 (editorial). 407. Contraindications to electroconvulsive therapy. Anesth Analg 1987; 66: 918 (letter). 408. A case of resistant schizophrenia. Br J Psychiatry 1987; 150: 562-563 (letter). 409. Book review: A.V. Valdman (ed.): Drug Dependence and Emotional Behavior: Neurophysiological and Neurochemical Approaches. Plenum Publ Co., New York, 1986. In Quart Rev Biol 1987; 62: 120-121. 410. Book review: W. Kalow, H.W. Goedde, D.P. Agarwal (eds.): Ethnic Differences in Reaction to Drugs and Xenobiotics. AR Liss, New York, 583 pp., 1986. In Quart Rev Biol 1987; 62: 124. 411. Book review: M.H. Van Woert, E. Chung (eds.): Cooperative Approaches to Research and Development of Orphan Drugs. AR Liss, New York, 204 pp., 1985. In Quart Rev Biol 1987; 62: 124-125. 35 �412. Book review: E.S. Valenstein. Great and Desperate Cures. Basic Books, New York, 338 pp., 1986. In Convulsive Ther 1987; 3: 79-81. 413. Book review: M. Brause, A.M. Zimmerman (eds.): Genetic and Perinatal Effects of Abused Substances. Academic Press, New York, 211pp., 1987. In Quart Rev Biol 1987; 62: 469. 1988 414. Prospective electroconvulsive therapy in delusional depressed patient with a frontal meningioma. Br J Psychiatry 1988; 153: 105-107 (with L.B. Greenberg, R. Mofson). 415. Convulsive therapy for affective disorders. In A. Georgeotas and R. Cancro (eds.): Depression and Mania. Elsevier, North Holland and New York, 1988; 29: 452-460. 416. Convulsive therapy: A manual of practice. Review of Psychiatry VII. 1988; 21: 482-497. APA Press, Washington DC. 417. The present status of electroconvulsive therapy: An update. F. Flach (ed.): Directions in Psychiatry 1988; 1-8. Hatherleigh Co., New York. 418. Forward. Electroconvulsive Therapy, Richard Abrams, 1st ed., Oxford University Press, New York, 1988; vii-x. 419. Forward. Electroconvulsive Therapy: The Myths and the Realities. N.S. Endler, E. Persad, Hans Huber, Toronto; 1988; ix-xi. 420. Fifty years of electro-convulsive therapy. Convulsive Ther 1988; 4: 2-4 (editorial). 421. ECT for Parkinson disease? Convulsive Ther 1988; 4: 189-191 (editorial). 422. How does ECT work? Psychopharmacol Bull 1988; 24: 385-386 (with W. Potter). 423. Neuroendocrine hypothesis of antidepressant action of ECT. Psychopharmacol Bull 1988; 24: 400-402. 424. Use of ECT in the United States. Am J Psychiatry 1988; 145: l33-134. (letter). 425. ECT instrumentation. Biol Psychiatry 1988; 24: 360-361. (letter). 426. The diagnosis and treatment of depression in the old. JAMA 1988; 260: 1405. (letter). 427. ECT: The continuing controversy. Consensus in Psychiatry 1988; 1: 1. 428. Brain imaging and pharmaco-EEG. Consensus in Psychiatry 1988; 1: 1-2. 429. Book review: Kurt Eissler: Freud as an Expert Witness. IUP Press, Madison CT, 1986. In Convulsive Ther 1988; 4: 250-251. 36 �430. Book reviews: M.A. Taylor, F.S. Sierles, R. Abrams. General Hospital Psychiatry. Free Press, New York, 1985; A. Stoudemire, B.S. Fogel (eds.): Principles of Medical Psychiatry. Grune & Stratton, Orlando FL, 1987; A.J. Frances, R.H. Hales (eds.): Review of Psychiatry VII, American Psychiatric Press, Washington DC, 1988. In Convulsive Ther 1988; 4: 175-177. 431. Book review: I. Rosenfield. The Invention of Memory: A New View of the Brain. Basic Books, New York, 1987. In Science Books & Films 1988; 24: 77-78. 432. Book reviews: B. Aperia. A Psychoendocrinological Study of Electroconvulsive Therapy in Major Depressive Disorder. Thesis. Department of Psychiatry, Karolinska Institute, St Gyran’s Hospital, Stockholm, Sweden, 1985. P. Silfverskiyld. Depression and Mania: Clinical and Neurophysiological Aspects and Effects of ECT. Thesis. Department of Psychiatry, University of Lund, Lund, Sweden, 1987. In Convulsive Ther 1988; 4: 177-179. 433. Book review: Current Approaches: ECT. J. Malkien, S. Brandon. Duphar Laboratories, UK, 1988. In Convulsive Ther 1988; 4: 335-336. 434. Book review: R.E. Hales, S.C. Yudofsky (eds.): Textbook of Neuropsychiatry. APA Press, Washington DC, 1987. In Neuropsychiatry, Neuropsychol Behav Neurology 1987; 1: 153-155. 435. Book review: P.H. Wender. The Hyperactive Child, Adolescent and Adult: Attention Deficit Disorder Through the Lifespan. Oxford University Press, New York, 162 pp., 1987. In Science Books & Films, 1988; 23: 244. 436. Videotape Review: Healthcare Information Network, Princeton NJ. Electroconvulsive Therapy: A New Age, A New Understanding. Series: Mind and Body. Distributed by MECTA Corporation, Portland OR, 1987. In Convulsive Ther 1988; 4: 180. 1989 437. Convulsive therapy: A reappraisal. In J.G. Howells (ed.): Modern perspectives in the Psychiatry of Affective Disorders. Brunner/Mazel Inc., New York, 1989; 22: 393-410. 438. Electroconvulsive therapy: The forgotten option in the treatment of therapy resistant depression. In I. Extein (ed.): Treatment of Tricyclic Resistant Depression. APA Press, Washington DC, 1989, 135-150. 439. A comparison of etomidate and methohexital anesthesia for electroconvulsive therapy. Annals Clin Psychiatry 1989; 1: 39-42 (with L.B. Greenberg, R. Boccio). 440. A neuroendocrine view of ECT. Convulsive Ther 1989; 5: 296-304 (with C.B. Nemeroff). 441. Convulsive therapy and kindling. In M. Trimble and T. Bolwig (eds.): The Clinical Relevance of Kindling. John Wiley & Sons, Chichester. 1989; 13: 195- 208. 442. Electroconvulsive therapy: A review. Organorama 1989; 26: 24-25. 443. Update on “Shock” therapy. Health & Medical Horizons. Macmillan Co., New York, 1989; 197-198 (commentary). 444. Recommendations for EEG and evoked-potential mapping. Neuropsychobiology 1989; 22: 170-176. International Pharmaco-EEG Group; (with W. Herrmann et al.). 37 �445. Reversible and irreversible dementia. Convulsive Ther 1989; 5: 123-125 (editorial). 446. ECT in Parkinson disease. The Psychiatric Times 1989; 63: 6-7. (commentary). 447. Maintenance ECT is a continuing saga. The Psychiatric Times 1989; 64: 13-14. (commentary). 448. Reversible dementia and ECT. The Psychiatric Times 1989; 65: 23-24. (commentary). 449. Primo Levi need not have died. The New York Times. January 5, 1989. A20. (letter). 450. The efficacy of electroconvulsive therapy in therapy-resistant psychotic patients. J Clin. Psychopharmacol 1989; 9: 231-232. (letter). 451. Max Hamilton. Biol Psychiatry 1989; 26: 218-219. (homage). 452. Maintenance ECT. In response. Jefferson Jrl Psychiatry 1989; 7: 71-72 (letter). 453. Videotape review: J. David. Four Lives: A Portrait of Manic Depression. Fanlight Productions, 1988. Hosp & Commun Psychiatry 1989; 40: 347-348. 454. Book review: Lader M., Lang R., Wilson G.D. Patterns of Improvement in Depressed In-Patients. Oxford University Press, Oxford UK, 1987, 118 pp. In J Nerv Ment Dis 1989; 177: 498-499. 1990 455. How does convulsive therapy work? Neuropsychopharmacology 1990; 3: 73-82. 456. Response to commentaries on “How does convulsive therapy work?” Neuropsychopharmacology 1990; 3: 97-100. 457. Electroconvulsive therapy and cyclophosphamide in combination for severe neuropsychiatric lupus with catatonia. Am J Medicine 1990; 88: 443-444 (with G.L. Fricchione, L.D. Kaufman, B.L. Gruber). 458. Rat brain concentration of fluphenazine during a course of electroconvulsive shock. Convulsive Ther 1990; 6: 273-9 (with I. Zervas, L.B. Greenberg, R.F. Suckow, T. Cooper, L. Jandorf). 459. Electroconvulsive therapy in the elderly. Psychiatric Annals 1990; 20: 99-101. (with L.B. Greenberg). (review). 460. Electroconvulsive therapy. Current Opinion in Psychiatry 1990; 3: 58-61. (review). 461. Electroconvulsive therapy of anxiety disorders. In R. Noyes, M. Roth, G.D. Burrows (eds.): Handbook of Anxiety IV: The Treatment of Anxiety. Elsevier Science Publishers BV, Amsterdam, Chap 25: 511-518, 1990. 462. A trial of ECT is essential before a diagnosis of refractory depression is made. In J.D. Amsterdam (ed.): Refractory Depression. Adv Neuropsychiatry Psychopharmacology 1990; 2: 87-92. Raven Press, New York. 463. Is catatonia a primary indication for ECT? Convulsive Ther 1990; 6: 1-4. (editorial). 38 �464. The 1990 APA task force report: A quiet revolution. Convulsive Ther 1990; 6: 75-78. (editorial). 465. ECT in modern literature. Convulsive Ther. 1990; 6: 191-193. (editorial). 466. Electrode placement: A clinician’s guide. Convulsive Ther. 1990; 6: 263-265. (editorial). 467. Clozapine and electroconvulsive therapy. Arch Gen Psychiatry 1990; 47: 290-291. (letter). 468. Continuation ECT today. Harvard Medical School Mental Health Letter. (forum). 1990; 6: 8. 469. Guidelines for the long-term use of convulsive therapy. JAMA 1990; 264: 1174. Questions and answers. 470. Book review: L.G. Kiloh, J.S. Smith, G.F. Johnson. Physical Treatments in Psychiatry. Blackwell Scientific, Melbourne, 1988. In Am J Psychiatry 1990; 147: 1239-1240. 471. …ibid., In Convulsive Ther. 1990; 6: 60-62. 472. Book review: M.R. Trimble, E.H. Reynolds (eds.): Epilepsy, Behaviour and Cognitive Function. John Wiley & Sons, Chichester UK, 1988. In Am J Psychiatry 1990; 147: 665-666. 473. Energy parameters of ECT devices need reassessment. Psychiatric Times 1990; 7: 23, 26. (commentary). 474. Catatonia and ECT. Psychiatric Times 1990; 7: 32-33. (commentary). 1991 475. Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy. Corticotrophin-releasing factor, betaendorphin and somatostatin. Br J Psychiatry 1991; 158: 59-63 with C.B. Nemeroff, G. Bissette G, H. Akil). 476. Catatonia: A separate category for DSM-IV? Integrative Psychiatry 1991; 7: 210 (with M.A. Taylor). 477. Impact of the anti-psychiatry movement on the revival of ECT in the U.S. Psychiatric Clinics N.A. 1991; 14: 793-801. 478. Electroconvulsive therapy, 1989-1990. Current Opinion Psychiatry 1991; 4: 73-77 (with I. Zervas). 479. The revival of ECT in America. Bolletino di Psichiatria Biologica. 1991: 6: 25-29. 480. What is an adequate treatment in convulsive therapy? Acta Psychiatr Scand 1991; 84: 424-427. 481. Electroconvulsive therapy. Review of APA Task Force report. Wn Jrl Med 1991; 155, 515. (review). 482. Present use of ECT. Integrative Psychiatry 1991; 7: 69-70. (letter). 483. Pharmacotherapy and ECT. Convulsive Ther 1991; 7: 77-80. (editorial). 484. A scientific society for ECT. Convulsive Ther 1991; 7: 155-156. (editorial). 39 �485. ECT for refractory Parkinson’s Disease. Convulsive Ther 1991; 7: 222-223 (with I. Zervas). (letter). 486. A historical review of electroconvulsive therapy. Jefferson Jrl Psychiatry 1991; 9: 97-99. (letter). 487. Steroid induced catatonia. Br J Psychiatry 1991; 159: 445. (letter). 488. ECT in long-term follow up of BPD. Biol Psychiatry 1991; 30: 1172. (letter). 1992 489. Soziale und politische Aspekte der Elektrokonvulsionstherapie in den USA: Lektionen fur die deutsche Psychiatrie. Social and political aspects of ECT in the U.S.: Lessons for German psychiatry). Biologische Psychiatrie. Springer Verlag, Heidelberg, 1992, 88-90. 490. The use of ECT in geriatric patients. In G.S. Alexopoulos (ed.): Clinics Geriatric Medicine 1992; 8: 349354, W.B. Saunders: Philadelphia (with L.B. Greenberg). 491. Electroconvulsive therapy. In E.S. Paykel (ed.): Handbook of Affective Disorders. 2nd ed. ChurchillLivingstone, London, 1992; 22: 359-368. (review). 492. Induced seizures ECT and memory. In D Barcia Salorio (ed.): Trastornos de la Memoria. Editorial MCR, Madrid. 1992; 5.1: 383-396. 493. Pharmaco-Electroencephalography: A science ignored. Pharmacopsychiatry 1992; 24: 183-184. (editorial). 494. Qualification for ECT. Convulsive Ther 1992; 8: 1-4 (with R. Abrams). (editorial). 495. ECT and public mental health services. Convulsive Ther 1992; 8: 87-91. (editorial). 496. Catatonia and DSM-IV. Convulsive Ther 1992; 8: 159-162. (editorial). 497. Book review: Electroconvulsive therapy. Psychiatric Clinics N.A. 1992; 14: 693,1020. In Convulsive Ther 1992; 8:54-55. 498. Book review: ECT awaits its Lavoisier. R. Abrams. Electroconvulsive Therapy, 2nd ed. Oxford University Press, New York, 340 pp., 1992. In Convulsive Ther 1992; 8:213-216. 499. Book review: B.N. Gangadhar (ed.). Proceedings of the National Workshop on ECT. NIMHANS, Bangalore, India, 264 pp., 1992. J Krzyzowski. Leczenie Elektrowstrzasami. Z.D. Poligraficzny, Warsaw, Poland, 215 pp., 1991. In Convulsive Ther 1992; 8: 216-217. 500. Failure to use ECT in a case of catatonia. Am J Psychiatry 1992; 149: 145. (letter). 501. The treatment of catatonia: Benzodiazepines or ECT? P.J. Rosebush, A.M. Hildebrand, M.F. Mazurek (letter). Dr. Fink replies. Am J Psychiatry 1992; 149: 1279-1280. (letter). 502. ECT response in catatonia. Am J Psychiatry 1992; 149: 581-582 (with A. Francis). (letter). 40 �503. Why not ECT for catatonia? Biol Psychiatry 1992; 31: 536-537. (letter). 504. ECT and delirium in Parkinson’s Disease. Jrl Neuropsychiatry & Clin Neuroscience 1992; 4: 231 (with I. Zervas). (letter). 505. Follow-up: Letter on review of APA Task Force report by Peter Breggin. Readings: A Journal of Reviews and Commentary. American Orthopsychiatry Association). 1992; 7:22-23 (with L. Eisenberg). (letter). 506. Role of Dopamine in mood disorders. Comprehens Psychiatry 1992; 33: 417-417 (with L. Fochtmann). (letter). 507. ECT and delirium in Parkinson's Disease. Am J Psychiatry 1992; 149: 1758 (with I. Zervas). (letter). 508. Missed neuroleptic malignant syndrome. BMJ 1992; 304: 1246. (letter). 509. Catatonia: incidence and treatment in a university hospital. Convulsive Ther 1992; 8: 60-61 (with I. Zervas, J. Pataki J). (abstract). 1993 510. Blood pressure, memory, and electroconvulsive therapy. Convulsive Ther 1993; 9: 14-22 (with I. Zervas, A. Calev, L. Jandorf). 511a. Caffeine pre-treatment enhances clinical efficacy and reduces cognitive effects of ECT. Convulsive Ther 1993; 9:95-100 (with A. Calev, G. Petrides, A. Francis, L. Fochtmann). 511b. Effect of ECT with caffeine pre-treatment on efficacy for depression and memory deficits. Biol Psychiatry 1993; 33:84A (with A. Calev). 512. Who should get ECT? In C.E. Coffey (ed.): The Clinical Science of Electroconvulsive Therapy. 1993; 1: 3-16. APA Press, Washington, DC. 513. Catatonia: A treatable disorder, occasionally recognized. Directions in Psychiatry. 1993; 13(3): 1-8 (with G. Bush, A. Francis). 514. Die Geschichte der EKT in den USA in den letzten Jahrzehnten. (Recent history of electroconvulsive therapy in the U.S.) Nervenarzt. 1993; 64: 689-95. 515. Subjective symptoms in depression and during the course of electroconvulsive therapy. Neuropsychiatry, Neuropsychol Behav Neurol. 1993; 6: 187-92 (with N. Tubi, A. Calev, D. Niga1, B. Shapira, H.L. Pass, L. Jandorf, B. Lerer). 516. Post-ECT delirium. Convulsive Ther 1993; 9: 326-330. (review). 517. Reversible dementia and affective disorder: The Rip van Winkle Syndrome. Convulsive Ther 1993; 9: 209-16 (with L. Bright-Long). (case report). 518. Combining drugs and electroconvulsive therapy: Safe and/or effective? J. Clin. Psychopharmacology 1993; 13 2): 85-86. (commentary). 41 �519. Prolonged seizures. Convulsive Ther 1993; 9: 87-89. (commentary). 520. ECT in children and adolescents. Convulsive Ther 1993; 9: 15S-7. (commentary). 521a. The next challenge: The mode of action of ECT. Convulsive Ther 1993; 9: 192-7. (annotation). 521b. The mode of action of ECT. Psychopharmacol. Bull. 1994; 30: 309-12, 1994. 522. ECT and drugs: Concurrent administration. Convulsive Ther 1993; 9: 237-40. (with C.H. Kellner). (commentary) 523. Commentary on J.B. Welch: Topographic brain mapping: Applications and pitfalls. Integrative Psychiatry 1993; 9: 67-8. 524. EEG and behavior: Association or dissociation in man? Integrative Psychiatry 1993; 9: 108-123. (hypothesis). 525. Catatonia and psychotic delusional depression, distinct syndromes in DSM-IV. Am. J. Psychiatry 1993; 150: 1130-1. (letter). 526. Using MEDLINE to solve clinical problems. JAMA 1993; 270: 2053 (letter). 527. Book review: “Round up a new set of suspects...” Review of M.K. O’Connor, T.A. Rummans (eds): Updating ECT. Psychiatric Annals, 1993; 23:1-47. In Convulsive Ther 1993; 9: 141-2. 528. Book review: Psychiatry: The next phase. Review of M. Taylor: The Neuropsychiatric Guide to Modern Everyday Psychiatry. The Free Press, New York, 530 pp., 1993. In Convulsive Ther. 1993; 9: 143-5. 529a. Question the Experts: Blood levels of nortriptyline. J Clin Psychopharmacology 1993; 13: 296. 529b. Reply to “Question the Experts.” J Clin. Psychopharmacology 1993; 13: 359. 530. Book review: Psychiatry’s frog or prince? Electroconvulsive Therapy. Richard Abrams, Oxford University Press, 1992. In BJP Review of Books 6:18-19, July, 1993. 531. Book review: Electroconvulsive Therapy. Richard Abrams, Oxford University Press, 1992, 2nd ed. In Am. J. Psychiatry 1993; 150:1747-8. 532. Book review: Neuropsychological Perspectives on Emotion. F.N. Watts. Hillsdale, NJ: Lawrence Erlbaum. In Science Books & Films 1993; 29:261. 533. Book review: Motor Disorders in Psychiatry. D. Rogers, Wiley & Sons, Chichester UK, 1992. In Neuropsychiatry, Neuropsychol Behav Neurol 1993; 6: 267-8. 534a. Catatonia: A rating scale and prospective study utilizing lorazepam and ECT. Amer Col Neuropsychopharmacology Abstracts, pg 88, December 1993 (with G. Bush, A. Francis, G. Petrides, F. Dowling). 534b. What is catatonia? The Harvard Mental Health Letter 1995; 11: 8 (with G. Bush, G. Petrides). (commentary). 42 �1994 535a. Continuation ECT for relapse prevention in depression. Convulsive Ther 1994; 10: 77 (with G. Petrides, D. Dhossche). (abstract). 535b. A prospective study of continuation ECT. Biol. Psychiatry 1994; 35: 652-3 (with G. Petrides , D. Dhossche, A. Francis). (abstract). 535c. Continuation ECT: Relapse prevention in affective disorders. Convulsive Ther 1994; 10: 189-94 (with G. Petrides G., D. Dhossche, A. Francis). 536. Indications for the use of ECT. Psychopharmacol. Bull. 1994; 30: 269-80. 537a. Combining electroconvulsive therapy and drugs: A review of safety and efficacy. CNS Drugs 1994; 1: 370-376. (review). 537b. ECT and psychoactive drugs combined. ASCP Progress Notes Newsletter 1994; (52): 3. (review). 538. Optimizing ECT. L’Encephale 1994; 20: 297-302. (review). 539a. ECT in adolescents. The Harvard Mental Health Letter 1994; 10: 8. (commentary). 539b. ECT in adolescents. Psychiatric Times 1994; 12: 18-19,1995. (commentary). 540a. Catatonia in DSM-IV. Biological Psychiatry 1994; 36: 431-3. (commentary). 540b. DSM-IV and catatonia. Psychiatric Times 1994; 11: 35. (commentary). 541. Public perceptions of ECT. Jefferson Jrl. Psychiatry 1994; 12: 83-86. (letter). 542. Administrative problems limiting electroconvulsive therapy. Br. J. Psychiatry 1994; 164: 850-1. (letter). 543. Diazepam or lorazepam for prolonged seizures? Convulsive Ther 1994; 10: 236. (letter). 544. Convalescence and ECT. Convulsive Ther. 1994; 10: 301-3. (letter). 545. Book review: The Clinical Science of Electroconvulsive Therapy. C.E. Coffey (ed.), American Psychiatric Press, Washington DC, 259 pp., 1993. In The Psychiatric Times, Feb. 1994, pg. 25. 546. Book review: Drugs and Disease. J. L. Harris. Twenty-First Century Books, New York, 1993. In Science Books 1994; 30: 82. 547. Book review: Cannabis, Politically Incorrect. Marihuana, The Forbidden Medicine. L. Grinspoon, J.B. Bakalar. Yale University Press, New Haven, CT, 1993. In Am. J. Psychiatry 1994; 151: 1091. 548. The half-age stimulation strategy for bilateral ECT. Biol. Psychiatry 1994; 35: 653 (with G. Petrides). (abstract). 549. Alternative stimulation strategies for bilateral ECT. Convulsive Ther 1994; 10: 77 (with G. Petrides). 43 �(abstract). 1995 550. Convulsive therapy in delusional disorders. Psychiatric Clinics North America 1995; 18 (2): 393-406. (review). 551. ECT and non-memory cognition: A review. Br. J. Clin Psychology 1995; 34: 505-15 (with A. Calev, E.A. Gaudino, N.K. Squires, I.M. Zervas). 552. Recognizing NMS as a type of catatonia. Neuropsychiatry Neuropsychol Behav Neurol. 1995; 8: 75-6. (commentary). 553. Treat NMS as catatonia. Psychiatric Times 1995; 12 (3): 34. (commentary). 554. ECT in mania: A rediscovered use. Psychiatric Times 1995; 12 (6): 16. 555. ECT and schizophrenia. Psychiatric Times 1995; 12 (10): 30. 556. Milton Greenblatt: a remembrance. Convulsive Ther 1995; 11: 151-3 (with F. Frankel). 557. Convalescence and ECT: Comment on Letter by Dr. Brackin. Convulsive Ther 1995; 11: 220-21. (letter). 558. ECT and young minds. Lancet 1995; 345: 519. (letter). 559. NMS and catatonia: Reply to Raja and Miti. Neuropsychiatry Neuropsychol Behav Neurol 1995; 8: 2301. (letter). 560. “An ethical dilemma ....” Psychiatric Bulletin 1995; 19: 650-1 (with D.F. Klein). (letter). 561. ECT and pre-pubertal children. J Am Acad Child Adolesc Psychiatry 1995; 34: 1256-7 (with G.A. Carlson). (letter). 562. Book review: F.E. Bloom, O.J. Kupfer (eds.): Psychopharmacology: The Fourth Generation of Progress. New York, Raven Press, 1995, 2002 pp. In Neuropsychiatry, Neuropsychol. & Behav Neurol. (84): 303-4. 563. Book review: Asaad, Ghazi: Understanding mental disorders due to medical conditions or substance abuse: What every therapist should know. Brunner Maazel, NY, 1995. In Science Books & Films 31 (5): 1345. (book review). 564. Book review: J. Morrison: DSM-IV Made Easy: The Clinician’s Guide to Diagnosis. Guilford Press, NY, 1995. In Science Books & Films 31 (8): 233. 1996 565. Atrial fibrillation, anticoagulation, and electroconvulsive therapy. Convulsive Ther. 1996; 12: 91-98 (with G. Petrides). 44 �566. Ambulatory electroconvulsive therapy. Task force report of the association for convulsive therapy. Convulsive Ther. 1996; 12: 42-55 (with R. Abrams, S. Bailine, R. Jaffe). 567. Convulsive therapy for schizophrenia? Schizophrenia Bull. 1996; 221: 27-39 (with H.A. Sackeim). 568. Catatonia: I: rating scale and standardized examination (with G. Bush, G. Petrides, F. Dowling, A. Francis). Acta psychiatr. Scand 1996; 93 (2): 129-36. 569. Catatonia: II. Treatment with lorazepam and electroconvulsive therapy (with G. Bush, G. Petrides, F. Dowling, A. Francis). Acta Psychiatr. Scand 1996; 93 (2):137-43. 570. Catatonia. In T.A. Widiger, A.J. Frances, H.A. Pincus et al. (eds.): DSM-JV Sourcebook, 1996; vol 2:181-192. 571. The “half-age” stimulation strategy for ECT dosing. Convulsive Ther 1996; 12: 138-146 (with G. Petrides). 572. Toxic serotonin syndrome or neuroleptic malignant syndrome? Pharmacopsychiatry 1996; 29: 159-161. (case report). 573. A second quiet revolution: Ambulatory ECT. Convulsive Ther 1996; 12: 1-2 (with C.H. Kellner). (editorial). 574. Seizure adequacy: Does EEG hold the key? Convulsive Ther. 1996; 12: 203-206 (with C.H. Kellner). (editorial). 575. Neuroleptic malignant syndrome and catatonia: One entity or two? Biol Psychiatry 1996; 39: 1-4. (editorial). 576. Ambulatory ECT and managed care. The Psychiatric Times 1996; 13: 42. 577. Response to “Neuroleptic malignant-like syndrome due to cyclobenzaprine?” J Clin Psychopharmacol. 1996; 16: 97-9. (letter). 578. “Abnormal EEG effects of Clozapine.” J Neuropsych Clin Neuroscience 1996; 8: 114-115. (letter). 579. Algorithm accuracy. Comment on the International Psychopharmacology Algorithm Project. Psychiatric Times 1996; 13(8): 5. (letter). 580. Treating the syndrome before the complications. Am J Psychiatry 1996; 153: 1371 (with A. Francis). (letter). 581. Choosing a dosing strategy for electrical stimulation in ECT. J Clin Psychiatry 1996; 57: 487. (with G. Petrides). (letter). 582. ‘Catatonic schizophrenia’ is not ‘schizophrenia.’ Schizophrenia Res 1996; 18: 118. (abstract). 583. Book review: C. P. Freeman (ed.): The ECT Handbook. Royal College of Psychiatrists, London, 153 pp., 1995. In Convulsive Ther 1996; 12: 127-130. 45 �584. Book review: Bergsholm P.: Electroconvulsive Therapy: Issues related to narcosis, physiology, radiological anatomy, electrode placement, and endocrinology. Forde/Bergen, University of Bergen, 1995. In Convulsive Ther 1996; 12: 131-132. 1997 585. Catatonia. In M. Trimble, J. Cummings (eds.): Contemporary Behavioural Neurology. 1997; Chapter 16; pages 289-309. Butterworth/Heinemann, Oxford, UK. 586a. Prejudice against ECT: Competition with psychological philosophies as a contribution to its stigma. Convulsive Ther 1997; 13: 253-265. 586b. Response to Zigmond M. Lebensohn. Convulsive Ther 1997; 13: 268. 586c. Electroshock and psychoanalysis: schism in American psychiatry. Convulsive Ther 1997; 13: 51-52. 587. Recognition and treatment of the catatonic syndrome. Jrl Intensive Care Med. 1997; 12: 135-147 (with G. Fricchione, G. Bush G, M. Fozdar, A. Francis). (review). 588. Neuroleptic malignant syndrome: Identification and treatment. Essential Psychopharmacology. 1997; 2: 209-16. (review and commentary). 589. Energy dosing in ECT: Threshold stimulation or formula? Convulsive Ther. 1997; 13: 4-6. (debate with Richard Weiner). 590. Clinical common sense versus theoretical correctness. Reply to Harold A. Sackeim. Convulsive Ther. 1997; 13: 41-43 (with G. Petrides). 591. The decision to use ECT: For Whom? When? In A.J. Rush (ed.): Mood Disorders: Systematic Medication Management. Modern Probl. Pharmacopsychiatry. 1997; 25: 203-214. Karger, Basel, Switzerland. 592. Electroconvulsive therapy in affective disorders: Efficacy and mode of action. In A. Honig, H.M. van Praag (eds.): Depression: Neurobiological, Psychopathological and Therapeutic Advances. 1997; Chapter 23, pages 397-412. John Wiley & Sons, Ltd. Sussex, England. 593. What is the role of ECT in the treatment of mania? The Harvard Mental Health Letter 1997; 18: 8. 594. Cognitive screening instruments in neuropsychiatry: A report of the committee on research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci. 1997; 9:189-97 (with P.F. Malloy, J.L. Cummings, C.E. Coffey, J. Duffy, E.C. Lauterbach, M. Lovel, D. Royall, S. Salloway). 595. Lethal catatonia, neuroleptic malignant syndrome, and catatonia: A spectrum of disorders. Reply. J Clin Psychopharmacol. 1997; 17: 237. (letter). 596. The importance of a differentiated psychopathology of catatonia. Acta Psychiatr. Scand. 1997; 95: 358-9 (with G. Petrides, G. Bush, A. Francis). (letter). 597. ECT Update. Psychiatric Times. 1997; 14: 39-41. (review and lesson). 46 �598. Catatonia and NMS: Recognition and treatment. The Psychiatric Times. 1997; 14: 42-49. (review and lesson). 599. A.E. Bennett and curare. Convulsive Ther 1997; 13: 92. (commentary). 600. Book review: Squire L. A History of Neuroscience in Autobiography. Washington DC, Society for Neuroscience. vol 1, 1996. In Science Books & Films 1997; 33: 137. 601. Book review: New histories of psychiatry: Somatic and dynamic views contrasted. Shorter E. A History of Psychiatry. From the Era of the Asylum to the Age of Prozac. John Wiley & Sons, N.Y. 1997; Stone MH. Healing the Mind. A History of Psychiatry from Antiquity to the Present. W.W. Norton & Co., N.Y. 1997. In Convulsive Ther 1997; 13: 280-1. 1998 602. Electroconvulsive therapy and managed care. Am Jrl Managed Care. 1998; 4: 107-112 (with S. Bailine). 603. ECT and managed care. 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Pharmaco-electroencephalography: A debate in psychopharmacology. In T. Ban, D. Healy, E. Shorter (eds.): The Rise of Psychopharmacology and the Story of the CINP, 1998; 151-6. Animula Publishing House, Budapest. 614. The case for formal certification in ECT. J ECT 1998; 14: 132. (abstract). 615. To titrate or not to titrate: A debate with a twist. J ECT 1998; 14: 133-4. (abstract). 616. Concurrent use of ECT and atypical antipsychotic medications. J ECT 1998; 14: 139-40 (with G. Petrides, A. Abaza, A. Francis). (abstract). 47 �617. Book review: Principles of Neuropsychopharmacology. R.S. Feldman, J.S. Meyer, L.F. Quenzer. Sinauer: Sunderland, MA, 1997. In Quart Rev Biol 1998; 73: 122. 618. Video Review: Brainstorm: The Hidden Epidemic of Depression. Filmakers Library, New York, 1998; 53 min. video. In Science Books & Films 1998; 34: 150. 1999 619a. ELECTROSHOCK: Restoring the Mind. Oxford University Press, New York, 157 pp. Re-issued in paperback as Electroshock: Healing Mental Illness, 2002. 619b. Eletrochoque. Restaurando a Mente. Portugese translation by Dra. Andrea Favano. Sao Paulo Brazil: Editora Roca Ltda, 2003. 620. www.electroshock.org. (website, July 1999). 621a. Electroconvulsive therapy and mental retardation. J ECT 1999; 15: 140-9 (with M. Thuppal). 621b. Electroconvulsive therapy and mental retardation. J ECT 1998; 14: 142 (with M. Thuppal). (abstract). 622. Delirious mania. Bipolar Disorders 1999; 1: 54-60. 623. ECT in delirious states. J ECT 1999; 15: 175-77. (editorial). 624. Convulsive therapy. In G. Adelman, B.H. Smith (eds.): Elsevier’s Encyclopedia of Neuroscience. Elsevier Science. B.V., New York and Amsterdam, 466-468, 1999. 625. Convulsive Therapy. In H. Freeman (ed.): A Century of Psychiatry, Mosby-Wolfe, London, 1999; I: 96-99; II: 229-32. 626. Ladislas J. Meduna. Images in psychiatry. Am J Psychiatry 1999; 156: 1807. 627. Intractable seizures, status epilepticus, and ECT. J ECT 1999; 15: 282-4 (with C. Kellner, H.A. Sackeim). (letter). 628. Pediatric ECT. Psychiatric Times 1999; 169: 63-5 (with C. Foley). 629. Neuroleptic malignant syndrome: Recognition and treatment. Psychiatric Times 1999; 16 (8): 6. (commentary). 630. Book review: J.L. Beyer, Weiner R.D., Glenn M.D.: Electroconvulsive Therapy: A Programmed Text. American Psychiatric Press, Inc., Washington DC, 1998, Am J. Psychiatry 1999; 156: 333. 48 �2000 631. Electroshock revisited. Amer Scientist 2000; 88 (2): 162-167. 632. Catatonia. In C. Andrade (ed.): Advances in Psychiatry. New Delhi, Oxford University Press. Chapter 2, pp. 26-44, 2000 (with G. Petrides). 633. A clinician-researcher and ECDEU: 1959-1980. In T. Ban, D. Healy, E. Shorter (eds.): The Triumph of Psychopharmacology and the Story of the CINP. Budapest, Animula, 2000, 82-96, 2000. 634. Can delirium relieve psychosis? Comprehens Psychiatry 2000; 41: 450-453 (with C. Malur, A. Francis). 635. ECT has proved effective in treating depression. Nature 2000; 405: 826. (letter). 636. The interaction of delirium and seizures. In P.T. Trzepacz (ed.) Seminars in Clinical Neuropsychiatry 2000; 52: 31-35. 637. Educational resources for electro-convulsive therapy. Arch Indian Psychiatry 2000; 6: 6-9. 638a. ECT in the management of delirium, NMS, and catatonia. Essential Psychopharmacology 2000; 3: 116. 638b. ECT in the management of delirium, NMS, and catatonia. Directions in Psychiatry 2000; 220: 367-376. (lesson). 639. Herman C.B. Denber. Neuropsychopharmacology 2000; 23:474-475. (obituary). 640. Undiagnosed Stupor: A treatable syndrome of catatonia? ASCP Progress Notes 2000; 10: 1,4,7. 641. Fixed high dose right unilateral ECT. (commentary). Evidence-Based Mental Health 2000; 3: 114-115. 642. Controversies in the diagnosis and treatment of manic-depressive illness. World Jrl Biological Psychiatry 2000; 1: 219. (letter). 643. NMS best treated as catatonia. Psychiatric Times 2000; 17 (11): 28-29. (commentary). 644. Book review: The Science of Happiness: Unlocking the Mysteries of Mood. Stephen Braun. NY, Wiley, 2000. In Science Books & Films, 2000:36 (5): 212. 645. A neuroendocrine view of convulsive therapy. Neuropsychopharmacology 2000; 23: S91. (abstract). 49 �2001 646. Convulsive therapy after 65 years. J Affective Dis. 2001; 63: 1-15. 647. ECT remission rates in psychotic versus non-psychotic depressed patients: A report from CORE. J ECT 2001; 17: 244-253 (with G. Petrides, M.M. Husain, R. Knapp, A.J. Rush, M. Mueller, T.A. Rummans, K.M. O’Connor, K.G. Rasmussen, H.J. Bernstein, M. Biggs, S.H. Bailine, C.H. Kellner). 648. The influence of age on the response of patients with major depression to electroconvulsive therapy. Am J Geriatr Psychiatry 2001; 9: 382-390 (with K.M. O’Connor, R. Knapp, M.M. Husain, T.A. Rummans, G. Petrides, G. Smith, M. Mueller, K. Snyder, H. Bernstein, A.J. Rush, C. Kellner). 649. ECT has much to offer our patients: It should not be ignored. World Jrl Biological Psychiatry 2001; 2: 18. 650. Electroconvulsive therapy in medication-resistant depression. In Jay Amsterdam, Mady Hornig-Rohan, and Andrew Nierenberg (eds.): Treatment resistant mood disorders. 2001; 11: 223-238. Cambridge University Press, Cambridge UK. 651. Convulsive therapy in the 21st Century. In M.G. Gelder, J.J. Lopez-Ibor and N.C. Andreasen (eds.): New Oxford Textbook of Psychiatry, Oxford University Press, London. Chap 6.2.9.1; pp. 1342-1352. 652. The many varieties of catatonia. European Arch Psychiatry Clin Neurosci 2001; 251: Suppl 1: 8-13 (with M.A. Taylor). 653. Catatonia: Syndrome or schizophrenia subtype? Recognition and treatment. J Neural Transmission 2001; 108: 637-644. 654. The broad clinical activity of ECT should not be ignored. J ECT 2001; 17: 233-235. (editorial). 655. New research improves ECT outcomes. Psychiatric Times 2001; 18: 21. (review). 656. Electrode placement and electroconvulsive therapy: A search for the chimera. Arch Gen Psychiatry. 2001; 58: 607-608. (with S. Bailine, G. Petrides). (letter). 657. Modal ECT is effective: Response to Letter by Sackeim et al. J ECT 2001; 17: 222-225. (letter). 658. Treating neuroleptic malignant syndrome as catatonia. J Clin Psychopharmacol. 2001; 21: 120-121. (letter). 659. Treating manic stupor. Indian J Psychiatry 2001; 433: 286-287. (letter). 660 Treating bipolar affective disorder. BMJ 2001; 322: 365. (letter). 661. Book review: A Century of Psychiatry. Hugh Freeman. London, Mosby-Wolfe Medical Communications. In Neuropsychiatry, Neuropsychology Behavioral Neurology 2001; 14: 77. 2002 662. The efficacy of ECT and “Treatment Resistance.” J ECT 2002; 18: 1-2. 50 �663. Move On! Commentary on R. Abrams: stimulus titration and EC T dosing. J ECT 2002; 18: 11-12. 664. Catatonia and ECT. Reconsidering Meduna’s hypothesis of a biological antagonism between dementia praecox and epilepsy. World Jrl Biol Psychiatry 2002; 3: 105-108. 665. The 21st century clinical evaluation of psychoactive drugs. In T. Ban, D. Healy, E. Shorter (eds.): From Psychopharmacology to Neuropsychopharmacology in the 1980s and the Story of CINP as told in Autobiography. Budapest: Animula Publishing, 2002; 21-26. 666. ECT: an effective, but ignored, treatment of psychosis. In B. Green (ed.): Focus on Antipsychotics. London: Librapharm/Petroc Press, 2002, 3: 10-17. 667. Equivalency of rTMS and ECT unproven. Biol Psychiatry 2002; 52: 1032-1033 (with C.H. Kellner, M. Husain, G. Petrides, T. Rummans). (letter). 668. Electrotherapeutics. J ECT 2002; 18: 114-115. 669. Catatonia and NMS. (Grand Rounds Response) Psychiatric Bull. 2002; 26: 393. (with M.A. Taylor). (letter). 670. ECT in neurological disorders. Psychiatric Times 2002; 19 (9): 28-29. 671. Catatonia in adolescents and children. Psychiatric Times 2002; 19 (9): 28-29. 672. Book review: American Psychiatric Association. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training and Privileging. 2nd ed. Psychiatric Services. 2002; 53: 1040-1041. 673. Book review: Rage Against Electroshock. Kneeland TW, Warren CAB. Pushbutton Psychiatry. Westport CT: Praeger, 2002. J ECT 2002; 18: 112-113. 674. Book review. Electricity in Medicine: Ugo Cerletti’s Contribution. Electric Bodies: Episodes in the History of Medical Electricity. Paola Bertucci, Giuliano Pancaldi (eds.). Bologna, Italy: Universita di Bologna, 2001. J ECT 2002; 18:165-166. 2003 675a. Catatonia. A Clinician’s Guide to Diagnosis and Treatment. Cambridge UK: Cambridge University Press (with M.A. Taylor). 675b. Catatonia. Guía clinica para el diagnóstico y el tratamiento. Translated into Spanish by Beatriz M. Ruiz and Miguel B. Arroyo. Barcelona: Masson, 2005. 675c. …ibid., Translated into Japanese by Kazumasa Suzuki. Tokyo: Seiwa Shoten, 2007. 676. Catatonia in psychiatric classification: A home of its own. Am J Psychiatry 2003; 160: 1233-1241 (with M.A. Taylor). 677. A Beautiful Mind and insulin coma: social constraints on psychiatric diagnosis and treatment. Harvard Review of Psychiatry 2003; 11: 284-290. 51 �678. A Gilles de la Tourette form of catatonia: Response to ECT. J ECT 2003; 19(2): 115-117. (with H. Trivedi, A. Mendelowitz). 679. ECT Update: Recognizing and treating psychotic depression. J Clin Psychiatry 2003; 64: 232-234. 680. Therapy-Resistant Depression: When to consider ECT. Algorithm seeks respect for neglected therapy. Current Psychiatry 2003; 2: 49-54. 681. Commentary on “Successful use of ECT as the sole modality of treatment in a case of motility psychosis”: The classification of catatonia. J ECT 191: 48- 49, March 2003 (with M.A. Taylor). 682. Electroshock 2003. Masterminds Indian Psychiatric Society (Jan) 2003, 3-4. 683. Letter from India: Conflicts in the use of ECT. Psychiatric Times 2003 (Mar); 20: 10. 684. Book review. A classic text updated. Abrams R: Electroconvulsive Therapy, New York: Oxford University Press. J ECT 2003; 19:123-124. ibid. Psychiatric Times 2003 (Jun); 20: 25. 685. Book review. D. Healy. The Creation of Psychopharmacology. Cambridge MA: Harvard University Press, 2002. Psychiatric Times 2003; 220: 29. 686. Book review. G. Parker, D. Straton, K. Wilhelm, P. Mitchell; M-P. Austin, K. Eyers, D. Hadzi-Pavlovic. Dealing with Depression: A Commonsense Guide to Mood Disorders. New South Wales: Crows Nest, 2002. Am J Psychiatry 2003; 160:1365-1366. 687. Book review: K. Hugdahl, R.J. Davidson. The Asymmetrical Brain. Cambridge MA: MIT Press, 2003. Science Books & Films 2003; 9: 160. 2004 688a. Ethics of Electroconvulsive Therapy. New York: Brunner-Routledge (with J.O. Ottosson). 688b. …ibid., Translated into Japanese by Mitsuru Nakamura. Tokyo: Seiwa Shoten, 2006. 689. Pharmaco-Electroencephalography: A Selective History of the Study of Brain Responses to Psychoactive Drugs. In History of CINP, vol IV. Edited by T. Ban, E. Shorter, D. Healy. pp. 661-672. 690. Speed of Response and Remission in Major Depressive Disorder with Acute ECT: A Consortium for Research in ECT (CORE) Report (with M.M. Husain, A.J. Rush, R. Knapp, G. Petrides, T. Rummans, M.M. Biggs, K.M. O’Connor, K. Rasmussen, M. Litle, W. Zhao, H.J. Bernstein, G. Smith, M. Mueller, S.M. McClintock, S.H. Bailine, C.H. Kellner). J Clin Psychiatry 2004; 65: 485-491. 691. Efficacy of ECT in catatonia. In S.Caroff, S.Mann, A. Francis, G Fricchione (eds.): Catatonia. From Psychopathology to Neurobiology. Washington DC: American Psychiatric Press. 13: 151-160 (with G. Petrides, C. Malur). 692. Induced seizures as psychiatric therapy: Ladislas Meduna’s contributions in modern neuroscience. J ECT 2004; 20: 133-136. (commentary). 693. Response to T.E. Schlaepfer: Learning from the history of neuroscience: Dogma and patient interests. J 52 �ECT 2004; 20: 138. 694. Melancholy or Malarky? In Spitzer R.L., First M.B., Gibbon M., Williams J.B.W. (eds.): Treatment companion to the DSM-IV-TR casebook. Washington DC: American Psychiatric Publishing, 2004; 112-119. 695. Response to critique: classification of catatonia. Am J Psychiatry 2004; 161: 1136 (with M.A. Taylor). (letter). 696. Response. Catatonia in psychiatric classification. Am J Psychiatry 2004; 161: 2328. 697. Non-convulsive status epilepticus and electroconvulsive therapy. J ECT 2004; 20: 131-2. (letter). 698. Treat TSS and NMS as malignant catatonia. BMJ (rapid responses) 2004; 329: 1333-1335. 699. Convulsive therapy electroshock (ECT). In G. Adelman, B.H.Smith (eds.): Encyclopedia of Neuroscience, 3rd ed. Amsterdam: Elsevier B.V., 2004. 700. Insulin coma therapy (ICT). Encyclopedia of Neuroscience. In G. Adelman, B.H. Smith (eds.): Encyclopedia of Neuroscience, 3rd edition. Amsterdam: Elsevier B.V., 2004. 701. About Meduna’s pioneer activity. Neuropsychopharmacol Hung 2004; 6: 39. (letter). 702. ECT: Serendipity or logical outcome? Psychiatric Times 2004; 211: 21-22. 703. A new appreciation of ECT. Psychiatric Times 2004; 214: 32-35. 704. ECT at 70: What have we learned? Psychiatric Times 2004; 21(8): 13-14. 705. Book review. The Mount Everest Challenge. Lisanby S.H. (ed.): Brain Stimulation in Psychiatry. Washington DC: American Psychiatric Publishing Inc. Am J Psychiatry. 2004 (161): 2149-2150. 706. Book review. Schroeder B.E.: Ecstasy. Philadelphia: Chelsea House, 2003. Science Books and Films 2004 (May-June); 127. 2005 707. Catatonia. Guia clinica para el diagnóstico y el tratamiento. (Spanish translation). Barcelona: Masson Elsevier. 708. Psychobiology of Electroshock. In J. Licinio (ed.): Biology of Depression. Weinheim, Germany: WileyVCH, 2004. Chap 7: 211-221. 709. Relief of expressed suicidal intent by ECT: A Consortium for Research in ECT Study. Am J Psychiatry 2005;162: 977-982 (with C.H. Kellner, R. Knapp, G. Petrides, M.M. Husain, T. Rummans, M. Mueller, H. Bernstein, K. Rasmussen, K. O’Connor, G. Smith, A.J. Rush, M. Biggs, S. McClintock, S.H. Bailine, C. Malur). 710. Should the dexamethasone suppression test be resurrected? Acta Psychiatrica Scandinavica 2005; 112: 53 �245-9. (commentary). 711. Is the practice of ECT ethical? World Jrl Biological Psychiatry 2005; 6 (Supplement 2): 38-43. 712. The “treatment resistant” label in bipolar disorder is a misnomer. Psychiatric Annals 2005; 35: 965-8. (review). 713. Predicting the response to ECT. J ECT 2005; 21(3): 137-8. (editorial). (with V. McCall). 714. William Karliner: practitioner, experimentalist, and teacher. Obituary. J ECT 2005; 21: 201-2. 715. Suicide risk reduced. Psychiatric Times 2005; 222: 94-95. 716. The bean-counters view of ECT. Psychiatric Times 22; 10: 54. 717. Continuation ECT Today: What we know and what we need to know. Psychiatric Times 2005; 2214: 7677. 718. Use of pharmacologic coma for adult status epilepticus. Epilepsy & Behavior. 2005; 6: 292 (letter). (with D. Anschel). 719. Cheap shot at ECT. Lancet 2005; 365: 937 (with C. Kellner, V. McCall). (letter). 720. Book review. Kelleher, C.A.: Brain Trust. New York: Paraview Pocket Books, 2004. Science Books and Films 2005; 41:105. 721. Book reviews. Scull A. Madhouse: A Tragic Tale of Megalomania and Modern Medicine. New Haven: Yale University Press, 2005; J. El-Hai. The Lobotomist: A Maverick Medical Genius and his Tragic Quest to Rid the World of Mental Illness. New York: Wiley, 2005. J ECT 2005; 21: 191-3. 722. Book review. A. Scull: Madhouse: A Tragic Tale of Megalomania and Modern Medicine. New Haven: Yale University Press, 2005. Science Books and Films 2005; 41: 251. 2006 723. Melancholia: The Diagnosis, Pathophysiology, and Treatment of Depressive Disorders. Cambridge UK: Cambridge University Press, 2006 (with M.A. Taylor). 724. Catatonia in autistic spectrum disorders: A medical treatment algorithm. In D. Dhosshe, L. Wing, M. Ohta, K-J Neumarker (eds.): Catatonia in Autism Spectrum Disorders. Amsterdam: Elsevier/Academic Press. Int Rev Neurobiology 2006; 72:233-244 (with M.A. Taylor, N. Ghaziuddin). 725. Patterns of Psychotropic Medication Use Among Severely Depressed Patients Referred for Electroconvulsive Therapy: Data from the Consortium for Research on ECT. J ECT 2006; 22: 116-123 (with K.G. Rasmussen, M. Mueller, C.H. Kellner, R.G. Knapp, G. Petrides, T.A. Rummans, M.M. Husain, K. O’Connor, J.L. Black, S. Sampson). 54 �726. Continuation ECT versus pharmacotherapy for relapse prevention in major depression: a multi-site study from CORE. Archives General Psychiatry. 2006; 63: 1337-44 (with C.H. Kellner, R.G. Knapp, G. Petrides, T.A. Rummans, M.M. Husain, K. Rasmussen, M. Mueller, H.J. Bernstein, K. O’Connor, G. Smith, M. Biggs, S.H. Bailine, C. Malur, E. Yim E, S. Sampson, M Fink). 727. The case against evidence-based principles in psychiatry. Medical Hypotheses 2006; 67: 401-410. (with R.L. Levine). 728. Catatonia: Subtype or syndrome in DSM? Am J Psychiatry 2006; 163 (11): 1875-6, (with M.A. Taylor). (commentary). 729. Challenges to British ECT clinical practice. J ECT 2006; 22: 30-32. (commentary). 730. ECT in therapy-resistant mania: Does it have a place? Bipolar Disorders 2006; 8: 307-9. (commentary). 731. The DST riddle. Psychiatric Times 2006; 23 (2): 25-26. 732. Should the diagnosis of melancholia be revived? Psychiatric Times 2006; 23 (6): 78-80. 733. The Camelford hysteria: A lesson for ECT? Psychiatric Times 2006; 23 (11): 69-72. 734. Interseizure EEG slowing after ECT is not NCSE. Pharmacopsychiatry 2006; 39: 119. (letter). 735. Neuroleptic malignant syndrome is malignant catatonia, warranting treatments efficacious for catatonia. Prog NeuroPsychopharmacol Biol Psychiatry 2006; 30:1182-1183. (with M.A. Taylor). (letter). 736. Book review: G.S. Ungvari. Catatonia: An anthology of classical contributions. Hong Kong: Scientific Communications Int. Ltd. 2006. J ECT 2006; 22: 277-8. 737. AV Review: Healthy Brains. Chip Taylor Communications. Science Books & Films 2006; 42: 138. (review). 2007 738. Resurrecting melancholia. Acta psychiatrica scandinavica 2007; Supplement 433: 14-20 (with M.A. Taylor). 739. Melancholia: Restoration in psychiatric classification recommended. Acta Psychiatr Scand. 2007; 115: 89-92 (with T.G. Bolwig, G. Parker, E. Shorter). (conference summary). 740. DSM melancholic features are unreliable predictors of ECT response: A CORE publication. J ECT. 2007; 23: 139-146 (with A.J. Rush, R. Knapp, K. Rasmussen, M. Mueller, T. Rummans, K. O’Connor, M. Husain, M. Biggs, S. Bailine, C.H. Kellner, and CORE group.) 55 �741. Antidepressant Treatment Failure Does Not Predict Lower Remission Rates with ECT for Major Depressive Disorder. A Report from the Consortium for Research in ECT. J Clin Psychiatry 2007; 68: 17011706 (with K.G. Rasmussen, M. Mueller, R.G. Knapp, M.M. Husain, T.A. Rummans, S.M. Sampson, M.K. O’Connor, G. Petrides, C.H. Kellner). 742. Electroconvulsive therapy: Evidence and challenges. JAMA 2007; 298: 330-332 (with M.A. Taylor). 743. Complaints of the loss of personal memories after electroconvulsive therapy: Evidence of a somatoform disorder? Psychosomatics 2007; 48: 290-293. 744. Data management and design issues in an unmasked randomized trial of electroconvulsive therapy for relapse prevention of severe depression. J ECT 2007; 23: 244-250 (with K.G. Rasmussen, R.G. Knapp, M.M. Biggs, G.E. Smith, T.A. Rummans, G. Petrides, M.M. Husain, M.K. O’Connor, C.H. Kellner). 745. Belling the cat: ECT practice standards in the United States. J ECT 2007; 23: 3-5 (with C.H. Kellner). (commentary). 746. What we learn about continuation treatments from the collaborative ECT studies. J ECT 2007; 23: 215218 (commentary). 747. Ambulatory electroconvulsive therapy. J ECT 2007; 23: 130. (history). 748. Antidepressant medications and other treatments of depressive disorders: A CINP Task Force report based on a review of evidence. International Journal of Neuropsychopharmacology 2007; 10: S1-S207. (with N. Sartorius, T.C. Baghai, D.S. Baldwin, B. Barrett, D. Brand, W. Fleischhacker, G. Goodwin, H. Grunze, M. Knapp, B.E. Leonard, J. Lieberman, Y. Nakane, R.M. Pinder, A.F. Schatzberg, J. Svestka, P. Baumann, K. Ghalib, J.C. Markowitz, F. Padberg, T. Furukawa, K.N. Fountoulakis, P. Jensen, S. Kanba, A. RiecherRossler). 749. Improving electroconvulsive therapy practice. Psychiatric Times 2007; 24 (4): 10-11. 750. Electroshock works. Why? Psychiatric Times 2007; 24 (6): 59-60. 751. Major studies on ECT for depression: What have we learned? Psychiatric Times 2007; 24 (12): 26-28. 752. Catatonia or no catatonia: Still beyond lorazepam/amobarbital. Letter and Reply. Am J Psychiatry 2007; 164: 525 (with M.A. Taylor). 753. The renaissance of ECT. Forward for Electroconvulsietherapie: Aanbevelingen voor de praktijk. P. Sienaert, J. De Fruyt, M. Dierick (eds.). Ghent: Academic Press, 2007: xv-xviii. 754. …ibid., Book review: Dukakis K, Tye L. SHOCK: The Healing Power of Electroconvulsive Therapy. New York: Penguin Group, 2006. J ECT 2007; 23: 131-133. Commentary: Ambulatory electroconvulsive therapy (p.130). 2008 755. Restoring melancholia in the classification of mood disorders. Jrl Affective Disorders 2008; 105: 1-14 (with M.A. Taylor). 756. The medical evidence-based model to identify psychiatric syndromes: Return to a classical paradigm. Acta Psychiatr Scand 2008; 87: 81-84 (with M.A. Taylor). 56 �757. Karoly Schaffer and his school: The birth of biological psychiatry in Hungary, 1890-1940. Eur Psychiatry 2008; 23(6):449-456. (with B. Baran, I. Bitter, G. Gazdag, E. Shorter). 758. Change in seizure threshold during ECT: A CORE study. J ECT 2008; 24: 114-116 (with G. Petrides, C.H. Kellner, M. Mueller, R. Knapp, M.M. Husain, K. Rasmussen, T.A. Rummans, K. O’Connor). 759. Outcome of ECT by race in the CORE multi-site study. J ECT 2008; 24: 117-121 (with M. Williams, T. Rummans, S. Sampson, R. Knapp, M. Mueller, M. Husain, K. Rasmussen, K. O’Connor, G. Smith, G. Petrides, C.H. Kellner). 760a. The efficacy of acute ECT in atypical depression. J Clin Psychiatry 2008; 69: 406-411 (with M.M. Husain, S.M. McClintock, A.J. Rush, R.G. Knapp, T.A. Rummans, K. Rasmussen, C. Claassen, G. Petrides, M.M. Biggs, M. Mueller, S. Sampson, S.H. Bailine, C.H. Kellner). 760b. ECT not proven for atypical depression. Response to Letter C.M. Swartz. J Clin Psychiatry 2008; 69: 1662-3. (with M.M. Husain, S.M. McClintock, A.J. Rush, R.G. Knapp, T.A. Rummans, K. Rasmussen, C. Claassen, G. Petrides, M.M. Biggs, M. Mueller, S. Sampson, S.H. Bailine, C.H. Kellner, S.H. Lisanby). 761. Conceptual issues in DSM-V development (commentary). Am J Psychiatry 2008; 165: 799. (with M.A. Taylor). 762. Continuation treatments for melancholic depression. Commentary to M. Webber: electroconvulsive therapy, BMJ 2008; 337: 2998 (rapid response). 763. Catatonia in autism is treatable. Psychiatric Times 2008; 25: 17, 20. 764. Why evidence-based medicine cannot be applied to psychiatry. Psychiatric Times 2008; 25: 10-12. 2009 765. Electroconvulsive Therapy: A Guide for Professionals & Their Patients. New York: Oxford University Press, 2009. 766. Serendipity and science: A double anniversary of a treatment and a journal. J ECT 2009; 25: 1-2. 767. Laszlo Meduna’s pilot studies with camphor induction of seizures: The first 11 patients. J ECT 2009; 25: 3-11 (with G. Gazdag, I. Bitter, G.S. Ungvari, B. Baran). 768. Electrotherapy of melancholia: The pioneering contributions of Benjamin Franklin and Giovanni Aldini. J ECT 2009; 25:15-18 (with T. Bolwig). 769. Induced therapy in man. In Encyclopedia of Neuroscience. 2009: 5: 117-123. Edited by Larry Squire, Floyd Bloom, Fred Gage, Nick Spitzer. Oxford: Academic Press. 770. Electroconvulsive Therapy. In New Oxford Textbook of Psychiatry. Edited by M.G. Gelder, J.J. LopezIbor, and N.C. Andreasen. New York: Oxford University Press, 2009, vol II;6.2.10.1: 1251-1259. 771. Catatonia: A syndrome appears, disappears, and is rediscovered. Can J Psychiatry 2009; 54: 23-31. 772. Catatonia: Forgotten but not gone. Arch Gen Psychiatry 2009; 66: 1173-77 (with M.A. Taylor). 57 �773. Catatonia in 100 words. Br J Psychiatry 2009; 194: 325 (with M.A. Taylor). 774. Melancholia in 100 words. Br J Psychiatry 2009; 194: 463 (with M.A. Taylor). 775. The electroshock riddle: effective but rejected. Br J Psychiatry 2009; 195: 390. 776. Biological markers for melancholic depression are effective. Comment on the WFSBP Task Force Report. World Journal of Biological Psychiatry 2009 (103):252-3 (with M.A. Taylor). 777. Seizure threshold in a large sample: Implications for stimulus dosing strategies in bitemporal ECT. A report from CORE (with G. Petrides, R.J. Braga, M. Mueller, R. Knapp, T. Rummans, M. Husain, K. Rasmuussen, S. Bailine, C. Malur, K. O’Connor, C.H. Kellner). J ECT 2009; 25: 232-237. 778. Electroconvulsive therapy in the treatment of intractable status epilepticus. Epilepsy & Behavior 2009; 16:189-90. (letter). (with C.H. Kellner). http://dx.doi.org/10.1016/j.yebeh.2009.06.022 779. DSM-V: Applying the medical model. Psychiatric Times. 2009, June 9: 26 (6): http://www.psychiatrictimes.com/display/article/10168/1420772. 2010 780. Endocrine Psychiatry: Solving the Riddle of Melancholia (with E. Shorter). Oxford University Press. 781. Remembering: the forgotten neuroscience of pharmaco-EEG. Acta Psychiatr Scand 2010; 121: 161-73. 782. Catatonia is not schizophrenia: Kraepelin’s error and the need to recognize catatonia as an independent syndrome in medical nomenclature. Schizophrenia Bulletin 2009; doi: 10.1093/schbul/sbp059; 2010; 36: 31420. (with E. Shorter, M.A. Taylor). 783. The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition (with M.A. Taylor, E. Shorter, N.A. Vaidya). Acta Psychiatr Scand 2010; 122: 173-183. 784. Phenomenology is not enough. J. McCarthy letter (response). Acta Psychiatr Scand. 2011; 123: 82-83. (with M.A. Taylor, E. Shorter, N.A. Vaidya). 785. The intimate relationship between catatonia and convulsive therapy. J ECT 2010; 26: 243-245. (commentary). 786. Catatonia in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A. Francis , F. Appiani, A. Bertelsen, T.G. Bolwig, P. Braunig, S.N. Caroff, B.T. Carroll, A.E. Cavanna, D. Cohen, Cottencin O, M.J. Cuesta, J. Daniels, D. Dhossche, G.L. Fricchione, G. Gazdag, N. Ghaziuddin, D. Healy, D.F. Klein, S. Krüger, J.W.Y. Lee, S.C. Mann, M. Mazurek, W.V. McCall, W.W. McDaniel, G. Northoff, V. Peralta, Petrides G, P. Rosebush, T.A. Rummans, E. Shorter, K. Suzuki, P. Thomas, G. Vaiva, L. Wachtel). J ECT 2010; 26: 246-248. (letter). 787. Whither melancholia? The case for its classification as a distinct mood disorder (with G. Parker, E. Shorter, M.A. Taylor, H. Akiskal, G. Berrios, T. Bolwig, W.A. Brown, B. Carroll, D. Healy, D.F. Klein, A. Koukopolous, R. Michels, J. Paris, R.T. Rubin, R. Spitzer, C. Swartz). Am J Psychiatry 2010; 167: 745-47. (letter). 58 �788. Laszlo Meduna’s immigration to the United States in 1939: Correspondence with Victor Gonda (G. Gazdag, M. Fink, G. Ungvari, E. Shorter). J ECT 2010; 26: 79-81. 789. The human side of Laszlo Meduna. J ECT 26: 77-78. (commentary). 790. ECT is equally effective in unipolar and bipolar depression (with S. Bailine, R. Knapp, G. Petrides, M. Husain, K. Rasmussen, S. Sampson, M. Mueller, S. McClintock, K.G. Tobias, C.H. Kellner). Acta Psychiatr Scand 2010; 121: 431-436. 791. Bifrontal, bitemporal, and right unilateral electrode placement in ECT: A randomized trial (with C.H. Kellner, R. Knapp, M. Husain, K. Rasmussen, S. Sampson, M. Cullum, S. McClintock, K. Tobias, C. Martino, M. Mueller, S. Bailine, G. Petrides). Br. J. Psychiatry 2010; 196: 226-234. 792. A randomized controlled trial comparing the memory effects of continuation ECT versus continuation pharmacotherapy: Results from the CORE study (with G.E. Smith, K.G. Rasmussen, M. Cullum, M.D. Felmlee, G. Petrides, T.A. Rummans, M. Husain, M. Mueller, H. Bernstein, R. Knapp, M.K. O’Connor, S. Sampson, S.H. Bailine, C.H. Kellner). J Clin Psychiatry 2010; 71: 185-193. 793. The end of the asylum era in Central-Eastern Europe. History of Psychiatry 2010; 21: 501-504. (with G. Gazdag, B. Baran, Z. Rihmer). 794. ECT (Electroconvulsive Therapy) as first line treatment for psychotic depression. Letter reply to B.S. Meyers, A.J. Flynt, A.J. Rothschild et al.: The Study of Pharmacotherapy of Psychotic Depression STOP-PD. Arch Gen Psychiatry 2009; 66:838-47. (with C.H. Kellner, K. Tobias, G. Petrides). Arch Gen Psychiatry, 9 Feb 2010. (letter). 795. F.D. Zepf et al.: A 16-year-old boy with severe gamma-butyrolactone (GBL) withdrawal delirium. Pharmacopsychiatry 2010; 43: 157-8. (letter). 796. The perplexing history of electroconvulsive therapy in three books. Psychiatric Times 2010; (Oct) 27: 31 (with C.H. Kellner). (book review). 797. Book Review. Hysteria: The Biography. Andrew Scull. New York: Oxford University Press, 2009. SB&F April 2010. 798. Obituary: Sidney Merlis, 1925-2010. Neuropsychopharmacology 2010:35: 2648. 2011 799. Catatonia from its Creation to DSM5: Considerations for ICD. Indian Jrl Psychiatry. 2011; 53: 214-217. 800. Melancholia is a distinct identifiable mood disorder that warrants a separate category in DSM5. In: C.R. Soldatos and D.G. Dikeos (Ed): Psychiatry and the Neurosciences: International Perspectives. Bologna Italy: Editografica, 2011: 5-13. 801. ECT resurrected: Its successes and promises after 75 years. Can J Psychiatry 2011; 56:3-4 (Commentary). 802. Presidential Perspective: Defining clinical diagnoses by the medical model. In: Cottler L (Ed): Mental Health in Public Health: The Next 100 Years, NY: Oxford University Press, 2011: 278-281. 59 �803. Anti-NMDA receptor encephalitis vs. pediatric catatonia. [Comment on Case Report "Anti NMDA receptor encephalitis" Am J Psychiatry 2011;168: 245-51]. Am J Psychiatry 2011; 168: 749. [Dhossche D, Fink M, Shorter E, Wachtel LE] (Letter) 804. Transcranial magnetic stimulation is not a replacement for electroconvulsive therapy in depressive mood disorders. J ECT 2011; 27: 3-4. (Commentary) 805. Stimulus dosing in electroconvulsive therapy. J ECT 2011; 27:268. [Petrides G, Braga RJ, Fink M, Mueller M, Knapp RG, Husain M, Rummans T, Bailine SH, O'Connor K, Malur C, Kellner CH.]. (Letter) 806. ECT for melancholia. New York City Voices 2011; 18: 16. (Letter) 807. A response to Not “Au Revoir” but "Merci Beaucoup. J ECT 2011; 27:339. [Bailine S, Petrides G, Kellner C, Fink M, Bolwig T, Freeman C, Greenberg R, Kramer B, Fox H, Francis A, O'Connor K, Ray L, Satin A, Guerra F, Hermann C, Kayne E, Sevi S, Braga R.] (Letter) 808a. Obituary: Alfred M. Freedman. Psychiatric Times, June 2011, pg 24. 808b. Obituary: Alfred M. Freedman. Neuropsychopharmacology 2011, 36:2784. 809. Book Review: Nash Boutros, Silvana Galderisi, Oliver Pogarell, Silvana Riggio: Standard Electroencephalography in Clinical Psychiatry: A practical handbook. Chichester UK: Wiley-Blackwell, 2011. Acta psychiatr scand 2011; 124: 239-40. 810. Book Review. Will I Ever Be the Same Again? Transforming the Face of ECT (Shock Therapy). J ECT 2011; 27:262-3 [Kellner CH, Fink M.] 811. Book Review. Hobson, J.Allan. Dream Life: An Experimental Memoir. Science Books & Films 2011; 47(4):186. 2012 812. Hidden in plain sight: Catatonia in pediatrics. Acta psychiatr scand. 2012: 125:11-12. [Commentary] 813. Oral History of Neuropsychopharmacology: The First Fifty Years: Neurophyiology. Thomas Ban and Max Fink, Editors. Brentwood TN: ACNP. Volume 2: 319 pp. 814. Book Review: Bor, Daniel The Ravenous Brain: How the New Science of Consciousness Explains our Insatiable Search for Meaning. Science Books & Films 2012; 48(9): 243-4. 815. The responsible role for ECT in suicide prevention and treatment. In: A. Shrivastava, M. Kimball, D. Lester (Editors): Suicide from a Global Perspective: Risk Assessment and Management. Chap 14: pg 119126. 2013 816. Rediscovering Catatonia: The Biography of a Treatable Syndrome. Acta psychiatr Scand. 2013; 127: Supplement 441;1-50. [Fink M.] 817. Clinical practice to change with divorce of catatonia and schizophrenia. J Clin Pychopharmacology 2013; 33(3): 287-88. [Fink M.] 60 �818. Electroconvulsive therapy (ECT) for children, adolescents and adults with developmental disability and severe mental illness: A call for action. Am J Psychiatry 2013 [Wachtel L. Dhossche D. Fink M, Jaffe R, Kellner CH, Weeks H, Shorter E.] (Editorial). 819. Are depression's causes biological? The New York Times, September 16, 2013; pg A22. Letter. [with Edward Shorter]. 820. Introduction. Electroconvulsive Therapy: A Guide for Professionals and their Patients. Korean Edition; translated by Sangsoo Lee. Seoul S. Korea: Hana Medical Publishing Co., 233 pp. [Fink M.] 821. The Diagnostic and Statistical Manual of Mental Disorders, Fifth edition, divorces catatonia from schizophrenia. J Clin Psychopharmacology. 2013; 33(3):1-2. 2014 822. The mechanism of action of ECT. In: N. Ghaziuddin and G. Walter (Eds.): Electroconvulsive Therapy in Children and Adolescents 2014. New York: Oxford University Press. Chap 2, pp 18-28. [Fink M.] 823. The role of ECT in suicide prevention. J ECT:30: 5-9. [Fink M, Kellner CH, McCall V.] 824. What was learned: Studies by the Consortium for Research in ECT (CORE) 1997-2011. Acta Psychiatrica Scand. 129: 417-426. [Fink M.] 825. Thirty years of publication and continuing. [Editorial] J ECT 30: 1-2 [McCall WV, Kellner CH, Fink M.] 826. Celebrating 80 years of inducing brain seizures as psychiatric treatment. JECT 2014; 30:90. [Fink M.] 827. Revive flurothyl inhalation treatment in psychiatry? Psychiatric Times March 19, 2014 [Fink M, Shorter E] 828. The seizure, not electricity, is essential in convulsive therapy: The flurothyl experience. J ECT 2014; 30:91-93. [Fink M.] 829. The chemical induction of seizures in psychiatric therapy: Were flurothyl (Indoklon) and pentylenetetrazol (Metrazol) abandoned prematurely? J Clinical Psychopharmacology. 2014; 34(5):602-7. [Cooper K, Fink M.] 830. Convulsive and non-convulsive treatments in psychiatry. In: S. Bloch, S. Green, J Holmes (Eds.): Psychiatry: Past, Present and Prospect. New York: Oxford University Press, 2014. 831. Obituary. Turan M. Itil. Neuropsychopharmacology 2014; 39:3133-3134 2015 832. Electroconvulsive therapy versus pharmacotherapy for bipolar depression. Am J Psychiatry 2015; 172(3) 295-6. [Kellner CH, Fink M.] 833. Reply. [Comment on Wachtel L: Recognition of neuroleptic malignant syndrome and delirious mania as malignant catatoniain an autistic man with prompt relief with ECT.] Acta Psychiatr Scand. 132:320 61 �834. Seeing the King’s frenzy as catatonia. Acta psychiatr scand 132(6): 500-501. 835. Book Review. Le Bihan, Denis. Looking Inside the Brain: The Power of Neuroimaging. Princeton U Press. AAAS Science Books & Films. 2016 836. Catatonia is a systemic medical disorder. Acta psychiatr scand. 2016; 133(1): 250-1. [Fink M, Fricchione G, Rummans T, Shorter E.] 837. Bearing Witness: Personal and poetic descriptions of seizure therapy. J ECT 2016; 32(1): 13-16. [Fink M.] 838. Optimizing ECT technique in treating catatonia. J ECT 2016; 32(3):149-150. [Fink M, Kellner CH, McCall V.] 839. Barbara Fish: In Memoriam. Neuropsychopharmacology 2016; 41(13): 3118. 840. Hyperthermia for Major Depressive Disorder? JAMA Psychiatry. 2016 Oct 1; 73(10): 1096. 2016.1627. [Fink M, Shorter E.] 2017 841. Katatonie: Často Sevyskytující Klinický Syndrom Rozpoznatelný a Léčitelný. Catatonia: A Common Systemic Clinical Syndrome, Recognizable and Treatable. Čes a slov Psychiat 2017; 113(2): 84–93. 842. Does persisting fear sustain catatonia? Acta Psychiatr Scand 2017; Nov; 136(5):441-444. [Fink M, Shorter E.] 843. To define melancholia, follow the path of catatonia. Bipolar Dis 2017;19(5);401- 2. 844. Electroconvulsive therapy for self-injurious behavior in autism spectrum disorders: Recognizing catatonia is key. Current Opinion. 2017 Dec 18 [Epub ahead of print]. [Wachtel LW, Shorter E, Fink M] 845. Book Review. Electroshock as Means for Social Control. Sadowsky, J. Electroconvulsive Therapy in America: The Anatomy of a Medical Controversy. JECT 2017; 33:144-5. 846. ECT for catatonia and melancholia: No need for ambivalence. Psychiatric Times 2017; Sep: 16-17F. (Kellner CH, Fink M). 2018 847. ECT for Self Injurious Behavior in Autism: A New Indication. Psychiatric Times. 56 (2): 6-9. [Wachtel LE, Kellner CH, Fink M.] 848. Book Review: Electroconvulsive Therapy: Revival in German speaking Countries. JECT 34:70-71. 849. The Madness of Fear: A History of Catatonia. NY: Oxford University Press. [E. Shorter, M. Fink] 850. Electroconvulsive therapy for self-injurious behavior in autism spectrum disorders: Recognizing catatonia is key. Current Opinion. 2018; 31(2):116-122 [Wachtel LW, Shorter E, Fink M] 62 �851. Induced seizure therapy (ECT): Effective and safe, but stigmatized. Scientific American Psychiatry. DOI 10.2310/7800.13068 08/17 852. A useful example of pharmaco-electroencephalogram science. J Clin Psychopharmacology 38(6): 552554. (Invited Commentary). 2019 853. Electroshock Therapy and Catatonia: A Productive Synergism. JECT 2019; 35(4):219-221. 854. Catatonia: A Recognizable and Treatable Systemic Syndrome. In: Oxford Textbook of Neuropsychiatry, Chap 36; 437-445. NY: Oxford University Press, 2019 855. Book review: Semple, David. Pragmatic Guidance for EEG Interpretation. 2nd edition. Amazon Digital Services LLC, JECT 35(4):e60-61.2020 2020 856. Expanding the catatonia tent: Recognizing electroconvulsive therapy responsive syndromes. JECT: 2020 Oct 27. doi: 10.1097/YCT.0000000000000729 857. A protocol for a prospective descriptive prevalence study of catatonia in an acute mental health unit in urban South Africa. BMJ Open. Zingela, Z, Cronje J, Fink M, Van Wyk, S. BMJ Open 2020;10:e040176. doi: 10.1136/bmjopen-2020-040176 2021 858. Random Controlled Trial of Sham ECT Therapy: A Historical Note. JECT 2021 Mar 4. doi: 10.1097/YCT.0000000000000759. Online ahead of print. PMID: 33661180 . 63 �64 �Internet, Web-Based Articles 1998 W.01 Is catatonia a subtype of schizophrenia? http://www.mhsource.com/whatsnew/mfin-cataton.html W.02 EEG monitoring in ECT: A guide to treatment efficacy. http://www.mhsource.com/pt/p980570.html with Richard Abrams 1999 W.03 Pediatric ECT: An update. http://www.mhsource.com/pt/p990963.html with Carmel Foley W.04 Electroshock. An effective treatment for mental illness. http://www.electroshock.org W.05a The use of ECT in bipolar disorder (Consumer) http://www.mhsource.com/bipolar/ect2.html W.05b The use of ECT in bipolar disorder (Professional) http://www.mhsource.com/bipolar/ect1.html 2000 W.06 Pediatric ECT . A Review, June 2000. http://www.electroshock.org/archives/adolescent_ECT_review.htm W.07 NMS is best treated as catatonia. http://www.electroshock.org/archives/NMS-catatonia_review.htm W.08 ECT 2000. http://www.longislandpsych.org/arch/ECT/ECTframe.html W.09 ECT 2000. http://www. mdvista.com/library/journal/psychiatry/electroconvulsive_therapy_2000.htm 2001 W.10 ECT is effective in bipolar disorder. http://www.BMJ.com/cgi/content/full/321/7272/1302 W.11 Treating bipolar affective disorder. http://www.bmj.com/cgi/content/full/322/7282/365/a> W.12 Neuroleptic malignant syndrome and malignant catatonia: Effective treatment, http://www. mdvista.com/ 2002 W.13 Insulin coma therapy. 65 �http://www.pbs.org/wgbh/amex/nash/filmmore/ps_ict.html 2005 W.14 The social sources of psychopharmacology. http://media.snow.utoronto.ca:8080/ramgen/extra4/BE2005/BE2005-April29-5.rm 2009 W.15 ECT in treating status epilepticus. http://dx.doi.org/10.1016/j.yebeh.2009.06.022 2011 W.16 The race to Patent bio-Tests for Schizophrenia and Depression. http://www.psychiatrictimes.com/schizophrenia/content/article/10168/1994367 Updated April 15, 2019 66 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Biographical Files Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Curriculum Vitae of Max Fink Subject The topic of the resource <a title="Autobiography" href="http://id.loc.gov/authorities/subjects/sh85010050" target="_blank" rel="noreferrer noopener">Autobiography</a>, <a title="Psychiatry" href="http://id.loc.gov/authorities/subjects/sh85108381" target="_blank" rel="noreferrer noopener">Psychiatry</a>, <a title="Neurosciences" href="http://id.loc.gov/authorities/subjects/sh91006099" target="_blank" rel="noreferrer noopener">Neurosciences</a>, <a title="Neurology" href="http://id.loc.gov/authorities/subjects/sh85091139" target="_blank" rel="noreferrer noopener">Neurology</a> Description An account of the resource The Curriculum Vitae or CV of Max Fink, updated in 2021. Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank" rel="noreferrer noopener">Fink, Max, 1923-</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Date A point or period of time associated with an event in the lifecycle of the resource 2021-03-25 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank" rel="noreferrer noopener">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Relation A related resource The Max Fink Collection Format The file format, physical medium, or dimensions of the resource application/pdf Language A language of the resource en-US Type The nature or genre of the resource text Identifier An unambiguous reference to the resource within a given context mfp-cv-20210325 Biographical http://exhibits.library.stonybrook.edu/mfp/files/original/35b321c800690bb601799adad174ab44.pdf 460a6759754060bc775314593ce1e71c PDF Text Text I ‘ Table I 30 Discharge Ratings of Improvement: Ratings of imw provement at the three hOSpitals varied in format and detail» The discharge rating at Menninger Hospital was tripartite with a sep~ arate evaluation for social, characterological and syndrome changes. Hillside Hospital and Massachusetts Mental Health Center had global ratings making it difficult to assess the contribution of each factor of the Menninger system (Table II)o For this study the Menninger syndrome rating was compared to the global ratings of the other institutions, Table B. II Inter—hospital Comparison 1» The Sociopsychological Variables distribution of the variables of social class, age, education and California F Scale score is presented in Table III. Table III among the three institutions . a) Social Class: The anticipated difference in social class composition of the three institutions was observed, At Menninger Hospital the population was predominantly upper class; At Hillside Hospital, middle class; and at Massachusetts Mental Health Center, predominantly lower class. b) Age: There were no differences in age distribution in the institutional populationso �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Subdural hematoma developing during hospitalization, Am J Psychiatry. 1950;107(5):381-3. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-001-1a-002 Date A point or period of time associated with an event in the lifecycle of the resource 1950 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/9cd1485c72c87cfe41a9b822584a53cf.pdf 399d53acd860a7f8f327c824ea2685e0 PDF Text Text Reprinted from the A. M. A. Archives of Neurology and Psychiatry October 1952, Vol. 68, pp. 481-490 Copyright, 1952, by American Medical Association EXOSOMESTHESIA OR DISPLACEMENT OF CUTANEOUS SENSATION INTO EXTRAPERSONAL SPACE MORTIMER F. SHAPIRO, M.D. MAX FINK, MD. AND MORRIS B. BENDER, M.D. NEW YORK phenomena that may be apparent during examination of patients with AMONG disease of the sensory pathways is mislocalization of a sensory stimulus. 'It has long been known that a person with a sensory defect, as seen in the common varieties of cerebral hemiplegia, may inaccurately localize stimuli applied on the paretic side. Such point mislocalizations are apparent in examinations using a single stimulus and have been described in detail by Head.1 These mislocalizations can be accentu— ated by the use of double simultaneous stimulation techniques.2 In addition, when these techniques of examination are employed, other varieties of mislocalization, such as displacement,3 become apparent. Displacement is the patterned mislocalization of one of two stimuli simultaneously applied to difi’erent body areas. The direction of displacement is in a definite pattern, which is dependent upon the parts of the body stimulated. Characteristic of mislocalization so far reported has been the fact that their extent was within the limits of the patient’s body. In the course of studies. of cutaneous perception, we observed a new form of displacement in which the patient consistently and in a predictable fashion mislocalized stimuli into extrapersonal space. This type of displacement we have termed “exosomesthesia.” 4 Exosomesthesia is not a commonly observed phenomenon. More than 400 patients with brain disease were examined at Psychiatric Pavilion of Bellevue Aided by a Fellowship from the National Foundation for Infantile Paralysis (Dr. Fink). This investigation was supported in part by research grant #MH-139 from the United States Public Health Service, National Institutes of Health. From the Department of Neurology and Psychiatry, New York University College of Medicine, and the Neurological Service of the Mount Sinai Hospital and Bellevue Hospital Center. 1. Head, H.: Studies in Neurology, London, Oxford University Press, 1920, Vol. 2. 2. Bender, M. B.; Shapiro, M. F., and Schappell, A. W.: Extinction Phenomenon in Hemiplegia, Arch. Neurol. & Psychiat. 62:717-724 (Dec.) 1949. Bender, M. B.: The Advantages of the Method of Simultaneous Stimulation in the Neurological Examination, M. Clin. North America 32:755—758 (May) 1948. 3. Bender, M. B.: The Phenomenon of Sensory Displacement, A. M. A. Arch. Neurol. & Psychiat. 65:607—621 (May) 1951. 4. The term was derived by Dr. Judah A. Jofie (Hinsie, L. E., and Shatzky, J.: Psychiatric Dictionary, New York, Oxford University Press, 1940) from the Greek 3w, out of ; mind, body, and al’dfiww, perception by the senses. �2 Hospital Center by routine and specialized sensory tests. Exosomesthesia was observed in only 15 cases, an incidence of about 3%.5 The following case reports illustrate the phenomenon and demonstrate some of the conditions under which it was observed. CASE REPORTS CASE 1.—H. M., a man aged 64, was admitted to the Psychiatric Pavilion of Bellevue Hospital with a history of progressive mental changes of six years’ duration. The first four years of illness were marked by slowly progressive impairment of memory, concentration, and other intellectual functions and by increasing apathy to his environment. In the last two years there was rapid exacerbation of this condition, resulting in the loss of his job as a store manager. During this period his speech became increasingly garbled and stammering. He vacillated between irritability and complete apathy. He was occasionally incontinent, ceased bathing, had difficulty in dressing, and was sometimes so forgetful and confused as to wander into the street without his trousers. Routine Neurologic Examination—In walking, the trunk was tilted to the right, and there was a tendency to drag the right lower extremity. However, there was no significant motor weakness, reflex change, or tonus abnormality. Coordination tests were well performed. The cranial nerve functions were intact. Vibration sense was correctly perceived only in the clavicles and the head, while position sense was lost in the fingers, wrists, toes, and ankles bilaterally. Temperature differences were poorly perceived except in the face area. His responses to touch and pinprick stimulation will be described later. A mild degree of “mixed aphasia” was present. This speech difficulty was evident only by special testing or when the patient was fatigued by prolonged examination. There was a fluctuating dyspraxia of moderate severity. Occasionally he had difficulty in dressing, being unable to handle buttons and sleeves. However, he could perform such functions as feeding himself, combing his hair, and other routine daily tasks. He was usually unable to mimic the more complicated patterns of the hand—praxis tests. An electroencephalogram showed bilateral diffuse abnormality, with decrease in amplitude and intermittent suppression of activity over the parietal regions. A pneumoencephalogram dis— closed bilaterally dilated ventricles and moderate “cortical atrophy,” particularly in the left temporal lobe. PsychiatricStatus—Although the patient was oriented for place and situation, he made errors as to date and time of day. There were defects in recent memory, concentration, calculation, and ability to assume the abstract attitude. He usually sat placidly staring into space or wandered aimlessly about the ward. He did not mix with other patients. When approached by members of the staff, he was friendly and passively cooperative. Testing procedures were approached with cheerful indifference. When, however, he was pushed into test situations greater than his capacity, he reacted with increasing irritability and tension, eventually culminating in a “catastrophic reaction.” At such times he would become red in the face, shout that he knew the answers but did not want to continue, and suddenly begin to weep. Body Schema—He was able to distinguish the right side of his body from the left, but was unable to make this distinction on the examiner’s body. He had no difficulty either in locating midline structures of his body, such as the nose, mouth, chin, umbilicus, and penis, or in pointing to his eyes. With eyes open he readily found both ears; but when his eyes were closed he groped about his face for several seconds before locating them. He could point to his thighs, knees, ankles, and toes but could not point to any specific toe other than the big toe. He frequently had difficulty in locating portions of his upper extremities. If asked to point to his shoulders, he correctly located one shoulder but then groped behind his neck looking for the other. This defect was even more noticeable in trying to find the “other” elbow and wrist, and greatest in trying to find the “other” hand. His search for the “other” hand or wrist was bizarre. He would look under the pillow or rummage under the mattress, becoming tense and ' Fink, M.; Green, M., and Bender, M. B.: The Face-Hand Test as a Diagnostic Sign of Organic Mental Syndrome, Neurology 2:46—58 (Jan-Feb.) 1952. 5. �3 insisting it was lost. It should be emphasized that, despite the great difficulty in locating parts of his body, the patient was able to name the body parts, except the fingers and toes. This was true whether the part pointed to was on the patient’s or on the examiner’s body. Sensory Stanton—(w) Single Stimulation: He had difficulty in differentiating between the sharp and the dull end of a pin. This defect was present throughout the body, although he made significantly fewer errors in the face and hands. Touch stimulation was poorly perceived. Usually he could not state whether or not he had been touched. Again, there seemed to be relatively better preservation of this modality in the hands and face. Except under special conditions of examination of the hands, to be described later, the patient was able to locate the site of a pinprick by pointing. However, if the pin was repetitively and rapidly applied to one region, or if the prick was steadily maintained at that one place, he could not locate the point of stimulation. He would make frantic, random searching movements over his body, and not infrequently around the bedclothes, grimacing as though in pain and exclaiming that he was trying to- remove the pin. If asked where he was being pricked, he disregarded the question and continued to try to remove the stimulus. This phenomenon occurred on stimulation of any portion of the body but was most apparent when the hand was tested. (17) Double Simultaneous Stimulation: The phenomena of extinction and displacement were frequently observed in tests of different body areas by simultaneous tactile stimulation. On stimulation of the face and hand, stimuli to the hand were not perceived or were mislocalized to the cheek. In tests of homologous body areas (as hand-hand) extinction of one percept was common. The side on which the stimulus was not perceived fluctuated, so that at one moment only a right—sided stimulus was perceived and a few moments later only a left-sided stimulus was perceived. Exosomesthesia.——Whenever his palm was in contact with a portion of his body or any other object, and the dorsum of that hand was pricked with a pin, the patient consistently mislocalized the stimulus. This mislocalization was to whatever object the palmar surface of the hand was touching. For example, if the patient’s hand was resting on his thigh and the dorsum of the hand was pricked, he insisted that the thigh had been touched, and not the hand. This mislocalization —exosomesthesia—occurred to the thigh, abdomen, leg, or face and was present with stimuli to either hand. It was observed even when the patient was urged to look at the hand during the application of the pin. Exosomesthesia could not be elicited, however, by stimulation of the palm or palmar surface of the fingers when the dorsum of the hand was resting on a portion of the body. Furthermore, localization of stimuli to the dorsum of the hand was correct if the hand was held in space. Mislocalization also occurred to objects external to his body. If his palm was resting on a table or on his bed, and the dorsum of the hand was pricked with a pin, he would point to these objects and state that the pin had been applied “there.” When questioned, he stated that the hand had been touched but continued to point to the bed or table. Frequently, however, he insisted that it was the bed or table that had been touched, and not his hand. If asked how he could feel the bed being pricked with a pin, he would become tense, avoid the question, and insist, “You touched the bed, not me.” Displacement into extrapersonal space was not eliminated by simultaneous stimulation, even when extinction of one of the percepts occurred. For example, if pins were simultaneously applied to the dorsa of the hands while the palms were resting on a table, he would report feeling only one pinprick, that on the left (or right, as dominance fluctuated) and point to the place where the left hand had been resting, saying. “You touched the bed there.” This phenomenon of displacement into extrapersonal space occurred daily during a period of more than two months. Comment—In this patient a requisite to displacement into space was that the palm of the hand be in contact with an external object. In other words, there were two cutaneous stimuli simultaneously in operation, namely, the pinprick on the dorsum of the hand and the pressure of the object in contact with the palm or fingers. A single stimulus, such as pricking the dorsum of a hand held in space, did not elicit the displacement. �4 Exosomesthesia was elicited only on stimulating the hands. This occurred even though single pinprick was perceived more sharply in the hands than in any other area except the face. Although this patient showed inability to locate correctly parts of his own and the examiner’s body, it does not necessarily mean that exosomesthesia is determined by this particular type of disorder in body scheme. The following case illustrates the phenomenon of exosomesthesia in the presence of the patient’s ability to locate body parts. CASE 2.-—E. K., a woman aged 52, was admitted to the neurologic service of the Mount Sinai Hospital in August, 1950, with a history of grand mal seizures. She had been in good health until 1947, when there appeared sporadic, momentary sensations of “blacking out.” About two years before admission she began to suffer monthly grand mal seizures. There was no aura. Routine examination on admission showed that her status was within normal limits except for anosmia in the right nostril. There was no organic mental syndrome. X—ray studies revealed evidence of a subfrontal neoplasm. On August 12 a craniotomy was done, and after amputation of a portion of the right frontal lobe, a large bilateral subfrontal meningioma was excised. Her postoperative course was stormy. For two weeks she was semistuporous. She responded only to massive, painful stimulation, and these responses were limited to vague, ineffective attempts to push away the stimulus. In this period she lapsed several times into coma and showed Cheyne—Stokes respiration. The Babinski response was obtained bilaterally. Her pupils did not react to light. From about Aug. 23, 1950, the patient improved slowly and steadily. She began to respond verbally, and contact could be maintained for short periods. Vision, which had apparently been absent, began to return, although right homonymous hemianopsia remained for some time. A marked organic mental syndrome characterized by confusion, disorientation, and anosognosia, was present. Routine Neurologic Examination—Neurologic examination in September, 1950, disclosed right homonymous hemianopsia, severe impairment of visual acuity with bilateral secondary optic nerve atrophy, nystagmus in all directions of gaze, a bilateral Babinski sign, and a mild degree of aphasia. Position sense, vibration sense, and temperature perception were unimpaired. There were difliculties in perception of touch and pinprick stimuli, as described below. Psychiatric Statue—The patient was usually friendly and cooperative. However, she was frequently irritable and would not permit examination. She was disoriented as to time and occasionally to situation, but not to place. There were defects in retention and recall, covered by confabulation. She was euphoric and displayed little self-restraint or concern in social situations. Usually she would lie with her body fully exposed. Not infrequently she ,soiled herself or wet the bed. Anosognosia was prominent. Body Schema—On command, the patient was able to identify and locate correctly parts of her own and the examiner’s body, such as the ears, eyes, feet, and parts of the upper extremities. She exhibited some confusion about the right and the left side of the body. Sensory Status.—(a) Single Stimulation: The patient perceived single pinprick stimuli well, although she made occasional nonpatterned errors in localization. These errors were more frequent on the left side. (b) Double Simultaneous Stimulation: On simultaneous application of pinprick to the two sides of the body, except the hands, extinction on the left or displacement on the left toward the level of the right-sided stimulus was the usual response. Homolateral simultaneous stimulation on the right side of the-body showed no extinction, but stimulation on the left side elicited frequent extinction and displacement. Exosomesthesia.——Displacement into extrapersonal space occurred when the left hand was pricked at the same time that either the right hand or the right cheek was stimulated. The phenomenon could also be elicited when the left hand and any other area of the left side of the body were simultaneously stimulated. Under these conditions the patient mislocalized the stimulus to the left hand into space near that hand, or to the object on which the hand was lying. For example, if pinpricks were �5 simultaneously applied to the right cheek and the left hand, the patient indicated she had been pricked on the right cheek and the arm of the chair on which her left hand had been resting. As a rule she answered by pointing. If asked to verbalize, she would say, “The right cheek and about here,” (pointing to the chair arm or into space near her left hand). If asked directly. “Was your hand touched?” she would avoid the question, responding only, “Here,” pointing at the same time to the left chair arm or into space. It is to be noted that, except under the special condition of simultaneous stimulation, the patient was always able to point to or to name her left hand on demand. If pricked simultaneously on the dorsa of the left and right hands, she correctly localized only the stimulus on the right, both by pointing and by stating, “My right hand.” The stimulus on the left, however, was localized only by pointing to the chair arm and saying, “Here.” If asked whether the chair arm and not her left hand, had been touched, she answered, “No, here,” pointing to the chair arm. When pinpricks were applied to the left hand and, at the same time, to another area on the left side of the body, a similar displacement into space was evident. Usually the stimulus to the left hand was mislocalized onto whatever structure the hand was resting or else into contiguous space. The other stimulus on the left side was usually correctly localized, though this stimulus, too, was occasionally displaced into space. When this double displacement occurred, the patient would state that she felt two stimuli and would point into space to the left of the arm, stating, “Here and here.” These mislocalizations were repeatedly observed during a period of a month and were not always limited to the left side. They were occasionally observed to occur on the right side. At these times localization on the left was always correct, as indicated by pointing and by verbalization. C 0mment.——Exosomesthesia was elicited in this patient only under the condition of multiple simultaneous stimulation. It could not be elicited by single—stimulation methods. Also significant is the fact that exosomesthesia was apparent even though there was no gross disorder in body scheme on routine testing. Furthermore, it is evident that her errors in localization were not simply inability to point to or identify parts of her body by name, as ordinarily she experienced no difficulty in doing this on command. Both patients mislocalized percepts to parts of the body, to objects, or into space contiguous with the area stimulated. Occasionally, we have also observed displacement of a stimulus to the person of the examiner. Usually such percepts are mislocalized to a homologous portion of the examiner’s body; e. g., a stimulus applied to the patient’s hand is reported by him as though it had been applied to the examiner’s hand. Rarely, the mislocalization is to any part of the examiner’s body. This type of displacement is illustrated in the following case. CASE 3.—R. M., a man aged 52, was admitted to the Psychiatric Pavilion of Bellevue Hospital with the complaint that he had become confused and depressed. For about a year he had been disoriented and confused as to date and his relationship to people and had wandered about the city aimlessly. He had been admitted to the Farm Colony about a half-year before and had worked as a barber until the week before his admission to the hospital. Routine N euro'logic Examination—Neurologic examination showed normal gait and station. Coordination tests were well performed. The reflexes were active bilaterally, with normal plantar and abdominal responses. Cranial nerve functions were normal. The sensory status showed changes, but only with special methods of testing. A pneumoencephalogram demonstrated moderately dilated ventricles, without shift or deformity, and some dilated cerebral sulci. Psychiatric StaWs.——-A severe organic mental syndrome was evident. In the ward he sat quietly for hours by his bedside, taking little interest in his surroundings. When approached by members of the staff, he appeared perplexed but was affable. During the testing procedures he was cooperative unless confronted by a test situation in which the examiner demanded tasks �6 , beyond his ability. At such times he showed a “catastrophic” reaction, became excited, and discontinued his efforts in the examination. He was disoriented for time, place, and situation. However, he was able to find his‘way about the ward, locating his bed, the nurses’ desk, the doctor’s office, and the lavatory. Severe difficulties in intellectual function were observed. He was unable to give an adequate history. He could not recall the examiner’s name or the events of several hours before but did not confabulate. Calculation and symbol-identification tests were poorly performed. Severe aphasic difficulties were evident. He was unable to name common objects, clothing, or most parts of the body. He could not comprehend written commands, nor could he write, but he was able 'to follow simple verbal commands. Mild dyspraxia was demonstrated in his attempts to imitate finger and mouth movements. However, he was able to dress, feed, and otherwise care for himself. Body Image.——He had difficulty both in naming body parts and in locating them by pointing. The defects were severest in the fingers, wrists, and elbows, and occasionally the feet. There was difficulty in right-left orientation. Sensory Statute—(a) Single Stimulation: Routine sensory studies of touch, pinprick, and vibration stimuli showed no consistent impairment. These stimuli were usually correctly localized and described. Occasionally a single stimulus to the hand or forearm was displaced to a contiguous object or to space about the upper extremity. (b) Double Simultaneous Stimulation: On double simultaneous [touch] stimulation the patient displayed extinction and displacement of tactile stimuli. This was most evident in trials of the face-hand test 6 but was seen in tests of other body parts as well. For example, on simultaneous stimulation of the cheek and the opposite hand, he would either report only the stimulus to the cheek (extinction of the hand stimulus) or report a stimulus to each cheek (displacement of the hand stimulus). The pattern of sensory dominance was that usually seen in diffuse cerebral disease, the face being most dominant, the hand least.5 There was no lateral dominance. ,Exosoimestheyiat—Displacement into extrapersonal space was occasionally observed on single stimulation. This displacement was from the hand, forearm, or elbow to space contiguous to the part touched. Exosomesthesia was, however, markedly exaggerated when double simultaneous stimulation was employed. Again, the areas from which the phenomenon was most frequently'observed were the hands, forearms, and elbows. For example, when stimuli were applied to the dorsa of the hands as they were lying on the patient’s lap, he pointed to space in front of his knees. If asked to state where he had been touched, he would say, “The hands,” but would continue to point to the space in front of his knees. Exosomesthesia was rarely noted when other body parts, such as the cheeks or shoulders, were simultaneously stimulated. Occasionally it was found that on tests with double simultaneous stimulation the patient mislocalized a stimulus from his body to the homologous region of the examiner’s body. For instance, when the hands were simultaneously touched, he would grasp the examiner’s hands and affirm he had been touched “there.” Despite the examiner’s insistence that the stimulus had been to the patient’s hands, the patient would persist in pointing to the examiner’s hands. When asked to name the parts touched, he would say “There, there.” The same phenomenon was occasionally observed on simultaneous stimulation of the two elbows or cheeks. It was significant that this mislocalization to the examiner’s body occurred even when the patient was urged to look at the stimulations. It was observed that emotional tension, increase in the rate of testing or undue prolongation of the examination increased the incidence of exosomesthesia. For example, to initial application of pinprick to the right hand and the left cheek, the patient reported only the face percept, omitting the hand stimulus. Later, he localized the two stimuli to the cheeks. As the examination progressed and the physician speeded up the testing, the patient became tenser. He then localized the face percept correctly but insisted that the hand stimulation was into space in front of the hand. Finally, both stimuli were displaced into space or to the examiner’s body. These phenomena were observed daily over a period of 2% months. Bender, M. B.; Fink, M., and Green, M.: Patterns in Perception on Simultaneous Tests of Face and Hand, Tr. Am. Neurol. A. 75:250-252 (June) 1950; Patterns in Perception On Simultaneous Tests of Face and Hand, A. M. A. Arch. Neurol. & Psychiat. 66:35-5-262 6. (Sept) 1951. ' - - �7 Comment—While single stimulation occasionally produced exosomesthesia in this patient, the phenomenon was more pronounced under conditions of double simultaneous stimulation. This patient also mislocalized stimuli to the examiner’s body. Emotional tension, prolonged examination, or increase in the rate of testing. exaggerated the phenomenon of exosomesthesia. GENERAL COM MENT On consideration of these cases, it is immediately apparent that exosomesthesia is associated with a severe organic mental syndrome. Therefore, it might be argued that exosomesthesia is merely a manifestation of the patient’s mental confusion; that the patient simply points into space because he is confused. However, we have examined many severely confused patients and found exosomesthesia only rarely. Moreover, exosomesthesia is a patterned phenomenon, demonstrable in each patient under defined conditions, predictable as to the area from which it will occur and the extrapersonal spatial region to which the sensation will be projected. For example, in Case 1 exosomesthesia could be elicited only from the hand, and only when the dorsum was stimulated at the same time that the palm or fingers were in contact with another object. Displacement under these circumstances was usually not haphazard. As a rule it occurred to the object touching the palm or fingers. In Case 2 exosomesthesia could be elicited only by double simultaneous stimulation. It was seen most clearly in the hand and could be elicited only unilaterally at any oneexamination. Again, the displacement was not haphazard; the stimulus as a rule was localized to extrapersonal space contiguous to the area actually stimulated. In Case 3 the phenomenon was observed again under conditions of double simultaneous stimulation, and the displacements were either to space contiguous to the stimulated area or to homologous areas of the examiner’s body. It is significant that these displacements could be elicited even when the patient was urged to look at the application of the stimuli. Moreover, even when the examiner pointed out the error in localization and emphasized the implausibility of the response, the patient characteristically insisted on the correctness of the mislocalization. Factors Influencing Exosomesthesia.—Many factors influence the appearance of exosomesthesia. Except in children under special conditions, it has been observed exclusively in patients with severe mental changes resulting from disease of the brain. It is influenced by the type of stimulus used and the rate of stimulation, as well as by the element of simultaneity of stimuli. Moreover, the emotional state of the patient has a significant effect on the phenomenon, as does the part of the body stimulated. In some cases exosomesthesia has been made apparent by administration of small doses of amobarbital sodium. These factors will be discussed. (a) Bilateral Cerebral Disease: The symptom background in everycase of exosomesthesia is an organic mental syndrome secondary to bilateral cerebral disease. We have not been able to demonstrate exosomesthesia in an adult unless there were severe mental changes. But, as previously noted, it is a rare phenomenon, and only a few patients with severe organic mental syndrome show it. In 400 patients with organic cerebral disease, of varying severity, exosomesthesia was observed in approximately 3%.5 Even in these patients it was not manifest in every examination, and its frequency was readily altered by changes in the conditions of testing. It is therefore evident that severe bilateral cerebral disease in itself is not sufficient to produce exosomesthesia. �8 Effect of Simultaneous Stimuli: That simultaneous stimulation may elicit sensory phenomena not apparent on single stimulation has previously been demonstrated.2 For example, a hemisensory syndrome in a hemiplegic patient may not be discernible except under conditions of double simultaneous stimulation. Thus, single stimulation may be well perceived and localized by the patient, but the addition of a second stimulus simultaneously applied may so affect integration that the phenomena of extinction, obscuration, and displacement become apparent. Similarly, simultaneous stimulation elicited exosomesthesia when it was absent on single-stimulus examination, or exaggerated it when it was occasionally manifest on routine stimulation. In Cases 1 and 2 simultaneous stimulation was a necessary condition for eliciting the phenomenon. It could not be demonstrated by single stimulation. In Case 3 exosomesthesia could occasionally be elicited on single stimulation, but with simultaneous stimulation the phenomenon was demonstrated with much greater frequency. (6) Type of Stimulus Most Effective: Of the various stimuli used in these examinations, such as single touch, single pinprick, repetitive touch, and repetitive pinprick, it was noted that repetitive touch stimuli were most effective in eliciting nexosomesthesia. This was especially true on double simultaneous stimulation. (d) Effect of the Patient’s Emotional State: Exosomesthesia was exaggerated by alterations in the test situation which made performances more difficult. Increasing the rate of stimulation or unduly prolonging the examination increased the displacements to extrapersonal space. If the examiner was deliberately critical of the patient’s errors, the phenomenon also appeared with greater frequency. These factors increased the emotional tension of the patient and if carried further produced a “catastrophic” reaction. (e) Effect of Drugs: It has previously been demonstrated that difficulties in perception may be exaggerated by barbiturate intoxicants.5 Amobarbital sodium was administered intravenously in doses of 3 to 7 grains (0.2 to 0.45 gm.) to patients with diffuse cerebral disease. Prior to administration of the drug, these patients manifested the phenomena of extinction and displacement of percepts on simultaneous tests, but not exosomesthesia. While under the influence of the barbiturate;'three patients showed exosomesthesia, in addition to extinction and displacement. In two other patients, in whom exosomesthesia had been elicited only after a protracted testing period, the administration of amobarbital sodium elicited exosomesthesia at the onset of testing and exaggerated the phenomena of extinction and displacement. Relation of Exosomest‘hesia to Extinction, Obscumtvian, and Displacement—In our experience, whenever exosomesthesia has been observed, the phenomena of extinction, obscuration, and displacement are also present. Exosomesthesia, however, is a rare phenomenon, whereas extinction, obscuration, and displacement are commonly observed. Moreover, whereas extinction, obscuration, and displacement are frequently seen in adult patients with mild cerebral dysfunction,5 displacement into extrapersonal space is present only in cases of severe mental changes due to disease of the brain. It may therefore be concluded that exosomesthesia in adults represents a severer type of cerebral dysfunction than other simultaneous stimulation phenomena. (13) �9 Relation of Exosomesthle'sia to- Body I wage—It might be said that exosomesthesia is a pathologic extension of the body image. The normal person is continually of cites the Head of examples For this boundaries example, the image. extending the woman with a feather in her hat who “feels” when the feather is touched, and the surgeon who handles his probe as though it were an extension of his fingers.1 In the normal person, however, these extensions of the body image are fluid, immediately reversible, and clearly recognized by the subject as artificial. The surgeon, for example, is able at any moment to redefine correctly his body image. He “knows” that the probe is not his finger. In the group of patients described above, however, the extension of the body image seems to operate in a pathologic, rigid form. Under certain conditions these patients lose the ability to maintain a realistic definition of the limits of their body. They behave as though portions of the contiguous external world are concretely incorporated into the inner image of their body’s extent. Although we may consider exosomestheisa as a specialized body-image disturbin identification difficulties show do who be not that noted should it patients ance, and location of body parts still may show mislocalization into extrapersonal space. On the other hand, patients with an inability to identify or locate their body parts on command do not necessarily manifest exosomesthesia. In similar fashion, there is no necessary relationship between exosomesthesia and of manifested who dis-placement A difficulties. 3) (Case patient position-sense sensation into extrapersonal space did not make errors in routine tests of position made by observations with is consistent previously This in extremities. the sense Head1 that localization of single stimuli is not functionally related to sense of position of the extremities. Role of the Hand—Although displacement into extrapersonal space has been elicited from various areas of the body, it has been observed to occur most frequently from the hand. Moreover, in no case has it been elicited from another area and been absent from the hand. This predilection for the hand is consistent with the manner in which other the when As functioning reflected. rule, of a the are nervous system dysfunctions of one side of the body is impaired through cerebral disease, the disorder is most manifest in the hand. Thus, in the usual hemiplegia resulting from a capsular lesion the paresis, body-image disturbance, and sensory loss are most prominent in the hand and fingers. of the cerebral diffuse disease, with phenomena in others and these In patients, extinction, obscuration, and displacement are also best elicited when the hand is tested. Furthermore, studies of the order of sensory dominance of various areas of the body demonstrate that the hand is in the lowest rank. This is true of the dominance order of patients with cerebral disease,5 and also of normal subjects, both adults and children.6 Similarly, when allesthesia is observed, it is seen most clearly in the hand. Ben7 described a case in which the clinical course was reflected in a Nathanson and der Bender, M. B., and Nathanson, M.: Patterns in Allesthesia and Their Relation to Disorder of Body Scheme and Other Sensory Phenomena, Arch. Neurol. & Psychiat. 64:501-515 7. (Oct) 1950. �10 waxing and waning allesthesia. As this patient improved, the areas from which the phenomenon could be elicited diminished, until finally allesthesia was demonstrable only in the hand. In autotopagnosia the hands are more profoundly affected than other regions. Finger agnosia, possibly the earliest sign of body-image disturbance, is frequently seen in the absence of other gross disturbances of the body schema. Furthermore, phantom limb, anosognosia, causalgia, and synesthesia are phenomena in which the role of the hand is especially prominent. Just as these pathologic phenomena are manifest in tests of other body parts, but are most clearly demonstrable in the hand, so, too, exosomesthesia, though occasion— ally demonstrable elsewhere, is most apparent in examination of the functions of the hand. Exosomesthesia in the Normal Child.—-It has been observed that sensory phenomena which occur in patients with cerebral dysfunction may be found in the nor— mal young child.6 Similarly, exosomesthesia, which we have never found in adults except when there is severe cerebral disease, can be readily observed in children up to the age of 4 years. In examination of a large series of normal children it was noted that the initial responses of children to double simultaneous stimulation frequently included exosomesthesia, although the commoner responses were extinction and displacement. Exosomesthesia was rare, however, after the initial few trials. The frequency with which exosomesthesia may be seen in children up to the age of 4 years suggests that it may represent, in the child, a “normal” developmental stage in the organization of perception. Its appearance in adults with severe brain disease may possibly be, as with other pathologic phenomena, a regression in function to a previous level of sensory integration. SUMMARY The patterned mislocalization of tactile stimuli into extrapersonal space is described and termed exosomesthesia. Exosomesthesia is observed in patients with severe organic mental syndromes. It is apparent only rarely on single tactile stimulation and is more readily elicited by the technique of double simultaneous stimulation. It is exaggerated by fatigue, rapid testing, and increased emotional tension. Barbiturate intoxication also may elicit or exaggerate the phenomenon. Exosomesthesia is most apparent in stimulation of the hand but has been observed in tests of other body parts. While it may be considered a pathologic extension of the body image, it is not dependent upon concomitant body-image disturbances. Although exosomesthesia has been observed chiefly in patients with severe mental changes, it is not a manifestation of confusion, but is a patterned, predictable phenomenon. It may be a regression, in patients with cerebral dysfunction, to a previously “normal” stage in sensory development, as suggested by the fact that it is readily observed in simultaneous tactile tests of young children. , Printed and Published in the United States of America � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Exosomesthesia; the displacement of cutaneous sensation into extra-personal space. Trans Am Neurol Assoc. 1952;56 (77th Meeting):260-2. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-001-6b-009 Date A point or period of time associated with an event in the lifecycle of the resource 1952 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprinted from the A.M.A. Archives of Neurology and Psychiatry, October 1952, Vol. 68, pp. 481-490 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/f7c87e4b8450f1ed2913d4dcd19d8101.pdf 28b2641c12bb8afccfb2c988034e1cc8 PDF Text Text Reprinted from the ISRAEL STRAUSS COMMEMORATIVE VOLUME Journal of the Hillside Hospital Volume V, Numbers 3 - 4 October, 1956 �DENIAL OF BLINDNESS FOLLOWING CEREBRAL ANGIOGRAPHY MAX FINK, M.D.1 In the fifty-eight years since the original report of Anton (1), there has been controversy in the literature as to whether denial of blindness is the result of a specific focal cerebral lesion or of a generalized disturbance of brain function without specific localizing significance.2 In reviewing the cases of denial of blindness, the majority of reports describe the patients as “confabulating,” “disoriented,” or “showing a Korsakoff psychosis.” Such descriptions lend support to the concept that denial occurs in a milieu of altered cerebral function. Studies of denial of hemiplegia, usually described under the term “anosognosia,” bring out identical arguments as to the significance of the phenomenon for localized dysfunction. Indeed, in many reports of denial of blindness, note is made of simultaneous denial of hemiplegia or of other defects. The literature of denial of illness, as well as clinical and experimental evidence to support their concepts, has been recently summarized by Weinstein and Kahn (23). They conclude that various forms of denial are a unitary phenomenon without cerebral localizing value, and that denial is an adaptation to a defect in the milieu of diffusely altered cerebral function. In this regard, most of the defects denied are of rapid onset, are not limited to one defect, are accompanied by confabulation, amnesia, changes in mood and absence of anxiety. The degree of altered cerebral function which provides the milieu for such adaptation is usually severe. Thus, their reports, as well as those of other authors cited (see footnote 2), Director, Research Service, Hillside Hospital, Glen Oaks, N. Y. 2The reviews of Critchley (6) and Weinstein and Kahn (23) present the two aspects of this problem. For specific reports ascribing the phenomena to focal cerebral disease see Barkman (2), Gerstmann (10), von Hagen and Ives (21, 22), Ives and Nielsen (l2), and Paul (16). Reports ascribing the phenomena to diffuse cerebral disturbances include Lunn (13), Redlich and Bonvicini (l7), Redlich and Dorsey (18), and Sandifer (19). 238 1 �DENIAL OF BLINDNESS 239 describe the phenomena of explicit denial of blindness and of hemiplegia as occurring in patients with brain tumors, subarachnoid hemorrhages and vascular disease. The following case history is presented as exemplifying various aspects of the syndrome of denial. The data support the thesis that the phenomenon is an adaptive response to a defect under the conditions of altered cerebral function, rather than the result of focal cerebral pathology. A patient, under observation for enlargement of the sella turcica presumably the result of pituitary adenomatous growth, was subjected to cerebral Iodopyracet (Diodrast) angiography. Before the procedure he was alert and oriented, but immediately following the second series of injections of Iodopyracet, he developed left hemiplegia, which gradually resolved. In the ensuing hours, blindness developed and was denied by the patient. The syndrome persisted for 48 hours, and then resolved. When the patient was seen in a follow-up visit eight months later there was an amnesia for the period of denial. Case Report:3 E. S., a 58-year-old right-handed male, was admitted for diagnostic study to the Montefiore Hospital with a sixmonths history of headaches and blurring of vision. Four months previously he had an episode of ptosis of the right lid associated with dilatation of the right pupil, which had persisted for a few weeks. Headaches became increasingly severe, and X—ray examination of the skull prior to admission demonstrated an enlarged sella turc1ca. He related his own history; appeared neither acutely nor chroni— cally ill; was alert, well oriented, and cooperative, with good memory and calculating ability. He was jovial, made friends readily, and was well liked. He denied previous severe illnesses, or persistent somatic complaints. He was fastidious about his personal belongings and was reluctant to intrude. The general examination was normal except for palpable enlargement of the right lobe of the thyroid gland. Neurological examination was normal except for the cranial nerve examination. His pupils were dilated, the right larger than the left. The reaction to light was sluggish on the right, and the pupils reacted well to near vision. The fundi showed well-outlined papillae with clear margins, definite temporal pallor, and normal vascularization. Visual acuity was 15/20 on the right, and 15/40 on the left. Visual fields to 1/2000 white test object demonstrated a relative bitemporal hemianopsia without macular sparing. The lumbar puncture and routine blood and urine studies were normal. Skull X-ray revealed enlargement of the sella turcica; atrophy of the anterior and posterior clinoids; and calcifications along 3 Patient studied through the courtesy of Dr. Nathan Savitsky at the Monte- fiore Hospital. �240 MAX FINK the lateral border of the sella. Pneumoencephalography demonstrated encroachment of the cisterna chiasmatis and pontis by a mass originating from the sella. An electroencephalogram showed a slight degree of electrical abnormality on the left side, mainly inferior and posterior. Alpha frequencies and amplitude were symmetric. For further clarification of the pathologic process, carotid angiography was recommended. Under local anesthesia, the right common carotid artery was exposed, and forty cc. of 35% Iodopyracet (Diodrast) was administered. Since the serial angiograms thus made were unsatisfactory, another injection of 15 cc. Iodopyracet was made. Immediately following this injection, the patient developed a complete left hemiparesis, including the face. He was restless, confused and irritable. He appeared drowsy; failed to obey commands and was irrelevant in speech. Vasodilators were administered, and the hemiparesis showed some improvement. That evening he was restless, directing his gaze most often to the right. When spoken to from his left side, he would turn his head to the right or backward, before finally localizing the voice correctly. He answered questions relevantly. Visual acuity was reduced to light perception, and pupillary reactions were present, though sluggish. He was unable to localize the position of a light nor identify fingers or objects; yet he denied his inability to see, confabulating seemingly appropriate responses. He was oriented for place but only approximately for time and date. Despite a large neck bandage, he denied the recent cutdown. A lumbar puncture was performed. The initial pressure was 140 mm. CSF, final pressure of 60mm. after the removal of 8 cc. of clear, colorless fluid which had no cells and a protein content of 43 mg%. Twelve hours later, now oriented in space and time on gross questioning, he was still unable correctly to localize light or perceive objects. There was a residual left hemiparesis. He denied both his weakness and his blindness. When walking about the room he stumbled over objects and bumped into the wall and the bed. He correctly identified the various examiners by their voices, and named a coin, key, pencil and comb by touch. There was no sensory loss on single stimulation; gait was hesitant; and the reflexes were increased on the left with bilateral Babinski responses and absent abdominal reflexes. Thirty-six hours later the hemiparesis had cleared except for a residual left Babinski response. He perceived light and localized it well in‘space, but image formation for reading or fine identification was impaired. Despite the partial nature of his vision, he still failed to recognize his impairment, confabulating many responses. An electroencephalogram at this time showed a change from the original record. There was bilateral asymmetry with high per cent time delta activity and a slowed, poorly organized alpha rhythm, mostly on the right. Forty-six hours later his vision had returned so that he was able �DENIAL OF BLINDNESS 241 to read. He was oriented, alert, affable and friendly. He maintained that he had been able to read and to see throughout the previous two days. He had an amnesia for the surgery, the hemiparesis and the blindness. During the ensuing weeks, visual acuity returned to normal; with visual fields manifesting minimal bitemporal hemianopic defect. An electroencephalogram one week later showed posterior voltages to be less depressed; per cent time delta activity had decreased; and there was desynchronization of the record on delta the of accentuation focal abnormality There was opening. eye in the right frontal leads. Three weeks later the electroencephalo— inwith abnormalities of the resolution increased showed gram creased and bilaterally equal per cent time alpha; decreased per cent time delta and resolution of the electrical asymmetry of the hemispheres. On examination eight months after this episode and after a course of radiation therapy for pituitary adenoma, this patient was alert, oriented and cooperative; with only occasional complaints of headache. The neurological examination was completely negative with normal visual acuity and a slight (10°) bitemporal hemianopic defect with 1/1000 white test objects. He denied any experience of blindness or weakness but did recall the neck dissection that preceded the angiography. When told of the experience, he jokingly denied the weakness and the blindness by saying that I was mistaking him for another patient. Discussion: Two aspects of this case report warrant amplification: the significance of the denial phenomenon and the cause of complications following cerebral angiography. The various aspects of denial of illness described by Weinstein and Kahn are well exemplified here. The acute onset of hemiplegia and blindness was followed by a period of restlessness, disorientation, and altered consciousness. Within a few hours, these gross symptoms were replaced by a calm, disinterested, smiling attitude in which the multiple defects of left-sided weakness and blindness were denied. He confabulated, was disoriented for time and date, and later was amnestic for this period. An electroencephalogram demonstrated bilateral diffuse slow wave activity of high voltage. Furthermore, despite the visual loss, the phenomenon of spatial inattention4 was observed. This complex of symptoms and signs is generally noted in diffuse cerebral disorders. While much effort has gone into localizing these defects, it is difficult to conceive a single focal lesion affecting the visual tracts bilaterally, the right hemisphere in an Various terms have been applied to the unawareness of one half of the body and the body space, such as imperception for one half of body (Schilder, 20), hemi-depersonalization (Ehrenwald, 7) and autosomatagnosia (Gerstmann, 10). See also Critchley (6, pp. 237-241), and Brain (4). 4 �242 MAX FINK area productive of hemiplegia and the frontal areas assumed to be productive of apathy, denial, and loss of anxiety. While the possibility of a focal lesion as the basis for this syndrome cannot be ruled out, it is more tenable to conclude that diffuse cerebral dys~ function was present. This conclusion is supported by the electroencephalogram, and also by experimental evidence noted below, demonstrating the effect of intra-arterial Iodopyracet as inducing severe vasospasm followed by generalized cerebral edema and increased permeability of the blood-brain barrier. The significance of the phenomenon of denial is to be seen in its defensive nature. While undergoing a test procedure, the patient suddenly suffers a catastrophic disability. His initial response of severe anxiety, manifested by restlessness, startle reaction, and irritability, is soon replaced by explicit denial. This primitive, “psychotic” defense is normally present only in childhood. But under the special conditions of cerebral dysfunction, with disturbances in spatial and temporal orientation and perception, denial of reality becomes tenable. It is maintained so long as the disability and the milieu of cerebral dysfunction persist. In this patient, as soon as visual perception was sufficient for reading, confabulation and explicit denial were no longer actively maintained for ongoing events. In the special situation of interviews with the staff during the period of visual and motor loss, the patient manifested no concern and confabulated responses readily. When visual acuity returned and his hemiparesis cleared, he maintained the same is imthis it In attitude. unconcerned regard affable, friendly, of denial in factor the explicit characterological to note portant illness. To the extent that the information is now available, this patient manifested a considerable number of the features described by Weinstein and Kahn (24). Special note should be made of the phenomenon of spatial inattention. The patient’s original visual complaint of blurred vision was accompanied by a minimal bitemporal hemianopia, apparent only on testing with 1/2000 white test objects. During the period of visual loss he was unable to locate a light and confabulated responses. One week later the bitemporal hemianopia was present to 3/2000 white test object, but in addition there was an irregular left homonymous upper temporal field defect to 5/2000 white. Evidence of a left homonymous field defect persisted in examinations for three weeks, after which only residual bitemporal defects were persistently reported. Left spatial inattention was prominent in the first 48 hours of this syndrome only, at the time when visual im- �DENIAL OF BLINDNESS 243 pairment was maximal, and when hemiparesis was present. When the hemiparesis receded, visual function returned, and orientation was intact, then spatial inattention disappeared. Thus, spatial inattention was an aspect of the total disturbance in function, possibly motivated by the left-sided defects, and was probably not dependent on a specific visual field defect. The syndrome of blindness and its denial following cerebral angiography is unique. Focal lesions producing transient hemiplegia, hemisensory defects, seizures, aphasia, and various cranial nerve syndromes have been described. In a series of 117 percutaneous carotid angiograms, Fink and Stein (9) noted an 8 per cent morbidity of such transient phenomena. Other series variously report such complications from 3 to 15 per cent of the cases.5 These figures do not include the few patients in whom the complications as hemiplegia, aphasia or exaggeration of their basic disease are permanent; or who succumb. In these studies of the complications of angiography, emphasis is placed on the relation of the concentration of the contrast medium, the rate and quantity of contrast substance injected and the time within which the injections are repeated. In experimental studies Olsson (14), Broman and Olsson (5) and Bloor et al. (3) demonstrated summation of toxic effects when the contrast substance was rapidly injected into animal arteries; and noted increased vascular permeability, cerebral edema and petechial hemorrhages not limited to the side of the injection. While it is possible that the complications of angiography are the result of thrombus formation at the needle site and focal embolization, it is more likely that diffuse toxic cerebral vascular changes are induced as seen experimentally. The diffuse character of the defects and the transient nature of the phenomena in this patient are readily understood in this context. Summary and Conclusions: In the course of carotid angiography in a patient with evidence of a pituitary adenoma, an acute transient episode of blindness and hemiplegia developed. Following a short period of restlessness and confusion, the patient became calm, denied his blindness and weakness, confabulated responses to questions, was disoriented, and manifested spatial inattention. The diffuse nature of the cerebral dysfunction underlying this syndrome is emphasized by noting the distribution of the presumed lesions, the bilateral, diffuse slowing of the electroencephalogram, 5For reviews of the complications of cerebral angiography, see Engeset Fink and Stein (9), Green and Arana (ll), (8), Perese et a1. (15) and Wickbom (25). �244 MAX FINK and the diffuse nature of the toxic sequellae of intra-carotid Iodopyracet (Diodrast). The defensive-adaptive significance of the syndrome of denial of blindness and hemiplegia is discussed, with emphasis on the development of this attitude under the special conditions of altered frames of temporal and spatial reference provided by altered cerebral function. REFERENCES (1) Anton, G.: Uber Herderkrankungen des Gehirnes welche von Patienten selbst nicht wahrgenommen werden. Wien. Klin. Wchnschr., 11:227-229, 1898. (2) Barkman, A.: De l’anosognosie dans l’hemiplegie cerebrale. Acta Med. Scand., 62:235-254, 1925. (3) Bloor, B. M.: Wrenn, F. R.; Margolis, 6.: Experimental Evaluation of Certain Contrast Media Used for Cerebral Angiography. ]. Neurosurg., 8:585—594, 1951. Brain, W.: Perception and Imperception. ]. Ment. Sci, 1022221-232, 1956. Broman, T. and Olsson, 0.: Tolerance of Cerebral Blood Vessels to a Contrast Medium of the Diodrast Group. Acta Radiol., 30:326-342. 1948. (6) Critchley, M.: The Parietal Labes. London: E. Arnold 8: Co., 1953 (see Chap. VIII, pp. 225-255; IX, pp. 258-263). (7) Ehrenwald, H.: Verandertes Erleben des Korperbildes mit konsekutiver Wahnbildung bei linksseitiger Hemiplegie. Mtschr. Psychiat. (2» Neural, (4) (5) 75:89-97, 1930. (8) Engeset, A.: Cerebral Angiography with Perabrodil. Acta Radial, Suppl, 56, 1944. (9) Fink, M. and Stein, J. M.: A Clinical Evaluation of Carotid Angiography. Confim'a Neural, 12:181-195, 1952. (10) Gerstmann, J.: Problem of Imperception of Disease and of Impaired Body Territories with Organic Lesions. Arch. Neural. (5' Psychiat, 48:890-913. 1942. J. R. and Arana, R.: Cerebral Angiography: A Clinical Evaluation Based on 107 Cases. Am. ]. Raentgenol., 59:617-650, 1948. Ives, E. R. and Nielsen, J. M.: Disturbances of Body Scheme. Bull. L. A. Neural. Soc., 22120-125, 1937. Lunn, V.: Uber mangelnde Wahrnehmung der eigenen Blindheit. Acta (11) Green, (12) (13) Psychiat. é} Neural, 16:191-242. 1941. (14) Olsson, 0.: Cerebral Angiography: Tolerance for Contrast Media of Diodrast Type. J. Neural, Neurosurg. é, Psychiat., 12:312-316, 1949. (15) Perese, D. M.: Kite, W. C.; Bedell, A. J.; Campbell, 12.: Complications Following Cerebral Angiography. A.M.A. Arch. Neurol. é} Psychiat., 712105-115, 1954. (16) Potzl, 0.: Uber Storungen der Selbstwahrnehmung bei linksseitiger Hemi- plegie. Ztschr. ges. Neural. (9 Psychiat., 93:117-168, 1924. (17) Redlich, E. and Bonvicini, G.: Uber das Fehlen der Wahrnehmung der eigenen Blindheit bei Hirnkrankheiten. Jahrb. f. Psychiat., 29:14.23, 1908. (18) Redlich, F. C. and Dorsey, J. F.: Denial of Blindness by Patients with Cerebral Disease. Arch. Neural. {‘7 Psychiat., 53:407-417, 1945. (19) Sandifer, P. H.: Anosognosia and Disorders of Body Scheme. Brain, 69:122137, 1946. (20) Schilder, P.: Localization of the Body Image. Assoc. Res. New. Dis., 13:466-484. 1932. {9'- Ment. �DENIAL OF BLINDNESS 245 (21) von Hagen, K. and Ives, E. R.: Anosognosia, Imperception of Hemiplegia. Bull. L. A. Neural. Soc., 2:95-103, 1937. (22) von Hagen, K. and Ives, E. R.: Two Autopsied Cases of Anosognosia. Bull. L. A. Neural. Soc., 4:41-44, 1939. (23) Weinstein, E. A. and Kahn, R. L.: Denial of Illness. Springfield, 111.: Charles C. Thomas, 1955. (24) Weinstein, E. A. and Kahn, R. L.: Personality Factors in Denial of Illness. A.M.A. Arch. Neurol. (5» Psychiat., 69:355-367, 1953. (25) Wickbom, I.: Angiography of the Carotid Artery. Acta Radiol., Suppl., 72,1948. �" Mamma: . mm. W W W6 63mm WWW mm,ljh9.* 3 Iran tau _.; a» V 1 3, Baum Sam», mill-ids Hospital, 61m Oaks, law mm ”imam, Rinaldo Hospital. 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Wu and own mmbmmmwomu. can» tabulated responses to questions. ‘ and m 6180an and manifested spatial mm» nature, at the annual mum underlying thin «yaw arm in mum by mung an distribuum of the pramd mam. ‘ 5 [the mmm5 wmmwmmmmemmmw» fuss nature at that m defend“ We aoqmllae at inn-«mud (mm). 1W:mm of aiminam o: the uyndrm of blindness and Mylegia is flawed, with emu-t m m a! ma atfitudo mm the mam. mum' of alum at bupawl and spatial aroma provided by altered comm Manna. a; adapts.” Wt m �um:- fiarchrkmnmgm do: Eskimo: Velma Anton, a. (1893), nelbst niaht 2 .. 9,. .1. A. {1925): DI WW £2“; mm. m. w.- Hahnmgg" 3;: 9 * van limaegmsio clans Patienm 227-239. Planning“ combmlm .5331; 34. 23545!» mow, 3.14., “rum, LR. and litmus, G. (1951); Maximal Mum 03m Gmtmt Media Used tar cerebral lagiograpiv. 5. Human“. of E! 5354“? ‘ . am; (1955), Parcaptian and Wampum. g. m. w. m: Brain, w. W32. Rm; '2. and Men, '0. (19143), 2019mm at 60:10me Blood Vessels to Cmtrast Mun at Grimm 24. m1. 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For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Denial of blindness following cerebral angiography. J Hillside Hosp. 1956:5:238-245. 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Reprint from the ISRAEL STRAUSS COMMEMORATIVE VOLUME Journal of the Hillside Hospital Volume V, Numbers 3-4 October,1956 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/11575e68e7e18c8231219284212ca0ba.pdf 8597351b5fddeee289bccffd6b5c1c4f PDF Text Text 9Q J. Hillside Heapital, 1957 6: 197-206, A UNIFIED THEORY OF THE ACTION OF PHYSIODYNAMICTHERAPIES1 MAX FINK, MD.2 The proper role of the physiodynamic therapies (convulsive, insulin coma and lobotomy) in psychiatry remains poorly defined. In part, this results from the lack of an adequate formulation of their mode of action. In the past six years increasing evidence for a neuropllysiologic-adaptive view of electroconvulsive therapy has been presented (41, 32, 38, I). This view ascribes the therapeutic process in electroshock to a persistent alteration in cerebral function which provides the milieu for a change in adaptation of the subject to his environment. The type of adaptation evoked is dependent upon the personality of the subject, the environmental situation, and the duration of the induced alteration in cerebral function. Concurrently, an awareness of a similar mode of action in insulin coma (31) and lobotomy (40) has developed. During the past four years we have studied the relation between alteration in various indices of brain function and the behavioral response of psychiatric patients to therapy. The neurophysiologicadaptive view of electroshock has been supported and amplified (11, 12, 13, 19, 21); evidence for a similar view of insulin coma has been presented (22); and recently the concept has been extended to the newer “tranquilizers" (9). These studies provide the basis for a generalization concerning the efficacy of these therapies. It is our purpose in this report to examine the experimental evidence to determine whether or not the mode of action of each of these thera— 1From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, N. Y. Read at the. 2nd International Congress of Psychiatry, Zurich, September 6, 1957. Aided by Grant M-927 of the National Institute of Mental Health, National Institutes of Health, U. S. Public Health Service; and the Board of Directors’ Research Fund of the Society of the Hillside Hospital. 2 Director, Department of Experimental Psychiatry, Hillside Hospital. 197 12-» �198 MAX FINK pies may result from their ability to induce sustained alteration in cerebral function; and the corollary question, whether measurable alteration in cerebral function is a necessary condition for the effi— cacy of these therapies, or a “complication" or "untoward effect." The indices of brain function used in these studies have varied. These include memory scales (2G), visual (20) and tactile (10) perceptual tasks, and changes in language patterns of orientation both clinically (19) and after intravenous amobarbital (21). In electroencephalographic studies of this problem, changes in the delta index, both in routine records (ll, 12) and after activation by intravenous thiopentone (32, 33), and in the beta index (16) have been applied Successfully. For this review, two indices will be stressed: changes in the delta index of the unactivated EEG, and clinical neurologic signs. These indices have been selected because of their successful application in the analysis of the electroshock process, and because data is available for each of the therapeutic modalities. OBSERVATIONS (a) Electroshock 4.1 "1M The following notes summarize our experimental studies of the role of 'changes in EEG delta activity in the response of subjects to electroshock (11, 13). In these studies, electroencephalograms were obtained before treatment, and at weekly intervals on a day after a treatment in consecutive electroshock referrals. Grand mal treatments were administered three times a week, for twelve to twenty treatments. The EEG records were quantitatively analyzed for the amount of induced delta activity, and classified into categories of “high,” “moderate” and “low” degrees of delta activity. At the end of treatment, the patients were independently rated for their shortterm clinical response into the categories of “much improved," “moderately improved” and “unimproved." In the initial series of patients, a significant relationship between the early induction of high degrees of delta activity, and clinical ratings of “much improved” was observed. Eighty per cent of the records in the much improved group were high degree delta by the fourth to sixth treatment; and the percentage was sustained at 90 per cent in the third’ and fourth weeks. In contrast, none of the unimproved patients developed high degree delta records in the first three weeks, and only 20 per cent of the records in the fourth week were so classified. In a subsequent predictive study, the EEG records during the a wan-pow �THEORY OF PHYSIODYNAMIC THERAPIES 199 second and third weeks of treatment were analyzed. Of the patients who had high degree delta records on both occasions, 67 per cent were rated as much improved, while of the patients without such records, 70 per cent were in the unimproved and moderately improved categories. Roth (82, 33), studying the EEG delta activity evoked by intravenous thiopentone after electroshock, has related both the stability and the rate of remission of patients with endogenous depressions to the peak value of the induced slow activity. He concluded that patients not attaining a specified delta activity level "have not acquired an adequate physiological basis for recovery,” and recommended measurement of delta activity levels after thiopentone as a guide to the clinical management of patients. Further information is obtained from convulsive-subconvulsive control studies. While convulsive electroshock induces degrees of delta activity that vary from low to high, subconvulsive therapy rarely alters EEG patterns or induces low degrees of delta activity (13). In their comparative study of different convulsive and subconvulsive techniques, Ulett, Smith and Gleser (38) demonstrated a significantly greater recovery rate for the convulsive than the subconvulsive group. In a similar study (13) recently completed here, twenty-seven patients received a course of subconvulsive therapy. Electroencephalograms, taken at weekly intervals, demonstrated minimal changes—none of the records were scored as middle or high delta activity. Of the twenty-seven patients, no change in behavior was noted in twenty-three, and of these, nineteen were referred for a second course of treatment. Grand mal electroshock induced a high degree of delta activity in fourteen. All patients in this group showed significant changes in behavior, while of the five who did not show the delta response, only two showed a behavioral change. Tranquilizing Drugs When the newer drug therapies are studied from the viewpoint of their electroencephalographic and clinical neurologic effects, a meaningful classification emerges. Furthermore, a relationship between the degree and type of induced change in cerebral function and therapeutic efficacy may be noted. The ability of these agents to induce such signs of central nervous system dysfunction as motor rigidity, depression, excitement and seizures are well known. Less well documented, however, are the clearly definable electroencephalographic patterns. Based on observations made in chronic admin(b) �MAX FIN K 200 istration of drugs in adult psychiatric patients, the EEG changes may be classified according to predominant changes in the frequency spectrum. There are three broad types: Increased slow wave activity with hypersynchrony (“bursts")—“delta shift" II._ Desynchronization with voltage and frequency irregularity and irregular theta activity—“desynchronization” III. Increased high voltage fast activity—“beta shift.” Of the group of drugs inducing a delta shift, the phenothiazine derivatives chlorpromazine, promazine, and perphenazine are clear examples. Each drug induces seizures in nonepileptics or exaggerates seizures in epileptic patients (7, 8, 15, 29, 37). Each drug induces clinical parkinsonian neurologic patterns when given in adequate dosage. In our laboratories, we have induced parkinsonism in all patients receiving chlorpromazine (l4) and have observed seizures in 10 per cent of a group of psychotic patients without previous ltistnl'y of seizures. Induced delta activity, including burst activity, \ms nlm-ned in more than half the patients in this series. Rrxrxpiue also ernkes delta activity when given in large doses (3- \t liitth tlnugt‘ levels. it exaggerates seizures in epileptics and "I'lihrs wzmtes in animals (35). .-\t the usual clinical dosages, howr.:-:, ”supine imluu's desynrhronization of frequencies with a t; w-lrtxh‘ mitease in theta activity (28), without seizure induction in: mm definite motor rigidities. In a series of patients treated here ("T'H. parkiuwuism was induced in all patients. EEG Changes were limited to desynchronization only, without delta burst activity. The primary response of two other drugs, mepazine and benacty. . Ime. is the induction of EEG desynchronization. Mepazine, a phen()t‘ttLt/mt‘ derivative. induces desynchronization with small amounts; it n\n\ \ \ l‘h'lt'h .‘n‘H\'n\ has nx‘u t\\\‘ll 'li‘it‘l‘fik‘n. nor have .-' m: Immd reports either of seizures or parkinsonism in the clinical literature. Benactyzine, a potent anticholinergic compound, induces a blocking of alpha, flattening of the record and occasional theta activity (5, 17). Neither seizures nor parkinsonism have been described for this agent. Meprobamate is the clearest example of the group of drugs inducing a beta shift in the EEG (3). This agent further differs from the phenothiazines and reserpine in not producing parkinsonism and not only are clinical seizures not induced, but definite antiepileptic activity has been described (30). Habituation is readily 1. x a w �THEORY OF PHYSIODYNAMIC THERAPIES f 201 achieved, and withdrawal phenomena of agitation and seizures have been observed (42). In these actions, meprobamate is more like barbiturates than like the other new tranquilizers. If we determine the clinical efficacy of these agents, we note a parallel between the induced EEG effects and their potency in altering behavior. The drugs that most readily induce a delta shift in EEG frequencies—the phenothiazine compounds—are those with the greatest clinical efficacy in the therapy of psychoses. The compounds with lesser activity in this direction are less efficacious clinically. i f ,1 ,i / I/ ! Insulin Coma Therapy The effects of insulin coma therapy on the nervous system are well documented. During each coma, EEG delta activity is induced, which usually persists for minutes to a few hours after gavage. Not infrequently, in approximately one third of patients receiving deep coma therapy in this hospital, seizures, aphasia or prolonged coma results. After such events, EEG changes of delta activity persist for days, and in cases of prolonged coma, for weeks and months (43). The relation between prolonged coma, altered brain function and behavioral response has been discussed at length. Revitch (31) reported eight cases of prolonged coma and concluded that improvement may be attributed to the induction of organic brain damage, similar to lobotomy. Yaeger, Simon, Margolis and Burch (43), describing twelve cases of prolonged insulin coma, noted a correlation between length of coma, degree of organic confusion, remission of mental symptoms and degree of EEG abnormality. Shagass and Rowsell (34), emphasizing EEG data, and Kwalwasser and Caplan (27) presented individual cases to support the same conclusion. We reported a similar relationship between prolonged coma and behavioral response in a case study (22). A 34-year-old schizophrenic patient with paranoid ideation developed a left hemiplegia during insulin coma therapy. With the onset of neurologic signs of hemiparesis, hemianopsia, hemisensory syndrome and spatial inattention, there was a marked change in speech and behavior. He became lucid, loquacious and denied his illness. His former paranoid-withdrawal type pattern was replaced by a friendly cooperative attitude. These changes were accompanied by delta changes in the EEG, as well as language changes after amobarbital indicative of altered brain function. The neurologic symptoms resolved, but the behavioral changes persisted so that he was discharged two months later as “much improved." , l 5, ' ‘ (c) m..- aunts..- 5 ’j 2 “ \lU, 5‘ r ' - �202 MAX FINK (d) Lobotomy to study lobotomy While we have not had the opportunity of of view of this summary, the reports the point from EEG patients a similar relationship. numerous observers clearly documentin all subjects postoperatively of changes of delta activity are present Walter et al. (40) in a study (6) and persist for varying periods. EEG persistence of abnormal 150 patients, found an 80 per cent be? relation noted a also authors activity after three years. These of postextent and and the degree tween clinical improvement operative slow wave activity. “complication," being variPostoperative seizures are a frequent (25). in up to 20 per cent of subjects ously reported as occurring of brain extent the between Furthermore, there is a relationship Circumscribed surgical tissue cut and the therapeutic outcome. improvement rate lower than lesions, regardless of locus, have an are frequently inadequate unilateral lobectomy; and these latter bilateral procedure (36). and are “improved” upon by a and i there havi Thfi tior the pa 5V 1,,“ F .'r' l s. l ‘_ DISCUSSION are essayed from the When the various physiodynamic therapies mode in brain function, a common point of view of an alteration which therapies represent devices of action becomes apparent. These function, with resultant change induce appreciable changes in brain and lobotomy induce measurable in behavior. Convulsive therapy directly; insulin coma primarily diffuse changes in brain function the phenothiazine and reserpine when complications ensue; and when given in adequate dosage. groups of tranquilizers function affect behavior is How persistent changes in cerebral“reversed" or “obliterated." is not not clear. Psychotic behavior the central nervous system milieu, in Rather, with an alteration of behavior including perception, there is an alteration in all aspects attitude. The specific adaptive mood, affect, memory, judgment and each subject and is dependent on numerous response is variable for Premorbid personality (18), historical and environmental factors. and the duration of environmental situation and expectations (13), have recently been discussed as the alteration in brain function (12) under these conditions. determinants of the behavioral response evaluated by the psychiaThe induced changes in behavior are the degree of “improvement." trist, administrator or family as to based the upon such factors as These ratings are value judgments, tolerance behavioral response, the environmental type of induced . JUN-laws �THEORY OF PHYSIODYNAMIC THERAPIES "Omy 0f ‘S E15G VC‘Iy } 'Of l EC ‘1 ’6 _ W . - . f . .-‘ i / / . ‘ y . “ (a 203 and the observer's expectations. In this context, the physiodynamic therapies do not induce “improvement"——-rather they induce behavioral change which is secondarily evaluated as improvement. The alteration of cerebral function is therefore not a “complication" or an "untoward effect" but the desired goal of these forms of therapy. Of the many “organic" therapies introduced during the past thirty years, none apparently has been a specific agent for the therapy of psychoses (in the sense that penicillin is specific for neurosyphilis and nicotinic acid for pellagra dementia), but rather devices with greater or lesser degrees of applicability and efficacy in altering behavior by altering the cerebral milieu. In this context, the various physiodynamic therapies are not specific for a type of psychosis. The early enthusiasm that reserpine or chlorpromazine was specific for schizophrenia, or hypotheses that ascribe significance to an antagonism between these drugs and “psychosis" or "schizophrenia" are not tenable. Similar enthusiasm claiming a specificity of insulin coma for schizophrenia is also untenable, and support for this view is presented in a recent chlorpromazine-insulin coma control‘study (l4). EEG analysis of these therapies permits a more explicit definition of the induced alteration in brain function. Changes in cerebral function reflected by a shift in the spectrum of EEG frequencies toward the slower range, with a concomitant increase in voltage and a periodicity described as “bursts" or “hypersynchrony” provide the change in milieu that is more effective in altering behavior. The significance of the delta shift has been clearly demonstrated in electroshock therapy; and can be inferred from the available data in lobotomy, insulin coma, and the tranquilizers. That a delta shift has some specificity is seen in the analyses of the drug effects. Those drugs that induce the delta shift—the phenothiazines and reserpine—have been consistently reported as effective modifiers of psychotic behavior. Changes in brain function reflected by EEG desynchronization only, or a shift in frequency spectrum to the faster range, have a limited efficacy in altering psychotic behavior.3 The significance of a delta shift is further seen in the limited efficacy of subconvulsive electroshock when compared to convulsive electroshock in the management of psychoses. Another aspect of the alteration in brain function which may be defined is the change in seizure threshold. With the delta shift in 3 These observations suggest the application of EEG screening of new chemotherapeutic compounds for therapeutic efficacy according to their ability to induce delta burst activity with a minimum of side effects. �MAX FINK 204 the EEG, an increase in clinical seizures would be anticipated. This is indeed true. Seizures have been described following electroshock (4, 24); they are prominent after lobotomy (40) and a common “complication” during and occasionally following insulin coma therapy (23). With the tranquilizers, the parallel of clinical efficacy and seizure induction is most striking. Phenothiazine compounds induce seizures commonly; reserpine rarely; benactyzine not at all; and meprobamate is a potent anticonvulsant! The lowering of seizure threshold parallels the extent of the EEG delta shift induced by these compounds. Similar analyses can be made for the potentiation of sedative action and induction of parkinsonism—both potent indices of an alteration in cerebral function. The neurologic basis for the delta shift and increase in seizure’ frequency is unclear. Whether this represents a persistent change in function of some specific brain stem nuclear system, as the centrencephalic, thalamic or hypothalamic, is conjectural. From the wide range of agents that can induce a delta shift, with or without hypersynchrony, it appears more likely that the EEG changes reflect an alteration in the diffuse biochemical activity of the nervous system rather than in a focal activity of specific cellular masses. SUMMARY 1. The neurophysiologic and clinical neurologic aspects of con- vulsive therapy, “tranquilizers,” insulin coma and lobotomy, are reviewed. 2. The efficacy of each therapy in the treatment of psychoses is related to the ability to induce a persistent change in cerebral function, of which a delta shift in the EEG spectrum and an increase in incidence of seizures are two indices. 3. Alteration in cerebral function is an essential prerequisite of behavioral change with each of these therapies. Such alteration is neither a “complication,” nor an “untoward effect," but is the sine qua non of the mode of action of these therapies. 4. No evidence has been educed in these studies that the physiodynamic therapies are specific agents for the relief of psychoses; nor do they affect a specific segment of the nervous system; nor do they induce specific behavioral'changes. 5. The therapeutic process of convulsive therapy, insulin coma, lobotomy and tranquilizers may be ascribed to the induction of a persistent alteration in cerebral function which provides the milieu for a change in adaptation of the subject to his environment. r.—-r,y.,.",,,, �THEORY OF PHYSIODYNAMIC THERAPIES 205 REFERENCES (1) (2 V i l l : Aird, R. B.: Strait, L. A.: Pace, J. “7.; Hernolf, M. K. 8: Bowditch, S. C.: Neurophysiologic Effects of Electrically Induced Convulsions. A.M.A. Arch. Neural. (9 Psychiat., 75:371-378, 1956. Arellano, A. P. 8.- ]eri, R.: The Ellcct of Reserpine on the Scalp and Basal Electrocncephalogram. EEG. Clin. Neurophysiol., 8:150 (abst.), 1956. Berger, F. M.: The Chemistry and Mode of Action of Tranquilizing Drugs. Ann. N. Y. Acad. Sci., 67:685-699, 1957. Blumenthal, I. j.: Spontaneous Seizures and Related Electroencephalographic Findings Following Shock Therapy. ]. New. & Ment. Dis., 122:581-588, 1955. Coady, A. 8.: jewesbury, E. C. 0.: A Clinical Trial of Benactyzine Hydro. chloride (“Suavital”) as a Physical Relaxant. Brit. Med. 1., Mar. 3, pp. 485- 487, 1956. Colin, R.: EEG Study of Prelrontal Lobotomy. Arch. Neurol. 65' Psychiat.,_ 532351-357, 1945. (7) Dcnber, H. C. B.: Discussion, Symposium on the Psychopharmacologic Approach to Schizophrenia. Second Int. Congress of Psychiatry, Zurich, 1957. (8) Fabisch, “7.: Effect of Chlorpromazine on the Electroencephalogram of Epileptic Patients. J. Neurol., Neurosurg., (‘5' Psychiat., 20:185-190, 1957. (9) Fink, M.: Therapy of Schizophrenia: Role of Alteration of Brain Function in Behavior. Presented Second Int. Congress of Psychiatry, Zurich, 1957. (10) Fink, M.; Green, M. A. 8: Bender, M. B.: The Face-Hand Test as a Diagnostic Sign of Organic Mental Syndrome. Neurology, 2:46-58, 1952. (11) Fink, M. 8: Kahn, R. L.: Quantitative Studies of Slow Wave Activity Following Electroshock. EEG Clin. Neuraphysial., 8:158 (abst.), 1956. (12)' Fink, M. Sc Kahn, R. L.: Relation of EEG Delta Activity to Behavioral Response in Electroshock: Quantitative Serial Studies. AM.A. Arch. Neurol. (‘5Psychiat., 78:516-525. 1957. (13) Fink, M.; Kahn, R. L. 8: Green, M. A.: Experimental Studies of the Electroshock Process. 1. New. (9- Ment. Dis. (in press). (14) Fink, M.; Shaw, R.: Gross, G. 8.- Coleman, F. 8.: Comparative Study of Chlorpromazine and Insulin Coma in the Therapy of Psychosis. ]. Am. Med. Assoc. (in press). (15) Hankoif, L. D.; Kaye, E.; Engelhardt, D. M. 8.: Freedman, N.: Convulsions (5) (16) 1946. (17) Jacobson, E.: Suavitil, et Nyt Stat Med Specifik Virkning pa Centralnervesystemet. Ugeskrift for Laeger, 117:1147-1151, 1955. (13) Kahn, R. L. 8: Fink, M.: Personality Factors in Behavioral Response to Electroshock Therapy. Conf. Neural. (in press). 8: (19) Kahn, R. L. Fink, M.: Changes in Languages During Electroshock Therapy. In: Psychopathology of Communication. New York: Grune 8c Stratton, (in press), 1957. (20) Kahn, R. L. 8c Fink, M.: Perception of Embedded Figures After Induced Altered Brain Function. Am. Psychal., 12:36] (abst.), 1957. (21) Kahn, R. L.; Fink, M. 8: Weinstein, E. A.: Relation of Amobarbital Test to Clinical Improvement in Electroshock. A.M.A. Arch. Neural. 6' Psychiat., 76:23-29, 1956. (22) Kahn, R. L.; Graubert, D. 8: Fink, M.: Delusional Reduplication of Parts of the Body After Insulin Coma Therapy. This Journal, 4:134-148, 1955. ~ ,,L...-.u.. . . Complicating Ataractic Therapy, Their Incidence and Theoretical Implications. N. Y. State J. Med., 57:2967-2972, 1957. Hoagland, H.; Malamud, W.; Kaufman, I. C. 8c Pincus, 0.: Changes in Electroencephalogram and in Excretion of l7-Ketosteroids Accompanying Electro-shock Therapy of Agitated Depression. Psychosom. Med., 8:246-251, �MAX FINK 206 and Other Hoch, P.: Shock Treatment, Psychosurgery 8c Stratton, 1952. Grune York: New Somatic Treatments in Psychiatry. This States Following Electroshock Therapy. (24) Karliner, W.: Epileptic Journal, 5:258-263, 1956. in Prefrontal Loof Seizures, with EEG Findings, (25) Klotz, M.: Incidence 1955. 74:144-148. 65' Psychiat, and botomy. A.M.A. Arch.8.- Neurol. Kwalwasser, 8.: Relation of Changes in Memory 1956. 16:88-96, (25) Korin, H.; Fink, M. Neurol., Electroshock. Conf. Learning to Improvement in A Case of Prolonged Insulin Coma: Treat8.- Caplan, M.: (27) Kwalwasser, S. 1952. ment. This Journal, 1:145-155, Drugs on EEG. EEG Clin. “Tranquilizing” of Effect T.: W. (23) Liberson, Neurophysiol., 8:523, 1956. Fits in LeuN.: The Occurrence of Epileptic (29) Liddell, D. W. 8: Retterstol, Neurol., Neuro]. Therapy. Chlorpromazine cotomized Patients Receiving 20:105-107, 1957. Disorders. surg, &» Psychiat., Miltown, Its Use in Convulsive and Related A.: M. (30) Perlstein, 1956. 161:1040, J. Am. Med. Assoc., ImproveOrganic Brain Damage and Clinical 28:79-92, 1954. (31) Revitch, E.: Observations on Quart., Coma. Psychiat. ment Following Protracted Insulin Produced by the EEG Under Barbiturate Anesthesia (32) Roth, M.: Changes in for the Theory of Significance Their and Treatment Electro-Convulsive 3:261-280, 1951. ECT Action. EEG Clin. Neurophysiol., and Pentothal K.; Shaw, J. 8: Green, ].: Prognosis W. D. M.: Kay, Roth, Treatment. (33) Electra-Convulsive in Induced Electroencephalographic Changes 1957. 9:225-238, EEG. Clin. Neurophysiol., and Clinical P. W.: Serial Electroencephalographic Neural. & (34) Shagass, C. 8: Rowsell, Arch. A.M.A. Coma. Insulin Studies in a Case of Prolonged Psychiat., 72:705-711, 1954. Interaction of A.: Mechanisms Involved in the (35) Sigg, E. B. 8: Schneider, J. Neurophysiol., 9: Clin. EEG. Reserpine. and Various Central Stimulants 419-426, 1957. M.: Unilateral and L. 11.; Adams, J. E. 8: Bowman, K. (35) Simon, A.; Margolis, A.M.A. Arch. Neurol. 6' Evaluation. Controlled A Bilateral Lobotomy: Psychiat., 66:494-503. 1951. Use to Activate Electroencephalographic (37) Stewart, L. F.: Chlorpromazine: 9:427-440, 1957. Neurophysiol., Clin. EEG Seizure Patterns. of Convulsive and SubEvaluation C.: 8c G. Gleser, K. (38) Ulett, G. A.; Smith, Am. J. Psychiat., Control Group. a convulsive Shock Therapies Utilizing (23) Kalinowsky, L. B. 8: . . 112:795-802, 1956. of A. G.; Fink, M. 8: Miller, J. S. A.: Evaluation (39) Wachspress, M.: Blumberg, Journal, 5:67-77, This of Anxiety. Relief for Reserpine Therapy High-Dose 1956. C. L.; Margolis, L. H. 8: Simon, A.: The EEG Changes 111:590(4°) Walter, R. D.; Yaeger, and Bilateral Frontal Lobotomy. Am. J. Psychiat., in Unilateral 594, 1955. and Physiologi8c Kahn, R. L.: Denial of Illness: Symbolic (41) Weinstein, E. A. 1955. cal Aspects. Springfield, Ill.: C. C. Thomas. Communication. (42) Wilder, A.: Personal L. H. 8: Burch, N. R.: Electroencephalo(43) Yaeger, C. L.; Simon, A.; Margolis, Ment. Dis., 118: Coma. ]. New. 6' graphic Studies in Posthypoglycemic 435-441, 1953. . 39W" _ . w . if �A Unified Theory of the Action of Physiodynamic Therapies Max Fink, M.D. From the Department of Experimental Psychiatry, Hillside Respital, Glen Oaks, Read at the 2nd International Congress of Psychiatry, Zurich, September 6, N.Y. 1957. of the National Institute of Mental Health, National Institutes of Health, U.S. Public acalth Service; and the Board of Directors' Research Fund of the Society of the Hillside Bbspital. Aided by 10-7-57 grant M-927 �Iv: unified A The 10/5/57 Theory of the Action of Physiodynamic Therapies proper role of the physiodynamic therapies (electroshock, insulin coma and lobotomy) in psychiatry remains poorly defined. In part, this results from the lack of an adequate formulation of their mode of action. In the past six years increasing evidence for a neurophysiologic-adaptive view of electro- (hl, 32, 38, 1). This view ascribes the there“ shock therapy has been presented peutic process in electroshock to a persistent alteration in cerebral function which provides the milieu environment. The for a change in adaptation of the subject to his type of adaptation evoked is dependent upon the personality of the subject, the environmental situation, and the duration of the induced alteration in cerebral function. Concurrently, of action in insulin coma (31) and lobotomy During the past four years we (MO) of psychiatric patients to therapy. The a similar view of insulin relation between and the behavioral response neurophysiologic-adaptive view of electroshock has been supported and amplified (9, 10, for mode has developed. have studied the alteration in various indices of brain function similar an awareness of a coma has been ll, 20, 21); evidence presented (19); and recently the concept has been extended to the newer "tranquillizers" (12). These studies provide the basis for a generalization concerning the efficacy of these therapies. It is our purpose in this report to examine the experimental evidence whether or not the mode of action of each of these therapies may to determine result their ability to induce sustained alteration in cerebral function; from and the coroln lary question, whether measurable alteration in cerebral function is a necessary �- - 2 condition for the efficacy of these therapies, or a "complication" or "untoward effect." The include indices of brain function used in these studies have varied. memory scales (26), visual (22) and tactile changes in language patterns of orientation both intravenous ambbarbital (20). changes in the clinically (21) and after In electroencephalographic studies of this problem, by intravenous thiopentone (32, 33), and successfully. For this review, have been (13) perceptual tasks, and delta index, both in routine records (9, delta index of the unactivated These and after activation in the beta index (16) have been applied two indices EEG, 10) and will be stressed: changes in the clinical neurologic signs. These indices selected because of their successful application in the analysis of the electroshock process, and because data is available for each of the therapeutic modalities . �OBSERVATIONS: (a) Electroshock: The role of changes in following notes summarize our experimental studies of the EEG delta activity in the response of subjects to electro- In these studies, electroencephalograms were obtained before shock (9, 11). treatment, and at weekly intervals electroshock referrals. week, for after a treatment in consecutive Grand mal treatments were administered treatments. 12-20 on a day The EEG three times a records were quantitatively analyzed for the amount of induced delta activity, and classified into categories of "high", "moderate" and "low" degrees of delta patients were independently the categories of In the At the end of treatment, the activity. rated for their short term clinical response into "much improved”, "moderately improved" and "unimproved". initial series of patients, a significant relationship between the early induction of high degrees of delta activity, and clinical ratings of "much improved" was observed. Eighty percent of the records in the much improved group were high degree delta by the h-6 treatment; and the percentage was sus- tained at 90% In contrast, none of the unimproved in the third and fourth weeks. patients developed high degree delta records in the 20% third weeks of treatment were analyzed. delta records on both occasions, 67% were patients without such records, categories. 70% and only classified. of the records in the fourth week were so In a subsequent predictive study, the and first three weeks, EEG Of records during the second the patients rated as who had high degree much improved, while of the were in the unimproved and moderately improved �*“1 h Both (32, 33) studying the EEG - delta activity thiopentone after electroshock has related both the evoked by intravenous stability and the rate of remission of patients with endogenous depressions to the peak value of the induced slow activity. activity level, He ...... " concluded that patients not attaining a specified delta have not acquired an adequate physiological basis for recovery," and recommended measurement of delta activity levels after thiopentone clinical as a guide to the management of patients. Further information is obtained from convulsive-subconvulsive control studies. While convulsive electroshock induces degrees of vary from low to high, subconvulsive therapy rarely alters duces low degrees of delta delta activity that EEG patterns or in- activity (11). In their comparative study of different convulsive and subconvulsive techniques, Ulett, Smith and Gleser (38) demon- strated a significantly greater recovery rate for the convulsive than the subconvulsive group. In a similar study (11) recently completed here, twenty-seven patients received a course of subconvulsive therapy. weekly Electroencephalograms, taken at intervals, demonstrated minimal changes as middle or high delta activity. Of - none of the records were scored the 27 patients, no change in behavior was noted in 23, and of these, 19 were referred for a second course of treatment. Grand mal electroshock induced a high degree of delta activity in fourteen. All patients in this group showed significant changes in behavior, while of the five who did not show the delta response, only two showed a behavioral change. (b) Tranquillizing Drugs: When the newer drug therapies are studied from the viewpoint of �-5their electroencephalographic and clinical neurologic effects, a meaningful classification emerges. Furthermore, a relationship between the degree and type of induced change in cerebral function and therapeutic efficacy may be noted. The ability of these agents to induce such signs of central nervous system dysfunction as motor rigidity, depression, excitement and seizures are well known. Less well documented, however, are the clearly definable electro— encephalographic patterns. Based on observations made of drugs in adult psychiatric patients, the EEG in chronic administration changes may be according to predominant changes in the frequency spectrum. classified There are three broad types: I. Increased slow wave activity with hypersynchrony ("bursts") - "delta shift" II. Desynchronization with voltage and frequency irregularity and III. Of irregular theta activity - "desynchronization" shift." Increased high voltage fast activity - "beta the group of drugs inducing a delta derivatives chlorpromazine, promazine, Each drug induces shift, the phenothiazine and perphenazine are clear examples. seizures in non-epileptics or exaggerates seizures in epileptic patients (7, 8, neurologic patterns 15, 29, 37). when given Each drug induces in adequate dosage. clinical parkinsonian In our laboratories, have induced parkinsonism in all patients receiving chlorpromazine have observed seizures in 10% (1%) and of a group of psychotic patients without previous history of seizures. Induced delta activity, including burst activity, observed in more than we half the patients in this series. was �-5Reserpine also evokes delta At high dosage levels, it activity when given in large doses (2). exaggerates seizures in epileptics and induces seizures in animals (35). At the usual clinical dosages, however, reserpine induces desynchronization of frequencies with a moderate increase in theta activity (28), without seizure induction but with definite motor rigidities. In a series of patients treated here (39), parkinsonism was induced in patients. EEG all changes were limited to desynchronization only, without delta burst activity. The primary the induction of EEG response of two other drugs, mepazine and benactyzine, is desynchronization. Mepazine, a phenothiazine derivative, induces desynchronization with small amounts of theta activity has not been described, nor or parkinsonism in the have we found activity (7). Delta reports either of seizures clinical literature. Benactyzine, a potent anticholin- ergic compound, induces a blocking of alpha, flattening of the record and 17). Neither seizures nor parkinsonism have occasional theta activity (5, been described for this agent. Meprobamate beta shift in the and EEG is the clearest example of the group of drugs inducing a (3). This agent further differs reserpine in not producing parkinsonism from the phenothiazines and not only are clinical seizures not induced, hut definite anti-epileptic activity has been described (30). Habituation is readily achieved, and withdrawal phenomena of agitation and seizures have been observed (h2). barbiturates than like the other If we determine the In these actions, meprobamate new is more like tranquillizers. clinical efficacy of these agents, we note a parallel �-7between the induced drugs EEG effects and their potency in altering behavior. that most readily induce a delta shift in thiazine compounds - are those with the therapy of psychoses. The compounds EEG frequencies - the The pheno— greatest clinical efficacy in the with lesser activity in this direction are less efficacious clinically. (c) Insulin Coma The well documented. Therapy: effects of insulin During each coma, persists for minutes to a few hours EEG coma delta activity is induced, after gavage. imately one third of patients receiving deep seizures, aphasia or prolonged coma therapy on the nervous system are coma which usually infrequently, in Not approx— therapy in this hospital, results. After such events, of delta activity persist for days, and in cases of prolonged changes EEG coma, for weeks and months (h3). relation between prolonged The coma, altered brain function ioral response has been discussed at length. Revitch of prolonged coma and concluded tion of organic brain damage, that (31) reported improvement may be insulin eight cases attributed to the similar to lobotomy. Yaeger, Burch (#3), describing twelve cases of prolonged and behaVo induc— Simon, Margolis and coma, noted a correlation between length of coma, degree of organic confusion, remission of mental symptoms and degree of EEG abnormality. Shagass and Rowsell (3h), emphasizing and Kwalwasser and Caplan (27) presented EEG individual cases to support the data, same conclusion. We reported a similar relationship between prolonged response in a case study (19). A 3h coma and behavioral year old schizophrenic patient with paranoid �-8ideation developed a left hemiplegia during insulin coma therapy. With the onset spatial of neurologic signs of hemiparesis, hemianopsia, hemisensory syndrome and inattention, there was a marked change in speech and behavior. loquacious and denied his illness. was by He ludic, became His former paranoid—withdrawal type pattern replaced by a friendly cooperative attitude. These changes were accompanied delta changes in the as well as language changes EEG, dicative of altered brain function. The neurologic after amobarbital symptoms in— resolved, but the behavioral changes persisted so that he was discharged two months later as "much improved." (d) Lobotomy: While we have not had the opportunity from the point of view of document a this summary, similar relationship. all subjects postoperatively (#0) in a study of 150 after three years. EEG (6) and to study patients lobotomy the reports of numerous observers clearly changes of delta activity are present in persist for varying periods. Walter et al., patients, found an 80% persistence of abnormal These authors also noted a EEG relation between clinical ment and the degree and extent of postoperative slow wave activity improve— activity. Postoperative seizures are a frequent "complication," being variously reported as occurring up to relationship between the 20% of subjects (25). Furthermore, there extent of brain tissue cut and the is therapeutic Circumscribed surgical lesions, regardless of locus, have an improvement lower than unilateral lobectomy; are "improved" upon by a and these a outcome. rate latter are frequently inadequate bilateral procedure (36). and �DISCUSSION: When view of an These the various physiodynamic therapies are assayed from the point of alteration in brain function, a therapies represent devices of action becomes apparent. common mode which induce appreciable changes in brain function, with resultant change in behavior. Electroshock and lobotomy induce measurable diffuse changes in brain function when directly; insulin coma primarily complications ensue; and the phenothiazine and reserpine groups of quillizers when given How tran— in adequate dosage. persistent changes in cerebral function affect behavior is not clear. Psychotic dehavior is not "reversed" or "obliterated". Rather, with an alteration in the central nervous system milieu, there is all aspects of behavior including perception, and attitude. is dependent The affect, alteration in memory, Judgment specific adaptive response is variable for each subject on numerous historical and environmental sonality (18), environmental situation of the mood, an alteration in brain function factors. and expectations (10) have (ll), and Pre-morbid perand the duration recently been discussed as determinants of the behavioral response under these conditions. The induced changes in behavior are evaluated by the administrator or family as to the degree of "improvement." psychiatrist, These ratings are value judgments, based upon such factors as the type of induced behavioral response, the environmental tolerance and the observer's expectations. In this context, the physiodynamic therapies do not induce "improvement" - rather they induce behavioral change which is secondarily evaluated as improvement. alteration of cerebral function is therefore not a "complication" or The an "untoward �-10.. effect" but the desired goal of these forms of therapy. therapies introduced during the past thirty years, Of the many "organic" none apparently, has been a specific agent for the therapy of psychoses (in the sense that penicillin is specific for neurosyphilis and nicotinic acid for pellagra dementia), but rather devices with greater or lesser degrees of applicability and efficacy in altering behavior by altering the cerebral milieu. In this context, the various physiodynamic therapies are not specific for a type of psychosis. was The early enthusiasm that reserpine or chlorpromazine specific for schizophrenia, or hypotheses that ascribe significane to an antagonism between these drugs and "psychosis" or "schizophrenia" are not tenable. Similar enthusiasm claiming a specificity of insulin coma for schizophrenia is also untenable, and support for this view is presented in a recent chlorpromazine— insulin coma EEG control study (1h). analysis of these therapies permits a the induced alteration in brain function. by a shift in the spectrum of EEG Changes more explicit definition of in cerebral function reflected frequencies toward the slower range, with a concomitant increase in voltage and a periodicity described as "bursts" or "hypersynchrony" provide the change in milieu behavior. The that is more effective in altering significance of the delta shift has been clearly demonstrated in electroshock therapy; and can be inferred from the available data in lobotomy, insulin coma, and the That a delta drug effects. reserpine tranquillizers. shift has Those drugs - have been some specificity is seen in the analyses of the that induce the delta shift - the phenothiazines and consistently reported as effective modifiers of psychotic �- 11 - of psychotic behavior. Changes in brain function reflected by EEG desynchroniza- tion only, or a shift in frequency spectrum to the faster range, have a limited efficacy in altering psychotic behavior. * The significance of a delta shift is further seen in the limited efficacy of subconvulsive electroshock when com- pared to convulsive electroshock in the management of psychoses. Another aspect of the is the change alteration in brain function in seizure threshold. delta shift in the With the in clinical seizures would be anticipated. which may be defined This been described following electroshock (h, 2h), EEG, an increase is indeed true. Seizures have are prominent after lobotomy (ho) and a common ”complication" during and occasionally following insulin coma therapy (23). With the tranquillizers, the parallel of clinical efficacy and seizure induction is most striking. commonly; reserpine rarely; benactyzine not at all; anticonvulsant! EEG Phenothiazine compounds induce seizures The lowering of delta shift induced and meprobamate is a potent seizure threshold parallels the extent of the by these compounds. Similar analyses can be made for the potentiation of sedative action and induction of parkinsonism - both potent indices of an alteration in cerebral function. The quency some neurologic basis for the delta shift and increase in seizure is unclear. Whether fre— this represents a persistent change in function of specific brain stem nuclear system, as the centrencephalic, thalamic or hypothalamic, is conjectural. From the wide range of agents that can induce a screening of new chemo— therapeutic compounds for therapeutic efficacy according to their ability to induce delta burst activity with a minimum of side effects. * These observations suggest the application of EEG �- 12 - delta shift, with or without hypersynchrony, EEG changes it appears more likely that the reflect an alteration in the diffuse biochemical activity of the nervous system rather than in a focal activity of specific cellular masses. �- 13 SUMMARY: 1. shock, The neurophysiologic and clinical neurologic aspects of electro- "tranquillizers, insulin H 2. The coma and lobotomy, efficacy of each therapy in the treatment of psychoses is related to the ability to induce a persistent of which a delta shift in the seizures are 3. two EEG change in cerebral function, spectrum and an increase in incidence of indices. Alteration in cerebral function is behavioral change with each of these therapies. a "complication," nor an "untoward mode of are reviewed. an essential prerequisite of Such alteration is neither effect," but is the sine 92a action of these therapies. h. No evidence has been educed in these studies that the physiodynamic therapies are specific agents for the relief of psychoses; nor specific non of the segment of the nervous system; nor do they induce do they affect a specific behavioral changes. 5. and The therapeutic process of electroshock, insulin tranquillizers may be in cerebral function coma, lobotomy ascribed to the induction of a persistent alteration which provides the milieu the subject to his environment. for a change in adaptation of �L.A., Pace, J.W., Hernoff, M.K. and Bowditch, S.C. (1956): Neurophysiologic Effects of Electrically Induced Convulsions, A.M.A. Arch. Neurol. & Psychiat. 15: 371-378. Aird, R.B., Strait, Jeri, R. (1956): The Effect of Reserpine on the and Basal Electroencephalogram, EEG. Clin. Neurophysiol. Scalp Arellano, A.P. and g: 150 (abet). Berger, F.M. (1957): The Chemistry and Mode of Action of Tranquillizing Drugs, Ann. N.Y. Acad. Sci. é]: 685-699. I.J. 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Neurol. & EEG Fink, M., Kahn, R.L. and Green, M.A.: Experimental Studies of the Electroshock Process, J. Nerv. Ment. Dis. (in press). Fink, M. (1957): Therapy of Schizophrenia: Role of Alteration of Brain Function in Behavior, Presented 2nd Int. Congress of Psychiatry, Zurich. �- 15 REFERENCES 13. Fink, M., Green, M.A. and Bender, M.B. (1952). The Face-Hand Test as a Diagnostic Sign of Organic Mental Syndrome, Neurology' 2: h6—58. 14. Fink, M., Shaw, R., Gross, G. and Coleman, F.S.: Comparative Study of Chlorpromazine and Insulin Coma in the Therapy of Psychosis, J. Amer. Med. Assoc. (in press). 15. Hankoff, L.D., Kaye, E., Engelhardt, D.M. and Freedman, N. (1957): Convulsions Complicating Ataractic Therapy, Their Incidence and Theoretical Implications, N.Y. State J. Med. 51: 2967-2972. l6. Hoagland, H., Malamnd, w., Kaufman, 1.0. and Pincus, G. 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Perlstein, D.w. and Retterstol, M.A. (1956): Disorders, J. Revitch, E. (l95h): Clinical N. Miltown, Its Use in Convulsive and Related Assoc. 161: thO. Am. med. Observations on Organic Improvement Following Psychiat. Quart. 28: 79-92. Brain Protracted Damage and Insulin Coma, (1951): Changes in the EEG Under Barbiturate Anesthesia Produced by Electro Convulsive Treatment and Their Significance for the Theory of ECT Action, EEG Clin. Neurophysiol. g: 261-280. 32. Roth, 33- Roth, M., Kay, D.W.K., Shaw, J. and Green, J. (1957): Prognosis and Pentothal Induced Electroencephalographic Changes in ElectroConvulsive Treatment, EEG. Clin. Neurophysiol. 2: 225-238. 3h. Shagass, C. and Rowsell, P.W. (195k): Serial Electroencephalographic and Clinical Studies in a Case of Prolonged Insulin Coma, A.M.A. Arch. Neurol. & Psychiat. 12: 705—711. 35- Sigg, E.B. and Schneider, J.A. (1957): Mechanisms Involved in the Interaction of Various Central Stimulants and Reserpine, EEG. Clin. Neurophysiol. 2: h19-h26. 36. Simon, A., Margolis, L.H., Adams, J.E. and Bowman, K.M. (1951): Unilateral and Bilateral Ldbotomy: A Controlled Evaluation. M. A.M.A. Arch. Neurol. & Psychiat. gg; ugh—503. �- 17 REFERENCES Chlorpromazine: Use to Activate Electroencephalographic Seizure Patterns, EEG Clin. Neurophysiol. 2: #27-hh0. 37- Stewart, L.F. (1957): 38. Ulett, G.A., Smith, K. Convulsive and Control Group, 6.0. (1956): Evaluation of Subconvulsive Shock Therapies Utilizing a and Glesser, Am. J. Psychiat. 112: 795-802. Wachspress, M., Blumberg, A.G., Fink, M. and Miller, J.S.A. (L956): Evaluation of High—Dose Reserpine Therapy for Relief of Anxiety, J. Hillside Hosg. 2: 67-77. #0. Walter, R.D., Yaeger, C.L., Margolis, L.H. and Simon, A. (1955): The EEG Changes in Unilateral and Bilateral Frontal Lobotomy, 111: 590-59h. Am. J. Psychiat. hi. Symbolic Weinstein, E.A. and Kahn, R.L. (1955): Denial of Illness: Thomas. C.C. and Physiological Aspects. Springfield, 111.: he. Wikler, A.: Personal Communication. (1953): Yaeger, C.L., Simon, A., fiargolis, L.H. and Burch, N.R.: Electroencephalographic Studies in Posthypoglycemic Coma, J. Nerv. & Ment. Dis. 118: h35—hhl. �A Unified Theory of the Action of Physiodynamic Therapies Max Fink, M.D. From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Read at the 2nd International Congress of Psychiatry, Zurich, September 6, N.Y. 1957. Institute of Mental Health, National Institutes of Health, U.S. Public Health Service; and the Board of Directors' Research Fund of the Society of the Hillside Hospital. Aided by grant M-927 of the National 10-7-57 �Iv: A The 10/5/57 Unified Theory of the Action of Physiodynamic Therapies proper role of the physiodynamic therapies (electroshock, insulin coma and lobotomy) in psychiatry remains poorly defined. In part, this results from the lack of an adequate formulation of their of action. In the past mode six years increasing evidence for a neurophysiologic-adaptive shock therapy has been presented (hl, 32, 38, 1). view of electro- This view ascribes the thera- peutic precess in electroshock to a persistent alteration in cerebral function which provides the milieu environment. The type for a change in adaptation of the subject to his of adaptation evoked is dependent upon the personality of the subject, the environmental situation, and the duration of the induced alteration in cerebral function. Concurrently, of action in insulin mode coma (31) and lobotomy (ho) has developed. During the past four years we have studied the alteration in various indices of brain function of psychiatric patients to therapy. The view of insulin relation between and the behavioral response neurophysiologic-adaptive view of electrhshock has been supported and amplified (9, 10, for a similar similar an awareness of a coma has been ll, 20, 21); evidence presented (19); and recently the concept has been extended to the newer "tranquillizers" (12). These studies provide the basis for a generalization concerning the efficacy of these therapies. It is our purpose in this report to examine the exPerimental evidence whether or not the mode of action of each of these therapies may to determine result their ability to induce sustained alteration in cerebral function; from and the corol- lary question, whether measurable alteration in cerebral function is a necessary �-2condition for the efficacy of these therapies, or a "complication" or "untoward effect." The include indices of brain function used in these studies have varied. These memory scales (26), visual (22) and tactile changes in language patterns of orientation both (13) perceptual tasks, and clinically (21) changes in the delta index, both in routine records (9, 10) and by intravenous thiopentone (32, 33), and successfully. For this review, have been selected because of after In electroencephalographic studies of this problem, intravenous amobarbital (20). delta index of the unactivated and in the beta index (16) have been applied two indices EEG, and after activation will be stressed: changes in the clinical neurologic signs. These indices their successful application in the analysis of the electroshock process, and because data is available for each of the therapeutic modalities . �OBSERVATIONS: (a) Electroshock: The role of changes in ll). shock (9, following notes summarize our experimental studies of the EEG delta activity in the response of subjects to electro- In these studies, electroencephalograms were obtained before treatment, and at weekly intervals on a day after a treatment in consecutive electroshock referrals. week, Grand mal treatments were administered for 12-20 treatments. The EEG three times a records were quantitatively analyzed for the amount of induced delta activity, and classified into categories of "high", "moderate" and "low" degrees of delta patients were independently the categories of In the activity. At the end of treatment, the rated for their short term clinical reaponse into "much improved", "moderately improved" and "unimproved”. initial series of patients, a significant relationship between the early induction of high degrees of delta activity, and clinical ratings of Eighty percent of the records in the "much improved" was observed. much improved group were high degree delta by the h-6 treatment; and the percentage was sus- tained at 90% in the third and fourth weeks. In contrast, none of the unimproved patients developed high degree delta records in the 20% three weeks, and only of the records in the fourth week were so classified. In a subsequent predictive study, the and first third weeks of treatment delta records were analyzed. on both occasions, 67% were patients without such records, categories. 70% EEG records during the second 0f the patients rated as who had much improved, high degree while of the were in the unimproved and moderately improved �Roth (32, 33) studying the EEG h . delta activity thiopentone after electroshock has related both the evoked by intravenous stability and the rate of remission of patients with endogenous depressions to the peak value of the induced slow activity. activity level, " He ...... concluded that patients not attaining a specified delta have not acquired an adequate physiological basis for recovery," and recommended measurement of delta activity levels after thiopentone as a guide to the clinical management of patients. Further information is obtained from convulsive-subconvulsive control studies. While convulsive electroshock induces degrees of vary from low to high, subconvulsive therapy rarely alters duces low degrees of delta delta activity that EEG patterns or in- activity (11). In their comparative study of different convulsive and subconvulsive techniques, Ulett, Smith and Glaser (38) demon- strated a significantly greater recovery rate for the convulsive than the subconvulsive group. In a similar study (11) recently completed here, twenty-seven patients received a course of subconvulsive therapy. weekly Electroencephalograms, taken at intervals, demonstrated minimal changes ~ none of the records were scored as middle or high delta activity. 0f the 27 patients, no change in behavior was noted in 23, and of these, 19 were referred for a second course of treatment. Grand mal electroshock induced a high degree of delta activity in fourteen. All patients in this group showed significant changes in behavior, while of the five who did not show the delta response, only two showed a behavioral change. (b) Tranguillizing Drugs: When the newer drug therapies are studied from the viewpoint of �-5. their electroencephalographic and clinical neurologic effects, a meaningful classification emerges. Furthermore, a relationship between the degree and type of induced change in cerebral function and therapeutic efficacy may be noted. The ability of these agents to induce such signs of central nervous system dysfunction as motor rigidity, depression, excitement and seizures are well known. Less well documented, however, are the clearly definable electroencephalographic patterns. Based on observations made of drugs in adult psychiatric patients, the EEG in chronic administration changes may be according to predominant changes in the frequency spectrum. classified There are three broad types: I. Increased slow wave activity with hypersynchrony ("bursts") - "delta shift" II. Desynchronization with voltage and frequency and III. irregular theta activity — "desynchronization" shift." Increased high voltage fast activity - "beta Of the group of drugs inducing a derivatives chlorpromazine, promazine, Each drug induces irregularity delta shift, the phenothiazine and perphenazine are clear examples. seizures in non—epileptice or exaggerates seizures in epileptic patients (7, 8, 15, 29, 37). neurologic patterns when given have induced parkinsonism in have observed seizures in 10% Each drug induces in adequate dosage. clinical parkinsonian In our laboratories, all patients receiving chlorpromazine (1k) and of a group of psychotic patients without previous history of seizures. Induced delta activity, including burst activity, observed in more than we half the patients in this series. was �- 6 - Reserpine also evokes delta activity At high dosage levels, it exaggerates when given in large doses (2). seizures in epileptics and induces seizures in animals (35). At the usual clinical dosages, however, reserpine induces desynchronization of frequencies with a moderate increase in theta activity (28), without seizure induction but with definite motor rigidities. In a series of patients treated here (39), parkinsonism was induced in patients. EEG changes were limited to desynchronization only, without all delta burst activity. The primary the induction of EEG response of two other drugs, mepazine and benactyzine, is desynchronization. Mepnzine, a phenothiazine derivative, induces desynchronization with small amounts of theta activity has not been described, nor or parkinsonism in the have we found activity (7). Delta reports either of seizures clinical literature. Benactyzine, a potent anticholin— ergic compound, induces a blocking of alpha, flattening of the record and 1?). Neither seizures nor parkinsonism have occasional theta activity (5, been described for this agent. Meprobamate beta and shift in the EEG is the clearest example of the group of drugs inducing a (3). This agent further differs from the phenothiazines reserpine in not producing parkinsonism and not only are clinical seizures not induced, but definite anti—epileptic activity has been described (30). Habituation is readily achieved, seizures have been observed (ha). barbiturates than like the other If we determine the and withdrawal phenomena of agitation In these actions, meprobamate new is and more like tranquillizers. clinical efficacy of these agents, we note a parallel �- 7 between the induced drugs that thiazine most EEG effects their potency in altering behavior. and readily induce a delta shift in frequencies - the pheno- the greatest clinical efficacy in the compounds - are those with therapy of psychoses. EEG The The compounds with lesser activity in this direction are less efficacious clinically. (c) Insulin Coma The well documented. Therapy: effects of insulin During each coma, persists for minutes to a EEG coma delta activity is induced, after gavage. few hours imately one third of patients receiving deep seizures, aphasia or prolonged coma therapy on the nervous system are coma which usually infrequently, in approx- Not therapy in this hospital, results. After such events, changes EEG of delta activity persist for days, and in cases of prolonged coma, for weeks and months (h3). relation between prolonged The coma, altered brain function ioral response has been discussed at length. Revitch of prolonged coma and concluded tion of organic brain damage, that (31) reported improvement may be insulin eight cases attributed to the induc- similar to lobotomy. Yaeger, Burch (h3), describing twelve cases of prolonged and behav- Simon, Margolis and correlation coma, noted a between length of coma, degree of organic confusion, remission of mental symptoms and degree of EEG abnormality. Shagass and Rowsell (3h), emphasizing and Kwalwasser and Caplan (27) presented EEG individual cases to support the data, same conclusion. we reported a similar relationship between prolonged response in a case study (19). A 3h coma and behavioral year old schizophrenic patient with paranoid �- 8 - ideation developed a left hemiplegia during insulin coma therapy. With the onset of neurologic signs of hemiparesis, hemianopsia, hemisensory syndrome and spatial inattention, there was a marked change in speech and behavior. loquacious and denied his illness. was by became He ludic, His former paranoidowithdrawal type pattern replaced by a friendly cooperative attitude. These changes were accompanied delta changes in the as well as language changes EEG, dicative of altered brain function. The behavioral changes persisted so that he neurologic was after amobarbital in- symptoms resolved, but the discharged two months later as "much improved." (d) Lobotomy: While we have not had the opportunity from the point of view of document a this summary, similar relationship. all subjects postoperatively (to) in a study of after three years. 150 EEG to study lobotomy patients the reports of numerous observers clearly changes of delta activity are present in persist for varying periods. Walter et al., patients, found an 80% persistence of abnormal EEG activity (6) and These authors ment and the degree and also noted a relation between clinical improve- extent of postoperative slow wave activity. Postoperative seizures are a frequent "complication," being variously reported as occurring up to 20% of subjects (25). Furthermore, there is a relationship between the extent of brain tissue cut and the therapeutic Circumscribed surgical lesions, regardless of locus, have an improvement lower than unilateral lobectomy; are "improved" upon by a and these outcome. rate latter are frequently inadequate bilateral procedure (36). and �DISCUSSION: When view of an the various physiodynamic therapies are essayed from the point of alteration in brain function, a therapies represent devices These of action becomes apparent. common mode brain which induce appreciable changes in function, with resultant change in behavior. Electroshock and lobotomy induce measurable diffuse changes in brain function when when given How clear. is primarily tran— in adequate dosage. persistent changes in cerebral function affect behavior is not Psychotic dehavior is not "reversed" or "obliterated". Rather, with alteration in the central nervous system milieu, there is all aspects of behavior including perception, and coma complications ensue; and the phenothiazine and reserpine groups of quillizers an directly; insulin attitude. The mood, affect, an alteration in memory, Judgment specific adaptive response is variable for each subject dependent on numerous historical and environmental sonality (18), environmental situation factors. and Pre-morbid per- and expectations (11), and the duration of the alteration in brain fUnction (10) have recently been discussed as determinants of the behavioral response under these conditions. The induced changes in behavior are evaluated by the psychiatrist, administrator or family as to the degree of "improvement." These ratings are value judgments, based upon such factors as the type of induced behavioral response, the environmental tolerance and the observer's expectations. context, the physiodynamic therapies induce behavioral change which do not induce "improvement" - is secondarily evaluated as In this rather they improvement. alteration of cerebral function is therefore not a "complication" or The an "untoward �- lo - effect" but the desired goal of these forms of therapy. therapies introduced during the past thirty years, Of the many "organic" none apparently, has been a specific agent for the therapy of psychoses (in the sense that penicillin is specific for neurosyphilis and nicotinic acid for pellagra dementia), but rather devices with greater or lesser degrees of applicability and efficacy in altering behavior by altering the cerebral milieu. this context, the various physiodynamic therapies are not specific In for a type of psychosis. was The early enthusiasm that reserpine or chlorpromazine Specific for schizOphrenia, or hypotheses that ascribe significane to an antagonism between these drugs and "psychosis" or "schizophrenia" are not tenable. Similar enthusiasm claiming a specificity of insulin also untenable, insulin coma EEG and support control study for this view coma for schizophrenia is is presented in a recent chlorpromazine- (1’4). analysis of these therapies permits a more explicit definition of the induced alteration in brain function. Changes in cerebral function reflected by a shift in the spectrum of EEG frequencies toward the slower range, with a concomitant increase in voltage and a periodicity described as "bursts" or "hypersynchrony" provide the change in milieu behavior. The that is more effective in altering significance of the delta shift has been clearly demonstrated in electroshock therapy; and can be inferred from the available data in lobotomy, insulin coma, and the That a delta drug effects. tranquillizers. shift has Those drugs some Specificity is seen in the analyses of the that induce the delta shift - the phenothiazines and reserpine - have been consistently reported as effective modifiers of psychotic �-11... of psychotic behavior. Changes in brain function reflected by tion only, or a shift in frequency Spectrum efficacy in altering psychotic behavior. is further to the faster range, have a limited * The significance of a delta shift seen in the limited efficacy of subconvulsive electroshock when Another aspect of the alteration in brain function in seizure threshold. change With the which may be defined delta shift in the in clinical seizures would be anticipated. This is indeed true. been described following electroshock (h, 2%), are prominent (to) and a common comp ‘ pared to convulsive electroshock in the management of psychoses. is the desynchroniza— EEG EEG, an increase Seizures have after lobotomy "complication" during and occasionally following insulin coma therapy (23). With the tranquillizers, the parallel of clinical efficacy and seizure induction is most striking. reserpine rarely; benactyzine not at all; commonly; anticonvulsant! EEG Phenothiazine compounds induce seizures The lowering delta shift induced and meprobamate is a potent of seizure threshold parallels the extent of the by these compounds. Similar analyses can be made for the potentiation of sedative action and induction of parkinsonism - both potent indices of an The quency some alteration in cerebral function. neurologic basis for the delta shift and increase in seizure fre- is unclear. Whether this represents a persistent change in function of specific brain stem nuclear system, as the centrencephalic, thalamic or hypothalamic, is conjectural. From the wide range of agents that can induce a * These observations suggest the application of EEG screening of new chemo~ therapeutic compounds for therapeutic efficacy according to their ability to induce delta burst activity with a minimum of side effects. �- 13 SUMMARY: 1. shock, The neurophysiologic and clinical neurologic aspects of electro- "tranquillizers," insulin 2. The coma and lobotomy, are reviewed. efficacy of each therapy in the treatment of psychoses is related to the ability to induce a persistent change in cerebral function, of which a delta shift in the seizures are indices. 3. two EEG spectrum and an increase in incidence of Alteration in cerebral function is behavioral change with each of these therapies. a "complication," nor an "untoward mode an essential prerequisite of Such alteration is neither effect," but is the gigs 333 299 of the of action of these therapies. M. No evidence has been educed in these studies that the physiodynamic therapies are Specific agents for the relief of psychoses; nor specific do they affect a segment of the nervous system; nor do they induce Specific behavioral changes. 5. and The therapeutic process of electroshock, insulin tranquillizers may be in cerebral function coma, lobotomy ascribed to the induction of a persistent alteration which provides the milieu the subject to his environment. for a change in adaptation of �- 1a - REFERENCBS Pace, J.w., Esrnoff, M.K. and Bowditch, 8.0. (1956): Neurophysiologic Effects of Electrically Induced Convulsions, A.M.A. Arch. Neurol. & Psychiat. 12: 371-378. Aird, R.B., Strait, L.A., Jeri, Arellano, A.P. and R. (1956): The Effect of Reserpine on the EEG. Clin. Neurophysiol. Scalp and Basal Electroencephalogram, §: (abet). 150 The Chemistry and Mode of Action of Drugs, Ann. N.Y. Acad. Sci. é]: 685—699. F.M. (1957): Berger, lizing I.J. Tranquil- Spontaneous Seizures and Related Electroo Following Shock Therapy, J. Nerv. Findings encephalographic Ment. Dis. 122: 581-588. Blumenthal, (1955): Coady, A. and Jewesbury, E.C.O. (1956): A Clinical Trial of Benactyzine Hydrochloride ("Suavital") as a Physical Relaxant, Brit. Med. Journ. Mar. 3, pp. h85-h87. Cohn, R. (l9h5): Study of Prefrontal Lobotomy, Arch. Neurol. fig; 351-357. EEG Psychiat. & Discussion, Symposium on the PsychOpharmacologic Approach to Schizophrenia, Second Int'l Congress of Psychiatry, Zurich. Denber, H.C.B. (1957): Fabisch, Effect of Chlorpromazine on the Electroencephalogram of Epileptic Patients, J. Neurol. Neurosurg. & Psychiat. g9: w. (1957): 185-190. Fink, M. and Kahn, R.L. (1956): Quantitative Studies of Slow Wave Activity Following Electroshock, EEG Clin. Neurophysiol. g: 10. Fink, M. 158 and Kahn, R.L. (1957): Relation of EEG Delta Activity to Behavioral Response in Electroshock: ‘Quantitative Serial Studies, 11. (abet). A.M.A. Arch. Neurol. & Psychiat. (in press). Fink, M., Kahn, R.L. and Green, M.A.: Experimental Studies of the Electroshock Process, J. Nerv. Ment. Dis. (in press). Fink, M. (1957): Therapy of Schizophrenia: Role of Alteration of Brain Function in Behavior, Presented 2nd Int. Congress of Psychiatry, Zurich. �- 15 REFERENCES 13. Fink, M., Green, MlA. and Bender, M.B. (1952): The Faceofiand Test as a Diagnostic Sign of Organic Mental Syndrome, Neurology .§= ”6‘58. 1h. Fink, M., Shaw, R., Gross, G. and Coleman, F.S.: Comparative Study of Chlorpromazine and Insulin Coma in the Therapy of Psychosis, J. Amer. Med. Assoc. (in press). 15. Hankoff, L.D., Kaye, E., Engelhardt, D.M. and Freedman, N. (1957): Convulsions Complicating Ataractic Therapy, Their Incidence and Theoretical Implications, N.Y. State J. Med. 21: 2967—2972. 16. Hoagland, H., Malamud, W., Kaufman, I.C. and Pincus, G. (l9h6): Changes in Electroencephalogram and in Excretion of 17 Ketosteroids Accompanying Electra-shock Therapy of Agitated Depression, Psychom. Med, g: 2h6~251. 17. Jacobson, E. (1955): Suavitil, et Nyt Stof Med Specifik Virkning pa Centralnervesystemet, Ugeskrift for Laeger, 117: llh7-1151. 18. Kahn, R.L. and Fink, M.: 19. Kahn, R.L., Graubert, D. and Fink, 20. Kahn, R.L., Fink, Personality Factors in Behavioral Response to Electroshock Therapy, Conf. Neurol. (in press). (1955): of Parts of the Body.After Insulin Hospital. ‘3: 13h-1h8. Coma Delusional Reduplication Therapy, J. Hillside and Weinstein, E.A. (i956): Relation of Amobarbital Test to Clinical Improvement in Electroshock, A.M.A. Arch. Neurol. & 21. M. M. Psychiat. {1§: 23~29. Changes in Languages During Electroshock Therapy, in Psychopathology;of Communication, Grune & Stratton, Kahn, R.L. and Fink, M. (1957): (in press). M. (1957): Perception of Embedded Figures After Brain Altered Induced Function, Am. Psychol. lg: 361 (abst.). 22. Kahn, R.L. and Fink, 23. Kalinowsky, L.B. and Koch, P. (1952): Shock Treatment, Psychosurgery and Other Somatic Treatments in Psychiatry, New York: Grune & 2h. Karliner, Stratton. W. (1956): J. Hillside Epileptic States Following Electroshock Therapy, Hosp. g: 258-263. �- 16 - REFERENCES Incidence of Seizures, with (1955): 25. Klotz, 26. Korin, H., Fink, M. Prefrontal lhh-lh8. Findings, in Psychiat. 13: EEG Lobotomy, A.M.A. Arch. Neurol & and Kwalwasser, S. (1956): Relation of Changes Memory and Learning to Improvement in Electroshock, in M. Conf. Neural. 1Q: 88-96. 27. Knalwasser, S. and Caplan, M. (1952): A Case of Prolonged Insulin Coma: Treatment, J. Hillsidewflosp. 1: 1&5-155. 28. Liberson, W. EEG T. (1956): Effect of "Tranquillizing" Clin. Neurophysiol. §: 523. (1957): The Occurrence of Epileptic Fits in Leucotomized Patients Receiving Chlorpromazine Therapy, J. Neurol., Neurosurg., & Psychiat. 29: 105-107. Betterstol, 29. Liddell, 30. Perlstein, 31. Revitch, E. (l95h): D.W. and N. Miltown, Its Use in Convulsive and Related Am. Med. Assoc. 161: thO. M.A. (1956): Disorders, J. Clinical Observations on Organic Brain Improvement Following Pszghiat. Quart. g§z 79—92. Roth, M. Drugs on EEG, Protracted Damage and Insulin Coma, (1951): Changes in the EEG Under Barbiturate Anesthesia Produced by Electra Convulsive Treatment and Their Significance for the Theory of ECT Action, EEG Clin. Neurophysiol. g: 261-280. 33- Roth, M., Kay, D.W.K., Shaw, J. and Green, J. (1957): Prognosis and Pentethal Induced Electroencephalographic Changes in ElectroConvulsive Treatment, EEG. Clin. Neurophysiol. ‘2: 225-238. 3h. Shagass, C. and Rowsell, PM. (195M: Serial Electroencephalographic and Clinical Studies in a Case of Prolonged Insulin Coma, A.M.A. Arch. Neurol. & Psychiat. lg: 705~711. 35- Sigg, E.B. and Schneider, J.A. (1957): mechanisms Involved in the Interaction of Various Central Stimulants and Reserpine, EEG. Clin. Neurophysiol. ‘2: h19-h26. 36. Simon, A., Margolis, L.H., Adams, J.E. and Bowman, K.M. (1951): Unilateral and Bilateral Lobotomy: A Controlled Evaluation. �- 17 - REFERENCES Chlorpromaiine: Use to Activate Electro~ encephalographic Seizure Patterns, EEG Clin. Neurophysiol. 2: h27-hh0. 37- Stewart, L.F. (1957): 38. Ulett, G.A., Smith, 39- Wachspress, M., Blumberg, A.G., Fink, #0. Walter, R.D., Yeager, C.L., Margolis, L.H. and Simon, A. (1955): The EEG Changes in Unilateral and Bilateral Frontal Lobotomy, 111: 590-59h. Am. J. Psychiat. kl. Weinstein, E.A. and Kenn, R.L. (1955): Denial of Illness: Symbolic and Physiological Aspects. Springfield, 111.: C.C. Thomas. #2. Wikler, A.: R3. Yaeger, C.L., Simon, A., Margolis, L.H. and Burch, N.R.: (1953): Electroencephalographic Studies in Posthypoglycemic Coma, J. Nerv. & Ment. Dis. 118: h35~hhl. Glesser, 6.0. (1956): Evaluation of Convulsive and Subconvulsive Shock Therapies Utilizing a Control Group, Am. J. Psychiat. 112: 795-802. K. and Miller, J.S.A. (L956): Reserpine Therapy for Relief of M. and Evaluation of High-Dose Anxiety, J. Hillside Hosp. E: 67~77. Personal Communication. �- 12 _ delta shift, with or without hypersynchrony, EEG changes it appears more likely that the reflect an alteration in the diffuse biochemical activity of the nervous system rather than in a focal activity of specific cellular masses. �gfiéW W ¢ mA/LWWW“??? flflmw ”fl 0 WA; .Wbfl' WV WW/W» Wfiwé W erflc/ééé/‘nggg WW Wan/Raw ,5, wage; 4* ”Jaw“ £5149 MM 55¢?” 44%“ €40» MW + mama 5-an we 9 MA 401: é’U—k , é1w%(b Wdyk 7" «anlwn/em r 6 MW Www MAM/:2 WAMWMmM ”acacia/77¢“ M 0.4.2. 407973 WWMMWM MWMA Wfl’wwvéob (law w W MfM 3k- (WALK-MW —~ c w mQa—éflaec. "1426 7'":wa flow szC 2’ , VM’bgek-«tk’ fl/Lf/wa «6% Egg kw Mgr , LWwaCA/I wwafl/VL/e .Z 9744M /,’_5._ J 1(HMWA‘QWW CWc/QW'OA‘: /\ ("‘1‘ fyék" W W “FM W (aw/WWW wa» W/MW W»! 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' ”i'QUq \ qi‘fi-«x;.¢'\§§\r "ix ‘3 ,, 3 F—J-n , r) ,, ., -- M A v = ‘\ - | J) J} \3_ } 9531‘wNAQDQ s;- "(f‘ LJ) ' l . 3 r k1\ J _ ‘53 x 1- 2' 743. \3: - 4344;- 3‘*‘ AV‘JJQ.» ’ ‘2‘J&\ I a “432.35 «3513:; )vaia r"3-1-3 51,5r ‘ *7 \ , ._3 ~ \ , . 3 (\x ,‘ .3-.M—vx;“* f T . . 3 \I-J‘IJL‘J ‘ ,3 3.3\J -\_)\r§ 3 Q [11-43) " j J—‘~f'\' {t ’3‘ .3. 3 3, u r “331,-. ‘ is m N3 a . v �QFURTHER OBSERVATIONS MADE SINCE THE ARTICLE "Electro-cncephalo- graphic Evidence of Bersonality Changes by Ataraxic Drugs in Mentally Disturbed Patients." WAS WRITTEN. l) A number of mistakes due to faulty or non-standardized technique in the assessment of alpha a) Duration of the recording: It was found that some activity for the first stability patients had were made. little alpha five to ten minutes of the who recording deve10ped a more stable alpha activity, later it is on. therefore suggested that samples of alpha activity should be taken at least ten minutes after the beginning of the E.E.G. recording. b) Period of the day: Slight differences of habitual alpha activity were observed in one and the same patient according to the time of the day when the E.E.G. recording was taken. applies also to the period of the last meal. It is therefore suggested that the E.E.G. tracings The same should be taken at the same time of the day and at the same intervals after the last mealhad been taken. c) Waiting of the patient before the E.E.G. recording. It observed that if patients had to wait for long periods in the waiting room before his E.E.G. recordwas ings were taken the alpha activity was poorer than on d) Noises. The effect of any noises, particularly of any talk, during the E.E.G. recording changed thexalpha E.E.G. pattern imedia-telyss It seems therefore that the total absence of any noise is necessary to produce a valid E.E.G. recording for the assessment of alpha 0) A stability. Special alpha run, allowing the simultaneous trac-' ing of temporal and parietal occipital alpha was found to be useful. �2) The alpha stabilizing effect of Largactil and Serpasil. a) Single administration: intravenous and intramuscular administration of a single large dose of Largactil (100 mg.) or Serpasil (5 mg.) often had little or no effect on the 1. The alpha stability. ii. The period of administration of the 3 days to 2 same drugs, over a weeks, did produce an alpha stabilization. b) Age groups: effect of these two drugs, in sufficient quantities, was observed in all children whose habitual alpha activity was poor. ii. In adults there were some exceptions to the rule, particularly elderly people suffering from depression. 0) Quantitl: The effect of alpha stabilization, even after a long period of administration, was sometimes only observed when large quantities of the drugs were given. It is therefore suggested that in case of a negative E.E.G. effect the test should be repeated after in1. The creasing the dosage of the drug. d) Temporal Alpha: It is observed that in sons cases the alpha stabilization occurred equally in the temporal and parietal occipital regions. Most often however, the alpha stabilization was more marked in the temporal regions, infrequently the alpha stabilization occurred in the temporal regions only. and not e) An experiment was conducted on 30 schizophrenic pmients, 10 patients received Serpasil 3 grs. daily, 10 patients received a new drug to be tested and 10 patients received a placebo. E.E.G. tracings were taken before the 'administration of the drugs and on one occasion after the course of drugs was started. Psychological tests were made to assess the clinical improvement. �It that the patients who had received Serpasil showed a statistically significant improvement of their alpha-stability. The ten patients who had received the new drug that was to be tested showed a significant diminution was found of alpha-stability in the temporal regions. The patients who received the placebo showed a random distribution of improvement or deterioration of their temporal alpha rhythm. The correlation between improvement of alpha-stability int.- the temporal region and clinical improvement was about +0.45 only, in all 30 cases, whether this was due to the effect of drugs or not. The Doctor who was conducting the experiment, the statistician of the Mental Hygiene Department and our own observations in our E.E.G. Department showed that many relevant factors during the psychological testing (in which unfortunately "socialis- ation“ was not a part) suggesting improvement were not controle' led. f) It is that alpha-stability may be correlated with relaxation and alpha-blocking with tension, though this is certainly not the full story, probably a reasonable hypothesis to assume only an approximation. About 80% of true melancholics, who are certainly not relaxed, have an exceptionally high alpha index. Ostow's suggestion thatwalpha activity generally respons to a preparation for constructive thinking and the disappearance of the alpha activity when the constructive process was put into action, probably, is nearer to the truth. The more correct hypothesis would seem to be that relaxed patients generally ruminate less than tense subjects. 3) Further references bearing on the subject of alpha stabilization: a) "By hypnotic suggestion to relax, Ford and Yeager reported the induction of "good" alpha patterns in several patients with anxiety states, whose previous E.E.G.'s showed little or no alpha-rhythm.' Relaxation suggestions were not followed by EE.G. changes in subjects whose E.E.G.'s rhythm." naturally showed "good" �- 4 _ Ford, W.L. and Yeager, C.L. "changes in the electroencephalogram in subjects under hypnosis. "Dis.nerv. systo 1948, 9, 190—192. H a) There are several references in the literature to the fact that short courses of electro-shock-treatment tend to increase the E.E.G. alpha activity. 4) W: quoting a reference of Ellingson a mistake occurred in my article which should be corrected. When Should read - preposition by Saul and Davis that passive indiv— iduals tend to have regular persistent alpha rhythms of high index has been often cited in the literature and “The appears to have been accepted as fact. Sisson and E11ingson reviewed the evidence upon which that preposition was based and found it unconvincing.” uni?“ �/ g , §n\3\ L. @ 6 W Q wwwwwsméo WfipfloA Ni Nf \\ WWUWMNW . w glwfig ENK :xWng W . (GMWECQMV wmim 3% 13mm v Eé . IVSNEPSNxMPIQXB \m\§§£§§w\% ‘ gmxmigg §§\ W I \KQ‘PVGV \um m EQ® “Sag V � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource A unified theory of the action of physiodynamic therapies. J Hillside Hosp., 6: 197-206. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-001-23-028 Date A point or period of time associated with an event in the lifecycle of the resource 1957 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource 5 items. 1: Xerox copy. 2: Two presentation copies. 3: Handwritten manuscript.4: Draft copy. 5: Chart. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/73f23282cc67af28739fea856ee770e8.pdf e300a093a9da17b1283d89c0561639fc PDF Text Text Reprinted from ”Electroencephalography and Clinical NeurOphysiology Iournal" Vol. 10, No. 1, February 1958. LATERAL GAZE NYSTAGMUS AS AN INDEX OF THE SEDATION THRESHOLD 1 MAx FINK, M.D. With the technical assistance of HANNAH MOSQUERA Department 0] Experimental Psychiatry, Hillside Hospital, Glen Oaks, N.Y. (Received for publication: October 17, 1957) On reading the report of Thorpe and Barker (1957) in the recent issue of the Archives, we were moved to assess our own experiences with the sedation threshold, and to report a clinical guide to the “inflection point” that we have found useful. Following the initial description of the technique by Shagass (1954), we modified our tests which included the administration of the amobarbital test for brain dysfunction (Weinstein et al. 1953) to obtain a measurement of the sedation threshold as well. Our technique was identical to that of Shagass, with the addition of the measurement of nystagmus on lateral gaze which the latter test required. The change in beta amplitude in the EEG was measured visually in consecutive samples of record, using the additive ruler described by Shagass. In the initial group of patients, two observers were unable to identify the onset of slurred speech with consistency. Disagreement led to administration of amounts of amobarbital greater than was required, with the frequent induction of sleep. As we were also obtaining a record of the induction of nystagmus on lateral gaze, we became aware that this index was reliably agreed upon by the two observers, and a correlation with the sedation threshold was sought. We, therefore, omitted the instructions regarding counting and substituted the following instructions. Subjects were told that at periodic intervals they would be requested to open their eyes and to look first to one side and then to the other at pre-arranged tion period. The administration of barbiturates con— tinued until nystagmus was observed, and then an additional 2 cc. were given. RESULTS To date, we have 91 measurements. The following table notes the difference between the number of milli- grams of amobarbital per kilogram body weight for the EEG measure (the sedation threshold) and for the onset of nystagmus. Differences greater than one unit did not occur in this series. The two measurements are seen to be reliably related by a unit of 0.5 or less in more than 90 per cent of the observations. M TABLE I Frequency Distribution of Difference in Amount of Amobarbital Necessary to Induce EEG Change and Nystagmus (mg. amobarbital/kg. body weight) No. Tests (91) 1 47 12 +0.5 +1.0 27 4 Test-Retest Reliability: During these studies we have also had the opportunity to repeat the sedation threshold measurement three to five times in the same patient at weekly intervals. These measurements were done in randomly selected patients receiving subconvulsive doses of elec- TABLE II Absolute Range of ST. Values Range 0 0.5 1.0 1.5 2.0 No. Subjects (16) 0 2 6 2 4 fixation points. This was repeated twice in each direction, usually within ten seconds, while the observer noted the development of sustained regular nystagmus on lateral gaze. Such observation was repeated after each injection of 1 cc. of amobarbital solution, between the 25th and 40th sec. of the injecSupported by the Board of Directors’ Research Fund of the Society of the Hillside Hospital. 1 2 tric current under barbiturate premedication as part of a study of convulsive-subconvulsive electroshock. The behavioral changes in this group were small 14 of the 16 were referred for grand mal electroshock within 4 weeks after the subconvulsive treatment -—— period. The range of sedation threshold measurements under these conditions is noted in table II. [162] �LATERAL GAZE NYSTAGMUS OF THE SEDATION THRESHOLD Being unable to ascribe greater validity to one reading than to any other, we determined the mean sedation threshold for each subject, and the range of variability about the mean. In table III we have listed the subjects in each range of variability about the individual mean value. Thus, the intra-patient inter-test variability for this test in this series is considerable. The test reliability of nystagmus as an index of the electroencephalographic change is well within the retest variability of the test in these subjects. 163 lographique mesuré chez ces malades et dont la validité a été démontrée. Il est recommandé d’utiliser cette méthode en remplacement de celle qui est basée sur l’apparence de troubles dysarthriques. ZUSAMMENFASSUNG Das Auftreten von Nystagmus mit lateralem Blick ist ein klinisches Mass fiir die Sedationsschwelle, welche gut mit dem gemessenen EEG-Index iibereinstimmt und dessen Verlasslichkeit nachgewiesen werden konnte. Gebrauch dieser Methode wird daher TABLE III Range of ST. Values from the Mean Range No. Subjects (16) 0.1—— 0.6—— 0 0.5 1.0 0 6 4 CONCLUSION The appearance of nystagmus on lateral gaze is a clinical guide to the sedation threshold, with a variability from the measured EEG index well within the test-retest reliability of the test itself. It is recommended as a substitute, therefore, for the onset of slurred speech. Further studies of the retest reliability of the sedation threshold are necessary. RESUME L’apparition d’un nystagmus dans le regard latéral est une mesure clinique de la sedation qui montre une bonne correlation avec l’index electroencepha- 1.1— 1.6— 2.0 >2.0 4 1 1 1.5 empfohlen als Ersatz fiir diejenige basiert auf dem Auftreten von verwischter Sprache. REFERENCES The sedation threshold. A method for estimating tension in psychiatric patients. EEG Clin. Neurophysiol, 1954, 6: 221-233. THORPE, J. G. and BARKER, J. C. Objectivity of the sedation threshold. A.M.A. Arch. Neurol. Psychiat, 1957, 78: 194-196. WEINSTEIN, E. A., KAHN, R. L., SUGARMAN, L. and LINN, L. The diagnostic use of amobarbital sodium (“Amytal Sodium”) in brain disease. Amer. J. Psychiat, 1953, 109: 889-895. SHAGASS, C. threshold. sedation the of index M. Lateral as an FINK, nystagmus Reference: gaze physiol, 1958, 10: 162-163. EEG Olin. Neuro- 63:3 �‘ “W 9.13.5? 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MMW‘Wflanmmwmnm W‘s-mm“ �mwas-mmmummsummmw ummmmwwmmuw. “MW unmm, Wm,mmmwfiww. WW �' 1_ W ' ”W «mummy MW “mm.“ wmmm.muwg mm Wigwam m3. é» 3n & 199:. W”; WW 4: ’ “ ' �W WWW Emmtxy WM? 13' 1957‘ W9; Miter, Section or Awhim Baumlm 5:. , AM. 29th a mu ham, W Wm, DP. Roy W mum. 0mm. 7 of ‘ ‘\ \ 16,, Dear Dr. Grimmer: W Inmadmzhoramtmmloafmmdmrmm pmblem. undead short 45an my am vb» m nth-mung an ”gamut of tho «mum tgnsumtofl this that. cmMahala," we are md to “(nativity at w M15192: than 111th this tout, u an as our solution to pufllol mama “the be of help to note W this note is I: the taunt. at pinned to follow your momma. would be for the Archives, I m Fink, 1w. K3563 �PUBLICATION OFFICE AMERICAN MEDICAL ASSOCIATION 535 NORTH DEARBORN STREET CHICAGO IO. ILLINOIS AUSTIN SMITH, EDITOR, A. M A. SCIENTIFIC PUBLICATIONS A. M. A. ArChives Of NEUROLOGY and PSYCHIATRY GILBERT s. COOPER, MANAGING EDITOR A. M. A. SPECIALTY JOURNALS SECTION ON PSYCHIATRY DR. EDITORIAL BOARD RCY R. GRINKER $R., M.D. CHIEF EDITOR. CHICAGO STANLEY COBB, M.D.. BOSTON GEORGE E. GARDNER, M.D.. BOSTON ““353?st JOHN WHITEHORN, M.D., BALTIMORE Institute for Psychosomatic and Psychiatric Research 29th Street and Ellis Avenue, Chicago 16 September 20, 1957 Max Fink, M.D. Department of Experimental Psychiatry Hillside HOSpital 75-59 263rd Street Glen Oaks, New York Dear Doctor Fink: it will not be possible to publish and we like to backlog, large have a wide selection of papers on many subjects and feel that we have published already all that seems important on the sedation threshold test as devised by Shagass.. I the in your paper am very sorry, but ARCHIVES. We have a Regretfully yours, Roy R. Grin er, M.D. Editor~in-Chief for Psychiatry RRszm enclosure �3.er Dr. Mort 3. Sam, General Putnamtu Boa: (7&3 {’4’ BOWEN, ah. 1957. Hospital, Mt Du:- Dr. Scarab: In vnading : recent. article on the ”mmuvity of the Station Threshold" in the Archives or Barclay and Paychntx-y, we were mud to parallel «panama with we test, as well as our 301an to the problm. I would appreciate your enumeration of this short clinical not» for the Section of 61mm. uni laboratory Notes of the mm m EEG hum]... Simon]: you", mm, 130th HE‘BJB or menu-m1 Paychutry; “on. �3-8200 EXT. 380 TEL. LAFAYETTE ROBERT s. SCHWAB. M.D. MASSACHUSETTS GENERAL HOSPITAL BOSTON 14 September 27, 1957 Dr. Max Fink 75-59 263rd Street Hillside Hospital Glen Oaks, New York _ C.N. #61 Dear Dr. Fink: received and I would like to conditionally accept for Clinical Notes in the EEG Journal as it stands subject to the approval Your manuscript has been it of the Bditor—in—Chief, Herbert Jasper. MW Yours very RSS:mc sincerely, Robert S. Schwab, M.D. �1g 33 ‘12, McGILL UNIVERSITY MONTREAL Department of Electrophysiology Allan Memorial Institute, 1025 Pine Avenue'West, Montreal. September 30 1957 Dr.Max Fink, Hillside Hospital, 75-59 263rd Street, Glen Oaks, New York. Dear Max, to see you for your note on the nystagmus. It was nice at Zurich, and I hope that we shall be able to meet Thank you again soon. My best regards. Sincerely, Cw CS/ef % , C. Shagass, M.D. �12/3/58 Discussion: Dr. Shagass Dr. H. Fink - Hillside HOSpital Dr. Thompson, Members and Guests: It is always a pleasure to read another chapter in the unfolding saga of sedative tolerance tests as they have been developed by Dr. Shagass.‘ This study, like its predecessors, relates neurophysiologic indices to behavioral measures this area of psychiatry, reflects a welcome application science to clinical problems. a and in of basic appropriate to examine this report in the perspective of recent concepts in experimental psychiatry. During the 1930's, when electroencephalography was a new science considerable effort It seems in relating EEG patterns to "personality types" or ”diagnoses,” without success. With more refined instrumentation, there have been sporadic re-assessments without noticeable success. In the sedation threshold, however, Dr. Shagass, did succeed in achieving such a relationship. In these earlier studies, he was expended related the amount of barbiturate necessary, under standard conditions of rate of administration and concentration, to induce a specific EEG voltage and frequency change, to the personality profiles of the Handsley-Eysenchian school. It is important to note that the relationship was not between any fixed aspect or index of the EEG and behavior but between a measure of reactivity or responsivity of clinical behavior. We may carry this description a bit-further. The electroencephalogram is a reflection of central or brain neurochenistry, and the reactivity of the electroencephalogram to any chemical stress, a measure of the reactivity, or reSponsivity, or bufibring the EEG and �of the biochemical enzymatic systems flat make up the nervOus system. It is in this organisnic biochemistry that much activity is now directed in experimental psychiatry. The wide variety of phrenotrOpic agents, the new and more potent hallucinogens, and the expanding technics of enzyme and steroid chemistry are providing experimental psychiatry with research tools of considerafle adaptability. One application of these technics highlighted yesterday by Dr. Gottlieb and his co-workers at the Lafayette Clinic,who reported their ihitial observations on the significant relationships between schizophrenic behavior was and the reactivity of insulin. These of the glucose-enzyme systems to the authors carefully noted that there stress was no relationship between the initial levels of their biochemical measures and behavior. Dr. Shagass' earlier studies of the sedation threshold - end-point - are clearly within this tradition. His report today is also in this general tradition, but instead of a neurophysiologic index of clear definition has utilized a clinical index ~ lack of a verbal motor response to a verbal command - as the end-point. In the report today, he has related the amount of pentothal necessary to induce this state of lack of response (which is defined as "sleep") with the affective state of the individual at the time of the experiment. He has observed that the more fearful,disturbed, tense, angry and worried a subject is, the more barbiturate is necessary to induce using an EEG �-3- quieter, more indifferent, inactive and retarded patient is, the less barbiturate is necessary for sleep. He sleep. a Ehe titration is thus achieving a biochemical titratinn, and is, in essence, measuring the subject's responsivity or reactivity to barbiturate. By repeating the studies seriatim, he is able to report shifts in this state of reactivity. In his desire to extend the sedation threshold technic to situations in which the EEG was not available, and provide for greater clinical applicability, some of the precision of the earlier studies has been forfeited. It is not unexpected, considering the lack of precise definition of behavior as well as the endpoint of titration, that the reactivity-clinical relationships I have noted two puzzling relationships. Increasing sleep thresholds are associated, on the one hand, with excitement, worry, restlessness and anger; but also, with clinical improvement in a course of convulsive therapy. Also, in one are somewhat cloudy. patient, transient induced psychosis sharp drop in threshold, while in the same a LSD is associated with patient, fear of a treatment, restlessness and increased tension are associated with rising thresholds. I would snapect that these apparent discrepancies arise frOm the non-Specific nature of behavioral reaponse to neuro— physiologic change and to the poverty of our descriptive language for behavioral change. I would wonder what shape the curves would take if the change in sleep threshold were plotted against other indices of brain function as predominant EEG frequency pattern or degree of synchronization; or such psychologig indices of brain function as the perception of embedded figures or OFF; or such behavioral indices as dyadic or syntactic linguistic �-hanalyses. Alternatively, more precise,— operational measures of the behaviorll subsumed under "anger," restlessness,¥ "worry” may proiido, again, the relationships indicated earlier by the sedation threshold studies. Lest these comments be misconstrued, let me say, in closing, that Dr. Shagass is to be warmly congratulated in these studies basis for the developing neurOphysiologicadaptive hypothesis of behavior. His demonstrations of central neurophysiologic reactivity in the sedation threshold are in the best exPerimental traditions. We are eagerly looking forward to further experimental neurophysiologic studies from his new which are providing a firm laboratories in Iowa. �12/3/58 Discussion: Dr. Shagass Dr. H. rink — Hillside Hospital Dr. Thompson, Henbers and Guests: It is always a pleasure to read another chapter in the unfolding saga of sedative tolerance tests as they have been developed by Dr. Shagass. This study, like its predecessors, relates neurophysiologic indices to behavioral measures and in /‘this area of psychiatry, reflects a welcone application or basic science to clinical problems. It seaas appropriate to examine this report in the perspective — of recent concepts in experimental psychiatry. During the 1930's, electroencephalography was a new science considerable effort was expended in relating EEG patterns to ”personality types" or "diagnoses," without success. With more refined instrumentation, there have been sporadic re-assessnents without noticeable success. In the sedation threshold, however, Dr. Shagass, did succeed in achieving such a relationship. In these earlier studies, he related the amount of barbiturate necessary, under standard conditions or rate of administration-and concentration, to induce a specific EEG voltage and frequency change, to the personality profiles of the Handsley-Eysenchian school. It is important to note that the relationship was not between any fixed aspect or index of the EEG when and behavior but between a measure of reactivity or resphnsivity of clinical behavior. The e1ectro~ We may carry this description a bit further. encephalogran is a reflection of central or brain neurochenistry, and the reactivity of the electroencephalogram to any chemical stress, a measure or the reactivity, or responsivity, or buflhring the EEG and �«2e- of the_biochenica1 ensynatic systems fiat make up the nervous system. It is in this organisnic biochemistry that much activity is now directed in experimental psychiatry. The wide variety or phrenotropic agents, the new and more potent hallucinogens, and the expanding technics of enzyme and steroid chemistry are providing experimental psychiatry with research tools of considerafls adaptability. One application or these technics was highlighted yesterday by Dr. Gottlieb and his co-workers at the Lafayette Clinic,vho reported their initial observations the significant refationships between schizophrenic behavior and the reactivity of the glucose-enzyme systems to the stress of insulin. These authors carefully noted that there was no on relationship between the initial levels of their biochemical measures and behavior. earlier studies of the sedation threshold using an EEG endspoint ~ are clearly within this tradition. Bis report today is also in this general tradition, but instead or a neurophysiologic index of clear definition has utilized a clinical index - lack of a verbal notor response to a verbal Dr. Shagass' - as the endnpoint.' In the report today, he has related the amount of pentothal necessary to induce this state of lack of response (which is defined as asleep“) with the affective state or the individual at the tins of the experiment. He has command observed that the more feartn1,distnrbed, tense, angry and worried a subject is, the more barbiturate is necessary to induce �-3sleep. the quieter, gore indifferent, inactive and retarded a patient is, the last barbiturate is necessary for sleep. He titration is/thna achieving a biochemicat titration, and is, in essence, measuring the subject's responsivity or reactivity to barbiturate. By repeating the studies seriatin, he is able to report shifts in this state of reactivity. In his desire to extend the sedation threshold technic to situations in which the EEG was not available, and provide for greater clinical applicability, eons of the precision of the earlier studies has been forfeited. It is not unexpected, considering the lack of precise definition of behavior as well as the endpoint of titration, that the reactivity-clinical relationships are somewhat cloudy. I have noted two finssling relationships. Increasing sleep thresholds are associated, on the one hand, with excitenent, worry, restlessness also, with clinical improvement in a course of convulsive therapy. also, in one patient, a transient LSD induced psychosis is associated with a sharp drop in threshold, while in the sane patient, tear of treatment, restlessness and increased tension are associated with rising thresholds. I would suspect that these apparent discrepancies and anger; but arise from the nonnspecific nature of behavioral response to neuro~ physiologic changa and to the poverty of our descriptive language for behavioral change. I would wonder what shape the curves would take if the change in sleep threshold were plotted against other indices of brain function as predominant EEG frequency pattern or degree of synchronisation; or such-psychologtg indices of brain function as the perception of embedded figures or 61?; or such behavioral indicee as dyadic or syntactic linguistic �l-h‘ analyses. Alternatively, more precise,~ ofierstionsl measures of the behavioral subsumed under ”anger,“ restlessness,1 “worry" hey provide, again, the relationships indiohted esrlier by the sedation threshold studies. Lest these comments he misconstrued, let me say, in closing, that Dr. Shegsss is to be warmly congratulated in those studies which are providing o firm basis for the developing neurophysiologica adsptive hypothesis of behavior. his demonstrations of central neurophysiologio reactivity in the sedation threshold are in the best experimental traditions. we are eagerly looking forward to further experimental neurophysiologic studies from his new laboratories in Iowa. �qt- I ZIN’EIQAL. 614245 ' ‘ QM r r; m Marlyn»; #ng /% 4n Z/{[ 5/ ’f/e. /3~f7 Ska/177m Amt gnaw; E u, . . 7:va E Wu” E :1va E I . m,“ 1W 1W" ‘ quwr—rrw—nw—v /M /W flaw @524: // M" am/ZEWW/éwu Lb 7%“ @43’ W WM &%M/w/’ Aruéda 54% E E E E M7424 - . �W we moved reading the report of Thorpe and ' in the to assess our own W5 /Q1(LLAAjr Barke%ajm issue of the Archives, we were experiences with the sedation threshold, and to (2 report anether clinical guide to the "inflection point" that useful. ' ‘ ’“ n U Following the initial description the adninistration of the amobarbital W / )1 "# WWW Our ’ ' / ' “‘ '* have found, we ,, I _ / " fir of the technique by Shagass we modified flat: is: iifi— our seaside which included test for brain dysfunction (-Weéna-teim, to obtain a measurement of the sedation threshold as well. technique was identical to that of Shagass, with the addition of the measurement of nystagmus on 775: lateral q change gaze which the latter test required. 7h4¢4ww¢16f EEG was done- visually ‘ ‘ in beta amplitude in the in consecutive samples of record, using the additive ruler described by Shagass. In the initial group of patients, two observers were unable to the onset of slurred speech with consistency. identify Disagreement led to administration of amounts of amobarbital greater than was required, with the frequent induction �-2l?!‘ sleep. gaze, As we were also We, ML. Wis-of :_ reliably that this index was we became aware observers, and w/umd 9/ obtaining /“45“¢’7"" nystagmus on ?/ lateral agreed upon by the slur-e W..a.correla.tion withthe sedation thresholdwv W/{Z‘ therefore, omitted the instructions. regarding counting stituted the following instructions. Subjects intervals they would one side and then be requested to were their open and sub- told that at periodic eyes and to look first to the other at pre-arranged fixation points. This to was repeated twice in each direction, usually within ten seconds, while the observer noted the development of Sustained regular nystagmus gaze. Such observation was repeated after The injection of lateral 1 cc of amo— N, ~: ‘ . “42" barbital solution, each on between the 25 and ho seconds of the injection period. administration of barbiturates continued until nystagmus was observed, and. MW ’00 (Lou and then ?WU°: ——————-—_ To more were given. date, we have 91 measurements. ,, difference between the number of thes926an threshold and W W . MW) not!“ the : milligramkl (/19 m7... of ambbarbitaljfo/r Mafia,” for the Onset of nystagmus, reflects-enemi- Differences greater than one unit did not occur in this series. The two measurements 7,2 79/1; following table 4 The arenreliably related by a unit of 0.5 or lessxw Wamflm~ Z... ‘ ' �-3I TABLE Frequency Distribution of Difference in Amount of Amobarbital Necessary to Induce EEG Change and Nystagmus (mg Amobarbital/Kilogram Body Weight) No. Tests .100 .005 0 +0.5 +1.0 l 12 h? 27 h \ ?// ; Test-Retest Reliability: During these studies all» we ' havenhad the opportunity to repeat the sedation threshold measurement three to five times in the intervals.- weekly These measurements were done patient at same in randomly selected patients receiving subconvulsive doses of electrnc current under barbiturate premedicationqi as part of a study of convulsive-subconvulsive electroshock. changes in this group were small - fourteen of the sixteen The were behavioral referred for /z~n/¢‘¢A{4”~*¢¢ég«~0 ' grand mal electroshock within four weeksye7/ngr . ‘ (fl/$4,224. The range of sedation threshold meaSurement?under these conditions noted in Table II. TABLE II Absolute Range of S.T. Values' Range My, Subjects (/4) 0 0.5 1.0 1.5 2.0 o 2 6 2 h >2.S 2 ff’a./§L»«# is �-hBeing unable to ascribe greater é validity . the we determined we have mean sedation threshold for each subject, subjects in the-m mdmadud MM. value. the listed WE: W W one reading than fies any each range of M basis variability ’ mean III TABLE Range Range /o. fiubjects (/5) other, of S.T. Values from the e 0.10.5 0.61.0 o 6 h 1.6- 101'- 1.5 ’ “N‘r‘m-wrv .,.m 52.0 2.0 7 h J Mi."- Mean 1 1 , . ., K.,.fim’WhfiW-am~w-.w:122-w 7 Wat, {is mus-patient;inter-test variability for this test in this series is considerable. test reliability of The electroencephalograpmzhc change is well within the retest variability of test in these subjects. Qéz: the adapted the appearance of nystagmus on m a ; / J1/ J 1/}, C- i ’ / A A f" is / / /z€—— "/5 I I , [KI-A ,5 - ,v clinical guide to a ‘4’; my: M , fl» gray 1.47! /’L! CW/m4‘4flt (331’; fi{ I, ;’(f fl ,Cy «a, ' M; gaze WWK .ma- Asa/2w ,Aaé .4 // My 4 Wfiffeéé: fr!» WI mat?» lateral WRfi—WW the sedation threshold, a; nystagmus as an index of the AA“: iséwtu/MA‘I (2: 7! /)/”/»£¢A/L.( M #63“e/ Ca” we '1’ .11“ fl¢»%flw//L{u¢{304?“:{3’ a? / ,. 3 if '4" ”17’2“" r , _.;__.‘ 4’ "I; a: A" {fi’flg‘t . ,, ,4? Ayifi ”(:4'5‘ Alt—‘3 / A’Jik �, ..‘ )- I *’ Wv .1. C . ya $407M Mann}; 4 M4, /:7 a4“!!- C . 74V galvauE/Zw/ I £44373; 59:7. Z—f: M4. 41% ’7sz /f4/A/75, (”fif) W77er?“ ' #1 %@‘*’5‘“ g CL .‘ «9-9/-'.?33, ‘ /7f¥, M . ‘ / $42M” ~ i ) fltm NA /‘J3, /flf: ff7~ff~c '/ $4,441,, V . flu d {7 . /% (1;.1'5 7. �THE LONG ISLAND JEWISH HOSPITAL 270-05 76th AVENUE Department of MEDICINE 0 NEW HYDE PARK, LONG ISLAND, N. Y. - TELEPHONE: Fleldstone 3-6700 �Suptonbar 21, 1961 ntrtin H. rats, Ph.n. Reiuurch Piyuholosint Paychophurnnaoloxy surviuc Cantu: o: nautnl Bonita lation:1 Institutg Md. Buthnldn 1h, Dcar _ flirtin, tour lattqr regarding 1 r0110! o: it: Iodaiitn thrcihold attack a oynpsthcsia chord, and I an caconr:god to share my Vitus with rat, Buvavcr, tin probla: in acuu plax tad perhaps no as: not anido tan. tin. in Huntington fur a dutuiled diacunuion. Hy interest in tho sedation thronhaid van cooulionnd onrlicr intarout in tho at. 0: intravoaonn snibirhitll an a fast tar brain dynrunation. Hoinltciu and Ichni Donitl at Illa-an c c. ThOIIl, 19 S) In tn. court. of ofcoifiucfioci 05:310., we curriod out many out13¢tau at tho 8.2. .36 can. to it. eontlalion taut sh. inst was phyliylogically and itchnically Hound. Finding dylgrthriu I difficult ondnpoiut, I lubntitnicd nyutccnuu; but in raulity, thin can b: dilponlod wish, ninco tn. acnlurod and-puini in to. EEO tbs 3.3995: by ny aarpud nhoui drunrthrin, corroct ll tar an int: hlvo (out, but thin dittiauliy intr.not inlnrunuBStblo, uni boar: no aigaitiaing rolgtion to the valet at $8. tout. the critic: who have The quantiann It inane trot II it. tlli stunt. in in: can. individual .v-rtiuo? 2. In thuro a charteturiltio tcapanao which boar: a oiguir10§nt1y high corroliticn with n bchnvioral Vlriibli - ntnnly, sh. oililifiottion by psychiatriltl a! tangent: iuia uolclogic (racy-9 1. �0-2- 3. Thirdlr, your quclhiou, “it true, it (8.1.) ahvioualy can b. very alarm! in trtttnaut firodiotion nhndicl'. 1. Out Inn uxp.richou indiohtUI that : high intrh~ individual variabiliir; a limited ran 0 at vuluon tar thc halt (tvclvc point. from 1-6 in half than. and an oqnivocnl EEG 0nd»point in 10-20! a: test: lit?! to nuko tha rnlihbla duturu ainntion if tho 8.!. difficult.’ that. vurinblcn soon inhurout in th. taut danish, and Ira not, in :1 opinion, I luck or know-haw by uh. ohlurvcrl. 2. no. Hy nogahiva unuwar to thin question is partly hhoad on (1); Ind partly on tho uuucl dittioaltios at nonology. in somewhat limplowmiadod to uspuat a high corrolntion It betwocn a 'uinplt’ phyiinloxic rotativity naulurc had a “90:91.3” hypnthctie clhatrnat with '0 Inch inhtront unhigui» 3 hy Ind variability. in: 3.2. may hat bu rnlutcd in diagnosis; aha the 3.T. h. unoful in truttacnt prediction? I think it uh: ha, ~~ not for hhc losicul raglan: anuuily IiVOI, but blcinll of the value of tha tout an I .anctivity” nth-urn. In the pulh tow ybnrn variouu indict: huvo blln nhaua to huar IOll rolatiou to trontnont or to diacnnlis ~hnd ouch influx it halt huh-ulna under tho hgru or a 'ruautivio influx”. HO utatod hhht pationth vhe chowod two or nor. tr laughing «hangs. utter intrtvonoun uncharhitnl war. nor. likely to thaw curly EEO ehnnsun httnr uloetrouhock, had to 3. Evan ihough aha: gruntor dncrucn or hohnviortl church and iuprovonnnt of Cenaunieatign, 126 - 139, 1958). Goldntn pantothnl burnt. tr. 010' ’3'; a o thin in uppchrsaoo in achiIOphronic nnhjocta, and ht! unod tout protnouticclly. Siuilhr mittencutl hart bath midi, in £36 Ctt‘uli nor. quantitttivo Itudinu, by Itil (Erlungun) (Milan), why havu rclntod thn changod EEO putt-run to corehrnl ltrophy on pucnnaoneophulozrtphy. In hnothcr type of studios, tho bland prolhnro rcupan-au to nocholyl and to harshnlin have bath roptahcdly Incgnutod an a dilflnflltic had prognontic 136.3. A cannon bhaiu in thcnc Ithdiou in that u link of reactivity or a alow ranchivihy in zanornlly taunted vith schiloyhruni: 0» brain atrophy ~~ a poor proxnoutic high to: the artillhlo thsrtpiol; whil. high rtnotivity in aquutnd with écprcauivc syndronon ~~10w: [and tauntivprognostic sign with awnilhblh thnrapitu. Than, invoked indux or but hi an high any your prtgnoling a: it: ruaahivity will bchr A high wurrulation with hshhvioral chaugu, had a varinhlo In. with inprOthont rutinzs. (3.0 �.3our views of beteviorel change and inpreveuent ratings, Arch. Gen. Feloniet. g; 259, end 5; 30, 1961) Thus, there is much merit in Shannen 8.1. -- not, in .my View as e diegnoetic index (for age is much more relieble and easier to ascertain), but ea one guide to neurophyeielegic reeetivity -- e eubaect that needs {nether study as e preg- noetic and as]: noeelogicel teal! I trust this in reeponeive to your inquiry. I would 16-1? ?) like to disease it acre fully in doWashington (October the 8.1., in end wenld recommend that if yen get interested on veriene reactivity that you consider 3 eeriee or aeetinge ueeeuree in plyehietry .. the neehelyl test, the 8.2. end the coldnen ee exemplee at the more explicit. My regerde. sincerely yours, Hrcdte ex n , “.5. �I1 I. I. I $5 I [3 EE P1 (3 55 F’ I'T'l\ I. FOR PSYCHIATRIC TREATMENT. TRAINING AND RESEARCH 75-59 263RD A. MILLER, M. D. , , Medical Director JOSEPH S. SIMON KWALWASSER, FIELDSTONE LEON LOWENSTEIN 8-7800 Department Of Experimental Psychiatry M. D. Assoc. Medical Director MAURICE STREET. GLEN OAKS. NEw YORK BACHRACH Honorary Chairman Board of Directors ROY .FOSTER Chairman Board Of DWWOH ALVIN E. COLEMAN Administrator President September 12, 1957. Dr. Roy Grinker, Editor, Section of Psychiatry, A.M.A. Archives Neurology & Psychiatry, 29th Street & Ellis Avenue, Chicago, 16, Illinois. Dear Br. Grinker: In reading the report of issue of the Archives, the sedation threshold, Thorpe and Barker in the latest (August) to assess our own experiences with and to report another clinical guide to the we were moved "inflection point" that we have found useful. During the past two years we have included a measurement of the sedation threshold in our tests of brain function. we initially followed the technique described by Shagass (EEG Clin. Neurophysiol. é: 221-233, l95h). Measurement of the beta amplitude reaponse is done visually in several samples of record using the additive ruler described by Shagass. initial group of patients, two observers were unable to onset of slurred Speech with any consistency. 'We, therefore, the identify omitted this step, and continued drug administration until gradually drowsiness was clearly manifest, combined by a statement by the technician that an increase in beta amplitude in the record had occurred at least 1% In the minutes before. that occasionally amounts of amoreach an inflection point were administered. We, barbital inadequate to therefore, began to note'the onset of nystagmus on lateral gaze as a guide to the sedation threshold. This technique had the drawback Subjects were told that at periodic intervals they would be requested to open their eyes and to look first to one side and then to the other at pre-arranged fixation points. This was repeated twice in each direction, usually within ten seconds, while the observer noted the development of sustained regular nystagmus on lateral gaze. The administration of barbiturates continued until nystagmus was observed, and then 2 cc more were given. The EEG records were then measured for the inflection point by the visual method. AN AFFILIATE OF FEDERATION OF JEWISH PHILANTHROPIES OF NEW YORK �Dr. Roy Grinker (Contd) -2— To date, we have 91 such.measurements. In the following table, the difference between the point of onset of nystagmns (nystagmus index) and the inflection point of beta amplitude change (EEG index) is reported. Difference .100 1 EEG Index s-Nystagmns Index .005 0 +05 +1.0 12 h? 27 h Differences greater than 1.0 unit did not occur. It is apparent that the nystagmus end point for the sedation threshold is reliably related to the EEG end point by a unit of % in more than 90% of the trials. Since the error of the sedation threshold under test - retest conditions is between 0.5 and 1.0 units, this nystagmus index is a satisfactory guide to the sedation threshold, as defined by Shagass. W In our continuing studies of the sedation threshold, we have, therefore, ceased measurement of slurred speech or drowsiness, but have relied on the onset of nystagmns as the clinical guide to this index. I trust that this data may be helpful to other investigators. Sincerely'yours, v ,4 a’V‘wflwc has: MF:JB _ Fink, mm. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Lateral gaze nystagmus as an index of the sedation threshold. Electroencephalogr Clin Neurophysiol. 1958 Feb;10(1):162-3. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-002-28-003 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource 12 items. 1: [Preprint]. 2: Reprint from Electroencephalography and Clinical Neurophysiology Journal Vol.10, No.1, February 1958. 3: Letter to Dr. Roy Grinker form Fink. 4: Letter from Grinker to Fink. 5: Letter to Dr. Robert S. Schwab from Fink. 6: Letter to Fink from Schwab. 7: Letter to Fink from C[harlie] Shagass. 8: [preprint] to Dr. Thompson, members and guests discussing Dr. Shagass (2 copies). 9: Handwritten notes. 10: Draft with edits. 11:Letter to Martin M. Katz from Fink. 12: Letter to Roy Grinker from Fink. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Mosquera, Hannah Published http://exhibits.library.stonybrook.edu/mfp/files/original/f8b5cf3cf6b847561379d21a8181ceef.pdf 550c4683b921dafa008583e1e9dd5aff PDF Text Text ��COPY Clinical Release PRODUCT Combination of 'Thorazine' and Diparcol (SKF #1026-A) Diparcol alone 'Thorazine' mg/cag. ca . FORMULAS 50.0 mg. H01 2.0 Magnesium.Stearate Lactose 200.0 -__- ---- mg. mg. 300.0 mg. is. Restricted Medical Utility Studies - Dr. Herman Denber TOXICITY Acute Intravenous Toxicity The intravenous acute toxicity of a combination of SKF #1026—A ('Diparcol') and 'Thorazine' in the ratio of 5:1 was determined. Intravenous LD50'S in male mice (CFl) were determined for SKF #1026-A, 'Thorazine' and a combination of SKF #1026-A and ‘Thorazine' in the ratio of 5:1. The mice were observed for a 2h hour period, at which time all surviving mice appeared — normal. Combination significantly more toxic than SKF #1026-A (T.R. = 1.2) 'Thorazine' ngt_significantly'more toxic than combination. (T.R. 'Thorazine' significantly more toxic than - 1.36) SKF #1026-A (T.R. = 1.13) acute intravenous toxicity in mice of a combination of 'Thorazine' and ‘Diparcol', in the ratio of 1 part of 'Thorazine' to 5 parts of 'Diparcol', did not differ significantly from that of 'Thorazine' alone. Such a comparison is valid since the slopes of the toxicity curves are parallel. The combination is significantly more toxic than 'Diparcol' alone, but the comparison is subject to criticism.that the slopes of the toxicity curves are not parallel. The December 9, 1955 �DIPARCOL In answer to your request an attempt has been made to find data comparing the anticonvulsant activity of Diparcol (Diethazine, SKF #1026) with.that of other phenothiazine derivatives: Phenergan (SKF 1&98), 'Thorazine‘ (SKF 2601), Promazine (SKF 3h06), 'Compazine' (SKF h657), SKF 5277 and SKF 5116. No such studies have been done in our laboratory. The only SKF lab report on Diparcol gives its toxicity as LDSO * 31.2 mg/Kg I.V. as compared with 22.9 mg/Kg I.V. for 'Thorazine'. Balestrieri (1955) compared Diethazine, Phenergan, Parsidol and chlorpromazine with respect to their protective action against electroshock and Metrazol seizures in rabbits. Phenergan and chlorpromazine showed no anticonvulsant action against electroshock seizures; Diethazine, 5 mg/Kg I.V. protected 2/5 animals and at 10 mg/Kg I.V. 3/5 animals. Parsidol protected 2/5 animals at both doses. These results confirm SKF data obtained using maximal electroshock seizures in mice which showed no anticonvulsant activity for SKF lh98, 2601, h657 or 5116. SKF 3h06 did protect mice against seizures; the ED§Q was 155 mg/Kg p.o. SKF 5277 also demonstrated anticonvulsant activity with an oral ED50 of 71.0 mg/Kg. , Balestrieri snowed chlorpromazine to be Metrazol seizures. Phenergan was inactive inactive in protecting at 5 mg/Kg I.V. rabbits against but a 10 mg/kg I.V. protected h/5 animals. Diethazine protected h/5 animals at 5 mg/Kg and 5/5 at 10 mg/kg. ParSidol protected 5/5 animals at both doses. ’No similar SKF data are available. The experiments of Anticonvulsant action and molecular structure of phenothiazine derivatives. .krch. Int. Pharmacodynam. 103:1-11, 1955 Balestrieri, HLM:pz hc A. �COPY- PHARMACOLOGY REPORT November 8, 1956 10-(2'-Diethy1aminoethyl)-Phenothiazine Hydrochloride 0R (Diparcol) SKF No. 1026-A Compound: Code No. Lot No. 99 Structure: )W ii /” '\\ K\//h\§v/\ EV 1 9H2 l c H2.N-( 02H37~2 mignzim.R.T.Cmma' Tested for: Dose Range - .HCl Mmda Studies in mice after intravenous administration (11/10/55) Observations Dose rug/kg side effects 2.5 No 5.0 2/2 slight depression, loss of pinnal reflex 2/2 ataxia, sl. depression, loss of pinnal reflex, 'Thorazine' walk. 2/2 ataxia, marked depression, dyspnea, 'Thorazine' walk, loss of pinnal reflex. 10.0 15.0 6/6 clonic convulsions, apnea, prostration, ataxia after recovery, hypotonicity, 3/6 dead 2/2 clonic convulsions, apnea, prostration, ataxia after re- 20.0 25.0 . cover h otonicit Note-—all animals recovered from.prostration within 60 minutes.. Summary: exhibited 'Thorazine'-like side effects after intravenous administration in mice. Slightly higher doses were required to produce depression than with 'Thorazine' and the depression produced was of shorter duration. SKF #1026—A 'Thorazine'-like Activity: Charge: Biological screening GW/IB/m/mh �LILLY LABORATORY FOR CLINICAL RESEARCH INDIANAPOLIS GENERAL HOSPITAL INDIANAPOLIS 7, U. S.A. December 29, 1955 Max Fink, MOD. Hillside Hospital 75-59 263rd Street Glen Cake, New York Dear Dr. Fink: In answer to your recent request, Storey et a1. (Antibiotic Med. & Clin. Therapy, 2c258, September, I§§STI though they do not report electroencephalogram findings, do discuss the behavioral effects of cycloserine. There have been no publications, to my knowledge, reporting EEG findings in patients receiving 'Seromycin' (Cycloserine, Lilly). Veterans Administration hospitals have been doing EEG tracings but their reports have not yet been published. They will probably present their data at the Veterans Administration Conference on the Chemotherapy of Tuberculosis to be held in St. Louis in February. do be not we of further please may assistance, any If hesitate to w rite us. The Very truly yours, f th, M.D. ri Clinical esearch Division R. mlw 18760EIGHTIETH ANNIVERSARY-1956 �TELEPHONE: LEHIBH Form 90a-Adm. 4-1300 State of New York Department of Mental Hygiene MANHATTAN STATE HOSPITAL JOHN H. TRAVIS, M. D. DIRECTOR IN Ward’s Island, New York City 35, N. Y. ANSWERING REFER To ______.______._____ Dr. Max Fink June 20, 1957 Hillside Hospital 75-59 263rd Street Glen Oaks, N. Y. Dear Max: your findings on I should like very much to include Chloram on I that writing the final in paper the 'Diparcol' me send Could of you Treatment Depression. promazine-Diethazine diethazine I.V. of the effects in general, note indicating, a brief on the EEG? Were there any concomitant psychological effects? of "personal reference under the of note I will course, this, communication." Many thanks. Sincerely yours, [/7 HD:SS Herman C. B. Denber, M. D. Director of Psychiatric Research �4;:- x} June a?) 1957. Dr. Hem 6. B. Ember, Dimmr of Payehiatma Bsmmh, Mahatma; State ammm, ”55W"! 1818M, ”at. f: , Dear Hm Itwaaaplmto Atlantic city. I am aomr that mm we We withyouandymwfiein mum could not. get. smother for "mucus“ much. Johanna and cmvisit. I social enjoyed bht very Mb: 5.3 who: moth with a wry Might. boy, But this yw' almdy may: Mahala, Ina 1mm. A9 fer our “parlance with your suggestion in 1 obtained some intmous manual from SKI. In the last 1w ‘mths we hm given it. to six ”news intmmly. Evin subject and tt. {um at" electroshock therapy and the trim of the I. of much. In sank instance high height. of m: mo 1n In: an the premix "mag abatmmphdogm u’mrity tam. the but situation, in which I and an we qmamm 3 and than remand after the parlour M the Watt-attests cf the d 50 2 of the The rate was mm. dosage drug gvmat smnmum. and than abuut for thirty ”cording a at. of the air. rate mast how the to for eight Manama unplug :pprmntnly mm hour. mm. mm mm, W 93.03th m m mm W» 6!me We: m. mum WW m W m ma Way m hiring the ministmtion, each patient Moped, batman the coma um fourth cc. m epdseda of waging. mare m macaw in breathing which an trunnion. This was the mat untoward attach a: m m alaotromcophnlosnphia ohms pared gradually but was mt. M: the: tho of minutes n injection. within tan 150 ace mm apparent. to thin tin mm veto mead rm a may a! than mansions 70 rum rmmyms toammcf in mm» Wt.- mmumm. tamper-u MWalimdzm;wnwegemmWoffimSma cent. tin 691th, however, mad about the sum. Mb 3:: «that peanut! far one to an hours and in :1]. WWW 1n the maples “loan about four to time: hours liter the Gilt: activity at at the pro-injection m1. In an. “outpatient:mdauutifltymmotthaomrofhto66330.3“ caplofion of the Winn in value” of he to 70 UN. mm the delta activity am: ”My ma in pomnt tiny and in voltage u: that. m an: amount! mam- him he Waits. nun appeand stupor-impound film �Dr» new at Bar mr, #2 a clearly defined 25 cpl. nativity... Tlmm records the the was an ”alerting? following. report Warmly animated by an incmaad methane” ai‘ we patient and a crust. “ibis greater difficulty in having the patient maintain his eyes gazed, ma tbs change in hm patients from: a "Home for this alerting phenm effect to a mgative am)... The changes in language after positive were the reverse of the changes in language which we have axperlmcod 131ml 1n the past after tho amatmtion a! mama-him. Since we use the identical w scone the changes in 11am in an Mammal fashion. In maimaim, three Mamas the questions prior to the of Dime}. wen 11-. and therefore to ovum.“ the changes in Imam. negative Waible & “manure" In one manna tha max-d changed in to an 1mm. mama clung» of the kind tkmt we see: with mbarbim. This dinmponcy I. cannot explain. m m m1 m 1mm W10 rm manna; am eontinning this study and I would 11m to pmmt the behavioral and electroeneephalog‘aphia effects My in the £111 to the Eastern EEG Association. Thaw observations are, of eourse, migratory and I am not 8m 8 UT the next batch or patients may not shot-7 us some other patterns. To tho flat extent. that. this inmatigation has confirmed the observations of Leann”, I an moat yieased. Ha I have no objection to war reporting some of this itfl'omtian in outline. If is of any help ta you, I will be pleased to see the paragraph: as yen intend to report, them and give you my reaction as to how they reflect. it our axpoziemaa, Sincerely yours,Kn: Fink, Dani-haunt at MFtJB mammal Pnyuhiatry. H.130 �“,f ‘i? ziirect i v . i of Diethazine on EEG ’5‘ 0+3 qt I for and Significance Theory of Convulsive Therapy Mauougflwk.fldb Previous studies of the role of EEG changes in convulsive therapy delta activity for have demonstrated the significance of the induced the behavioral re3ponse. Investigations concerning the biochemical substrate of delta in electroShock and convulsions EEG have indicated significance for the cholinesterase - acetylcholine system. reports on by Ulett concerning the effects of atropine and Recent 00’ scogfilflhine the delta response-effihe-EEE-showed a reversal of the-induced patterns. Boncurrent iswmvafi. reports by r and of diethazine on normal EEG and that following Lechner on the EEQ effects trauma provided the stimulus for the study of the effects of this drug in electroshock. Subjects: Twenty voluntary psychiatric patient in an openyward/psychiatric hospital have been tested to date. d " £5? During recording, at various maturing (Biparcol) is administred intravenously at per minuteI Maw “'5’57- £155; xi treatmen . rmi 94°" " the rate of 25 milligrams ‘1 250 milligrams, {My diethazime 70.,qu * �Observations : a) by the of All dryness cmgling, respond subjects Behavioral“ mouth and thickness of speech. Feelings of weakness of extremities illusory sensations are and There common. is an increase in rest- lessness and difficulty in maintaining eyes closed. In patients who have had sufficient electroshock to manifest syntactic and orientation language changes indicative of altered cerebral function, is there ‘ b) EEGSq a reversal of language patterns. . In all subjects there is desynchronization of frequencies \ and decrease in voltage. Alpha rhythms are less prominent. ! low Occasionally, \ -—-a c" In voltage “ILA 577’ frequencies appear. \ voltages-a25of delta with degrees varying activity, patients in decrease‘, frequencies decrease and burst activity disappears. Irregular alpha and beta frequencies of low voltage become c) The EEE and persist clinical effects consist for gradually disappear. one mmminent. to three hours, and �Discussion: The pharmacologic effects of diethazine are described as "anti- cholinergic" and "atropine-like," and in patients with altered brain function may be h described as "allert‘ electroshock induced m (Ulett). EEG delta is P The action of diethazine an 0 . scopfll ine similar to atropine and eeelpalemine (Zinc floss observations era‘similar to those in subjects with head injury (Jeéhker and Lechner). Conclusion: ‘1'“ Based on this data, as well as the cerebr¢{:§pinal fluid cholin- esterase studies of Bornstein) and Tower and McEachern, . fuedJLb£1 diethazine hes-e ready that: (l) ' ' it is .: enter the central axrhnL; and trauma induced electroshock by by delta system3(2) a . concluded nervous 4' may similar A have biochemical substrate;(3) electroshock may be looked upon as a controlled 6F Alana; method tc.indnge ce ebral dysfunction for The its induced behavioral significance of these observations for EEG studies of head trauma and the mode of action of gin-ilpconvulsiVe therapy discussed. effects. will be �//— £3th at Diethuine on 3%: and Significance for Theory at Germanium mm Previous studies of the rule of have demtrnted EEG changes in convulsive thenpy the eigmfieam or the induced delta activity for the behwioral response. Imeatigetions containing the substrate of EEG 1:10ch delte 1n electroshock and convulsions have inflated significance for the eholinestemae - mtwlchonne system. reports Ulatt concerning the «treats a! atropine and by anthedalta patterns, response otheEEGshemdamml of napalm theinducedm Goncurrent reports by Jemkner and Lochner an the offliethum «1110;14:11me Recent. effects mtrmmmmmmm atimelua for the study of the effects or this drug in electmahock. Subagetet Twenty voluntary psychiatric patimte in en upward/psychiatric hospital have been tested to date. Electroencephalogm have been obtained mutant. During the recording, at. various fines during (limit) is administer! intmemualy per me until at. the 250 Milligrams have been rate of Metered. diethume 25 milligrams a an �¢2~ mumations: a.) Behavioral - 51]. subjects respand by coming, dryness (J the math and thickness of speech. Feelings of weakness of extremities and mm. illusory sensations are Mamas is news in mt. an difficulty in maintaining eyes closed. In pgtients 3nd who have had There Mficient ehctmhwk to manifest syntactic and onentation language changes indicative of altamd cerebral function, them in a reversal of language pattern» b) EEG ~ In all subjects than in Voltage. and decrease Damionflly, 10w is «synchronization Alpha W of Inqueneies are less prominent. tnqmncies appear. voltnga In pstinnta with varying dogma of delta activity, voltaga is deemed, tmquemiea in “cram am} burst wtivity disappears; Irregular alpha and but: fmqmnoioa of law voltage become more a) Tho W and liy clinical eflwta diuppnr. . pox-stat mm gamut. for om to than hours, and �A! mammalian The phnmaeolog'ic effects of diethuine are described as ”anti- cholinergia“ and “atmpimlflm,” and in patients with altered brain function may be doacribod an ”martini." The action of electroshock induced (Butt). EEG delta is 3min:- to atropine Also, than. observations with hast! 11131211 («bunker and m diothum 8nd n W napalm 51:11” to than in subdue“ Mr). 091191113th Band on this data, us all 0 as the carom spinal fluid wanna «tea-am swarms of Bernstein and Tower and IicEnchem, it is minded that: (1) diothuine has a randy ability to enter the central nervous system (2) delta induud by electroshock and by trauma my have similar Mommioal substrate (3) electroshock my be loolwd upon as a controlled m’chod to induce cerebral dysfunction for Ema tm its induced behavim'al effects. hand for'EEG of atxfiias of these obsamtiona significant: and the mode of discussed. act-.1031 of electmcomluvo therapy will. be �MM or blow swam m and Gmmlaim Therapy on m m, for 1119on of 24.13. me changes in wmulsive therapy have the signifiam of the induced delta actdxiw for the biochemm umoarning the Invasfigatlans tome. have EEG and indicated electroshock emulsions of delta in mutate nignfimm tor the ahonmuem - mmdcholine system mm. Pruvioua studies Wand 1:6de at the rails of. otatropdmandaoopolmo Wbymttcommmgmeflw EEG induced showed EEG or cloctrashook a moral in an pattom. am: Comm-rent reparts by Janka»: and Lechner an the: extent: of on mm]. EEG and that. following tram provided this stimulus far the study of the effects at this drug in electroshock. mm Salaam” treatment various during ht stages patina“ puma-lo in an open—ward voluntary psychiatric hospital have been tested to (Dimmol) is manicured date. "During EEG recording, int-.mwaly at the rate of 25 milligrams- por minute, for a total at 2% Twenty diam W0 Mmtionu ' : a) %: b) m m All subjects respond by coughing, dryness of the thickness of mach. Feelings of weakness of emu-mitten mm and illusory marathons are cam. more is an immune 1h restless. mas and mamty 1n maintaimng eyes clued. In patients who have had sufficient. electroshock to manila“ syntactic and orientation language changes indicative of album earabral function, there is a reversal of language patterns. more 13a doaynchrmiuuon of rmmdes down» in voltage. Alpha rhythms are less lament. Occasionally, 1m? voltage theta frequencies appear. In all subjects In patients with varying demos of delta activity, voltageand burnt increase frequencies activity disappears. Irregular decmo, alpha and beta Imumcies of low voltage become prominent. c) The EEG and clinical effects persist for one to three hours, and gradually disappear. Fm Department of men Oaks, ELY. than 1.1-6.5? - EAEEG mmm Psychiatry, Hillside Hospital, �‘5 of downbeat afloat: dawn» m Wohgie u ”antiwhonmtgie" and 'ttropine‘uka," and in patina“ With slated brain imam any be 6030de as ”wrung.” the mum at on ahctroshack induced EEG delta is amm to atropine 610mm um! £39me (010%). mm ebmmfiom an aim similar to firm in aubjccta with bud injury (Janina: and helmet). The cmcluaiam Mac! on this duh, as «11 as this cerebmspinal fluid cholimatamso studios of Ben-MW, and Tower and Wuhan, is wmludod that: (1) damn» mam entm the «antral nervous system; (2) delta nativity inducod kw alwtrodmck and and by tram may ham: 3 similar (3) mutate: mm be lookad upon an o. watt-0119c! ”that! of naming «mural to: its behaviaral affaa‘w. it mmwu m Wanna The «:1ng the or action of convulsive: therapy will trauma and node of thew than mamtiom for m ”adieu or had be animated. �v -r:‘V?\'(‘r.uv' w--w—ILW|>L‘»V‘V'~B—w"y:mm w—r-mw-vwn»vww.,u—A » v —.-.r. -- .vr. w—y ~ w — "av/\— <7 r ,rw-I'IWK . aw u 'mwl' - - - "a.“ AM'HV'Wwv _,,, A was �wan-my r'm ��Form 90-Adm. éhhft$nk jfluh fisgrlfiatrit gustitute 722 WEST 188'"! STREET. LAWRENCE B. KDLI, M. D. nlnlm'run NEW YORK December 4, 1957 Dr. Max Fink Dept. of Experimental PSychiatry Hillside Hospital 75—59 263rd Street Glen Oaks, New York Dear Max: feelings about Saturday night are reciprocal. Weihoroughly enjoyed the gracious company of you and Martha. With the intuitive perceptiveness of the female, Yetta informed me of a forthcoming event in your family, and we Wish you the best of everything. I indeed look forward to the reprints on your Work which you described in your letter and our discussing them together. The next edition of the Kalinowsky and Hoch will be expanded to include tranquilizers, and I would also appreciate any reprints of yours in this area. I have enclosed my own reprint on the clinical effects of Win-2299 and the basic paper by Luduena and Lands. As you will note, the compound is a peripheral anticholinergic and produces a "disorientative" reaction in cats by central action. Its psychotomimetic action in man appears basically to be an acute toxic reaction type. I would imagine that its central mech~ anism of action is similar to that of atropine (which also produces acute confusional states in high doses). Win—2299 is effective at much lower dosages than atro— pine. Possibly both atropine and Win—2299 both produce central effects by an anticholinergic action but, as far as I know, this modus operandi has not been pinned down crucially as far as the C.N.S. is concerned. I would not expect all anticholinergic agents to be psychotomimetic, of course. Win-2299 is a tertiary amine. Monodral is a closely related drug, differing only by quaternization of the terminal nitrogen in Win—2299. It is Win~4369 in the paper of Luduena and Lands (p.283), i.e. the methobromide form. According to Winthrop-Sterling, it is a peripheral anticholinergic in man in doses of 5-40 mg. per day. Central or psychic actions are not mentioned in their account. Presumably, quaternization reduces central activity by reducing permeability. Our �Dr. Max Fink (cont'd) ’ -2— I imagine that other agents in the Win series with central effects in cats might also be active as psychotomimetics in man. I am not familiar with the formula of diparcol and if you have it available would appreciate learning where to look it up. The drug is not covered by Goodman and Gilman. I would appreciate return of the Luduena and Lands paper when it has served your needs. We gave the Win—2299 the orally, The compound being drug was supplied as the supplied in tablet form. racemic mixture, the asymmetric carbon atom being terminal in the aliphatic chain. Sterling—Winthrop may have it for intravenous use and I suggest that you write M. L. Tainter, M.D., Director, Sterling-Winthrop Research Institute, Rensselaer, N.Y. about it. Our oral supply was used up in the study. As you know, all psychotomimetics not only create new symptoms in mental patients but also intensify or revive pre-existent symptoms. Best of luck. Cordially, ”2a Harry Pennes, H. HHP/ys Encl. M.D. �PA if .. _ * (on 1M5? I Effect of Diethazine on EEG and we Significance for Theory of Convulsh M Therapy MD Mow In a previous report to-this society we noted the relationship between the degree of induced delta activity during the course of therapy and the behavioral reSponse to electroshock. Those patients, in delta activity were induced early, and were degrees of behavioral change, as well as a significantly greater percentage W gm vial £64414a Law In. Box} EH: acetylcholine and in whom only low degrees were induced (Fink and Kahn, 1957). activity 1, (ii; '1.) high degrees of sustained, manifested the greatest of improvement and recovery than those patients of delta whom ,hML-wQA‘O‘ . a, W" , ‘Jawc‘z MM L Mkfil‘g‘f‘” ’M‘Af‘z‘ mv’efrff " in!“ (.4 Mfianges infree” ' a variety é‘fu‘reports, cholinesterase in the Spinal fluids of patients (Sachs, 9. Ward) and animals (Bdrnstein, Tower and McEachern) following head Wig; . . I the observations that by trauma M o (Bfrnstein, flue/4% In 1956 .c‘ E agents liq—alter the EEG patterns induced Ward, Jenkner-Lechner) and by electroshock ( “knew“at?mp (Ulett)pu_l Ulett reported that atropine g’scbpolaminerwhea-aéiénéstered— / W, blocked the appearance of the delta wea»...have come to associate with - _,-.,..«-'V'F-r -v~ WWW ahaaul,” "‘4“qu w. traumalawfl electroshock therapy. A!” 791’] am’LlLJ/g/J M ’L “‘2‘“ 4“““4/ié’MWrrW ”“an“ j?” activity {lama/Wye? v» �-ebeervetions~ Previously, ward (193) following the suggestion of Bornsteiny (19h6) had noted that atropine altered both the EEG patterns and the neurologic signs induced in.man by head trauma. afiereT-tee, the side ZZ,AQA7V ~effects were marked. In 1955: Jenkner and Lechner reported that EEG behavioral effects similar to atropine were achieved by diethazine istered in patients with head trauma.‘ They and admin— also reported the effect‘of diethazine in normal subjects. It is the purpose of this report to describe the effects of intravenous diethazine on the EEG of patients during electroshock therapy; and to relate their these findings to the present neurophysiologic-adaptive hypothesis of the ndde of~action of convulsive therapy. w ‘flwmwmflmwwwfl_fl____.imm 3" Diethazine is a soluble phenothiazine compound with phamacologic properties similar to atropine. In experimental animals, (19h?) have noted that diethazine blocks vagal slowing of the heart‘) M suppresses the bradycardia, bronchospasm, salivation, and fasciculation and seizures induced by acetylcholine, DFP ‘‘‘‘‘ ‘wywwflfimgimww‘fizoxsum-“:- w' ”mm—«MA..- and pilocaxxfixg and induces dry mouth, mydriasis and hypotension. L/——' / Heymans EE.E£ a“: nevus-aw» 4.: '2‘ YW',‘47"’~"5‘W1‘-05 Emma-gwhz - .— ' .~_4~:_MD~J �93" ”w W Subjects: Twenty-two psychiatric 42‘ patients,” various stages of electro- shock treatment in an open-ward, voluntary psychiatric hOSpital have been studied. the laboratory. Following a routine EEG administered intravenously at the rate of of 2630 to 250 mgm, the i Tl’br.‘ EEG 25 mgm per minute, for a total effects. Prior to the historical interview and a structured questionnaire period were tape-recorded. EEG recording, diethazine was depending upon the behavioral drug administration, an unstructured both EEG gubjects were tested in Following drug administration, recording‘ and recorded interview periods were continued until record again manifested.the pre-injection patterns on visual inspection. Mm New. ‘>IIVW~.. Qbservations: in Le ,, (a) Clinical: AH su jects manifesm Spontaneous coughing mutual-i33- @ followed by a dryness of the mouth and a thickness of speech. flgrtrf They note‘, ' 3'37 a feeling of lassitude and weakness of the extremities? soon followed by increased restlessness and difficulty in maintaining eyelid closure. phenomena were PSymW/clearly between 15 and 30 minutes . manifested in after some subjects. In the rest period drug administration, six subjects spontan- ..,. _‘ ... _ A �4,. eously voiced feelings of unreality, visual and haptic illusions, and delusional thoughts about their illness, the setting of the test procedures or our identity. Such patterns were transient and had disappeared In by the termination of the experiment,-asaallyhiééfifiurdfinnxrdnmzns. three subjects, increasing agitation . and panic led to a cessafion of the recording. éHere7-tccy—restétation_a£—pme—énjenfifinnrdnfiuufiuuaauua I 'li' g“, , I! i . fiilliwuwfi (b) In previous studies, the intimate relationship we had noted between changes in syntactic language patterns with alteration in cerebral function induced by electroshock. In subjects tested prior to electroshock, diethazine induced changes in syntactic pattern of an "alerting" variety. I - gal [5% In subjects with elta activity‘ with clinical syntactic patterns indicative of an alteration in cerebral function, diethazine induced a transient dis- appearance or minimzation of Such language in language (c) was concurrent with changes EEG Patterns: In all patterns. The period of changes in electroencephalogram. records, there is a decrease in voltage and desynchronization of frequencies. There is a decrease in prominence of prevailing rhythms. In patients without delta activity (pre-electrodhock)’ �-s5‘ 4/ this deéhronization and voltage decrease is occasionally accompanied by the appearance of small amounts of low voltage These are demonstrated in Slides 1, not appear to be altered. The and 2. The 5’7 '5' cps activity. basic alpha rate does build-up in voltages and appearance of thm slower frequencies with hyperventilation is blocked. In patients with varying degrees of induced high voltage activity voltage”, both random and 4 This change It and 3 dub is a decrease in burst delta activity disappears; and irregular, / low voltage alpha and beta frequencies become prominent. are noted in Slides delta These changes LL. 5W in is manifest in appears during drug administration, and all electroshock subjects. persists for awe. [WM filwwx 13% 2/1. floncurren WithAelectroencephalographic hours vtwv ‘ ”fly to three age MM» Wrens-em fiith the 8&3 17TH 770 n moustita—tion— of the pre-injectionEl'I} patterns, the pre-injection behavioral and language patterns again appeared. �DISCUSSION: report of Jenkner and Lechner of the t”t.¥£~£ dikd/“4lz‘ijzz7' effects of diethazine in"normal" subjects. 'Wa.alsa—nnta_tha§21iethazine These observations confirm the alters records-snd-fiith electroshock induced delta activity in‘a fashion similar to atropine and scopolamine, as described by Ulett, A Mada» W was. . 1%,. is apparent, therefore, thatngfi readily affects the central nervous and.é53 duration system, ofiactivity is most useful for experimental purposes. The-previeusiy—eitnd studies by numerous Observers of nervous system effects of head trauma point to an intimate relationship between the degree of neurologic dysfunction, the degree of EEG alterationjgand the level of free acetylcholine in the spinal fluid. The effect of atropine both the Echand ill on concomitantly on behavior in subjects with head trauma lends further support to the significance of figs: acetylcholine as the biochemical basis for the observed EEG patterns. In these studies of diethazine electroshock, the intimate relationship between EEG patterns and and behavior �-7have been reported. We note the parallel to the observations in head \ trauma. On the basfis of these observations, as well as studies of Spinal fluid Woholinesterase levels; (Tower we would and HoEachern, Fink and Goldenberg)‘ suggest that the biochemical substrate of the electroshock process. is isimilar to that of head controlled trauma.9 method of inducing ectroshock hLauri. may be looked upon cerebral dysfunction for its as a behavioral effects. Previous studies have demonstrated that alteration in cerebral function provides the physiologic basis for the behavioral changes in electroshock (Fink and Kahn, 1957). Such alteration in cerebral function provides the milieu for a change in the organism's adaptation to his environment. aSpects of behavior, as perception, language, mood, recall, memory, All affect, undergo change, and provide the basis for the therapist's evaluation of improvement. The studies of diethazine amplify this neurophysiologic 9.39.9. adaptive hypothesis of electroshock by suggesting the type of biochemical substrate that underlies both the physiologic and the behavioral changes. �Mm= 0 Diethazine, a pftent anti-cholinergic compound, u was experimentally introduced intravenously in psychiatric subjects,;fi various stages of convulsive therapy. Electroencephalograms manifested a desynchmnization of frequenciesfue («C decrease in voltage records without prior delta activity. Records with delta activity showed similar changes with disappearance of delta burst activity. Concomitant with the electrographic patterns indicative of It is concluded a effects, behavioral reversal of the electroshock effect enters the central nervous System upon intravenous (b) The biodemical basis for that of head trauma; (c) therapy The may EEG compound that readily adninistration. changes in electroshock is similar and biochemical basis of the lie in were observed. that: (a) Diethazine is a Bitent anti-cholinergic to and language mode of action of convulsive the acetylcholine-cholinesterase system. a, �@ Research and Development Division SMITH, KLINE & FRENCH LABORATORIES PHILADELPHIA - I ESTABLISHED I84| December 11, 1956 Max Fink, M.D. Director of Research Hillside Hospital 75—59 263rd Glen Oaks, Street New York Dear Doctor Fink: associate, Mr. C. W, French, has referred your letter of November 12 requesting a supply of diethazine to me for reply. It has taken me a little While to uncover-sufficient supplies for the short clinical trial you want to conduct since our interest in diethazine alone and in come bination with 'Thorazine' isn't too great at this time. My not have this compound available in 500 mg. capsules as you requested. It is only available in 250 mg. tablets. A supply of this strength has been sent to you together with a supply of the intravenous we do material so that you is all the literature we this will be of some help. Enclosed hope the may Observe EEG effects on 10 have available on Sincerely yours, .\ to 15 patients. diethazine. I , J”, Meagan? Ms (,7 . John F. Buckley a Research Associate / ’ ' Medical Department JFB:hc Enclosures P.S. Will you kindly sign the enclosed FDA card and return so that we may keep our files up-to-date. it to us � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Effects of Diethazine on EEG and significance for theory of convulsive therapy. Electroencephalogr Clin Neurophysiol. 10 207-208. (abstract). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-002-29a-004 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource 13 items. 1: Handwritten notes. 2: Clinical Release. 3: Diparcol. 4: Pharmacology Report. 5: Letter to Fink from R. S. Griffith. 6: Letter to Fink from Herman C. B. Denber. 7: Letter to Denber from Fink. 8: Draft with edits. 9: Two drafts. 10: Handwritten notes. 11: Letter to Fink from Harry H. Pennes. 12: Draft with edits. 13: Letter to Fink from John F. Buckley Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/78017191476d8e778612e5c61eff422b.pdf 82ede86cdae7bcc77cb09f6c0bbd0389 PDF Text Text Mammal in studios of Germain find Drug max-span mun-ya Theofitio Imitation! In swans a: aonvnluivo, payohophumcmgic and inaulin a» therapist, msalon of "idem tar a mmphysiolozimpuve W011! or the and. of these flux-apt!» has wwmhtod. This hypotmsia “crib“ the officwy 01' each therapy in the trantaont of wohma to their ability to induae a persistent alternates: in cerebral function. mien provides the am“: for u changa in adaptation of the subject to his anviroment. In those studies, in Em have been and as indie» of uttered brain tumuom In convulsive thong, the shift in EEG tmuoneias to the delta range has been directly rented to the behavioral changa (AMA, Arch, Emmi. and analyses at r3;chiat. (J: com be (n) «hangs: 16;: 516, 1957). A maid. H292. 5: “1&1;in has been observed 31:11.: Bk. 1955). classified ascending to their EEG From flat fnqucncios, with in- (mpmbmu, barbiturates); and (c) (domains, bemctysine and asp-nine). then analyses, a shirt in unused synchronisation tnnquiliutim m EEG mggasmd sedation. 1.957): mums». pruning, perphenaame, reserpine); (b) indueo a ahifl. to crewod synchronization frequencies Viviana psychophameologe uganta can offsets: (J. Hillside Ham. 9; 197, mum a mm to delta frequenciu and high dose to insulin «mama frequencies to delta range and in» u the nmrophysiologic concomitanta mmphyaiologimdaptim hypothoais hm applicatim to the ammonia of physiodymmic mempiee, acmning or psychoplumeologic agents and as a trans of refemnce for the study a: bmior arid of and The mmphyaiology. From L010, the Dayna-meat “at; or Workman. rm. Hemlogical Society, MAR 2 6‘85 Why, Hillaido Hospital, Glen mks, March 11, 3.958. �«W W WWW AFTER 225 mg. PRE-DRUG LF-LO RF-RO WIN/WWW SOyvl _ #I64IHH �PRE- DRUG AFTER 150 mg �W WW ”“va W W W WW WW WW + PRE-DRUG + 25 mm 200 mg. LF-LO WWWNVMMJVW RF R0 NWvaw-AAW “T'RWWJWMM H ”fin. MM LF-RFNWWN WWW” LPT'LO WWWM 50 )Lvl I $|631 NH �PRE-DRUG @. AFTER 250 mg. W W W W W W W W W W WW 50pvl_ SEC. 1 #IZQS NH �Effect of Anti-Cholinergic Agent, Diethazine, Significance for Theory of Max From the Department of Experimental L015, NJ. Fink, on EEG and Behavior: lesive Therapy 14.1). Psychiatry, Hillside Hospital, Glen Oaks, in part, by grant M-927 of the National Institute of Mental Health, National Institutes of Health, U.S. Public Health Service. Aided, (in part) at the meeting of the Eastern Association of Electroencephalographers, N.Y., December 1957,‘ 4.7444417 Jazz; Read 33?: 3-58 /“ a M 14/11.” 050,?wa �3.3-58 Effect of Anti-Cholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy Recent investigations of convulsive therapy have emphasized EEG delta activity as the neurophysiologic basis for the induced behavioral change (1,2,3,h,5). Little study, however, has been given to the biochemical effects of this therapy, except in the course of investigations of head injuries. In investigations of head trauma significance has been ascribed to in the acetylcholine-cholinesterase systems both for the behavioral and the electroencephalographic effects. An increase in free acetylcholine (6) and an alteration of the ratio of cholinesterases (7) in the spinal fluid have been positively correlated with the degree of EEG abnormality changes and degree of heurologic improvement deficit. in clinical status The EEG patterns were "blocked," and was reported following atropine (7,8). In convulsive therapy, atropine observed to block the appearance of delta some the administration of and scopolamine were activity, (9) although the systemic effects of the large doses of these agents were marked. Recent reports (10) noted that EEG and behavioral effects similar to atropine {were achieved in patients with head trauma by intravenous diethazine a phenothiazine compound systemic effects. with anticholinergic properties - with minimal In our continuing studies of the role of delta activity in electroshock (3), the effect of diethazine was studied. It is the purpose of this report to describe the effects of diethasine on EEG patterns and on behavior of patients during electreconvulsive therapy; and to relate these observations to the present neurophysiologic-adaptive hypothesis of the mode of action of convulsive therapy. �SUBJECTS AND METHODS: Forty psychiatric patients, at various stages of electroshock therapy in an open-ward, voluntary psychiatric hospital have been studied. All observations have been Following a routine at the rate of EEG made in acute experiments in the laboratory. recording, diethazine was administered intravenously 25 ngm per minute, upon the behavioral EEG effect. for a total of Dosage varied from to 250 mgn, depending 2.8 to h.0 mgm per kilogram 175 body weight. Diethazine is a soluble phenothiazine compound with pharmacologic properties similar to atropine. In experimental animals, diethazine blocks the bradycardia, bronchospasm, salivation, fasciculation and seizures induced by acetylcholine, di-isopropyl fluorophosphate and pilocarpine. suppresses salivation, and induces mydriasis and hypotensicn EEG It (ll). Anilxses: Recording was continuous for the duration of the observation period, except during interview periods. Needle electrodes, and an Moderaft instrument were used. All records were analyzed delta activity (3); the per cent time the relative amount of fast activity. measured in anterior temporaldvertex, and The and 8 channel for the degree of principal alpha frequency; and alpha and delta activity were parietal-ear ldbe lead coMbinations. Behavior measures: Prior to drug administration an unstructured psychiatric historical interview and a structured questionnaire period (12) were tape recorded. Following drug administration, periods of recorded interview were alternated �~3- with EEG recording periods, until the me had again manifested the pre- injection pattern on visual inspectioné Two estimates of behavioral effects were used: clinical descriptions subject, interviewer and technician - of the changes occurring during the drug period, and language analyses of the recorded interviews. Changes in language were evaluated by a syntactic analysis (12) and an analysis of the variability in verbal interaction in the dyad (13,1h).* by the participants ~ Both measures have been shown to be sensitive to induced by changes in the central nervous system. * Detailed analyses of these observations DPS. J. Jaffe alterations in behavior and Re In Kahn. will be reported separately by �OEERVATIONS: (a) Clinical: Within two to five minutes of the start of the injection, subjects manifested spontaneous coughing follow ed by a dryness of the of speech. and a thickness They reported a feeling of lassitude, mouth and a heaviness and weakness of extremities which was soon succeeded by increased difficulty in maintaining eyelid closure. Reports of visual and haptic illusory sensations, feelings of unreality distance, and delusional thoughts about their illness, the setting of restlessness and and test procedures or identity were voiced Spontaneously in eighteen subjects in the period between 15 and 60 minutes after drug adninistration. the our In three instances, increasing agitation and panic led to a cessation of the In two subjects withdrawal and negativism was the prominent recording. behavioral response. Such patterns of behavior were transient and had disappeared in (b) EEG 1% - h hours in all subjects. Patterns: Alteration in the EEG patterns was concurrent with the behavioral effects. In all records, changes occurred during drug administration and were sustained, with gradual diminution and restitution of the pre-injection patterns, in one to five hours. The initial response was a decrease in voltage and desynchronization of all frequencies. There prominence of prevailing rhythms. was a decrease in In patients without delta activity (pm-electroshock), desynchronization and voltage decrease was occasionally activity, symmetric and prominent in frontal and anterior temporal leads (Figure l, 2). The alpha frequency was not altered. accompanied by low voltage 5-? cps �~5The build-up in voltage and appearance of slower frequencies with hyper- ventilation was blocked. In patients with varying degrees of high voltage delta activity there was a prominent decrease in voltage and desynchronization of the record. burst delta activity diminished or disappeared, and irregular voltage alpha and beta frequencies became prominent (Fig. 3, h). The Both random and low hyperventilation response was no longer apparent. (c) Language Patterns: In previous studies, an intimate relationship between changes in syntactic language patterns and the behavioral response in electroshock had been reported (12). With alteration in brain function, increased use of third person, veroal denial, qualification, displacement and cliches became prominent. These effects could be enhanced by the administration of intravenous amobarbital (1h). In the subjects in the present study, syntactic analyses demonstrated a reversal of the patterns noted in electroshock. Use of third person, qualification and displacement decreased. Explicit verbal denial was modified and replaced by minimization and displacement, or by a reiteration of complaints of illness. In dyadic analyses, the verbal interaction was characterized by a greater diversity of vocabulary and less variability in the diversity scores for 25 word units. qualitative nature of these changes in the language patterns is opposite to that of amobarbital and electroshock. The duration of language changes was concurrent with the changes in the electroencephalogram. The �DISCUSSION: These observations confirm the report of Jenkner and Lechner of the effects of diethazine in "nonmal" subjects (10). Diethazine also alters electroshock induced delta activity in a fashion similar to atropine and sncpolamine, as described by Ulett and Johnson (9), with minimal unpleasant symptoms. EEG The effects of intravenous diethazine are immediate, both and behavior, and thus provides a cholinergic" properties. Two on the useful experimental agent with "anti- aSpects of these experimental observations warrant discussion: the role of acetylcholine-choldnesterase in the electroconvulsive therapy progress, and the significance of die thazine "alerting" for concepts of hallucinogenic activity. 1. Biochemical Basis of the Convulsive Therapy‘l’rocess: While there has been considerable study of the psychologic neurophysiologic aspects of convulsive therapy, biochemical processes is available. The little and infomation concerning studies of biochemical changes following head trauma and spontaneous seizures provide some analogic data. Bernstein (6), in a classical experimental study of head trauma in cats, that within a few minutes after trauma, free acetylcholine appeared in the Spinal fluid and persisted for periods up to 148 hours. He further demonstrated a positive relation between the severity of head trauma demonstrates and the quantity of free acetylcholine, degree of electroencephalographic the severity of the behavioral changes. The electroencephalographic records initially showed short periods cf high voltage fast activity, alteration and transient period of flattening of electrical activity, followed by prolonged periods of high amplitude sharp waves in the delta frequencies. Concomitantly, a �-7alteration in consciousness, changes in reflexes seizures EEG change. Tower and HbEachern (7) confirmed studies in man. In post-traumatic highest concentrationSOf free acetylcholine were most prominent with and greatest degree of and 112 neurologic these observations in clinical patients, free acetylcholine was found in the cerebrospinal fluid only in patients following head trauma and recent grand mal seizures; and the level of free acetylcholine varied directly with the degree of cerebral damage. In addition, these authors assayed the cholin- esterase activity of the spinal fluid, (7, 16). In patients following head trauma, they noted a sharp rise in non-specific cholinesterase (benzqylcholine- in.the specific cholinesterase (meoholyl-splitting) activity of the spinal fluid. No such inversion was noted in fluids containing splitting) and a drop free acetylcholine following spontaneous seizures. Electroencephalograms were taken at varying intervals following correlation of the extent of EEG trauma, and demonstrated a direct abnormality and the appearance of free acetylcholine in the spinal fluid. Tower and MhEachern also reported observations in six patients In patients after 3-7 induced convulsions, they noted free acetylcholine in the spinal fluid in two, and an increase in non-Specific cholinesterase with reversal of the cholinesterase ratio in five receiving electroconvulsive therapy. of the six. They concluded that the spinal fluid changes in electroshock are more like those of craniocerebral trauma than those found in epilepsy. * patient of the six who failed to show either free acetylcholine or a reversal of the cholinesterase ratio, they noted: “It is interesting that this patient was the only one of the six to show no * Regarding the one response to treatment." �-8recently, Sachs (17) confirmed the reports of free acetylcholine in the spinal fluid after head trauma and after electroshock. In his studies, Bornstein (6) administered 0.5-1.0 lug/kg atropine Mcre effects, and a modification of the behavioral and neurologic signs. Atropine also blocked the EEG and clinical signs induced by intracisternal acetylcholine. and demonstrated a reversal or a blocking of the Ward (8) applied these observations with varying degrees of head trauma. atropine induced both clinical EEG to the treatment of Subcutaneous doses of 0.1 mg/kg of improvement and reversal of These observations were recently confirmed by Sachs Hughes (19). Based on subjects human these observations, Ulett (l7), EEG effects. Rugs (16) and and Johnson (9) noted the effect of atropine and scopolamine in blocking the Em changes of electroshock tharapy, without noting the effect on clinical behavior. Concurrently, Jenkner and Lechner (10) reported effects similar to those of Ward, in studies of diethazine in cases of head injury. Another group of investigations complete the available data. Studies of anticholinesterases, as DFP (di-isopropyl fluorophosphate) and (tetraetlwl-pyrophosphate), which block the enzymatic TEPP breakdcvm of acetyl- choline, demonstrate the development of high amplitude rapid frequency mac patterns similar to status epilepticus as well as lesser degrees of abnormality as noted in post-tramnatic states (20, 21, 22, 23). In these studies, atropine blocked both the electroencephalographic and the clinical toxic effects. Thus, both from experimental and trauma we may assume clinical studies of craniccerebral that (a) the acetylcholine activity of the spinal �-9- fluid increases; (b) pseudo-cholinesterase activity increases with a reversal of the ratio of cholinesterases; (c) slowing agents From parallel these biochemical alterations; may EEG tamer-synchrony and and (d) anticholinergic block both the electroencephalographic and the clinical effects. it is probable that the biochemical basis the data available convulsive therapy is similar to that of craniocerebral trauma. of Convulsive therapy results in free aoetylcholine in the spinal fluid (7, l7) and a reversal of cholinesterase ratios (7, 16). The electroencephalographic effects of repeated induced convulsions is the developnent of high voltage, activity, occasionally with spike activity (3, 2h, 25), which is similar to that observed in severe head trauma (26, 27). In symmetric slow wave previous studies we have reported the relationship between the degree of activity and behavioral reaponse (3). The studies reported here and that of Ulett and Johnson (9) demonstrate a reversal of the EEG and the behavioral effects of convulsive therapy by antiinduced slow wave cholinergic In each characteristic, convulsive therapy is thus compounds. similar to cerebral trauma. While the acetylcholine-cholinesterase system is highlighted (17). These studies, other enzyme systems may also be altered studies also suggest that convulsive therapy provides an by these excellent experimental method for studies of craniocerebral trauma. Studies of the brain stem activating system by Jasper and DroogleverFortuyn (28) and Lindsley gt a}, (29) had laid the foundation for the prevailing conclusion that symetric EEG slow wave activity has its origin in mesencephalic structures, and that these structures intimately affect the states of "alerting" and "drowsiness." More recently, Rinaldi and �-10- site of action of atropine and cholinergic to this mesodiencephalic activating system. It is also probable that Himwich drugs (30, 31) have related the these structures may be selectively affected by the convulsive therapy process, and that both the clinical and electrographic effects may be intimately related to changes in this systan. 2. Diethazine "Alerting" The and Hallucinogenic Activity: behavioral effects of diethazine provide information regarding another aspect of the convulsive therapy processxs. In patients without prior convulsive therapy, illusory phenomena and feelings of unreality were observed. These were similar to the hallucinogenic effects of and mescaline (33). Again analogic data about the of these agents may provide some no change, (31;) clinical and EG effects noted that the intermittent or continuous increase in alpha frequency. (32) information about convulsive therapy. In studies of mescaline, Wikler either LSD low voltage EEG danonstrated fast activity or Denber and Merlis (35) noted a similar acceleration of alpha frequency, decrease in per cent tine alpha including its disappearance, and non-specific random beta activity. Delta activity did not occur. In patients with delta activity induced by electroshock, Merlis and Hunter (38) noted that intravenous mesoaline markedly diminished the amplitude and per cent time delta activity with an increase in per cent time alpha activity. The effects of LSD on EEG are similar. Gastaut at g. (36) noted an acceleration of alpha frequency of 0.5 to of beta rhythms. Rinkel gt 9;... 14.0 (37) confirmed cps with an aocentuation this observation and noted, �-11- in addition, a reduced reaponsivity to hyperventilation.* In summarizing his studies Wikler (3h) concluded that " . . . regardless of the drug administered, shifts in the pattern of electroencephalogram in the direction of desynchnonization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness." This generalization provides a meaningful construct may be assessed. Agents that in which these agents evoke EEG desynchronization tend to be are clear examples. Agents that synchronize frequencies, such as barbiturate and meprobamate in the beta delta frequency range, and chlorpromazine, promazine and hallucinogenic, and mesoaline and LSD Wainthe frequency range (39) tend to be sedatives, euphoriants and relaxants. 'Ihe observations on diethazine reported here are consistent with this hypothesis. In patients without delta activity, the EEG demonstrated desynchronization of frequencies, and this was associated with clinical illusory phenomena. In patients with delta activity desynchronieation occurred, and alerting and reversal of the speech patterns induced by electroshock were observed. Electroconvulsive therapy We *- have previously noted a may also be understood in this framework. direct relationship between clinical evaluations Studies are now in progress of the effects of LSD, Win-2299, benactyzine and other anticholinergic compounds on post-convul sive EEG delta activity. Initial experiments m. ah intravenous ISD (50-100 gamma) demonstrated marked diminution in per cent time and amplitude of delta activity. �of improvement and the degree of conditions, sedation Under these EEG slowing induced by electroshock (3). and euphoria are most prominent and hallucinatory activity diminished. In patients in not induced, behavioral change is limited whom hypersynchrony and 'improvement' does is not occur (in) . Previously that the we have concluded therapies is based on the mode of action of convulsive induction of a state of altered cerebral function, in which changes in adaptive interpersonal behavior occur, preted as 'improvement' (3, h, 39). The inter- present studies amplify two aspects of. this neurophysiologc-adaptive hypothesis. substrate of the behavioral change and are is reflected by an The biochemical alteration in the acetylcholine-cholinesterase relationships of the central nervous system. It is also probable that EEG basis of the milieu change euphoria and mpersynchrony provides the neurophysiologic which is evaluated as is clinically manifest as sedation and 'imprcvement.‘ The neuropklysiologi.C-adaptive hypothesis of convulsive therapy has provided a meaningful basis for studies of other physiodynamic therapies (39) . In this study, it has been possible to amplify our understanding of neurophysiologic aspects of hallucinogens as well. �SUMMARY: effect of an anticholinergic agent, diethazine, on the behavior and language patterns was observed in to psychiatric patients, 1. EEG, The at various stages in the course of electrooonvulsive treatment. (a) Behavior: Increased restlessness and agitation, haptic and visual illusory sensations, and delusional thoughts about their illness or examiner's identity were observed. (b) Egg; Alteration in There was a decrease in voltage EEG was concurrent with behavioral changes. and desynchronization of In patients with delta activity, the per cent time all frequencies. and voltage of delta activity decreased. (c) Language: Syntactic patterns described for convulsive therapy were reversed. Use of third person, qualification and displacement decreased. In dyadic analyses, there was a decrease in the coefficient of variation. 2. These observations are discussed in the framework of the neuro— physiologic-adaptive hypothesis of the action of convulsive therapy; and it is concluded that: (a) the biochemical basis for convulsive therapy is similar to that of craniocerebral trauma; (b) changes in acetylcholine-cholinesterase metabolism are intimately related to the behavioral effects; (c) EEG desynchronization may be and a physiologic concomitant of hallucinogenic activity; and EEG-hypersynchrony associated with euphoria and sedation. �.m. W 1. Weinstein, E. and Kahn, R.L.: Denial of Illness, 0.0. Thomas, Springfield, I110, 1955. 2. Roth, M., Kay, D.W.K., Shaw, J. and Green, J.: Prognosis and Peutdzhal Induced Electroencephalographic Changes in Electroconvuleive Treatment, EEG 225‘237’ 1957. Clin. Neurophxsiol. 2: and Kahn, R.L.: Relation of Electroenecephalographic Delta Activity to Behavioral Response in Electromock, A.M.A. Arch. Neurol. and Psychiat. 1Q: 516-525.. 1957. 3. Fink, h. Fink, 24., Green, M.A. and Kahn, R.L.: Experimental Studies of the Electroehock Pracess, Dis, Nerv. SE . (in press). 5. Ulett, G.A., Smith, 6. Bornstein, M.: Presence and Action of Acetylcholine in Experimental Brain Trauma, J. Newcphzsiol. 2: 3113-366, 191:6. 7. Tower, 13.3. and McEachern, D.: Acetylcholine and Neuronal Canad. J. Research, 3.1: 105-131, 191:9. 8. Ward, A.: Atropine 9. Ulett, M. K. and Glaser, G.C.: Evaluation of Convulsive and Subconvulsive Shock Therapies Utilizing a Control Group, Am. Jo Pszghia‘b. gala-3 795’802, 1956c in the Treatment of Closed Neurosurg., 1: 398—102, 1950. G.A. and Johnson, M.W.: Head Effect of Atropine Injury, Activity, ,1. and Scopelamlne Electroencephalographic Changes Induced by Beetroconvulsive Therapy, EEG Olin. Neurophlsiol. 2: 217-2224, 1957. Upon 10 . Jenkner, F.L. and Lechner, H.: The Effect of Diparcol on the Electroencephalogram in the Normal Subject and in Those with Cerebral Trauma, EEG Olin. Neuromzsio . _7_: 303-305, 1955. 11. Heyman, Sur la 0., Estable, J.J. and de Bonneveaux, 8.0.: de la menothiazinyl-Etlnrldiethylandne (2987 R.P.) , Pharmac 12. in Language During Electroshock in {exchomthologg of Communication, pp. 126-139, Stratton’ NoYo 9 o Kahn, R.L. and Fink, 11.: Changes Therapy, Gr‘me 13. . 12: 123-138, 1919. Pharmacologie Arch. Int. Jafi‘e, 8C Objective Study of Comuufication in Psychiatric Interviews, J. Hillside Hospital, é: 207-215, 1957. J.: An �.15.. Jaffe, J.: Language of the Dyed: A Method of Interaction Analyses in Psychiatric Interviews, mchiatgy, (in press). 15. 16. Weinstein, E.A., Kehn, R.L., Sugarman, L.A. and Linn, 1...: Diagnostic Use of Amobarbital Sodium in Organic Brain Disease, Am.J. mchia . 1-}.2.‘ 889-8911, 1953. Tower, D.B. and McEechern, D.: The Content and Characterization of Cholinesterases in Human Cerebrospinal Fluids, Canad, J . Research, 21: 132-115, 19349. 17. Sachs, E.: Acetylcholine and Serotonin in the Spinal Fluid, Neurosurg., 11*: 22-27, 1957. 18. Rugs, D.: The Use of Cholinergic Blocking Agents Cranio-Cerebral Injuries, J. Neurosurg., ,1. in the Treatment of I_l._1_: 77-83, 19514. Injury, J. Neural. of Acetylcholine in Head 1957. chia . g9; p.70, 19. Hughes, B.: The Role Neurosur . and 20. Freedman, A.M., Bales, P.D., Willis, A. and Himwich, H.E.: Experimental Production of Electrical Major Convulsive Patterns, 21. Am. J. @8101” fig: 117-1214, 19149. GrOb, Do, Harvey, A.M., Iangworthy, 00R. and Lilienthal, Jolie 3 The Adminis tration of Di-Isopropyl Fluorophosphate (DFP) 257.266, 19,47. Man, B11110 Jo H0215. Hogan, to a: 22. McCauley, A. and Hinmich, H.: Effects of Di-Isopropyl Fluorophosphate (DFP) on mectroencephalogram Hampson, J., Essig, C.F., EEG 23. 01in. 3: 141448, Neuropflsio . Activity, angocmlinesterase 19 . Himwich, H.E., Essig, C.F., Hampson, J.L., Bales, P.D. and Friedman, A.M.: Effect of Trimethadione (Tridone) and Other Drugs on Convulsions Caused by Di-Isopropyl Fluorophosphate (DFP), J. Psychiat., 106: 816-820, 1950. Am. 2h. Callaway, E.: Slow Wave Phenomena in Intensive Electroshock, Egg. Clin. Neurophysiol., g: 157-162, 1950. 25. Green, 26. Jasper, H.H. , Kershman, J. and Elvidge, A.: Electroencephalographic Studies of Injury to the Head, Arch. Neural“: Psychiat” 1A: Significance of Individual Variability in EEG Reaponse to Electroshock, J. Hillside Hosp” _6_: 229-2ho, 1957. M. : 328~3h8’ 19,400 �~16~ W Ostow, M. and Greenstein, L.: Dia Gmne 8: Stratton, N.I., ostic $35. Electro- 27. Strauss, H., 28. Jasper, H.H. and Droaglever-Fortuyn, J .: Experimental Studies on the Functional Anatonw of Petit Mal Epilepsy, Res. Publ. A. Nerv. Mt. Dis. 2-6-3 272-298’ 19117. Lindsley, 1)., ‘Schreiner, L.H., Knowles, W.B. and Magoun, H.W.: Behavioral and EG Changes Following Chronic Brain Stem Lesion in the Cat, EEG Olin. Neuropmsiolu 2: 1:83-1:98, 1950. Rinaldi, F. and Him-rich, H.H.: Alerting Responses and Actions of Atropine and Cholinergic Drugs, A.M.A. Arch. Neural. and 29. - PfizChiate, 123 387-395) 19530 31. Himwich, H. and Rinaldi, F.I:'The Effect of Drugs on Reticular System, in Brain Mechanism and Dru Action, 15-4411, C.C. Thomas, Springfie d, 19 7. 32. Stall, W.: Lysergsaure Phantaetikum aus der Arch. Neurol. PsEhiat. , §_Q: diethylamid, ein -Schweiz Mutterkomgruppe, 1-h7, 19m. ' Neural. Psychiat., 1-315, 33. Beringer, K.: Der 'Meskalinrausch Springer, Berlin, 1927. 3h. Wikler, A.: Clinical and Electrencephalographic Studies on the Effects of Mescaline, N-allylnarmorphine and Morphine in Man, J. Nerv. Wilt. 1318., 120: 157-175, 19%. i Monog. on Mescaline I: Action in Schizo~ Psychiat. Quart., g2: 1.21-1.29, 1955. 3.: Studies 35. Denber, H. and Merlis, 36. Gastaut, H., Ferrer, S. and Castello, 0.: Action de la diethylamide de l'acide d-lysergique (LSD 25) sur lee fonctions psychiques at l'electroencephelograxme, Conf. Neuro1., 12: 102-120, 1953. 37- Rinkel, H., DeShon, H.J., Hyde, R.W. and Solomon, H.C.: Experimental Schizophrenia-Like Symptoms, Am. J. Psychiat., 108: 572-578, 1953. 38. Merlis, S. and Hunter, W.: Studies on Mesaaline II: nectroencephalogram in Schizophrenics, Psychiat. Quart. , g2: 1:30-4:32, 1955. 39. Fink, M.: ha. Fink, phrenic Patients, A Unified Theory of the Action of Physiotbmamic Therapies, J. Hillside Hosp. , {3: 197—206, 1957. and Green, M.A.: Electroencephalographic Correlates of the Electroshock Process (in proparation). M. ‘ ��~24... 1m 1955. mm:- and WM )mpwm that EEG and human-n oflam swim to abopinn were achieved by mm mama in pafienta with head trauma. Fran thaw report in mute“. the ayatemic attacks of We at ( am- theme and diam nppamd mam. intamt in the nativity 1n enmeshed: r613 of 6311;: ), an immigauon a: the «that of dint-hum, in patients manning eomlain therapy wmsuport to describe the oft-hats bazwiw sf pitienta mm in was both m EEG and behavior, mama. It in the puma «mm mthexmmdm aux-lag olwhmflmek’ therapy; and to unto the” obsomtiom to the meant neurapbyaioloac adaptive hypothesis a! the mode of widow: of convulaive them. Wamwthodg: mum pitta cuts, at. “nuns sagas or electroshock flmmpy in an awn-mad, volmtu'y psychiatric haepital have been studiad. All mum hm ham EEG and. Mot-ding, diafhuine 25 mm per minute, in the me laboratory. 3‘an a mum m amateur! intravenously at. the for a total of 175 to .200 mm, depending upon rate of the �uh Wm: «that. Ins/k8 1» wording to m ram, (SW mm mm 2.8 b0 Int/ks. mum is a column Wino W: with am to “reprint. “perineum the Wen. bmnehm, Wmtim, rummum lawman «mm by mfiylmolm, «1»:meth 15W “Maiden, M and «1 and ‘ A mum: in» (DFP and plum-pins. new Wis 1nd momma (Raymu- 19189): All records were unlisted the por car animals, 22:: We mi: time and fast nativity. far the: dams of dolta aébiviw principal 31pm “fluency; Drug errata were emailed find the relative meant as synchronising (I) or Warning (n) «@0ng to the mam mama by um» ( In In W, mm, tapers]. both and 81m parietal and )3 ( ). mu nativity was mum in natal-ion» m m m mum. War Wm: Prim to drug twain-rattan an mmzmmd psychiatric historical �.3;- intern“ and a structmd Wm 1?ng drug achinistmtian, pat-1363 altamted with ma EEG mm. period 1mm tape 31’ taps new 13me m ”cording parieda, until the again. manifested EEG 1236 Macaw pattern 0213131231 inspection. M Minutes or behaviorai by the m“. a offsets warn and: 311111331 Maithmjoct, 1mm:- and Mam naming and , aux-mg drag W 6:13.616 period, and in language were «- awriptions at the was: 1mm annlynn of tha awarded inten- named by a syntactic minis of the amtfleient of variability mm (x. a r) (63113).“ M~3W1; (t) W: W mm of the start of the injection, the math subaaeta mitigated apaxtmeoua 0011M follow by mm hm to five a. and a thinness of speech. 11337111333 m6 weakness mammalian 6 and 31‘ They I. feeling of hasitude, and 3 was: mien us difficulty in W136 mlynoa worked of trace 31‘ soon mceedud by 33mm cyclic: «gleam. obmtim will appear separately. {mama �Marts of visual and baptis illusory mantiann, rulings a! witty and diam», and aslunisml thsugats about their films”, the setting of the tact. prams can can identity wax-s winsd apmtan» 1 annular mm in the mat period batman in after «hag satinistrntim. In thus panic lad and ts a suhaostn. W m disappomd in W! sitscta. In all retards, wars in éanon W by!!! ;of .. h Such pattsms sf bum in all Wm; and mutation sf tha wan-injection pattanm in ms to five hours. Wings. and instants, vathdrwal shaman mam-Nd during, drug administration and Mama, with gradual 1 1% and m pattsms m smut with tbs behavioral Alteration in the ‘ one smut Miami-a1 response. behavior slam transient and mm W8, harassing agitatian newsman of the mar-ding. In negativisn was tbs 15 amt 30 pmailing its initial mouse of all W. ancias. was a dwram in Thar-a was a 63mm In patients without dalta activity shatmsbock) , dasymhmnixafim and voltage ésmasa was messiamlly �”mania by low voltage 5-? frontal and anterior tampon: intimacy was not altered. Ops nativity, um. The (Figum 1, 2). The basic alpha build-m: in voltage and aim: immanent: with mementmmn In patients with flying there was a mm. Writ; and prominent in W ma mm. am: at of high valtugo data «cavity Want deem” 1n mum; and «mm-am of tin Both random and 1w mltaéu alpha and burst beta mm nativity Imemiaa diaappearad and irregular, banana pronnenb (Fig. 3. h); ‘ (a) ’ Pammz ' In previous «main, an intimate in We language mun-nu hid been mported ( mtimmxn batman amass maths Won]. ). with diorama: in 13min weapon” in electmahack function, increased as? a! third person, verbal denial. qmlifimtian, displaoomi; am] 311011” Name lax-Wat. Those «mm mum ha mhanced by the adamant-.1011 ef intrmmua mobarbiml ( ). In the subjects in the man’s study, syntactic a reversal of the pattoma noted in ehctrmhock. Use mm WM of mm mm, ��us» ”mama aspects of wmldm threw, 1.1m» infomuw cumming Mechanical We”: is «mum. Mac of biochemical mama 1'0an head trim and spontaneous mums ( ), in a that am a W provide am analogs data. Romain expat-1mm “My of had tmm in «ta, ammo: after tmm, than appoarod few free mtylaholino which permit“! far periods up ta 1n 1:8 dunmatmted the spinal fluid, hours. Bernstein Wr max-um positive mint-1m batman the annuity of 1&0 hand trams and ma quantity of fun autylehaum, degree of alasbmmephalagnphic W Warn]. changea. and tha newt-My of tho martin initially abound shcrt. The pounds a: tug: voltage electroenmpmlomphic fut nativity. and a trmaimt period of flattering at alwtriml nativity followed by pmlonged wands of hm amplitude ahup man in the delta {mmnciam Gmfltmtly, altemfim in consciousness, ohms“ in reflexes. and pout-tramtie mama mm most prominent with highest mueammtion of true acetylcholim and mum W Tmr and m stadium the of mm «hinge; mm in man. In ( ) mammal bu obsomtim in 31mm Wham patients, true mtyldmlim m fluid pm in 31.1mm following head trauma and town! mm in �g9... gum m1 Minna: tad that the M761 011‘ true acetylchonm varied W. dimctly with the degree of mmbéal In addition, We authors swam the «hummus. nativity of the spinal fluid. In Quanta taflwing head mm, my (Whhofimaplitung) 110th a I and m rise in drop in the spooiflc «immanent-use (matchb- splitting) activity or the spinal fluid. Whining man-Speeific cholineatoraae no such rm mtylohaline following apontamous seizures. those subdue“, electroencephalogram were taken ing mama, and damonatrfited a direct new in fluid: inversion me: In most at at “wing intervals ram.- emulation of tha extant of EEG «morality md the amaranca 9f free acetyloholine in the spinal fluid. In their reporta, Tm and fishermen; report «on via: aeivixg electrocanvuniw thumpy. swaying the patients convulsions, they reported rm and an imam aateraaa rad-.19 Micheline in patients ro- after 34-? Sadness! the spinal fluid in m, in non-specific ohelineatamo with reversal of the abounin five 91‘ the six patients. They concluded that {m apinal I 6W3 flute! than are in electroshock and than row in opium} more like those of nraflnworebml trauma many, Sachs ( ) cuiflmd tbs a? the. six who max in show gum fm “It. 13 Mare patient WW at cholimatem mun, they note: an mum). at a. Em one this patient was the only one of the 31:: to mm interesting that tmtmant.” show no response to ��‘ YEP? («mun/1 the ensyutie , mien bleak pyraphoaphate). 13:9an 91' tmtyloholim, demonstrate the cf high amplitude rapid frequemy mm Malawi. similar to status epileptmug u “11 as lessor demos of abmmality noted in postutramtio status ( , , ). In those swam, ntmpina blocked both the algatm mauphalmsphic and clinical talc “feats. m, both in maximum and clinical studies of cmmbnl we my mum that (a) the mtylehulim nativity of the spinal fluid increases, (b) pundwhounestamae nativity 231' the: ratea of mung"; ad chommflseu; (6) that (6) me change: with a mama]. 13.111101 than bioehoflcal mtigholimgm «wounds my block both the shown- whalomphic mad the clinica stints. proth memes From the data available it. that the Mechanical basis of the eonvulsive therapy process in am to that of nth amowmbml trauma. infrae mtylcholine inthe spimlflnid£ imatamae mum ( ). g. Gmlaivc Manny results )m amenal of chol-v m alanimcaphuomphic affects of ”pasted manned convulaims is tha amazement of high voltago, slaw is ma activity, mmimlly with spike activity ( -. , mimic ), �awe» mid'xiemtosmmhoadhrAWC , studies-we have reported the relationship hem the degree of WW fit»! me utivity and behavioral respme (i). thbe a moml of the 61W my ‘ The studies method here. new «feet: at cumin“ the Marion). In each ehmeterietie, emuisive Wheemimmbni tnm.imhthemmm1im~ system is Weave by those studies, other animals mm am be altered provides In and cm. therapy by antichoiinergie Wrapyisthul EEG L Inpmim g ). ( Theta «mam suggest that mum mm «comet experimental maxed fer studios of emioeembni ensue Baum mains of the brain stem activating system by Jasper and mmmrem ( fer the wailing nomination its erigln 1n the mtraymm at and mm ( ) and Waleyw. ( ”macaw that “matures, Morning? and , ) have ehoiinergic drugs to this ”mute ) bed “We! thmfom, that. the» structures are Here may, Rama. ream: the hits of nation masodiWMg4.,mnung ”M prohehie, we nativity hm ma aim and that. than stmehm’ec may be we the feundntion at umpim m6 We It is 3130 selectively affected! �hr; the Wire therapy pm”, and that. both the clinical and electrou angina streets my be intimately muted to shanghai in thin mm. �m um *13- «mu of mm mm wax-nation ”mmmammammym.mw patients without may Wu and findings WW thorny or mm mm, 111nm at many um mmmmWemmotm( W. Thane were ).uaennm( mum human“ mm£2dcmm1omammwmmmm “Imumu-WwWWMWm about mm. them. Inatndiunfum,mkhr( )wmmmma Mata-um am no m, mumm an- em 1a values :mmntywmmmamtm.‘mma&mn( ) Wammmmotmrmm,mmmnmtm aw infinding its diam, and We w W. mmwmmammmm. Belt: «mum did random bots nativity. wunJ )nm 11130003.th dfm1Wfi0aSWhuflmuihmteaMflm wmum.m1otn( ) WWnpm'hmmd, in mm, 3 mm aspen-131w to mus-mam». ), �.31... In punish with 601k mdfiutaW W «adv by dwhromok, mm.- )ammtmmmmmmmwmmm mummmmmmumuuw uthanimminpmm ammuwy EWWWIMI‘( )mnaludedthat“... mammmmm,m1nmepmmdmam memmumw ”9061an m, ddsmhrmtutimommd in m, W Winona nth 9W3, similar: W." MmMnWanmehmmw mmmwmtwwmummmwn with hallucination... a! in the manna. mums or m: or mdmm,MaMMmfimm.Wthh mm” Wamfiummuwuwmuumum rang“, and Wine, lira-um dem in the an: mean an manymmmmmm. Jthe mm on ammm mm hire am also amine-at War. In 3W without we: mum the m Wham mmmumqums, andthismmociaud umamm with this illusory Momma In gamma with ma mama dammit-am mmwamwmmoxmwpmmmmw �~65- WW ( ) mm Wwwmamhmmmmrw. MmemmaWnuumummmmfim «Wmmamormummwamm( )a mm, mm upland: are mt Wat. In puma“ mmammwummmwmumm ma Radar than and ‘mmat‘dmwtm. WmWWflWtWMfiwfimdflm «mnwmmasrmmwmioaatamanumm Man, in mm W. in mm” inmm We: cam, MWWM'W'C , , )Jhemmtm wmmwwummmmwmm. Thu mmmmmofflwbmmmwh,orwha mm by, an aluminum in the mwlahelmmehonmsm mum” at the mm: muons man. It in also probable that. mmmmmmummmmimmmmamwm momwaammnwmummmmmmummm u ’Wflt’ ., �WWW at cm“ thirty form mWanu blathuamdnitmmlmufihtonwxym flmmdodynnue thanpfiu( mammamotmmmsunn. �Effect of Anticholinergic Agent, Diethazine, on EEG and Behavior Significance for Theory of Convulsive Therapy MAX FINK. M.D.. GLEN OAKS. N. Y. �Reprinted from the A. Ill. A. Archives of Neurology 6“ Psychiatry September 1958, Vol. 80, pp. 380—387 Copyright 1958, by American fliedical Association Effect of Antieholinergic Agent, Diethazine, on EEG and Behavior Significance for Theory of Convalsive Therapy MAX FINK, M.D., Glen Oaks, N. Y. Recent investigations of convulsive therapy have emphasized EEG delta activity as the neurophysiologic basis for the induced behavioral Changel"5 Little study, however, has been given to the biochemical effects of this therapy, except in the course of investi— gations of head injuries. In investigations of head trauma signifi— cance has been ascribed to» changes in the acetylcholine—cholinesterase systems both for the behavioral and for the electroencephalo— graphic effects. An increase in free acetyl‘6 choline and an alteration of the ratio of cholinesterases 7 in the spinal fluid have been positively correlated with the degree of EEG abnormality and degree of neurologic defi— cit. The EEG patterns were “blocked,” and some improvement in clinical status was reported following the administration. of atropine.“8 In convulsive therapy, atropine and scopolamine were observed to block the appearance of delta activity,9 although the systemic effects of the large doses of these agents were marked. Recent reports 10 noted that EEG and behavioral effects similar to atropine were achieved in patients with head trauma by intravenous diethazine—a phenothiazine compound with anticholinergic properties— Submitted for publication March 24, 1958. From the Department of Experimental Psy— chiatry, Hillside Hospital. Aided, in part, by Grant M-927 of the National Institute of Mental Health, National Institutes of Health, U. S. Public Health Service. Read (in part) at the meeting of the Eastern Association of Electroencephalographers, New York, December, 1957. Awarded A. E. Bennett Psychiatric Research Award of the Society of Biologic Psychiatry, May, 1958. 380 with minimal systemic effects. In our con— tinuing studies of the role of delta activity in electroshock,3 the effect of diethazine: was studied. It is the purpose of this report to describe the effects of diethazine on EEG patterns and on behavior of patients during electroconvulsive therapy, and to relate these observations to the present neurophysiologic— adaptive hypothesis of the mode of action of convulsive therapy. Subjects and Methods Forty psychiatric patients, at various stages of electroshock therapy in an open-ward, voluntary psychiatric hospital were studied. All observations were made in acute experiments in the EEG lab— oratory. After a routine EEG recording, diemhazine was administered intravenously at the rate of 25 mg. per minute, for a total of 175 to 250 mg, depending upon the behavioral effect. The dosage varied from 2.8 to 4.0 mg. per kilogram of body weight. Diethazine is a soluble phenothiazine compound with pharmacologic properties similar to those of atropine. In experimental animals, diethazine blocks the bradycardia, bronchospasm, salivation, fasciculatio-n, and seizures induced by acetylcholine, fluorophosphate, and pilocarpine. It suppresses salivation and induces mydr‘iasis and hypotension.11 EEG Analyses.~—Recording was continuous for the duration of the observation period, except dur— ing interview periods. Needle electrodes, and an eight—channel Medcraft instrument were used. All records. were analyzed for the degree of delta activity,3 the per cent time and principal alpha frequency, and the relative amount of fast activity. The alpha and delta activities. were measured in anterior temporal—vertex, parietal-ear lobe, and frontal-occipital lead combinations. Behavior Mensures—Prior to drug administra— tion an unstructured psychiatric historical interview and a structured questionnaire period” were tape-recorded. Following drug administration, �EFFECT OF ANTICHOLINERGIC AGENT ON EEG periods of recorded interview were alternated with EEG recording periods, until the EEG had again manifested the preinjection pattern on. visual inspection. Two estimates of behavioral effects were used: clinical descriptions by the participants—subject, interviewer, and technician—of the changes oc— curring during the drug period, and language analyses of the recorded interviews. Changes in 1“ evaluated by a syntactic analysis language were and an analysis of the variability in verbal interaction in the dyad?"14 * Both measures have been shown to be sensitive to alterations in behavior induced by changes in the central nervous system. W W W W WW W WW AFTER I50 mg. PRE-DRUG LF-LO RF.“ LAT‘LF RAT-RF LF-RF LPT-LO 0-0 RPT-RO WWW-MN WWW“ MWVVUWVV’WMWM 50va___ SEC. l Observations (a) C1inicwl.—Within two to five minutes of the start of the injection, subjects mani— fested spontaneous coughing followed by a dryness of the mouth and a thickness of speech. They reported a feeling of lassi— tude and a heaviness and weakness of the extremities, soon succeeded by increased restlessness and difficulty in maintaining eye— lid closure. Reports of visual and haptic illusory sen— sations, feelings of unreality and distance, and delusional thoughts about their illness, the setting of the test procedures, or our identity were voiced spontaneously by 18 subjects in the period between 15 and 60 minutes after drug administration. In three instances increasing agitation and panic led Detailed analyses of these observations will be reported separately by Dr. J. Jaffe and Dr. R. L. Kahn. * AFTER 225 mg. PRE-DRUGI 0-0 W {Wyn-— SEC. =0? IGQI HH 1 Fig. 1.—Effect of intravenous diethazine prior to electroshock in a man aged 27. Fin/e #1125 NH Fig. 2.——Effect of intravenous diethazine prior to electroshock in a woman aged 57. to a cessation of the recording. In two subjects withdrawal and negativism were the prominent behavioral response. Such patterns of behavior were transient and had disappeared in one and one~half to four hours in all subjects. (I?) EEG Potterns.——Alteration in. the EEG patterns was concurrent with the be— havioral effects. In all records, changes oc— curred during drug administration and were sustained, with gradual diminution and resti— tution of the preinjection patterns, in one to five hours. The initial response was a decrease in voltage and desynchronization of all frequencies. There was a decrease in prominence of prevailing rhythms. In patients without delta activity (preelectro— shock), desynchronization and voltage decrease were occasionally accompanied by low—voltage 5—7 cps activity, symmetric and prominent in frontal and anterior temporal leads (Figs. 1 and 2). The alpha frequency was not altered. The build—up in voltage and appearance of slower frequencies with hyperventilation were blocked. In patients with varying degrees of high— voltage delta activity, desynchronization of the records became prominent, with a sig— nificant decrease both in voltage and in per cent time of slow wave activity. From an average per cent time delta of 45% in frontal—occipital leads, there was a reduction to a mean of 20%. Both random and burst delta activity diminished or disap‘ 381 �A. M. A. ARCHIVES OF NEUROLOGY AND PSYCHIATRY PRE-DRUG AFTER 250 mg. W W ”W W W W W WW W W WW WW W LAT-LF/W RAT WWWW‘ WWWW RPM/MW LF- +5HRS. +|.HR WVJMWWVV' LPT'LQ’W’W‘VWW 0 ° ”WNW RPT—RW WMw/V *1249 SOpv [TEE—C HH Fig. 3.—Effect of intravenous diethazine on delta activity after electroshock. peared, and irregular low—voltage alpha and beta frequencies became prominent (Figs. 3 and 4). The hyperventilation response was no longer apparent. (c) Language Patterns.——In previous studies, an intimate relationship between changes in syntactic language patterns and the behavioral response in electroshock had been reported.” With alteration in brain function, increased use of the third person, verbal denial, qualification, displacement, and cliches became prominent. These: ef— fects could be enhanced by the administra— tion of intravenous amobarbital.15 In the subjects in the present study, syntactic analyses demonstrated a reversal of the patterns noted in electroshock. Use of the third person, qualification, and dis— placement decreased. Explicit verbal denial was modified and replaced by minimization and displacement, or by a reiteration of complaints of illness. In dyadic analyses, the verbal interaction was characterized by a greater diversity of vocabulary and less variability in the diversity scores for 25 word units. The qualitative nature of these changes in the language patterns is opposite that of amobarbuital and electroshock. The duration of language changes was concurrent with the changes in the electroencephalogram. Comment These observations confirm the report of Jenkner and Lechner of the effects of di— ethazine in “normal” subjects.10 Diethazine also alters electroshock—induced delta activity in a fashion similar to atropine and scopolamine, as described by Ulett and Johnson,9 with minimal unpleasant symptoms. The effects of intravenous diethazine are immediate, both on the EEG and on W W “MW MN “$wa W W WM W W W W “”wa PRE-DRUG + 200 mg. +25 min. + 70min. LF-LO Rm MWWW st UT'LWMW ”NM-«MW WVMW“ LF-RF LPT~LO °'° WWW WWW/“M 5°}‘VL._. ISEC. WWW/WWW #l637 HH Fig. 4.—Effect of intravenous diethazine on delta activity after electroshock. 382 Vol. 80, Sept, 1958 �EFFECT OF ANTICHOLINERGIC AGENT ON EEG behavior, and thus provide a useful experi— mental agent With “anticholinergic” proper— ties. Two aspects of these experimental observations warrant discussion: the role of acetylcholine-cholinest‘erase- in the electroconvulsive therapy process, and the signifi— cance of diethazine “alerting” for concepts of hallucinogenic activity. 1. Biochemical Basis of the Convulsive Therapy Process.——While there has been considerable study of the psychologic and neurophysiologic aspects of convulsive therbiochemi— information little concerning apy, cal processes is available. The studies of biochemical changes following head trauma and spontaneous seizures provide some analogic data. Bornstein,‘6 in a classical experi— mental study of head trauma in cats, demonstrated that within a few minutes after trauma free acetylcholine appeared in the spinal fluid and persisted for periods up to 48 hours. He further demonstrated a posi— tive relation between the severity of head trauma and the quantity of free acetylcholine, the degree of electroencephalo— graphic alteration, and the severity of the behavioral changes. The electroencephalographic records initially showed short peri— ods of high—voltage fast activity, and a transient period of flattening of electrical activity, followed by prolonged periods of high—amplitude sharp waves in the delta frequencies. Concomitantly, alteration in consciousness, changes in reflexes, and post— traumatic seizures were most prominent with highest concentrations of free acetylcholine and greatest degree of EEG change. 7 Tower and McEachern confirmed these observations in clinical studies in man. In 112 neurologic patients, free acetylcholine was found in the cerebrospinal fluid only in patients following head trauma and re— cent grand mal seizures, and the level of free acetylcholine varied directly with the degree of cerebral damage. In addition, these authors assayed the cholinesterase activity of the spinal fluid.7’1‘6 In patients following head trauma, they noted a sharp rise in. nonspecific cholinesterase (benzoylcholine— Fink splitting) and a drop in the specific cholin— esterase (methacholine—splitting) activity of the spinal fluid. No such inversion was noted in fluids containing free acetylcholine following spontaneous seizures. Electroen— cephalograms were taken at varying inter— vals following trauma and demonstrated a direct correlation of the extent of EEG abnormality with the appearance of free acetylcholine in the spinal fluid. Tower and McEachern also reported ob— servations in six patients receiving electro— convulsive therapy. In patients after three to seven induced convulsions, they noted free acetylcholine in the spinal fluid in two pa— tients and an increase in nonspecific cholinesterase with reversal of the cholinesterase ratio in five of the six. They concluded that the spinal fluid changes in electroshock are more like those of craniocerebral trauma than those found in epilepsyj' More re17 Sachs confirmed the reports of cently, free acetylcholine in the spinal fluid after head trauma and after electroshock. In his studies, Bornstein6 administered 0.5—1.0 mg/kg. of atropine and demonstrated a reversal or a blocking of the EEG effects and a modification of the behavioral and neurologic signs. Atropine also blocked the EEG and clinical signs induced by intra— cisternal acetylcholine. Ward8 applied these observations to the treatment of human subjects with varying degrees of head trauma. Subcutaneous doses of 0.1 mg/kg. of atropine induced both clinical improvement and reversal of EEG effects. These observations were recently confirmed by Sachs,17 Ruge,18 and Hughes}9 On the basis of these observations, Ulett and Johnson 9 noted the effect of atropine and scopolamine in blocking the EEG changes of electroshock therapy. Con— 10 currently, ]enkner and Lechner reported ' Regarding the one patient of the six who failed to show either free acetylcholine or a re— versal of the cholinesterase ratio, they noted: “It is interesting that this patient was the only one of the six to show no response to treatment.” 1‘ 383 �A. M. A. ARCHIVES OF NEUROLOGY AND PSYCHIATRY effects similar to those of Ward, in studies provides an excellent experimental method for studies of craniocerebral trauma. of diethazine in cases of head injury. Studies of the brain—stem—activating sys— Another group of investigations complete the available data. Studies of anticholines— tem by Jasper and Droogleever-Fortuyn 28 terases, such as fluorophosphate, and tetra— and Lindsley et al.2‘9 had laid the founda— ethylpyrophosphate (TEPP), which block tion for the prevailing conclusion that sym— the enzymatic breakdown of acetylcholine, metric EEG slow—wave activity has its demonstrate the development of high-ampli— origin in mesencephalic structures, and that tude rapid—frequency EEG patterns similar these structures intimately affect the states to those of status epilepticus, as well as of “alerting” and “drowsiness.” More reslighter degrees of abnormality, as noted in cently, Rinaldi and Hivaich 30"” have re— post—traumatic states.”23 In these studies, lated the site of action. of atropine and atropine blocked both the electroencephalo— cholinergic drugs to this mesodiencephalic activating system. It is also probable that graphic and the clinicaltoxic effects. these be structures may selectively affected clinical and both from experimental Thus, studies of craniocerebral trauma we may by the convulsive therapy process, and that both ef— clinical the and the of electrographic the that acetylcholine activity (a) assume the spinal fluid increases, ([9) pseudo- fects may be intimately related to changes in cholinesterase activity increases, with a re— this system. 2. Diethazine “Alerting” and Hallucinoversal of the ratio of cholinesterases, (c) EEG hypersynchrony and slowing parallel gem'c Activity—The behavioral effects of these biochemical alterations, and (d) anti— diethazine provide information. regarding cholinergic agents may block both the elec— another aspect of the convulsive therapy troencephalographic and the clinical effects. process. In patients Without prior convul— From the data available, it is probable that sive therapy, illusory phenomena and feelthe biochemical basis of convulsive therapy ings of unreality were observed. These is similar to that of craniocerebral trauma. were similar to the hallucinogenic effects of Convulsive therapy results in free acetylcho— lysergic acid diethylamide (LSD32) and line in the spinal fluid 7'17 and a reversal of mescalinef“3 Again, analogic data about the clinical and EEG effects of these agents cholinesterase ratios.”6 The electroencepha— information provide about some con— may induced effects of con— repeated lographic vulsive therapy. is the development of high—voltage, vulsions 34 noted In studies of Wikler mescaline, symmetric, slow—wave activity, occasionally that the EEG demonstrated no change, or is which similar to with spike: activity,3"24’25 intermittent continuous low—voltage fast or trauma..2627 that observed in severe head increase in activity, or alpha frequency. In previous studies we have reported the Denber and Merlis 3'5 noted a similar accel— relationship between the degree of induced eration of decrease in per alpha frequency, slow—wave activity and behavioral response.3 cent time alpha, including its disappearance, The studies reported here and, the work of and random beta nonspecific activity. Delta 9 Ulett and Johnson demonstrate a reversal activity did not occur. In patients with of the EEG and the behavioral effects of delta activity induced by electroshock, Mer— convulsive therapy by anticholiner‘gic com— lis and Hunter 38 noted that intravenous pounds. In. each characteristic, convulsive mescaline markedly diminished the ampli— therapy is thus similar to- cerebral trauma. tude and per cent time delta activity with While the acetylcholine—cholinesterase sys— an increase in per cent time alpha. activity. tem is highlighted by these studies, other The effects of LSD on EEG are similar. enzyme systems may also be altered.17 These Gastaut et al.3‘6 noted an acceleration of studies also suggest that convulsive therapy alpha frequency of 0.5 to 4.0 cps, with an 384 Vol. 80, Sept, 1958 �EFFECT OF ANTICHOLINERGIC AGENT ON EEG accentuation of beta rhythms. Rinkel et al.3‘7 confirmed this observation and noted, in addition, a reduced responsivity to hyper— ventilation: In summarizing his studies, Wikler 34 concluded that “regardless of the . . drug administered, shifts on. the pattern of elec— troencephalogram in the direction of de— . synchronization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness.” This generalization. provides a meaningful construct in, which these agents may be assessed. Agents that evoke EEG desynchronization tend to be hallucinogenic, and mescaline and LSD are clear examples. Agents that synchronize frequencies, such as barbiturate and meprobamate in the beta frequency range, and chlorpromazine, pro— mazine, and perphenazine in the delta fre— 39 tend to be sedatives, quency range euphoriants, and relaxants. The observations on diethazine reported here are consistent with this hypothesis. In patients without delta activity, the EEG demonstrated desynchronization of f requen— cies, and this was associated with clinical illusory phenomena. In patients with delta activity desynchronization occurred, and alerting and reversal of the speech patterns induced by electroshock were observed. Electroconvulsive therapy may also be understood in this framework. We have previously noted a direct relationship be— tween Clinical evaluations of improvement and the degree of EEG slowing induced by electroshock.3 Under these conditions, seda— tion and euphoria are most prominent, and hallucinatory activity diminished. In, pa— tients in whom hypersynchrony is not in— of iStudies are now in progress on the effects LSD, Win—2299 (2~diethylarminoethy1-cyclo— pentylhydroxy—Z-thienylacetate), benactyzine, and other anticholinergic compounds on postconvulsive EEG delta activity. Initial experiments with these compounds have demonstrated marked diminution in per cent time and amplitude of delta activity associated with behavioral changes similar to those seen with diethazine. Fin/a duced, behavioral change is limited, and “improvement” does not occur.4 Previously we have concluded that the mode of action of convulsive therapies is based on the induction of a state: of altered cerebral function, in which changes in adap— tive interpersonal behavior occur, and are interpreted as “improvement.” 3'4'39 The present studies amplify two aspects of this neurophysiologic-adaptive hypothesis. The biochemical substrate of the behavioral change is reflected by an alteration in the acetylcholine—cholinesterase relationships of the central nervous system. It is also prob— able that EEG hypersynchrony provides the neur‘ophysiologic basis of the milieu change, which is clinically manifest as sedation and euphoria and is evaluated as “improvement.” The neurophysiologic-adaptive hypothesis of convulsive therapy has provided a meaningful basis for studies of other physiody— namic therapies.39 In this study, it has. been possible to amplify our understanding of neurophysiologic aspects of hallucinogens as well. Summary and Conclusions The: effect of an anticholinergic agent, diethazine, on the EEG, behavior, and lan— guage patterns was observed in 40 psychiat— ric patients, at various stages in the course of electroconvulsive treatment. (0) Behavior: Increased restlessness and agitation, haptic and visual illusory sensa— tions, and delusional thoughts about their illness or the examiner’s identity were ob— served. (b) EEG: Alteration in EEG were con— current with behavioral changes. There were a decrease in voltage and desynchroni— zation of all frequencies. In patients with delta activity, the per cent time and voltage of delta activity decreased. (c) Language: Syntactic patterns de— scribed for convulsive therapy were re— versed. Use of third person, qualification, and displacement decreased. In dyadic analyses there was a decrease in the coeffi— cient of variation. 385 �A. M. A. ARCHIVES OF NEUROLOGY AND PSYCHIATRY These observations are discusSed in the framework of the neurophysiologic—adap— tive hypothesis of the action of convulsive therapy, and it is concluded that (at) the biochemical basis for convulsive therapy is similar to that of craniocerebral trauma; (1)) changes in acetylcholine-—cholinesterase metabolism are intimately related to the be— havioral effects, and (c) EEG desynchroni— zation may be a physiologic concomitant of hallucinogenic activity, and EEG hyper— synchrony, associated with euphoria and sedation. Mrs. Hannah Mosquera gave technical assistance in the EEG recordings, and Dr. Joseph Jaffe and Dr. Robert L. Kahn made the analyses of the tape recordings. Diethazine was made available through the courtesy of Smith, Kline & French Laboratories, Philadelphia. Hillside Hospital, 75—59 263d St. REFERENCES Weinstein, E. A., and Kahn, R. L.: Denial of Illness: Symbolic and Physiological Aspects, Springfield, 111., Charles C Thomas, Publisher, 1. 1955. 2. Roth, M.; Kay, D. W. K.; Shaw, J., and Green, J.: Prognosis and Pentothal Induced Elec— troencephalographic Changes in Electroconvulsive Treatment, Electroencephalog. & Clin. Neuro— physiol. 9:225—237, 1957. 3. Fink, M., and Kahn, R. L.: Relation of Electroencephalographic Delta Activity to Be— havioral Response in Electroshock, A. M. A. Arch. Neurol. & Psychiat. 78:516—525, 1957. 4. Fink, M.; Green, M. A., and Kahn R. L.: Experimental Studies of the Electroshock Process, Dis. Nerv. System, 19:113—118, 1958. 5. Ulett, G. A.; Smith, K, and Gleser, G. C.: Evaluation of Convulsive and Subconvulsive Shock Therapies Utilizing a Control Group, Am. J. Psychiat. 112:795—802, 1956. 6. Bornstein, M.: Presence and Action of Acetylcholine in Experimental Brain Trauma, J. Neurophysiol. 9:349—366, 1946. 7. Tower, D. B., and McEachern, D.: Acetyl— choline and Neuronal Activity, Canad. J. Res. 27: 105-131, 1949. Ward, A.; Atropine in the Treatment of Closed Head Injury, J. Neurosurg. 7 :39‘8-402, 1950. 9. Ulett, G. A., and Johnson, M. W.: Effect of Atropine and Scopolamine upon Electroencephalo— graphic Changes Induced by Electroconvulsive 8. 3.86 - 7 Therapy, Electroencephalog. & Clin. Neurophysiol. 92217—224, 1957. 10. Jenkner, F. L., and Lechner, H.: Effect of Diparcol on the Electroencephalograim in the N ormal Subject and in Those with Cerebral Trauma, Electroencephalog. & Clin. Neurophysiol. 7:303- 305, 1955. 11. Heymans, C.; Estable, J. J., and de Bonne— veaux, S. C.: Sur la Pharmacologie de la phénothiazinyl-éthyldiéthylamine (2987 R. P.), Arch. internat. Pharmacodyn. 792123438, 1949. 12. Kahn, R. L., and Fink, M.: Changes in Language During Electroshock Therapy, in Psy— chopathology of Communication, edited by P. H. Hoch and J. Zubin,.New York, Grune: & Stratton, Inc, 1958, pp. 126-139. Jaffe, J.: An Objective Study of Communication in Psychiatric Interviews, J. Hillside Hosp. 13. 6:207—215, 1957. 14. Jaffe, J.: Language of the Dyad: A Method of Interaction Analysis in Psychiatric Interviews, Psychiatry, to be published. 15. Weinstein, E. A.; Kahn, R. L.; Sugariman, L. A., and Linn, L.: Diagnostic Use of Amobarbital Sodium in Organic Brain Disease, Am. J. Psychiat. 112:889—894, 1953. 16. Tower, D. B., and McEachern, D.: The Content and Characterization of Cholinesterases in Human Cerebrospinal Fluids, Canad. J. Res, Sect. E. 27:132—145, 1949. 17. Sachs, E., Jr.: Acetylcholine and Serotonin in the Spinal Fluid, J. Neurosurg. 14:22-27, 1957. 18. Ruge, D.: Use of Cholinergic Blocking Agents in the Treatment of Cranio—Cerebral Injuries, J. Neurosurg. 11:77—83, 1954. 19. Hughes, B.: Role of Acetylcholine in Head Injury, J. Neurol. Neurosurg. & Psychiat. 20:70, 1957. 20. Freedman, A. M.; Bales, P. D; Willis, A., and Himwich, H. E.: Experimental Production of Electrical Major Convulsive Patterns, Am. J. Physiol. 146:117-124, 1949. 21. Grob, D.; Harvey, A. M.; Langworthy, O. R., and Lilienthal, J. L.: The Administration of Di-Isopropyl Fluorophosphate (D‘FP) to Man, Bull. Johns Hopkins Hosp. 81 :257—266, 1947. 22. Hampson, J. L. ; Essig, C. F.; McCauley, A., and Himwich, H.: Effects of Di—Isopropyl Fluorophosphate (DFP) on Electroencephalogram and Cholinesterase Activity, Electroencephalog. & Clin. Neurophysiol. 2:41—48, 1950. 23. Himwich, H. E.; Essig, C. F.; Hampson, J. L.; Bales, P. D., and Friedman, A. M.: Effect of Trimethadione (Tridone) and Other Drugs on Convulsions Caused by Di—Isopropyl Fluorophosphate (DFP), Am. J. Psychiat. 106:816—820, 1950. 24. Callaway, E.: Slow Wave Phenomena in Intensive Electroshock, Electroencephalog. & Clin. Neurophysiol. 2:157-162, 1950. Vol. 80, Sept, 1958 �EFFECT OF ANTICHOLINERGIC AGENT ON EEG M.: Significance of Individual Variability in EEG Response to Electroshock, J. Hillside 25. Green, Hosp. 6:229-240, 1957. 26. Jasper, H. H.; Kershman, J., and Elvidge, A.: Electroencephalographic Studies of Injury to the Head, Arch. Neurol. & Psychiat. 44:328-348, 1940. 27. Strauss, H.; Ostow, M., and Greenstein, L.: Diagnostic Electroencephalography, New York, Grune & Stratton, Inc, 1952. 28. Jasper, H. H., and Droogleever—Fortuyn, J.: Experimental Studies on the Functional Anatomy of Petit Mal Epilepsy, A. Res. Nerv. & Ment. Dis., Proc. 26 :272-298, 1947. 29. Lindsley, D. B.: Schreiner, L. H.; Knowles, W. B., and Magoun, H. W.: Behavioral and EEG Changes Following Chronic Brain Stem Lesion in the Cat, Electroencephalog. & Clin. Neurophysiol. 2 :483-498, 1950. 30. Rinaldi, F., and Himwich, H. H.: Alerting Responses and Actions of Atropine and Cholinergic Drugs, A. M. A. Arch. Neurol. & Psychiat. 73 :387395, 1953. 31. Himwich, H., and Rinaldi, F.: Effect of Drugs on Reticular System, in Brain Mechanism and Drug Action, edited by W. S. Fields, Springfield, Ill., Charles C Thomas, Publisher, 1957. Fink 32. Stoll, 'W. A.: Lysergsaure—Diathylamid, ein Phantastikum aus der Mutterkorngruppe, Schweiz. Arch. Neurol. u. Psychiat. 60:279—323, 1947. 33. Beringer, K.: Der Meskalinrausch, Seine Geschichte und Berlin, Erscheinungsweise, Springer—Verlag, 1927. 34. Wikler, A.: Clinical and Electroencephalographic Studies on the Effects of Mescaline, N— Allylnormorphine and Morphine in Man, J. Nerv. & Ment. Dis. 120:157—175, 1954. 35. D‘enber, H., and Merlis, S.: Studies on Mescaline: I. Action in Schizophrenic Patients, Psychiat. Quart. 29:421-429, 1955. 36. Gastaut, H.; Ferrer, S., and Castells, C.: Action de la diéthylamide de l’acide d—lysergique (LSD 25) sur les fonctions psychiques et l’électroencéplhalogramme, Confinia neurol. 13:102— 120, 1953. 37. Rinkel, M.; DeShon, H. J.; Hyde, R. W., and Solomon, H. C.: Experimental Schizophrenialike Symptoms, Am. J. Psychiat. 108:572—578, 1953. 38. Merlis, S., and Hunter, W.: Studies on Merscaline: II. Electro—Encephalogram in Schizophr‘enics, Psychiat. Quart. 29:430—432, 1955. 39. Fink, M.: A Unified Theory of the Action of Physiodynamic Therapies, J. Hillside Hosp. 6: 197—206, 1957. 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They also noted that the dose of atropine necessary to affect the EEG-was such as to be associated with unpleasant systemic effects. The reports describing diethazine as an anticholinergic by Jenkner and Lechner (2) compound with potent neurologic but minimal systemic effects led us to undertake studies similar to those of Ulett and Jehnson; and these observations, in turn led to an investigation of other similar agents. clinical and EEG It is correlations the purpose of this report to describe the on the intravenous administration of various hallucinogens and anticholinergic agents in psychiatric patients it various stages of convulsive therapy; and to relate these observations to the recently expressed neurophysiologic-adaptive hypothesis of the mode of action of convulsive therapy and of hallucinogens. Subject and Mathod: Our subjects were consecutive referrals for convulsive therapy in an open ward voluntary psychiatric hospital. Patients have various stages of therapy, with observations being in the 17 EEG laboratory. Following a standard leads using needle electrodes, the intravenously at a made been studied in acute experiments 8 channel EEG compound under at recording from study was administered set rate per minute, until clinical behavioral or �electrographic changes diethazine, were observed. Win 2299*, LSD-25, benactyzine, Diethazine was administered at 25 mgm;'Win-2299 and benactyzine at 10 gamma per minute per minute for 1.2-3.6 mgm. at 0.5 for 50-150 studied The compounds JB—318* and JB-336.* per minute, for a mgm gamma; have been total per minute for 2-5 of 175-250 mgm; LSD-25 and JB~318 and JB-336 at 0.h mgm mgm. Observations: the administration of diethazine, in 15 patients prior to convulsive therapy, there was a decrease in voltage and a desynchronization of all On frequencies. Prevailing rhythmic patterns some instances, symmetric prominent in the was not hy frontal altered, but the became low voltage 6-? cps and less prominent. In activity appeared, most anterior temporal leads. in voltage build—up The alpha frequency and slower frequencies induced hyperventilation was blocked (Fig. 1, 2). In 17 patients during convulsive therapy, with varying degrees of induced high voltage delta activity, there was a significant decrease both in voltage and in per cent time of slow wave activity. From an average per cent time delta of h5% in the fronto-occipital leads, there was a reduction to a mean of 20%. Both random and burst delta activity diminished voltage alpha and beta frequencies became prominent. response was no longer apparent. hyperventilation electrographic effects persisted for is 2-diethy1aminoethyl cyclopentyl (2-thienyl) ggycolateg is n-ethyl-B-piperidylbenzilateg JB-336 is memethyl-3-piperidy1benzilate. ”'Win-2299 JB-313 These The and low �one to five hours (Fig. 3, h). Concurrent with these Patients changes. EEG became more effects, we observed irritable and distinctive behavioral restless and complained of sensations of unreality with dysesthesias of the extremities. Visual illusory phenomena and delusional thoughts about their illness, the setting of the test procedure or the examiner's identity were described. Their language patterns were characteristically altered in a fashion opposite to that previously described for amobarbital (3), so that verbal denial, minimization, cliches, third person mode and past tense became less prominent. The These changes were concurrent with maximum electrographic change. behavioral observations with diethazine led to a review of the effects of hallucinogens on EEG activity. In 1955 Denber and Merlis (h) had reported that mescaline altered EEG delta activity induced by electroshock, in a fashion similar to diethazine. They described a marked reduction in amplitude and per cent time of high voltage symmetric slow wave bursts with an increase in alpha per cent time and in low voltage, random leW'wave activity. Reports by fennes (5) that an experimental compound, Win-2299 manifested both potent anticholinergic activity and induced hallucinations in to our study of this compound. The effects were (Fig. 5). led similar to that observed in the diethazine group. In patients pre-convulsive therapy, desynchronization and decrease in voltages of man all frequencies EEG were induced In eleven patients with high voltage delta activity there was a decrease in amplitude and per cent time of slow wave activity with an increase in alpha and beta frequencies. activity dropped from 50% to 23% The mean per cent time delta in these subjects. Associated with these �-helectrographic effects and hallucinatory and clinical patterns of restlessness, excitement, illusory activity (Fig. 6). As the hallucinogenic were activity of LSD-25 was well established, these studies were next repeated with this compound. Here, too, the behavioral and electroencephalogrgphic effects, was a administration, on intravenous were similar to diethazine. There difference in the time constant in that the behavioral effects occurred 1% to 2 after hours drug administration, but the electrographic changes were concurrent with the behavioral change. While there was desynchronization with Mean LSD, less the delta activity was significantly repressed. fell per cent time delta activity in five subjects from h7% to 16% (Fie- 7, 8, 9). Recalling reports that benactyzine, a potent anticholinergic compound, induced EEG desynchronization next administered this we compound intravenously in eleven subjects, and again observed similar clinical and electrographic patterns. Both in the well modulated alpha record and in the record with high voltage delta activity, desynchronization was prompt. Delta activity decreased from a subjects (Fig. 10, ll).’ clinical restlessness same per cent time of electrographic patterns 39% to 17% we in 8 were accompanied by and excitement. While we did not observe hallucinatory activity, in the These mean illusory or did note that the language patterns were altered fashion as with the other agents tested. Lately, following reports by Abood (6) that various piperidylbenzilates had potent anticholinergic properties and induced activity, we patterns were tested two of these, clinical hallucinogenic JB~318 and JB-336. identical to those of Win-2299 and The electrographic in each instance in which desynchronization was observed, clinical restlessness and hallucinatory �~5- activity for l to (Fig. 12, 13). was noted 3 The hallucinatory activity persisted hours, and during this period, electrcgraphic alteration was prominent. Thus, six compounds have been shown to have similar electrographic and behavioral effects. Each has definitive anticholinergic activity. Each induces hallucinogenic or excitatory activity; and these behavioral changes are accompanied by desynchronizaticn. compounds have a vamine EEG Furthermore, these similar chemical structure (Fig. 1h). The tertiary in a substituted diethylaminethanol is prominent, corroborating the recent reports by Denber (7) on the hallucinogenic activity of tertiary amines, and amplifying his studies by the common concurrent electrographic patterns. These observations amplify our understanding of the convulsive therapy process. In earlier studies high voltage slow wave activity we indicated that the development of was the neurophysiologic correlate of behavioral change in convulsive therapy, and a necessary, though not sufficient, condition for clinical years, studies improvement (8). During the past ten by Bernstein, Tower and MeEachern, ward, Sachs, Bugs and others have noted similarities in the biochemical changes in convulsive therapy to craniocerebral trauma (9). They reported an elevation of free acetylcholine and pseudonholinesterase in the spinal fluid during convulsive therapy. In addition, topical administration of acetylcholine induces high voltage bursts uni spike activity. Ulett and Johnson emphasized the blocking of these cholinergic effects by the anticholinergic activity of atropine and scopolamine. The obsumvaticns on this report on �~6- diethazine, Win-2299, benactyzine and the piperidylbenzilates ISDbZS, support their observations. Each of these compounds has potent anticholinergic clinical behavioral and language effects areqpposite to those described for convulsive therapy. we may thus amplify the earlier conclusion that the neurophysiolegic basis for behavioral change in activity and the convulsive therapy by noting is that this the development of high.voltage slow wave EEG change activity reflects an alteration in the acetylcholine- cholinesterase relations of the nervous system, probably in the direction of increased cholinergic activity. These observations lend themselves to application in studies of craniocerebral trauma. .ward's (10) reports of the efficacy of high doses of atropine in altering the clinical manifestations of head trauma also indicated that effective doses brought with It would more them severe systemic be advisable to repeat these studies, neurologically specific anticholinergic utilizing such effects. more compounds as used potent, in these experiments. Finally, these observations, and our earlier reports significance of EEG on the delta activity in convulsive therapy, support the his report on mescaline, morphine with the comment that: "... regardless observation of Wikler (11) n-allylnormorphine and who concluded of the drug administered, shifts in the pattern of the electroencephalogram in the direction of desynchronization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness." This conclusion, supported by our observations, permit a more meaningful �.7- ._ generalization of the recently expressed neurophysiologicuadaptive twpothesis of the mode of action of somatic therapies in psychiatry. We may infer that agents that synchronize EEG in the beta frequency range frequencies, like barbiturate and and chlorpromazine, promazine and perphenazine in the delta frequency range, tend to while agents that evoke hallucinogenic, as EEG meprobamate be sedative, euphoriant and relaxant; desynchronization tend to be excitant and was noted for diethaaine, mescaline, and the piperidylbenzilates. LSD-25, Win-2299, benactyzine, �~8~ In summary, and the effects of various hallucinogenic we have observed anticholinergic compounds on the electroencephalogram and behavior in psychiatric patients at various stages of convulsive therapy. Behaviorally, these compounds induced increased restlessness, haptic and visual illusory sensations and delusional thoughts about the illness or the examiner's identity. The subject's syntactic language patterns described for convulsive therapy and barbiturate were reversed. Concurrent with these changes were a decrease in voltage and a desynchronization of all freQuencies in the In patients with high voltage delta EEG. activity, the per cent time and voltage of the delta activity were markedly decreased. These observations have been discussed common in the framework of the biochemical structure and anticholinergic properties of these agents with the conclusion that: (a) The biochemical basis for convulsive therapy and for>high alteration in the acetylcholinecholinesterase relation of the nervous system, probably in the direction voltage EEG delta activity may be an of increased cholinergic activity. (b) of the mode The recently expressed neurophysiologic-adaptive hypothesis of action of somatic therapies in psychiatry is amplified to encompass the action of hallucinogens. It is cholinergic more recommended compounds that further studies of the effects of anti- in creniocerebral trauma to neurologically specific Win-2299. compounds be undertaken, utilizing as diethazine, benactyzine and �REFERENCES 1. .2. Ulett, Effect of Atropine and Scopolamine Electroencephalographic Changes Induced by ElectroOlin. Neuro aio . 2; 217-22h, 1957. convulsive Therapy, G.A. and Jehnson,1MJfl.: Upon Jenkner, F.L. and Lechner, H.: wig; 19 3. 5. ,6. Effect of Diparcol on the . in Kahn, R.L. and Fink, M.: Changes Therapy, In Grune ,h. The Electroencephalogram in the Normal subject and in Those Cerebral Trauma, EEG Olin. ' NeuropQXSiol. I; 303-305, & EEZOhOEEthOlOEY Stratton, Denber, H. and marlis, N.Y. 19 8. 8.: Studies Language During Eleotroshook of Communication, pp. 126-139, on Nescaline I: Action in Schizophrenic Patients. Efiychiat. Quart., g2; h21-h29, 1955. Pennes, H. and Koch, P.: Paychotomimetics, Clinical and Theoretical Considerations, Amer. J. Psychiat. _1_1_;: 887-892, 1957. Abood, L.G., Catfield, A.M. and Biel, J.: A New Group of Psychotomimetic Agents, Proc. Soc. Exp. Biol. Mad. 21: h83‘h861 1958 o 7. Denber, H.C.B.: Drug-Induced States Resembling Naturally Occurring Paychosee, in ggzchotrogic DEEES: eds. Garattini, S. and .8. - , l9 7. Fink, M. and Kahn, R.L.: Relation of EEG Delta Activity to Behavioral Response in Electroehock: Quantitative Serial Studies, A.M.A, Arch. Neurol. & Psychiat. 1Q} 516-525, 1957. Ghetti, V., Elaevier, 9. Fink, M.: Effect of Anti-Cholinergio Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy, A.M.A. Arch. Neurol. a Psychiat. §Qr W88, 1958. 10. Ward, A.: Atropine in the ”heatinent of Closed 398.).‘02’ 1950. 7: Neurosurg., Head Injury, ,1. Clinical and Electaoencephalographic Studies on the Effects of Mescaline, Nealkylnormorphine and Morphine in ‘Wikler, A.: Man, J. Nerv. Ment. 1318., 120: 157.175, 195h. �Effect of Anti-Cholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Omleive merepy Max From LOI.’ Fink, 14.1). the Department of Experimental Psychiatry, Hillside Hospital, NOYI Glen Oaks, in part, by grant M-927 of the National Institute of Mental Health, National Institutes of Health, U.S. Public Health Service. Aided, Read (in part) at the meeting of the Eastern Association of Electroenceplmlo- graphers, N.Y., December 1957. SBP: 3-58 �3-3-58 Effect of Anti-Cholinergic Agent, Diethazine, Significance for Theory on EEG-and Behavior: oi Convulsive Therapy Recent investigations of convulsive therapy have emphasized EEG delta activity as the neuroprxyaaoiogic basis for: the induced behavioral change (l,2,3,h,5). Little study, however, has been given to the biochemical effects of this therapy, except in the course of investigations of head injuries. In investigations of head trauma significance has been ascribed to in the acetylcholine-cholinesterase systems both for the behavioral and the electroencephalographic effects. An increase in free acetylcholine (6) and an alteration of the ratio of cholinesterases (7) in the spinal fluid have been positively correlated with the degree of EEG abnormality changes and degree of neurologic improvement deficit. in clinical status The EEG patterns were "blocked," and was reported following some the administration of atropine (7,8). In convulsive therapy, atropine and scopolamine were observed to block the appearance of delta activity, (9) although the effects of the large doses of these agents were marked. Recent reports (10) noted that EEG and behavioral effects similar to systemic atropine were achieved in patients with head trauma by intravenous diethazine a phenothiazine compound with anticholinergic properties - with minimal systemic effects. In our continuing studies of the role of delta activity in electroshock (3), the effect of diethazine was studied. It is the purpose of this report to describe the effects of diethazine on EEG patterns and on behavior of patients during electroconvulsive therapy; and to relate these observations to the present neurophysiologic-adaptive hypothesis of thexnode of action of convulsive therapy. �SUBJECTS AND METHODS: Forty psychiatric patients, at various stages of electroshock therapy in an open-ward, voluntary psychiatric hospital have been studied. All observations have been made in acute experiments in the EEG laboratory. Following a routine recording, diethazine was administered intravenously per minute, for a total of 175 to 250 mgm, depending the behavioral effect. Dosage varied from 2.8 to h.0 mgm per kilogram at the rate of upon EEG 25 mgm body weight. Diethazine is a soluble phenothiazine compound with pharmacologic properties similar to atropine. In experimental animals, diethazine blocks the bradycardia, bronchospasm, salivatim, fasciculation and seizures induced by acetylcholine, di-isopropyl fluorophosphate and pilocarpine. It suppresses salivation, and induces nwdriasis and hypotension (11). me An ses: Recording was continuous for the duration of the observation period, except during interview periods. Needle electrodes, and an Medcraft instnnnent were used. All records were analyzed delta activity (3) 5 the per cent time the relative amount of fast activity. measured in anterior temporal-vertex, and The and 8 channel for the degree of principal alpha frequency; and alpha and delta activity were parietal-ear lobe lead combinations. Behavior Measures: Prior to drug administration an unstructured psychiatric historical interview and a structured questionnaire period (12) were tape recorded. Following drug administration, periods of recorded interview were alternated �+3- with EEG recording periods, injection pattern on until the EEG had again manifested the pres visual inspection; No estimates sf behavioral effects were used: clinical descriptions by the participants - subject, interviewer and technician - of the changes occurring during the drug period, and language analyses of the recorded interevaluated by a syntactic analysis (12) views, Guanges in language were .* and an analysis of the variability in Verbal interaction in the dyad (13.11:) Both measures have been shown induced by changes in the to be sensitive to alterations in behavior central nervous system. * Detailed analyses of these observations Drs. J. Jaffe and R. L. Kahn. will be reported separately by I �OBSERVATIONS: (a) Clinical: Within two to five minutes of the start of the injection, subjects manifested spontaneous coughing followed by a dryness of the anzl a thickness of speech. They reported a feeling of lassitude, mouth and a heaviness and weakness of extremities which was soon succeeded by increased difficulty in mintan eyelid closure. Reports of visual and haptic illusory sensations, feelings of unreality distance, and delusional thoughts about their illness, the setting of restlessness and and test procedures or identity were voiced Spontaneously in eighteen subjects in the period between 15 and 60 minutes after drug aduinistration. the our In three instances, increasing agitation and panic led to a cessation of the recording. In two subjects withdrawal and negativism was the prominent behavioral response. Such patterns of behavior were transient and had disappeared in (b) EEG 1% - 14 all subjects. hours in Patterns: Alteration in the EEG patterns was concurrent with the behavioral effects. In all records, changes occurred during drug administration and were sustained, with gradual diminution and restitution of the pre-injection patterns, in one to five hours. The voltage and desynchronization of initial response was a decrease in all frequencies. praninence of prevailing rhytlms. There was a decrease in In patients without delta activity (pm-electroshock), desynchronization and voltage decrease was occasionally activity, symmetric and prominent in frontal and anterior temporal leads (Figure l, 2). The alpha frequency was not altered. accompanied by low voltage 5—7 cps �~5The build-up in voltage and appearance of slower frequencies with hyper- ventilation was blocked. In patients with varying degrees of high voltage delta activity there was a prominent decrease in voltage and desynchronization of the record. burst delta activity diminished or disappeared, and irregular voltage alpha and beta frequencies became prominent (Fig. 3, h). The Both random and low hyperventilation response was no longer apparent. (c) Language Patterns: In previous studies, an intimate relationship betwaen changes in syntactic language patterns and the behavioral response in electroshock had been reported (12). With alteration in brain function, increased use of third person, verbal denial, qualification, displacement and cliches became prominent. These effects could be enhanced by the admirfistration of intravenous anobarbital (1h) . In the subjects in the present study, syntactic analyses demonstrated a reversal of the patterns noted in electroshock. Use of third person, qualification and displacement decreased. Explicit verbal denial was modified and replaced by minimization and displacement, or by a complaints of illness. In dyadic analyses, the verbal characterized by a greater diversity of vocabulary and reiteration of interaction was less variability in the diversity scores for 25 word units. qualitative nature of these changes in the language patterns is opposite to that of amobarbital and electroshock. The duration of language changes was concurrent with the changes in the electroencephalogram. The �DISCUSSION: report of Jenkner and Lechner of the effects of diethazine in "normal" subjects (10). Diethazine also alters electroshock induced delta activity in a fashion similar to atropine and These observations confirm.the s cpolamine, as described by Ulett and Johnson (9), with minimal unpleasant symptoms. EEG The effects of intravenous diethszine are immediate, both and behavior, and thus provides a on the useful experimental agent with "anti- aspects of these experimental observations warrant discussion: the role of acetylcholine-cholinesterase in the electrocholinergic" properties. The convulsive therapy progress, and the significance of diethasine "alerting" for concepts of hallucinogenic activity. 1. Biochemical Basis of the Convulsive Therapy Process: While there has been considerable study of the psychologic neurophysiologic aSpects of convulsive therapy, biochemical processes is available. The little and information concerning studies of biochemical changes following head trauma and spontaneous seizures provide some analogic data. Bernstein (6), in a classical experimental study of head trauma in cats, demonstratadthat within a few minutes appeared in the Spinal fluid and after trauma, free acetylcholine persisted for periods up to h8 hours. He further demonstrated a positive relation between the severity of head trauma and the quantity of free acetylcholine, degree of electroencephalographic alteration and graphic records the severity of the behavioral changes. initially showed short periods The electroencephalo- of high voltage fast activity, transient period of flattening of electrical activity, followed by prolonged periods of high amplitude sharp waves in the delta frequencies. Concomitantly, a �.7 - alteration in consciousness, changes in reflexes and post-traumatic seizures were most prominent with highest concentrationsof free acetylcholine and greatest degree of EEG change. Tower and HbEachern (7) confirmed studies in man. In 112 neurologic these observations in clinical patients, free acetylcholine was found in the cerebrospinal fluid only in patients following head trauma grand mal seizures; and the level of free acetylcholine varied the degree of cerebral damage. and recent directly with In addition, these authors assayed the cholin- esterase activity of the spinal fluid, (7, 16). In patients following head trauma, they noted a sharp splitting) and a drop rise in non-specific cholinesterase (benzoylcholine- in the specific cholinesterase (mecholyl-splitting) activity of the spinal fluid. No such inversion was noted in fluids containing free acetylcholine following spontaneous seizures. Electroencephalograms were taken at varying intervals following correlation of the extent of EEG trauma, and demonstrated a direct abnormality and the appearance of free acetylcholine in the spinal fluid. Tower and MbEachern also reported observations in six patients receiving electroconvulsive therapy. In patients after 3-7 induced convulsions, they noted free acetylcholine in the spinal fluid in two, and an increase in non-specific cholinesterase with reversal of the cholinesterase ratio in five of the six. They concluded that the spinal fluid changes in electroshock are more like those of craniocerebral trauma than those found in epilepsy. * patient of the six who failed to show either free acetylcholine or a reversal of the cholinesterase ratio, they noted: "It is interesting that this patient was the only one of the six to Show no response to treatment." * Regarding the one �-8recently, Sachs (17) confirmed the reports of free acetylcholine in the spinal fluid after head trauma and after electroshock. In his studies, Bernstein (6) administered 0.5-1.0 mg/kg atropine More and demonstrated a reversal or a blocking of the EEG effects, and a modification of the behavioral and neurologic signs. Atropine also blocked the EEG and clinical signs induced by intracisternal acetylcholine. Ward (8) applied these observations with varying degrees of head trauma. atropine induced both clinical to the treatment of subjects human Subcutaneous doses of 0.1 mg/kg of improvement and reversal of EEG effects. recently confirmed by Sachs (1?), Huge (18) and these observations, Ulett and Johnson (9) noted the These observations were Hughes (19). Based on in blocking the Em changes of electroshock therapy, without noting the effect on clinical behavior. Concurrently, Jenkner and Lechner (10) reported effects similar to those of Ward, in effect of atropine and scopolamine studies of diethazine in cases of head injury. Another group of investigations complete the available of anticholinesterases, as DFP data. Studies (di-isopropyl fluorophosphate) and (tetraethyl-pyrophosphate), which block the enzymatic TEPP breakdown of acetyl- choline, demonstrate the development of high amplitude rapid frequency EEG patterns similar to status epilepticus as well as lesser degrees of abnormality as noted in post-traumatic states (20, 21, 22, 23). In these studies, atropine blocked both the electroencephalographic and the clinical toxic effects. Thus, both from experimental and trauma we may assume clinical studies of craniocerebral that (a) the acetylcholine activity of the Spinal �-9- fluid increases; (b) pseudo-cholinesterase activity increases with a reversal of the ratio of cholinesterases; (c) EEG hypersynchrony and slowing agents From parallel these biochemical alterations; may and (d) anticholinergic block both the electroencephalographic and the clinical effects. the data available convulsive therapy it is probable that the biochemical basis is similar to that of craniocerebral trauma. of Convulsive therapy results in free acetylcholine in the spinal fluid (7, 17) and a reversal of cholinesterase ratios (7, 16). The electroencephalographic effects of repeated induced convulsions is the development of high voltage, symmetric Slow wave activity, occasionally with spike activity (3, 2h, 25), which is similar to that previous studies we have observed in severe head trauma (26, 27). In reported the relationship between the degree of activity and behavioral response (3). The studies reported here and that of Ulett and Johnson (9) demonstrate a reversal of the EEG and the behavioral effects of convulsive therapy by anti- induced slow wave cholinergic compounds. In each characteristic, convulsive therapy is thus similar to cerebral trauma. While the acetyloholine-cholinesterase system studies, other enzyme systems may also be altered studies also suggest that convulsive therapy provides an is highlighted (17). These by these excellent experimental method for studies of craniocerebral trauma. Studies of the brain stem activating system by Jasper and DroogleverFortuyn (28) and Lindsley gt|§l. (29) had laid the foundation for the activity has its origin in mesencephalic structures, and that these structures intimately affect the states of "alerting" and "drowsiness." More recently, Rinaldi and prevailing conclusion that symmetric EEG slow'nave �-mrelated the site of action of atropine and cholinergic drugs to this mesodiencephalic activating system. It is also probable that Himwich (30, 31) have these structures may be selectively affected by the convulsive therapy process, and that both the clinical and electrographic effects may be intimately related to changes in this system. 2. Diethazine "Alerting The and Hallucinggenic Activity: behavioral effects of diethazine provide information regarding another aSpect of the convulsive therapy processt. prior convulsive therapy, illusory phenomena and In patients without feelings of unreality were observed. These were similar to the hallucinogenic effects of and mescaline (33). Again analogic data about the of these agents may provide some no change, (31;) noted that the intermittent or continuous increase in alpha frequency. (32) and EG effects information abmt convulsive therapy. In studies of mescaline, Wikler either clinical LSD low voltage EEG demonstrated fast activity or Denber and Merlis (35) noted a similar acceleration of alpha frequency, decrease in per cent time alpha including its disappearance, and non-specific random beta activity. Delta activity did not occur. In patients with delta activity induced by electroshock, Merlis and Hunter (38) noted that in travenous mescaline markedly diminished the amplitude and per cent time delta activity with an increase in per cent time alpha activity. similar. Gastaut gt g. (36) noted an acceleration of alpha frequency of 0.5 to h.0 cps with an accentuatim of beta rhythms. Rinkel 33 al. (37) confirmed this observation and noted, The effects of 151) on EEG are �4L1- in addition, a reduced responsivity to hyperventil‘afion.* In smnmariaing his studies Wikler (3h) concluded that " . . . regardless of the drug administered, shifts in the pattern of electroencephalogram in the direction of desynchnonization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness.“ This generalization provides a meaningful construct may be assessed. Agents that hallucinogenic, and mascaline in which these agents evoke EEG desynchronization tend and 1813 to be are clear examples. Agents that synchronize frequencies, such as barbiturate and meprobamate in the beta frequency range, and chlorpromazine, promazine and pezfimaz‘mainthe delta frequency range (39) tend to be sedatives, euphoriants and relaxants. The observations on diethazine reported here are consistent with this hypothesis. In patients without delta activity, the EEG demonstrated desynchronization of frequencies, and this was associated with clinical illusory phenomena. In patients with delta activity desynchronisati.on occurred, and alerting and reversal of the speech patterns induced by electroshock were observed. Electroconvulsive therapy We ~31- have previously noted a Studies are now may also be understood in this framework. direct relationship between clinical evaluations in progress of the effects of LSD, Win-2299, benactyzine other anticholinergic compounds on post-convul sive EEG delta activity. Initial experiments w- ah intravenous LSD (SO-100 gamma) demonstrated marked dinfinution in per cent time and amplitude of delta activity. and �of improvement and the degree of Under these conditions, sedation EEG slowing induced by electroshock (3). and euphoria are most prominent and hallucinatory activity diminished. In patients in whom hypersynchrcny is not induced, behayicral change is limited and 'imprcvement' does not occur (hO) . Previously we have concluded therapies is based on the that the mode of action of conVulsive induction of a state of altered cerebral function, in which changes in adaptive interpersonal behavior occur, and are inter» preted as 'hmprovement' (3, h, 39). The present studies amplify two aspects of this neurcphysiologic—adaptive hypothesis. The biochemical substrate of the behavioral change is reflected by an alteration in the acetylchcline-cholinesterase relationships of the central.nervous system. It is also probable that EEG basis of the milieu change hypersynchrony provides the neurophysiologic which is clinically manifest as sedation and euphoria and is evaluated as 'imprcvement.‘ The neurophysiologic-adaptive hypothesis of convulsive therapy has provided a meaningful basis for studies of other physiodynamic therapies (39). In this study, it has been possible to amplify our understanding of neurophysiologic aspects of hallucinogens as well. �SUMMARY: effect of an anticholinergic agent, diethazine, on the behavior and language patterns was observed in to psychiatric patients, 1. EEG, The at various stages in the course of’electroconvulsive treatment. (a) Behavior: Increased restlessness and agitation, haptic and visual illusory sensations, and delusional thoughts about their illness or examiner's identity were observed. (b) pg: Alteration in There was a decrease EEG was concurrent with behavioral changes. in voltage and desynchronization of all frequencies. In patients with delta activity, the per cent time and voltage of delta activity decreased. (c) Language: Syntactic patterns described for convulsive of third person, qualification and displacement decreased. In dyadic analyses, there was a decrease in the coefficient therapy were reversed. Use of variatian. 2. These observations are discussed in the framework of the neuro- physiologic-adaptive hypothesis of the action of convulsive therapy; and it is concluded that: (a) the biochemical basis for convulsive therapy is similar to that of craniocerebral trauma; (b) changes in acetylcholine-cholinesterase metabolism are intimately related to the behavioral effects; (c) EEG desynchronization of hallucinogenic activity; and and sedatidn. EEG may be a and physiologic concomitant hypersynchrony associated with euphoria �.Ih~ REFERENCES 1. Weinstein, E. and Kahn, R.L.: Denial of Illness, C.C. Thomas, Springfield, 111., 1955. 2. Roth, M., Kay, D.W.K., Shaw, J. and Green, J.: Prognosis and Pentcthal Induced Electroencephalographic Changes in Electroconvulsive Treatment, EEG 225-237. 1957. Clin. Neurophysiol. 2: R.L.: Relation of Electroenecephalographic Delta Activity to Behavioral Response in Electromock, AMA. Arch. Neurol. and Psychiat. '_?_8_: 516-525, 1957. 3. Fink, h. Fink, M., Green, M.A. and Kahn, R.L.: Ehcperimental Studies of the (in press). Electroshock Process, Dis. Nerv. 5. Ulett, G.A., Smith, 6. Bornstein, M.: Presence and Action of Acetylcholine in Experimental 7. Tower, D.B. and McEachern, 13.: Acetylcholine and Neuronal 8. Ward, A. : Atropine 9. Ulett, M. and Kahn, st. K. and Glaser, 6.0.: Evaluation of Convulsive Shock Therapies Utilizing a Control Group, Subconvulsive and m. J. chhiat. 1.2-: 795‘802, 19560 Bra-in Jo Neurophym:01. 2.: 3:49.366, 19,460 Tram, Canad. J. Research, g1: 105-131, 19h9. in the Treatment of Closed Neurosurg., 1: 398-1102, 1950. Head Injury, Activity, ,1. Effect of Atropine and Scopolamine Induced by Electroconvulsive Upon Electroencephalographic Changes 1957. Therapy, EEG Clin. Neurophysiol. 2: 217-221;, G.A. and Johnson, M.W.: 10 . Jenkner, F.L. and Lechner, H.: The Effect of Diparcol on the Electroencephalogram in the Normal Subject and in Those with Cerebral Trauma, EEG Olin. Neurophysio . 1: 303-305, 1955. 11. Heyxnan, C., Estable, J.J. de and de Bonneveaux, la menothiazinyl-Ethyldiethylamine Pharmacggyg. 12: 123-138, 19119. 12. 13. 5.0.: Sur la mamacologie (2987 R.P.) , Arch. Int. in Language During Electroshock in Mogatholo% of Cannmnicaucn, pp. 126-139, Grune & Stratton, .Y. 9 . Jaffe, J.: An Objective Study of Communication in Psychiatric 207-215, 1957. Interviews, J. Hillside Hospital, Kahn, R.L. and Fink, H.: Changes Therapy, _6_: �.15.. 15. Jaffe, J.: Language of the Dyed: A Method of Interaction Analyses in Psychiatric Interviews, Exchiatgz, (in press). Weinstein, E.A.. Kahn, R.L., Sugarman, L.A. and Linn, L.: Diagnostic Use of Amobarbital Sodium in Organic Brain Disease, Am.J. Egzchia o 2:12.: 889-391;, 1953. Characterization of 16. Tower, D.B. and McEachern, D.: The Content and 17. Sachs, E.: Acetylcholine and Serotonin in the Spinal Fluid, ,1. Neurosurg., g: 22-27, 1957. Ruge, D.: The Use of Cholinergic Blocking Agents in the Treatment of Cranio-Cerebral Injuries, J. Neurosurg., 2.3;: 77-83, 1951;. 18. Cerebrospinal Fluids, Canad, J. Cholinesterases in Research, 21: 132-115, 19h9. Human 19. Hughes, B. : The Role of Acetylcholjne in Head Injury, his . _2_9_: p.70, 1957. Neurosur . and 20. Medman, 21. Grob, 1)., Harvey, A.M., Langworthy, 0.11. and J. Neurol. Bales, Pens, Willis, A. and HiRMiCh, HeEe: Ehrperimental Production of Electrical Major Convulsive Patterns, Am. J. @5101 a , 1146: 11.7.1211, 19,49 0 AoMo, Lilienthal, J.L.: The Administration of Di-Isopropyl Fluorophosphate (DFP) 257.266, 191,7. Man, Bull. J. H025. Hosp., to §_:_L_: 22. McCauley, A. and Hinmich, H.: Effects of Di-Isopropyl Fluorophosphate (DFP) on Electroencephalogram Hampson, J., Essig, C.F., andsoCholinesterase Activity, l9 . EEG Olin. Neuropgxsio . _2_: Bales, PUD. and Friednlan, A.M.: Effect of Trimethadione (Tridone) and Other Drugs on Convulsions Caused by Di-Isopropyl Fluorophosphate (DFP), Am. J. PSyChiat., 106: 816‘820, 1950. 23. Him-1°11, HQEQ, E55518, CeFe, Hampson, Jolie, 2h. Callaway, E.: Slow Wave Phenomena in Intensive Electroshock, Clin. Neurophysiol., a: 157-162, 1950. 25. Green, 26. ’41-'48, 3133. Significance of Individual Variability in EEG Response to Electroshock, J. Hillside Hosp., 9: 229-2ho, 1957. hic Jasper, H.H., Kershman, J. and Elvidge, A.: Electroencephalogra:£1; : Neurald: Arch. Psychiat. Head, the to of Studies , Injury M. : 328-3h8, 19h0. �W ~16- Ostow, M. and Greenstein, L.: Dia ostic Grune & Stratton, N.Y., 1935. Electro- 27. Strauss, H., 28. Jasper, H.H. and Drooglever-Fortuyn, J .: Experimental Studies on the Functional Anatomr of Petit Mal Epilepsy, Res. " " A.' Nerv. " Publ. 29. 30. Lindsley, D., Schreiner, L.I-I., Knowles, W.B. and Magoun, H.W.: Behavioral and EG Changes Following Chronic Brain Stem Lesion in the Cat, EEG Olin. Neuroplgsiol” _2_: h83-h98, 1950. of Rinaldi, F. and Himwich, H.H.: Alerting Responses and Actions and Atropine and Cholinergic Drugs, A.M.A. Arch. Neurol. ngchiatu 1;: 31. ' ' Ment. Dis. gg: 272-298, 191.7. 387-395, 1953. Himich, H. and Rinaldi, F.: The Effect of Drugs on Reticular System, in Brain Mechanism and Dru Action, 15-1114, C.C. Thomas, Springfield, 1937. aus der 32. dietmrlamid, ein Phantastikmn Stoll, W.: Lysergsaure - Schweiz Neurol. 33. Beringer, K.: Der Meskalinrausch Springer, Berlin, 1927. 35. Wikler, A.: Clinical and Electrencephalograwic Studies on the Effects of Mescaline, N—allylnormorphine and Morphine in Man, J. Nerv. mnto D180, 120: 157-175, 19%. Denber, H. and Merlis, 3.: Studies on Mescaline I: Action in Schizophrenic Patients, PsEhiat. Quart. , 2_9_: 1421-1429, 1955. Gastaut, H. , Ferrer, S. and Castello, 0.: Action de la diethylamide de l'acide d-lysergique (LSD 25) sur lee fonctions psychiques at l'electroencephalogranme, Conf. Neum1., 3;: 102-120, 1953. 36. Pslchiat. , Arch. Mutterkomgruppe, 1-h7, 19m. Monog. §_Q: Neural. Psychiat., 1-315, 37. Rinkel, M., DeShon, H.J., Hyde, R.W. and Solomon, H.C.: Experimental Schizophrenia-Like Symptoms, Am. J. Pszchiat" 108: 572-578, 1953. 38. Merlis, S. and Hunter, W.: Studies on Mescaline II: Electroencephalogram in schizophrenics, Psychiat. Quart., g2: 1.30-1.32, 1955. 39. Fink, M.: ho. Fink, A Unified Theory of the Action of mysiodynamic Therapies, J. Hillside M. Hosp. , é: 197-206, 1957. and Green, M.A.: Electroencephalographic Electroshock Process (in preparation). Correlates of the ��j: q-»-\’X mm or mumma manganese» w Panama“ m and Behavior 4" tho abmfim at W Fm;black-d the W mek, m mathem- diam!” induced «synchronization of ma fmquamisa and in ”mums. In ptfient! with dais: activity, voltage flowed, nativity diuppeumd. mufims, m, amt mm mm function. ath an was amt alpha and beta and bdnvioral changes Wynn in mm“ therapy. the behavioral wager? airflow}: 11:01:16.6 mm o! the language patterns indicative psychotonmotio nativity nf 2299, um mm frame“: increased WV Mutton and withdrawal, immaod asthma, in maintaining eyelid closure, of 1115”“ and W muuhdmrgic comm, amine. tine of delta nativity and burnt. “W that «It: w’dflty .méucad by convulsiw mum, studies mm max-tutu: with a and Jamie»: 419mm led 1» may of Mme sum or cmlsive for ml: of mu W: In recordings of compounds 1:: tbs dons matreutmt, each MOW. m amt induced memmauon at can record with momma in beta “unity, mm, par-1103.06 mm md 1n fmuemy and per-cent time at alpha. m nativity, both the mug. and ppm meat. was “at Imam" mm, nativity. In ”cards with 01w was of thin: activity and film alpha Wan}. Bombwnt of mm: W58 APR 2 :5: tummy immacd. (many: new concurrent with than ehctmgnphic manages, use both mm inhibited by Pram the mm, mtmm WW mummsim. Psychiatry, Hillside Kama, Cam Oaks, LL, NJ“. �nfia‘ m alumna” are Mar ta thwa of Dunbar a}. 3;. tor Winn. Wt Michalimmio prawn", and significanaa structurally, each contain: 1 mm nitrogen linkage. Each of theme compounds have The 01’ than fianrapy of amatima far the theazy of film made of nation at convulsiw mama‘s. as will u tor the wommbmr and Wing $.13 1:311qu 1:111 b0 discusud. K �new cat Antichollnergle Game at mmmm me and Bob-71w * 3mm the observations 2: 217, 1957) by cumin ergie (W. file“ and Johnson um. atropine and 309130le blocked the delta wtiuty induced than”, dMlar studies were undemken with another madmanof diet-henna. Prenloe’oroehock, dietbuine induced demahrmiution tuuuaned.“ end a decrease/1n voltages. In peasants with delta. activity, compound, of ER; voltage md pennant time of delta emvity hemmed, frequencies increased and burst activity diuppeared. dam all” end beta . Concurrent behavioral mum, illusory maid ideetion and withdrawal, increased restlessness, difficulty in maintaining eyelid closure, and reversal of the language patterns «scouted with altered eerebml function after canvulsive changes included therapy (m amt. tholog 9; Gomniggtion, _ The Gram a: Sure/atom, pg. 126, 1958) psychotoulmtle aunt}; of diethuim led to the study at hear-ac and diethyhflde, Win 2299 and bemtysim in voluntary momma patients at venous stages of convulsive firm-aw. These antichaunerglo compounds were Metered intmenously in amounts! of 50-150 gm, 2 to S m and 1.5 m respectively, dung“ mder continuous and language mum-es mutmtmt, nah compound EEG mm. ‘For «ch compound the behavioral peremled those of diethuine. In ma meanings induced EEG demchmieeuon with an increase in beta activity and in the alpha fmqueney. In renews with slow wave activity, both the voltage and pop-neat time of this activity decreased, pement time feet rmuemlea manned, and the alpha frequency increased. Behavioral ahmgea mm concurrent with these ehctrographlc changes, and both were inhibited by intravenous uhlorpmmine. A it Fm: the 61.1}. m. Amos Mia/SB fluent of Experimnbal Psychiatry, Hillside Hospital, .1. NW York. �«a. 3mm ahauntim for muslin. we boon reported by Dunbar. We and (W. W want]. the 33: m. 1955). of postoonvulain Em and bah-uric: pattoma by these potent “mallow «unwound: “was“ a naumphyuiologic but: for comma“ thorupy. Purim 39mm acted that. the clinical ropoma to manned comm m «peach; m the dmlemfit af Wain hiya voltnga aim: we nativity (W. my than be 19,: 516.. mmiaud with ma 1957). An 1mm in ahalinorgic nativity Wchrazv and clinical sedation and whom. SWy. a decrease in choumrgia activity may bu associated with EEG «syncing-am mum and 6111:1031 psychotmuc nativity. as therapy or the mad. or whim of amulaiu ”exam and tho mou- phyamlogic «float: of mfiebalmergic command- will be dismantled. �\\ "v Mint: of Ant-1011mm: W311: Minimums on Wm E39 and neopolmim blocked the dclta activity induced by convulsive therapy, studies are Wart-ken with moflar mama“ 0136th dinthuim «cram in voltages. induced compound, diothuine. m. «mm-m on of frequencioa and In putianta with delta activity, volfige and pen-mt m of delta nativity acct-cu», tramway immune and law“ activity disappears. Concurrent behavioral chanson: 11:01am imam and withdrawal, illusory sensations, paranoid incmaod ”flatleusnass, difficulty in maintaining mud. of the ham patterns indicative of altered The apparent. hallucinogenic activity m to any of eyelid cio'sum, and «mm. flirtation. various Wu inoluang The of hmetysim LSD. Win 2299, bohuvionl changes in the dam dawns. In m6 Hoarding intizm at the record with an employed were mutmhaant, «eh mousse in '58" parallel to those agent indmd «manom- an fmuemiu, max-cue in alpha Inquency, and alpha voltaga tad para-mt 601%: and masculine. tins. In records mm activity, both the valtagc md pox-«mt tins of delta. activity duel-sand, �duh 4..., par-43m tine fut {maintains Manama, Behavioral (changes were ugd both wm inhibited by and. alpha Inquancy increased. emmnt with than electramphie mung», intramm «human-um. 00de hm patent mticholimrgic properties a wall as n W tertiary W W... Wm“ or them absent»Each at then The um 29:: thus timery :5 of thg an“ a: nation or combs.” therapy in payments, all «a fur the mumphysialogy and pinmcology of hallumogana 61mm. 11.111 be �Effect of Anticholinergic * Compounds an Post—Convulsive EEG and Behavior Following the observations of Ulett and Johnson (EEG Clin. Neurophysiol. 2; 217, 1957) that atropine and scopolamine blocked the delta by convulsive therapy, similar studies were undertaken with ergic of compound, EEG activity induced snail-l anticholin- diethazine. Pre-electroShock, diethazine induced desynchronization frequencies and a decrease in voltages. In patients with delta activity, voltage and per-cent time of delta activity decreased, donfinant alpha and beta frequencies increased and burst activity disappeared. Concurrent behavioral illusory sensations, paranoid ideation and withdrawal, increased restlessness, difficulty in maintaining eyelid closure, and reversal of the language patterns associated with altered cerebral function after convulsive changes included therapy. The apparent psychotomimetic activity of diethazine led to the study of lysergicl;:dudiethylamide, benactyzine in voluntary psychiatric Win 2299 and patients at various stages of convulsive therapy. were administered intravenously mgm in reSpectively, under continuous These anticholinergic amounts of 50-150 gamma, EEG recording. 2 EEG 5 mgm and 1:5 For each compound the behavioral changes and language measures paralleled those of diethazine. pre—treatment, each compound induced to compounds In EEG recordings desynchronization with an increase in in the alpha frequency. In records with slow wave activity, both the voltage and per—cent time of this activity decreased, per~cent time fast frequencies increased, and the alpha frequency increased. Behavioral beta activity and changes were concurrent with these electrographic changes, and both were inhibited by intravenous chlorpromazine. % From the Department Glen Oaks, AEEG: L.I. u/3/58 New of Experimental Peychiatry, Hillside Hospital, York. ' . H.“ as... �a-2-n Similar observations for mscaline have been reported by Denber, Merlis and Hunter . w» “inhuman“. fiJ/A‘revious reportstzgoted that the clinical response to induced convulsions the development of extensive high voltage was dependent upon slow wave,activity.QAaH7k7~Aznh.aNauroi7v9SyChtat?"j§7"516?“t959}n The reversal of postconvulsive cholinergic compounds suggcrests and euphoria ’ WC fies G The EEG and behavior “patterns thatEEmersynchrony by these potent and anti- [clinical sedation {increase in cholinergic acti@ desynchronization and clinical psvchotomimetic activity,ere 4:. decrease in cholinergic activl$291 5M7 Wild relation of these observations to studies of head trauma, and to the neurophysiologic-adaptive hypothesis of the convulsive therapy will be discussed. mode of action of �Effect of Anti cholingeric Compounds on Post Convulsive EEG and Behavior , In 1956 Ulett and Johnsgon repcrted to this society that large doses (jig of atropine erscopolamine blocked the appearance of high voltage delta ,. Its-their—smdyzhey noted 6? activity usually induced by convulsive therapy. that the dose! of atropine necessary to affect the W" ' with“ carried m unpleasant W5 mic ”We effects. ‘ ' Jenkner and Lechner M compound. It is m were these-sthet—else— Following. £23 reports by Modiethazine 4 a—peten-‘t (Mf‘iam facts aw cw. anticholinergic compound with minimal systemic 9 those of Ulett and Johnson EEG W. 1' Mi! W XMMA‘.‘ ”fir/félcm studies to similar W Our observations with led to an investigation of other anticholinergic this. the purpose of this report to describe the clinical and EG correlations on intravenous A administration of LSD-25, Win-2299, benactyzine and diethazine . n Z; in pSychiatric patients at various stages of convulsive therapy; and relate and these observations to thekneurophysiolog'c-adapative hypothesis of the mode of action of convulsive therapy and of hallucinogens. Subject and Method: Our km subjects ass consecutive referrals for convulsive therapy in an open ward voluntary I psychiatric hospital. Patients have been studied at �.2— [ll observations mg: made in acute is? laborah'y. Following a standardfirecording from experimnts in the W 17 leads, the compound under study #8 administered intravenously at a W various stages of therapy, EEG 1-: rate per minute , until clinical behavioral or electrographic changes m I observed. The compounds studied have been diethazine, Win-2299, LSD-25 p and benactyzine . Fig. I- Diethazine was administered at Win-2299 and benactyzine mgm; 10 gamma Chemistry structure 25 mgn. per minute, at 0.5 per minute for 50-150 mgm for a total of 175-250 per mimte for 2—; men; and )5atI LSD gamna. Observations: ‘ low If; patients (Q Wm ' there decrease in voltage and a desynchronization of rhythmic patterns became less prominent. In all frequencies. Prevailing some voltage 6-7 cps activity appeared, most prominent temporal leads. m The alpha frequency was not 993 $9321; Wm was a instances, symmetric in low the frontal and anterior a; altered, and? the build-up an by hyperventilation was blocked, �-u-u— -- .— --- —-.— --—--- Fig. 2’ \‘V 93 \. W; Diethazine - EEG - g Pre-Cenvulsive Treatment vi; .........._.-- __ W , /7 “I at! 3 InApatients during convulsive therapy, with varying degrees offlhigh ,5 (V significant decreaseA in voltage and in We}? ‘1‘! a W K%W W aways... Flusucu/ISlow per-cent time of delta activity. Both random and burst delta activity is voltage delta activity, there M a M 4 V - ~ I 0’3 diminished and low voltage alpha and beta frequencies The hyperventilation respoxaewas — no Fig. Diethazine --—---- .- EEG - Patients ’4, S Convulsive Treatment EEG effects, “wwwwww for irritable Mdysesthesias 1:3» and patterns were ‘ ,m to five hours. I Me dest-tive restless behavioral and complained of of the extremities. W. Visual illusory their illness, the setting of the test W1 46M! procedure; or the examiner's identity were MAM Myopposite one we observed phenomena and delusional thoughts about ‘ / #‘X became more sensations of unreality prominent. longer apparent. @hctrographic effects persisted changes. been .— Concurrent with these . l4» "— ' Their language L w to that previously described for amobarbital) 5 �- 80 W thatkdehial, minimization, cliches, third person were of 4:mode and less prominent. These behaVioral changes were pun-at. during the period 46W W W W W M maximum EG- chani gs. We: led to i. :qs's’ diethazine of other-imam hallucinogens Aru— m Denber and Merlis had W W mmdhfimmndm They WAWWM t-L similar to diethazine. «mt fiche-high voltage symmetric slow wave time and in w ”Mutant low voltage, ‘9” WW W wand M ”ma,”led to ‘x ’ril' ‘ ~ MWMJ MIM‘M? - MAM“? Ffiffiw' W this compound. study ELIZA; —— 51/ bursts were-diminished WW activity. random slow wave //{/,{r_,,"" fa. etagrm with an increase in alpha per/cent ”.WMM @ports by Pennes and anticholinergic altered mescaline . it: EEG changes“induced by electroshock in a fashion The past tense M. ‘ x-Jyx'yfl effects were similar to that: in the diethazine group. Inpatients pres convulsive therapy, 4,.v‘. I EEG .4 ‘ '7 .“-' ’ ' , I desynchronizationéwas induced. Fig. Win 2299 - 6 Pm-Cpnvulsive Treatment .I‘.\ In patients with high voltage slow wave activity induced by convulsive therapy, �.5. P, . \B ‘2‘ 9 \C . there was of slow wave adecrease in amplitude and per-cent time " OLE, & WA. LC— "1L” . ”I , ‘ r '1‘.“ I activity ' with an increase in alpha and beta frequencies. AA‘ssociated with these electrographic effects were clinical patterns of restlessness, excitement, / _.__ , Win 2299 and hallucinatory and - Post Fig. 7 Convulsive Treatment We firemefikwawAfl illusory activity. . I, Th? studies yore7/"repeated with intravenous -' 4 LSD {if/(MW isWM inMcbwLW W MAL/”3‘ W. l /.I ( V W A’M/[F There m behavioral effects] W €265 a difference In the time constant bee—names In line/- M electrographio changes-.flkhh 144. ’1» A—‘nfilvj 5—6796 mi there me less desynchronization 2-bit the delta activity WrepressedmMkw M “(p/7L “79% M7 mifllméw} __ (5‘; a I/L-v ‘ I, . Wfi‘fi’Wxfii Mose-Al} Recalling the- reports that benactyzine induced l . “Mflx I)?“ ‘ EEG W '3 desy‘nchmnization 5 we / adninistered the- ccmpound intravenously: and again! observed similar clinical and is electrographic patterns. In the well modulated alpha record, desynchronization prcmpt. In the record with high voltage delta activity, desynchronization �~6- ' MWMKL Wdelta I790: V13. activity 3903+} __ Fig. 11,’ 12 Bemctyzine WWW These pattems were accompanied by While we did not observe - EEG clinical restlessness and excitement. illusory or hallucinatory activity, mguagew m and Mo diethazine, ‘éu-e ”,ij Cl w w IL: cc te-theé-r EEG M M M3 a: W desmchrmizWeWw, thficue M compounds , an, Malt/71,) aaflwf/‘04 WM have In: W11 chemical structure W Jaw/554m these did note the Am to have similar electrographictand behavioral effects. minced I”) we Win-2299 and LSD. Thus, four compounds shown M awffiijfj d‘u a M M “by; have been {m W’MM 0’}; Ag,“ écfmmnmé’ é; 444-“ my 1“.” “In diethyl-anfino-ethyl organization. ' 7544.. (5y --------m-- ---~Repeat Fig __________________ WM”; WWWtK’L/océeufiflfinféawhhmva\ «a �. ' I I I These observations therapy process. In high voltage slow a; i Ii . site amplify our understanding of the convulsive earlier studies wave activity was . we indicated that the development of the neurophysiologic correlate of behavioral change in convulsive therapy, and a necessary, though not sufficient, condition for clinical improvement. During the past ten years, studies by Bornstein, Tower and McEachern, Ward, Sachs, Bugs and I“.— of convulsive therapy have noted similarities in the biochemical to craniocerebral trauma. acetylcholins They reported thatqguring convu Sl and pseudocholinesterase others erap free are-eiouated in the Spinal fluid. In addition, topical administration of acetyicholine induces high voltage burst and Spike activity. Ulstt and cholinergic effects ‘ The by the Johnson emphasized anticholinergic the blocking of these i::;::§§s;7:;ropine and 5v . . observation in this report on dietha21ne,‘Win-2299, support their observations. Each of these activity and the clinical behavioral 6 AldAbév‘ that the neurophvsiologic eerreiate compounds has and language thfse described for convulsive therapy. LSD-25 and thus scopolamine. benactyzine potent anticholinergic effects are apposite to we may/amplify the earlier conclusion behavioral changes in convulsive therapy �.5- is the development of high voltage slow wave activity, by this EEG tag—ion that reflects an alteration.in the acetylcholine-cholinesterase change "L”! J‘ relation of the basin, probably in the direction of increased cholinergic activity} [Tl' These observations lend themselves to application in studies of cranio- h9,41;r17§ cerebral trauma. The-repeat—ef Ward ll“ e clinical efficacy of high doses of atropine in altering the clinical manifestations of head trauma/also noted that effective doses brought with be advisable them severe peripheral effects. to repeat these studies, utilizing such neurologically Specific anticholinergic more potent, It would more compounds as Win-2299, diethazine or benactyzine. Finally, these observations, of EEG (l95h) and our earlier reports on the significance delta activity in convulsive therapy, support the observation of Wikler who concluded with the comment his report that: ".... on mascaline, n-allylnormorphine and morphine regardless of the drug administered, shifts in m the pattern.ofnelectroencephalogram.in the direction of desynchronization occurred in association with anxiety, hallucinations, fantasies, illusions or �tremors, and in the direction of synchronization with euphoria, relaxation M or drowsiness." This conclusion, supported by these observations, permit a more near meaningful generalization of the recently expressed neurophysiologic - adaptive hypothesis of the We may mode of action of somatic therapies in psychiatry. infer that agents that Synchronize frequencies, like barbiturate ”fl . and meprobamate phenazine EEG in the in the be r ge and chlorpromazine , promazine and deltm; tend to be sedativel, while agents that evoke EEG euphoriant and relaxantl; desynchmnization tend to be excitant and halluc- inogenic, as was noted for diethazine, In smmnary, per- we have observed pf 161), Win- 2299, benactyzine and meccaline. the effects of various compounds as diethazine, ,x/ Win~2299, LSD, benactyzine and mescaline on the electroencephalogran and behavior? in psychiatric patients at various stages of convulsive therapy. Behaviorally, these compounds induced increased restlessness, haptic and visual illusory sensations and delusional thoughts about the subject's illness or the examiner' 5 identity. The syntactic language patterns described for Wham/C convulsive therapy were reversed. Concurrent with these changes were a decrease in voltage and a desynchronization of all frequencies in the EEG. In patients with high voltage delta activity, the per-cent time and voltage �.10.. of the delta activity were marhedly decreased. These observations have been discussed in the framework of the common biochemical structure - that of a substituted diethylanimoethanol thééIanticholinergic properties with the conclusion that: (a) The // - and £74kfzitiég‘ biochemical basis for convulsive therapy;may be an alteration in the acetylcholine-dholinesterase relation of the nyrvous system, probably in the direction of increased cholinergic (b) The (Z? encompass the activity. recently expressed neurophysiologic adaptive hypothesis of the mode of action of somatic therapies action of hallucinogens; studies of the effects of anticholinergic trauma be undertaken, utilizing more in psychiatry is amplified to t is recommended that further compounds in craniocerebral neurologically Specific as diethazine, benactyzine and Winr2299. lfiffig’ compounds �Effect of Antichelinergic Hallucinogen: on Post Convaleive EEG _and Behavior * tron the Department of Experimental Psychiatry, Hillside Hospital, GlQn OIkB, L010, 3.1. part, by grant H—927 and HI~2092 of the National Institute of Hental Health, National Institutes of Health, 0.8. Public Health Aided, in Service. Read at the v1: 1/59 ~ American EEG. EEG Society neeting, Atlantic City, June, 1958, �Effect of Anticholinergic Hellocinogens on Poet Convnleive EEG and Behavior In 1956 Ulett and Johnson ( ) reported that atropine and ecopolanino blocked the appearance of the high voltage delta activity usually induced by convulsive therapy. They that the dose of atropine necessary to affect the also noted EEG was each as to be associated with unpleasant systemic effects. Reports by Jenkner conponnd us 90 this J Leehner (r) describing diethaeine as an antioholinergic bet minimal eyatenic effects led vith potent neurologic endertake studies similar to those of Ulett and Johnson using compound ( )y and these observations, in turn, led to an investigation of other experiaental enticholinergic agents. is the purpose of this report to describe clinical and It electro~ encephalographic observations on the intravenous administration of various anticholinergic agents in psychiatric patients at various stages of convulsive therapy and to relate these obeervationa to hypotheses concerning the node of action of convulsive therapy and the physiology o: hallucinogens ( ). ( ) �-2SUBJECTS AND METHOD: Our subjects were consecutive referrals for convulsive therapy in an open ward voluntary psychiatric hospital. numbers of While varying subjects have been studied for each compound, Ages ranged from 18 in 10k eXperinents have been assayed. subjects 86 to 67 years, and diagnoses include schizophrenic reactions, manic-depressive and involutional depressive psychoses. Patients have been studied at various stages of the treatment process. observations were The laboratory. 1 standard 8 made channel EEG in acute experiments in the EEG recorder and needle electrodes applied in 17 lead placements following Strauss 22.2; ( ) were In each experiment, the compound under study was edninistered used. intravenously at a set rate per minute, until clinical behavioral or electrographic changes were observed. The compounds studied have been diethasine, Win-2299, benaetyaine, Each is a potent JB~318, JB-336, and atropine. anticholinergic agent in vitrc. Diethasine (diethylaaineethyl~n~dibensoparathiasine), for example, induces mydriesis and hypotension, suppresses salivatien and blocks the �-5. bradycardia, aalivation and soizuros cf acctylchcline and fluorophosphatc ). ( Win-2299 (2-diotylaminoothy1 cycloponty1—2-thieny1~ 1 (2-diethy1aninoathyl benzilato) are similar to atropine pcgflLt central offocts synthetic anticholinorgic agents/but with glycolatc) and minimal and benactyzino : peripheral effects ( , ). JBo318 and JB-336 (N~ethy1o3-piperidy1bensilate, H-nethyl~3-piperidy1bonsilato) , . are two at a rccant series or synthetic anticholinergic 33:3: coupounda of high ( ). Diathazino total or minute central potency was 2 to 5 hallucinogenic activity adminiatcrod at 25 ngn. per minute for a 175—250 ngn; Win—2299 for and high ngn.3 and anqbonactynine at 0.5 nan. par JB—BIB) ngnt per minute for 1.2 to h.o ngn. JB-336, and atropine at O.h �OBSERVATIOHS: (a) Diethezine: A: previously reported administration or diethezine in 15 ), the ( patients prior to convulsive ron therepy resulted in a decrease ib volteges and a deeychnnnization or all frequencies. Prevailing rhythmic patterns became lees In some inetences, symmetric low voltage 6-7 ope prominent. activity appeared, nest proninent in the frontal temporal leads. The and anterior elphe frequency was not altered, but the build-up in voltage and the slower frequencies induced by hyper- ventilation vere blocked (fig. 1). acetone-ounces- In 25 petiente during convulsive therapy, with varying degrees of induced high voltage delta activity significant decrease both in voltage slow wave activity. From an and in ( ) there was a per cent time or everage per cent tine delta or hSI in the £ronte~occipita1 lends, there was 1 reduction to e neen per cent tine of 201. Both random and burnt delte �-5- activity diminished became proninent. and low increase in degree of slow The hyperventilation was on effects persisted for voltage alpha and bets frequencies longer apparent. no one activity wave These electrographic to five hours (Fig. 2). fi-‘-¢’---‘ Fig. 2 --‘------Concurrent with these electrographic effects, distinctive behavioral changes. Patients and restless and conplained of we observed irritable became more sensations of unreality and or dysthesias of the extremities; Visual illusory phenomena and delusional thoughts about their illness, the setting or the test procedure or the examiner’s identity were reported. syntactic language patterns a ( were Their . characteristically altered in fashion opposite to that previously described for snobarbital ), so that verbal denial, minimisation, cliches, third person node and past tense hsaanaflhax becane less prominent. changes were concurrent with maximum These electrographic change. �«6» (b) Win-2299: Reports by Pennee compound, Win 229?, manifested both and induced compound. excitetory etatee in The ( ) that an eXperimental potent anticholinergic actiity nan led to our study or this observations were einilar to those observed with diethazino. In five patients without slow wave activity, deeynchronisation of frequencies and decrease in voltages of all frequencies were noted in tour (Fig. 3). noofiflfl‘vw Pig. 3 ”------In 11 patients with high voltage delta activity there was a decrease in amplitude and per cent tine of slow wave activity with an increaee in alpha and beta frequencieec The mean per cent tine delta activity dropped from 50% to 23% (Fig. h). Fiz.\h -‘-‘---“ Associated with these electrographio effects were clinical patterne of reatleaeneea and and excitenent. Patients became fearful tenee. Visual seneatione were reported and in three subjects, delusional elaboraticne about their hospital experience were �-7. proninentdheee behavioral changee appeared during drug administrau tion or within ten minutes, ' levels, within to Reports that benactycine induced (c) Benactzaine: diethazine and disappeared, at these dosage tea three hours. two deeynchronization and ( its structural similarity both to and ) Win~2299 EEG led to our testing of this coupoond. Intravenous administration in 12 oubjecto elicited oiuilar clinical and electrographic patterns. Both in the well modulated alpha record and in the record with high voltage delta activity, deeynchroniaation was prompt. Delta activity decreaeed from a mean per cent tire of to 171 in 391 ‘--“‘-C“--“ PigS. 5’ 8 cuhjecte (Figs. 5, 6). 6 fi“-~--‘---These electrographic patterns were accompanied by clinical reetleeeoeee, irritability was more difficult. dittaanxt The thoughts econ with the dosage levels. In and excitement. Artifact-free recording illusory sensations initial compounds were and delusional not noted at these patients with manifest dieorientation language changee associated with convulsive therapy ( and ), however, �‘8‘ there wee en alerting and e revereal or the language patterns. (d) Piperiqzibenziletee: Abood ( ) that various piperidylbenziletea both manifested entioholinergic activity subjects, The Following recent reports by we tested and induced two or these, hallucinations in psychiatric JB-318 and JB—336 in 2b subjects. electrographio patterne were identicel to those other deeynohronination was during - Onset of inaynshxlaxxntx experimental oonponnde. injection or within 15 ninntee and persisted for one to four hours (Fig. 7, 8). -“Q.*.‘..--‘U.Figs. 7, 8 -nfl-~fi--.‘-‘--animation was observed, In each instance in whioh deeynchrntxixx clinical restlessness activity changes. were and exoitenent, illusory and hallucinatory noted, and were concurrent with the electrographio In two inetanoee the behavioral changes were halted by the subsequent intravenous adninietration of chlorpronaaine. �(e) Atrozine: Continuing our etudy or enticholinergic compounds, we edniuietered atropine intraveneuely in 12 subjects, in dosages of 0.8 to h.0ngn. Systemic erreeta were prenineut during the injection with increased respiratory rate, puller, dial dry akin and dry mouth, preeorttxxx cenpleinte and eerked teehy~ eerdie (Figs. 9, 10). und.~¢...mnd.¢Figs. 9, 10 ‘b.-’~.fi-‘----Subjects beenne reetleee end feertul (as did the obeervergp) end Seekxxxnptenxxunxnxpxenixentxlxxte recording became difficult. Within ten minutes these symptoms subsided and the subjects became drowsy and relaxed. In subjects without delta activity in the initial record, to leeeitude by decreased slowing (Fig. little be followed during change was seen the period at voltages, desychrenization and increased 9). Fig. 9 In subject: with delte activity, there wee en initial decreeee in voltage and per eent time or such activity during the period or �~10... reatlonancaa, following by an increaao during tho period of quiotudc (Fig. 10). --fi---.-‘&-flw Fig. 10 “.Q‘....‘.‘.‘ �-11DISGUSSIOH: i Various compound: with measurable anticholinorgic activity have that been effects. Thoco shown to have similar oloctrographic and bohovioralw oxporinontal compounds oxhibiting the greater facility in altoring cloctrcgraphic patterns structure oach containing a have a cannon tortiory nitrogen with linkage to varying roota (Fig. ll); a diothyl whilo atropine, rolativoly inpotont in altering oloctrcgraphic patterns contains a quaternary nitrogen. Bohaviorolly each compound induces stimulating, excitatcry and illusory and hallucinatory activity. Electro- graphically each induces dcaynchronication of frequencioa, and docroaac in voltages, most prominent in anhycta with delta activity c 7 following thoropcntically induced convulsions. (a) Convulsive theragy process: Those observations amplify our understanding of the convulsive therapy process and at the induced activity. In earlier studios or high voltoho slow wave ccrroloto or bohoviordl we slow wave indicated that the development activitr chango EEG woo tho nonraphyaiologic in convulsive therapy, and a �-12- - heceslary, though not sufficient, condition for clinical improvement ( ). During the past ten years, .1ncluding Bernstein, have reported numerous Tower and HoEachern, Ward, similarities in the biochednicsl authors Sachs, Rugs changes or the central nervous system in convulsive therapy to that seen in craniocerebral trauma ( ). They observed an inorease in cholnerzic activity as manifest by an elevation of tree acetylcholine and pseudocholinestereses in the spinal fluid. In addition, the direct increase in central nervous system acetyloholine activity by topical administration or eoetyloholine induced high voltage bursts and spike activity. Ulett and Johnson ( enphesised the blocking of the behevioral and electrographic effects by the antioholinergic activity of strapine The observations in this report on end scopolenine. dietheziue, Win-2299, benectysine and the piperidylbenziletes support their observations. The potent enticholinergic activity of such of these compounds (with apparent predoninant locus of activity in the central nervous system) expliries the suggestion that the beechenical basis for the induced slow wave activity of oonvulsivei therapy results from �an increased lova4tf control acetylcholine-cho1inesterase activity. Support for such a hypothesis considerable degrees of slow adniniotrotion of DE? wave is also seen in the activity observed after the (di-ioopropylrlnorophoophote) - a potent oholinootoraoo blocking agent. Uhilo these observations demonstrate that anticholinorgic compounds or. affective in reducing slow wovo activity,.roporto of othor compounds with similar effectihavo also appeared. ‘Anphotanino (Bonaodrino) ( acid diothylonido and diphenhydronino (Bonodryl) ( ) ), moocalino ), lyoorgic ( ( have been reported as rodncing post-convulsive slow wave These compounds ) activity. are primarily described as oymphthominotio and ontihiatoninio in phornncologio activity, yet each has exoitotory ond stimulating effofioto on bahnvior ( , , , ). The relations or those observations to than. soon in this report are possibly boat assessed in relation to synaptic activity. In t study of tho effects or vorioua agonta on the EEG and behavior of unanosthotizod cats with chronic inpltnted electrodes, �-1hBradley and Elkee ( ) postulated the exietence of two, or pcesibly three, types of interacting chemoreaponeive receptors within the central nervous system: cholinergic, non~cholinergie eheeeptible to amphetamine, and nonecholinergic susceptible to LSD and tryptaminie derivatives. Marezei and Hart ( ) exploring intercortical-(transcollosel) partwaye in the cat, described the effects of various compounds on direct electrical stimulation. They on the evoked potentials postulated the presence of two chenoreeeptive potentialities of the synapse - cholinergic and adrenergic ~ with Opposing stimulatory and inhibitory aetien. In both constructs, the administration at antifcholinergie agents, or at eympatheniaetic agenta, results in equivalent eynaptic .electrieal effects. LSD Thus adrenaiine, amphetamine, meecaline inhibit the electrical activity recorded afcreee and a synapse. in ddentieal effect is achieved with atropine. In the light or these suggestions, the present experiments permit a.mere specific hypothesis regarding the pharmacologic baeie of the convulsive therapy preceee. Repeated induced convulsions leads to an increase in synaptic eheliaergie activity with an �-15- increase in the level at electrical activity of the central nerveue system, which 1e recorded by surface electrodes es augmented high voltage slow wave activity. Adainietratien of entieholinergic agents reduces the leveflef synaptic activity, resulting in a decrease in tbe manifest cortical electrical activity to pre-convulsive levels. The administration of ayapathomimetic agente, however, also achieve: the seme etiolate, not by altering the by increasing the aloe EEG uni“ chelinergic ectivity but level of adrenergic activity. activity, wave so preninent and so or the poet-seizure state electrical ( The manifest persistent in the ) may waking thus be related to a pereiatent alteration in synaptic transmission activity of large numbers of The delicate thin balance is seen in the ready reversibility with a! Venture or alerting calls at the centre‘rerveee system. ( ), tine agents neted hare. ( ) and the wide variety or pharmacologie Repeated induced convuleione nay thus be described an a device to creete bioeheaieal changes in the brain �.16. for their resulting behavioral effects. fornuletion is Such a consistent with the view that convulsive therapy is therapeutic process non~apecitic ). ( initial suggestion The a ( ) for the convulsive therapy process may that the pharmacologio basis lie in alteration in an acetylcholine-cholinaeteraeo relationships, can, thus on be focused the alteration in the level of synaptic activity. 11:? regard, the observation that diphonkydranine anti~hystaninic agent, also reduces slow convulciono amount of ), ( and wave Innzyknhni In this primarily an , activity of induced the observations by Sacha ( ) that increased cerotinin appear in the spinal fluid otter convulsion: cuggeet that this image of synaptic activity in convulsive therapy is oversimplified. Nevertheless, further animal studies or the effects of various drugs on the poat~seizure electrical activity are warranted. (b) Neurophysiologz;pf hallucinogenic activitz: These observations of anticholinergic compounds delta activity also nay activity. be on EEG related to concepts of hallucinogenic Each of the compounds studied induced excitatory �-17behavior including illusory and hallucinatory phenomena.* Here, - too, synaptic models nescaline, may be useful. Sympathomimetie agetts, as amphetamine, and LSD, and entieholinergie agents es those described here, are equally potent hellucinogene, The neurophermacologic basis for such behavior may be characterized ee en alteration in synaptic balance in the direction of increased inhibition (decreeeed.trenenieeion) of stimuli. clinical efficacy of convulsive therapy in The hallucinatory ectivity.ney the: lie in biochemical level. known alteration at this Equally eignifieent are the effects of other cin entiehellunuiogene, ee chlorpromezine end reserpine, electrical activity. in an modifying men ( nedceline ), block the ( ), and Both compounds induce EEG EEG on hypersynohrony deeynehronieing effects of LSC.end in animal studies, block behavioral and electrogrephic effects ( ,). LSD and mesoeline The nonospecific nature of the neurophysiologic basis of orperimental hallucinatory activity ia thus emphasized. In the doses need, hellucinetory phenomene were not observed for benectyeine. A report of such activity was reported at higher doeege ( ). � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Effect of anticholinergic agent, diethazine, on EEG and behavior; significance for theory of convulsive therapy. AMA Arch Neurol Psychiatry. 1958 Sep;80(3):380-7 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-002-29b-005 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource 6 items. 1: Experimental Studies of Convulsive and Drug Therapies in Psychiatry: Theoretic Implications (one page). 2: Small graphs. 3: [preprint]. 4: Draft. 5: Reprint from the A. M. A. Archives of Neurology and Psychiatry September 1958, Vol. 80, pp. 380—387. 3: File copy. 4: Handwritten notes. 5: 8 drafts. 6: [preprint]. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/41d2ce5a639c29832746c6ec9a762f69.pdf be29ea3cfc0ebd057d49979acc6884d6 PDF Text Text �Reprinted from Biological Psychiatry Grunt & Stratton, Inn, 1959 Printed in (1.8.4. CHAPTER 14 Effect of An Anticholinergic Agent, Diethazine, on EEG and Behavior: Significance for Theory of Convulsive Therapy By MAX FINK, M.D. of convulsive have therapy emphasized EEG RECENT delta activity as the neurophysiologic basis for the induced behavioral change.“5 In investigations of head trauma significance has been ascribed to changes in the acetylcholine-cholinesterase systems both for the behavioral and the electroencephalographic effects. An increase in free acetylcholine6 and an alteration of the ratio of cholinesterases7 in the spinal fluid have been positively correlated with the degree of EEG abnormality and degree of neurologic deficit. The EEG patterns were “blocked,” and some improvement in clinical status was reported following the administration of atro8 pine.“ In convulsive therapy, atropine and scopolamine were observed to block the appearance of delta activity,9 although the systemic effects of the large doses of these agents were marked. Recent reports10 noted that EEG and behavioral effects similar to those produced by atropine were achieved in patients with head trauma by intravenous diethazine—a phenothiazine compound with anticholinergic properties—with minimal systemic effects. The effect of diethazine was studied in the course of our continuing studies of the role of delta activity in electroshock.3 It is the purpose of this report to describe the effects of diethazine on EEG patterns and on the behavior of patients during electroconvulsive therapy, and to relate these observations to the present neurophysiologicadaptive hypothesis of the mode of action of convulsive therapy. INVESTIGATIONS From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Long Island, N. Y. Aided, in part, by grant M-927 of the National Institute of Mental Health, National Institutes of Health, U.S.P.H.S. Co-recipient of the 1958 A. E. Bennett Foundation Award for research in biological psychiatry. Reprinted by permission from the A. M. A. Arch. Neurol. & Psychiat. 8: 38 (Sept) 1958. I am indebted to Mrs. Hannah Mosquera for her technical assistance in the EEG recordings, and to Drs. Joseph Jafl'e and Robert L. Kahn for their analyses of the tape recordings. Diethazine was made available through the courtesy of Smith, Kline and French Laboratories, Philadelphia, Pa. 184 �EFFECT OF AN ANTICHOLINERGIC AGENT 185 SUBJECTS AND METHODS Forty psychiatric patients, at various stages of electroshock therapy in an openward, voluntary psychiatric hospital have been studied. All observations have been made in acute experiments in the EEG laboratory. Following a routine EEG recording, diethazine* was administered intravenously at the rate of 25 mg. per minute, for a total of 175 to 250 mg., depending upon the behavioral efi'ect. Dosage varied from 2.8 to 4.0 mg. per Kg. body weight. EEG Analyses: Recording was continuous for the duration of the observation period, except during interview periods. Needle electrodes and an 8 channel Medcraft instrument were used. All records were analyzed for the degree of delta activity,3 the of fast relative and the amount time and frequency, alpha principal cent per activity. The alpha and delta activity were measured in anterior temporal-vertex, and parietal-ear lobe lead combinations. Behavior Measures: Prior to drug administration an unstructured psychiatric historical interview and a structured questionnaire period12 were tape-recorded. Following drug administration, periods of recorded interview were alternated with EEG recording periods, until the EEG had again manifested the preinjection pattern on visual inspection. Two estimates of behavioral effects were used: clinical descriptions by the particithe drug of the during occurring and changes interviewer technician) (subject, pants period, and analyses of the language of the recorded interviews. Changes in language were evaluated by a syntactic analysis12 and an analysis of the variability in verbal interaction in the dyad 1" “1' Both measures have been shown to be sensitive to alterations in behavior induced by changes in the central nervous system. OBSERVATIONS Clinical: Within two to five minutes after the start of the injection, subjects manifested spontaneous coughing followed by dryness of the mouth and thickness of speech. They reported feelings of lassitude and heaviness and weakness of extremities, soon succeeded by increased restlessness and difficulty in maintaing eyelid closure. Reports of visual and haptic illusory sensations, feelings of unreality and distance and delusional thoughts about their illness, the setting of the test procedures or our identity were voiced spontaneously in 18 subjects in the period between 15 and 60 minutes after drug administration. In three instances, increasing agitation and panic led to a cessation of the recording. In two subjects withdrawal and negativism were the prominent behavioral had and transient of behavior disappeared Such were patterns responses. in one and one-half to four hours in all subjects. *Diethazine is a soluble phenothiazine compound with pharmacologic properties similar to those of atropine. In experimental animals, diethazine blocks the bradycardia, bronchospasm, salivation, fasciculation and seizures induced by acetylcholine, di-isopropyl fluorophosphate and pilocarpine. It suppresses salivation, and induces mydriasis and hypotension.11 'j'Detailed analyses of these observations will be reported separately by Drs. J. J affe and R. L. Kahn. �186 BIOLOGICAL PSYCHIATRY WWW Wm mm PRE-DRUG LF-LO RF-RO 0-0 RPT-RO AFTER 225 mg. WWW/«WNW WWW WW 50flVl—— l FIG. l.—-EHect SEC. of intravenous diethazine, pre-electroshock (male, age 27). PRE-DRUG 0-0 1r I64l HH AFTER I50 mg. WW 5°)‘VL— SEC. I FIG. 2.—Efi'ect of we I725 HH intravenous diethazine, pre-electroshock (female, age 57). �187 EFFECT OF AN ANTICHOLINERGIC AGENT PRE-DRUG W W ”W W W W W W W W W W W WW + 200 mg. + 25 min. 4- 70min. “WWW- 50 )‘VI I SEC. #l637 HH 3.—Eflect of intravenous diethazine after electroshock (note especially effect on delta) . FIG. PRE-DRUG +|HR AFTER 250 mg. W W W W W W W W W W WW SGML...— I FIG. 4.——-Effect of on delta) . SEC. + 5 HRS. WwL/M *l249 HH intravenous diethazine after electroshock (note especially effect EEG Patterns: Alteration in the EEG patterns was concurrent with the behavioral effects. In all records, changes occurred during drug administration and were sustained, with gradual diminution and restitution of the preinjection patterns in one to five hours. The initial response was a decrease in voltage and desynchronization of all frequencies. There was a decrease in prominence of prevailing rhythms. In patients without delta activity (pre- �188 BIOLOGICAL PSYCHIATRY electroshock), desynchronization and voltage decrease were occasionally accompanied by low voltage 5 to 7 cps activity, symmetric and prominent in frontal and anterior temporal leads (FIGS. 1 and 2). The alpha frequency was not altered. The build-up in voltage and appearance Of slower frequencies with hyperventilation were blocked. In patients with varying degrees of high voltage delta activity there was a prominent decrease in voltage and desynchronization of the record. Both random and burst delta activity diminished or disappeared, and irregular low voltage alpha and beta frequencies became prominent (FIGS. 3 and 4) . The hyperventilation response was no longer apparent. Language Patterns: In previous studies, an intimate relationship between changes in syntactic language patterns and the behavioral response to electroshock had been reported.12 With alteration in brain function, increased use Of third person, verbal denial, qualification, displacement and clichés became prominent. These effects could be enhanced by the administration of intravenous amobarbital.“ In the subjects in the present study, syntactic analyses demonstrated a reversal of the patterns noted in electroshock. Use of third person, qualification and displacement decreased. Explicit verbal denial was modified and replaced by minimization and displacement, or by a reiteration of complaints of illness. In dyadic analyses, the verbal interaction was characterized by a greater diversity Of vocabulary and less variability in the diversity scores for 25 word units. The qualitative nature of these changes in the language patterns is Opposite to that of amobarbital and electroshock. The duration of language changes was concurrent with the changes in the electroencephalogram. DISCUSSION These Observations confirm the report of Jenkner and Lechner of the effects Of diethazine in “normal” subjects.10 Diethazine also alters electroshock-induced delta activity in a fashion similar to atropine and scopolamine, as described by Ulett and Johnson,” with minimal unpleasant symptoms. The effects of intravenous diethazine are immediate, both on the EEG and behavior, and it is thus a useful experimental agent with “anticholinergic” prOperties. Two aspects Of these experimental Observations warrant discussion: the role of acetylcholine-cholinesterase in the process of electroconvulsive therapy, and the significance Of diethazine “alerting” for concepts of hallucinogenic activity. Biochemical Basis of the Convulsive Therapy Process: Bornstein,6 in a classic experimental study of head trauma in cats, demonstrated that within a few minutes after trauma free acetylcholine appeared in the spinal fluid �EFFECT OF AN ANTICHOLINERGIC AGENT 189 and persisted for periods up to 48 hours. He further demonstrated a positive relation between the severity of head trauma and the quantity of free acetylcholine, degree of electroencephalographic alteration and the severity of the behavioral changes. The electroencephalographic records initially showed short periods of high voltage fast activity and a transient period of flattening of electrical activity, followed by prolonged periods of high amplitude sharp waves in the delta frequencies. Concomitantly, alteration in consciousness, changes in reflexes and post-traumatic seizures were most prominent with highest concentrations of free acetylcholine and greatest degree of EEG change. Tower and McEachern7 confirmed these observations in clinical studies. In 112 neurologic patients, free acetylcholine was found in the cerebrospinal fluid only in patients following head trauma and recent grand mal seizures; and the level of free acetylcholine varied directly with the degree of cerebral damage. In addition, these authors assayed the cholinesterase activity of the 16 fluid.“ spinal They noted a sharp rise in nonspecific cholinesterase (benzoylcholine-splitting) and a drop in the specific cholinesterase (mecholylsplitting) activity of the spinal fluid in patients following head trauma. No such inversion was noted in fluids containing free acetylcholine following spontaneous seizures. Electroencephalograms were taken at varying intervals following trauma, and demonstrated a direct correlation of the extent of EEG abnormality and the appearance of free acetylcholine in the spinal fluid. Tower and McEachern also reported observations in six patients receiving electroconvulsive therapy. ’In patients after three to seven induced convulsions, they noted free acetylcholine in the spinal fluid in two, and an increase in nonspecific cholinesterase with reversal of the cholinesterase ratio in five of the six. They concluded that the spinal fluid changes in electroshock are more like those of craniocerebral trauma than those found in epilepsy.* More recently, Sachs17 confirmed the reports of free acetylcholine in the spinal fluid after head trauma and after electroshock. In his studies, Bornstein6 administered 0.5 to 1.0 mg./ Kg. atropine and demonstrated a reversal or a blocking of the EEG effects, and a modification of the behavioral and neurologic signs. Atropine also blocked the EEG and clinical signs induced by intracisternal acetylcholine. Ward8 applied these observations to the treatment of human subjects with varying degrees of head trauma. Subcutaneous doses of 0.1 mg./Kg. of atropine induced both clinical improvement and reversal of EEG effects. These observations were recently confirmed by Sachs,17 Ruge,18 and *Regarding the one patient of the six who failed to show either free acetylcholine or a reversal of the cholinesterase ratio, they noted: “It is interesting that this patient was the only one of the six to show no response to treatment.” �190 BIOLOGICAL PSYCHIATRY Hughes.19 Basing their study on these observations, Ulett and Johnson" noted the effect of atropine and scopolamine in blocking the EEG changes of electroshock therapy. Concurrently, Jenkner and Lechner10 reported effects similar to those of Ward, in studies of diethazine in cases of head injury. Another group of investigations complete the available data. Studies of anticholinesterases, such as DF P (di-isopropyl fluorophosphate) and TEPP (tetraethyl-pyrophosphate) , which block the enzymatic breakdown of acetylcholine, demonstrate the development of high amplitude rapid frequency EEG patterns similar to status epilepticus as well as lesser degrees of abnormality as noted in post-traumatic states.”23 In these studies, atropine blocked both the electroencephalographic and the clinical toxic effects. Thus, both from experimental and clinical studies of craniocerebral trauma we may assume that (a): the acetylcholine activity of the spinal fluid increases; (b) that pseudo-cholinesterase activity increases with a reversal of the ratio of cholinesterases; (c) that EEG hypersynchrony and slowing parallel these biochemical alterations; and (d) that anticholinergic agents may block both the electroencephalographic and the clinical effects. From the data available it is probable that the biochemical basis of convulsive therapy is similar to that of craniocerebral trauma. Convulsive therapy results in free acetylcholine in the spinal fluid“ 17 and a reversal of cholinesterase ratios.“ 16 The electroencephalographic effects of repeated induced convulsions is the development of high voltage, symmetric slow wave activity, occasionally with spike activity,3' 24’ 25 which is similar to that observed in severe head trauma.” 27 In previous studies we have reported the relationship between the degree of induced slow wave activity and behavioral response.3 The studies reported here and that of Ulett and Johnson" demonstrate a reversal of the EEG and the behavioral effects of convulsive therapy by anticholinergic compounds. In each characteristic, convulsive therapy is thus similar to cerebral trauma. While the acetylcholine-cholinesterase system is highlighted by these studies, other enzyme systems may also be altered.17 These studies also suggest that convulsive therapy provides an excellent experimental method for studies of craniocerebral trauma. Studies of the brain stem-activating system by Jasper and DroogleverFortuyn28 and Lindsley et al.29 had laid the foundation for prevailing conclusion that symmetric EEG slow wave activity has its origin in mesencephalic structures, and that these structures intimately affect the states of “alerting” and “drowsiness.” More recently, Rinaldi and Himwich30’ 31 have related the site of action of atropine and cholinergic drugs to this mesodiencephalic activating system. It is also probable that these structures may be selectively affected by the process of convulsive therapy, and that �EFFECT OF AN ANTICHOLINERGIC AGENT 191 both the clinical and electrographic effects may be intimately related to changes in this system. Diethazine “Alerting” and Hallucinogenic Activity: The behavioral effects of diethazine provide information regarding another aspect of the convulsive therapy process. In patients without prior convulsive therapy, illusory phenomena and feelings of unreality were observed. These were similar to the hallucinogenic effects of LSD32 and mescaline.33 Again, analogic data about the clinical and EEG effects of these agents may provide some information about convulsive therapy. In studies of mescaline, Wikler34 noted that the EEG demonstrated either no change, intermittent or continuous low voltage fast activity or increase in alpha frequency. Denber and Merlis35 noted a similar acceleration of alpha frequency, decrease in per cent time alpha including its disappearance, and nonspecific random beta activity. Delta activity did not occur. In patients with delta activity induced by electroshock, Merlis and Hunter38 noted that intravenous mescaline markedly diminished the amplitude and per cent time delta activity with an increase in per cent time alpha activity. The effects of LSD on the EEG are similar. Gastaut et a136 noted an acceleration of alpha frequency of 0.5 to 4.0 cps with an accentuation of beta rhythms. Rinkel et a1.37 confirmed this observation and noted, in addition, a reduced responsiveness to hyperventilation.* In summarizing his studies Wikler34 concluded that “ . . . regardless of the drug administered, shifts in the pattern of electroencephalogram in the direction of desynchronization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness.” This generalization provides a meaningful construct in which these agents may be assessed. Agents that evoke EEG desynchronization tend to be hallucinogenic, and mescaline and LSD are clear examples. Agents that synchronize frequencies, such as barbiturate and meprobamate in the beta frequency range, and chlorpromazine, promazine and perphenazine in the delta frequency range89 tend to be sedatives, euphoriants and relaxants. The observations on diethazine reported here are consistent with this hypothesis. In patients without delta activity, the EEG demonstrated desynchronization of frequencies, and this was associated with clinical illusory phenomena. In patients with delta activity desynchronization occurred, and alerting and reversal of the Speech patterns induced by electroshock were observed. *Studies on the effects of LSD and such anticholinergic compounds as Win-2299, benactyzine, and hallucinogenic piperidyl benzilates (JB-318, 336) demonstrated marked diminution in per cent time and amplitudes of delta activity, associated with behavioral changes similar to those seen with diethazine.“ �192 BIOLOGICAL PSYCHIATRY Electroconvulsive therapy may also be understood in this framework. We have previously noted a direct relationship between clinical evaluations of improvement and the degree of EEG slowing induced by electroshock.3 Under these conditions, sedation and euphoria are most prominent and hallucinatory activity diminished. In patients in whom hypersynchrony is not induced, behavioral change is limited and ‘improvement’ does not occur.‘1 Previously we concluded that the mode of action of convulsive therapies is based on the induction of a state of altered cerebral function, in which changes in adaptive interpersonal behavior occur, and are interpreted as 4’ 39 ‘improvement’F" The present studies amplify two aspects of this neurophysiologic-adaptive hypothesis. The biochemical substrate of the behavioral change is reflected by an alteration in the acetylcholine-cholinesterase relationships of the central nervous system. It is also probable that EEG hypersynchrony provides the neurophysiologic basis of the milieu change which is clinically manifest as sedation and euphoria and is evaluated as ‘irnprovement.’ The neurophysiologic-adaptive hypothesis of convulsive therapy has provided a meaningful basis for studies of other physiodynamic therapies.39 In this study, it has been possible to amplify our understanding of neurophysiologic aspects of hallucinogens as well. SUMMARY The effect of an anticholinergic agent, diethazine, on the EEG, behavior and language patterns was observed in 40 psychiatric patients, at various stages in the course of electroconvulsive treatment. Behavior: Increased restlessness and agitation, haptic and visual illusory sensations, and delusional thoughts about their illness or examiner’s identity were observed. EEG: Alteration in the EEG was concurrent with behavioral changes. There was a decrease in voltage and desynchronization of all frequencies. In patients with delta activity, the per cent time and voltage of delta activity decreased. Language: Syntactic patterns described for convulsive therapy were reversed. Use of third person, qualification and displacement decreased. In dyadic analyses, there was a decrease in the coefficient of variation. 2. These observations are discussed in the framework of the neurophysiologic-adaptive hypothesis of the action of convulsive therapy; it is concluded that: (a) the biochemical basis for convulsive therapy is similar to that of craniocerebral trauma; (b) changes in acetylcholine-cholinesterase metabolism are intimately related to the behavioral effects; and (c) EEG desynchronization may be a physiologic concomitant of hallucinogenic activity; and EEG hypersynchrony may be associated with euphoria and 1. sedation. �EFFECT OF AN ANTICHOLINERGIC AGENT 193 REFERENCES . Weinstein, E. A., and Kahn, R. L.: Denial of Illness, Illness: Symbolic and Physiologic Aspects, Springfield, Ill., C. C. Thomas, 1955. Roth, M., Kay, D. W. K., Shaw, J. and Green, J.: Prognosis and pentothalinduced electroencephalographic changes in electroconvulsive treatment. EEG & Clin. Neurophysiol. 9: 225-237, 1957. Fink, M. and Kahn, R. L.: Relation of electroenecephalographic delta activity to behavioral response in electroshock. A.M.A. Arch. Neurol. & Psychiat. 78: 516—525, 1957. Green, M. A. and Kahn, R. L.: Experimental studies of the electroshock, process. Dis. Nerv. Sys. 19: 113-118, 1958. Ulett, G. A., Smith, K. and Gleser, G. C.: Evaluation of convulsive and subconvulsive shock therapies utilizing a control group. Am. J. Psychiat. 112: 795-802, 1956. Bornstein, M.: Presence and action of acetylcholine in experimental brain trauma. J. Neurophysiol. 9: 349-366, 1946. Tower, D. B. and McEachern, D.: Acetylcholine and neuronal activity. Canad. J. Research. 27: 105-131, 1949. Ward, A.: Atropine in the treatment of closed head injury. J. Neurosurg. 7: 398-402, 1950. Ulett, G. A. and Johnson, M. W.: Effect of atropine and scopolamine upon electroencephalographic changes induced by electroconvulsive therapy. EEG & Clin. Neurophysiol. 9: 217-224, 1957. Jenkner, F. L. and Lechner, H.: The effect of Diparcol on the electroencephalogram in the normal subject and in those with cerebral trauma. EEG & Clin. Neurophysiol. 7: 303-305, 1955. Heymans, CL, Estable, J. J. and de Bonneveaux, S. 0.: Sur la pharmacologie de la phenothiazinyl—ethyldiethylamine (2987 R. P.). Arch Int. Pharmacodyn. 79: 123-138, 1949. Kahn, R. L. and Fink, M.: Changes in language during electroshock therapy. In Hoch, P. and Zubin, J. Eds: Psychopathology of Communication. New York, Grune & Stratton, 1958, pp. 126—139. J affe, J.: An objective study of communication in psychiatric interviews. J. Hillside Hospital. 6: 207-215, 1957. : Language of the dyad: A method of interaction analyses in psychiatric interview. Psychiatry. 21: 249-258, 1958. Weinstein, E. A., Kahn, R. L., Sugarman, L. A. and Linn, L.: Diagnostic use of amobarbital sodium in organic brain disease. Am. J. Psychiat. 112: 889-894, 1953. Tower, D. B. and McEachern, D.: The content and characterization of Cholinesterases in human cerebrospinal fluids. Canad. J. Research. 27: 132-145, , 10. 11. 12. 13. 14. 15. 16. 1949. 17. Sachs, E.: Acetylcholine and serotonin in the spinal fluid. J. Neurosurg. 14: 22-27, 1957. 18. Ruge, D.: The use of cholinergic blocking agents in the treatment of craniocerebral injuries. J. Neurosurg. 11: 77-83, 1954. 19. Hughes, B.: The role of acetylcholine in head injury. J. Neurol. Neurosurg. and Psychiat. 20: p. 70, 1957. 20. Freedman, A. M., Bales, P. D., Willis, A. and Himwich, H. E.: Experimental production of electrical major convulsive patterns. Am. J. Physiol. 146: 117124, 1949. �194 BIOLOGICAL PSYCHIATRY 21. Grob. D., Harvey, A. M., Langworthy, O. R. and Lilienthal, J. L.: The administration of di-isopropyl fluorophosphate (DFP) to man. Bull. the Johns Hopkins Hosp. 8]: 257-266, 1947. 22. Hampson, J. L., Essig, C. F ., McCauley, A. and Himwich, H. E.: Effects of diisopropyl fluorophosphate (DF P) on electroencephalogram and cholinesterase activity. EEG & Clin. Neurophysiol. 2: 41-48, 1950. 23. Himwich, H. E., Essig, C. F., Hampson, J. L., Bales, P. D. and Friedman, A. M.: Effect of trimethadione (tridone) and other drugs on convulsions caused by di-isopropyl fluorophosphate (DFP). Am. J. Psychiat. 106: 816-820, 1950. 24. Callaway, E.: Slow wave phenomena in intensive electroshock. EEG. & Clin. Neurophysiol. 2: 157-162, 1950. 25. Green, M.: Significance of individual variability in EEG response to electroshock. J. Hillside Hosp. 6: 229-240, 1957. 26. Jasper, H. H., Kershman, J. and Elvidge, A.: Electroencephalographic studies of injury to the head. Arch. Neurol. & Psychiat. 44: 328-348, 1940. 27. Strauss, H., Ostow, M. and Greenstein, L.: Diagnostic Electroencephalography. New York, Grune & Stratton, 1952. 28. Jasper, H. H. and Drooglever-Fortuyn, J.: Experimental studies on the functional anatomy of petit mal epilepsy. Res. Publ. A. Nerv. Ment. Dis. 26: 272-298, 1947. 29. Lindsley, D., Schreiner, L. H., Knowles, W. B., and Magoun, H. W.: Behavioral and EEG changes following chronic brain stem lesion in the cat. EEG & Clin. Neurophysiol. 2: 483-498, 1950. 30. Rinaldi, F. and Himwich, H. E.: Alerting responses and actions of atropine and cholinergic drugs. A.M.A. Arch. Neurol. & Psychiat. 73: 387-395, 1953. 31. Himwich, H. and Rinaldi, F.: The effect of drugs on reticular system. In Brain Mechanism and Drug Action. Springfield, 111., C. C Thomas, 1957. 32. Stoll, W.: Lysergsaure—diethylamid, ein Phantastikum aus der Mutterkorngruppe. Schweiz Arch. Neurol. Psychiat. 60: 1-47, 1947. 33. Beringer, K.: Der Meskalinrausch, Monog. Neurol. Psychiat. Berlin, Springer, 1927. 34. Wikler, A.: Clinical and electroencephalographic studies on the effects of mes35. 36. 37. 38. 39. 40. caline, N-allylnormorphine and morphine in man. J. Nerv. Ment. Dis. 120: 157-175, 1954. Denber, H. and Merlis, 8.: Studies on mescaline. I: Action in schizophrenic patients. Psychiat. Quart. 29: 421-429, 1955. Gastaut, H., Ferrer, S. and Castello, 0.: Action de la diethylamide de l’acide d-lysergique (LSD 25) sur les fonctions psychiques at l’electroencephalogramme. Conf. Neurol. 13: 102-120, 1953. Rinkel, M., DeShon, H. J., Hyde, R. W. and Solomon, H. 0.: Experimental schizophrenia-like symptoms. Am. J. Psychiat. 108: 572-578, 1953. Merlis, S. and Hunter, W.: Studies on mescaline. II: Electroencephalogram in schizophrenics. Psychiat. Quart. 29: 430-432, 1955. Fink, M.: A unified theory of the action of physiodynamic therapies. J. Hillside Hosp. 6: 197-206, 1957. Effect of Anticholinergic Compounds on Post-convulsive EEG and . Behavior, EEG and Clin. Neurophysiol. 10: 776 (Abst.) 1958. #3....” � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Effect of anticholinergic agent, diethazine, on EEG and behavior; significance for theory of convulsive therapy., In JH Masserman (ed.), Biological Psychiatry. Grune and Stratton, New York, 1959, 1:184194. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-002-29c-006 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprinted from Biological Psychiatry Grune & Stratton, Inc., 1959 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/4d1964245452e951a0fc4a640e62c9dc.pdf 68280c1aa72a42e9812ae2fd531e09b0 PDF Text Text 50 ALTERATION OF BRAIN FUNCTION IN THERAPY MAX FINK following summary of observations made at a 200-bed voluntary, nonprofit, open-ward psychiatric hospital during the past three years is presented as the basis for discussion. The major interest of our Research Service is an investigation of the mode of action of various somatic therapies, especially electroshock and drugs. The disciplines represented in the research unit are clinical and psycho« dynamic psychiatry, neuropsychology, and experimental and clinical psychology. The following data summarize various studies that have previously been reported only in part: (I) High-dose reserpine for relief of anxiety: double-blind placebo study. (2) Chlorpromazine-insulin coma study. (3) Electroencephalographic effects of various drugs. (4) Electroshock process: concurrent psychiatric, psychologic, and neurophysiologic observations. HE OBSERVATIONS Reserpine In a placebo-controlled, double-blind study of oral and intramuscular reserpine, consecutive patients referred for drug therapy were rated for degree of manifest anxiety.1 The patients with high degrees of anxiety received randomized three-week periods iof reserpine therapy, divided into the following daily dosage periods: 10 mg. of reserpine (5 mg. oral, 5 mg. intramuscular), 5 mg. of reserpine (oral or intramuscular), or Reprinted from Psychopharmacology Frontiers. Proceedings of the Psychopharmacology Symposium of the Second International Congress of Psychiatry held in Zurich, Sw1tzerland on September 2-4, 1957. Published and copyrighted 1959 by Little, Brown and Company, Boston 6, Massachusetts, USA. �326 PSYCHQPHARMACOLOGY FRONTIERS placebo. Drugs were administered daily. None of the observing therapists knew which sequence was being followed or the dosages administered. Relief of anxiety symptoms related to drug dosage was seen in 20 per cent of the group. In 80 per cent no relief was noted, and of these, onethird exhibited severe depressive reactions which eventually responded to electroshock therapy. The high doses of reserpine administered resulted in significant clinical manifestations in every patient. The be~ havioral changes induced were directly related to the degree of concomitant physiologic disturbance. It was the conclusion of this study that high-dosage reserpine therapy has limited usefulness in the relief of anxiety symptoms. The dangers of induced depressions were clearly manifest, and the uncomfortable nature of the side effects of drug administration has resulted in a limited application of this drug in this environment. Chlorpromazine-insulin coma During a fifteen-month period, all patients referred by the supervising psychiatrists at this hospital for insulin coma therapy were divided by random sampling into an experimental group and a control group.2 The control group received classical insulin coma treatment, following the basic technique of Sakel. All patients received fifty comas, each of a duration of one hour or longer, at the physiologic level of Babinski reflex or absent lid reflex or deeper. The experimental group received chlorpromazine therapy in rapidly increasing dosages until toxicity had been induced. When toxic signs of rigidity, drooling, fixed facies, seizures, dermatitis, or marked weakness appeared, the dosage was gradually reduced until a maintenance level was obtained. Patients were sustained on this regime for a period of three to four months. In both groups, behavioral observations were made by investigators none of whom was the for referred treatment, resulting were Sixty patients therapist. patient’s in two groups of 30 each. The maintenance dosage of chlorpromazine was 300 to 2000 mg. daily. Initial dosages ranged from 1400 to 3600 mg. daily. Chlorpromazine induced motor retardation in all subjects. Overactive, destructive behavior rapidly disappeared, and the patients were more tractable, less negativistic, and less violent. One-third of the patients were more sociable and less seclusive, and were noted to care for themselves in a more presentable fashion. In the instances where severe parkinsonism supervened, however, the patients were less able to care for themselves, became sloppy, and failed to dress. Affective changes during chlorpromazine were varied. Four patients became increasingly agitated, tense, and tremulous, and either refused to continue on the drug regime or were induced to do so only with �MODE or ACTION 327 difficulty. Such an affective .storm appeared early in the therapy and persisted. .. In 4 other cases, depressive symptoms were significantly relieved, with an increase in affective lability and responsivity. In 2 patients, depressive ideation increased and was associated with complaints of insomnia. The medication was continued, however, with eventual alleviation. In most patients mood changes were small. Ideation was altered during the period of chlorpromazine therapy in 12 of the patients. Eight patients had a loss or a significant diminution of psychotic ideation. In 5, the hallucinatory and referential experiences were no longer reported even on inquiry, and in 3 others, delusional ideation was less prominent. In 1 patient, however, paranoid ideation became more prominent. This was associated with increasing anxiety and panic during drug administration, with resultant discontinuation of the drug regime. The clinical effects of insulin coma therapy have been exhaustively reported, and the findings in this series are comparable to those previously published. With regard to the evaluation of improvement, all 60 patients of this study have been discharged from the hospital. Table I lists patients according to the four-fold classification in use in the hospital at the discharge conference. TABLE I DISCHARGE RATINGS Chlorpromazine Insulin Coma Recovered Much improved Improved Unimproved 2 4 0 5 l7 l5 7 10 Inherent in the design of this study were high doses of chlorpromazine, pushed until symptoms of toxicity appeared. In this context, therefore, all patients developed significant drug effects. In all, rigidity of extremities appeared, frequently accompanied by a decrease in facial expression, drooling, and festination. Untoward complications are listed in Table II. Electroencephalograms were obtained in 20 of the chlorpromazine patients. On adequate doses, concomitant with a change in clinical behavior a moderate amount of low-voltage 4 to 7 cps delta and theta activity was observed. This activity was exaggerated by hyperventilation. In the 3 patients in whom seizures were induced, the delta activity was not significantly different from the remainder of the group. There was a �328 PSYCHOPHARMACOLOGY FRONTIERS suggestive relationship between the degree of the induced slow-wave activity and the drug dosage. TABLE II COMPLICATIONS Chlorpromazine Agitation and panic Dermatitis, severe Seizures Refusal of further therapy Hypotension Secondary reaction, frequent Prolonged coma (more than 6 hours) Insulin resistance Regression of behavior 4 3 3 2 Insulin Coma 3 5 2 2 — — Dab—409ml 2 It was the conclusion of this study that neither Chlorpromazine in high doses nor insulin coma is a specific treatment for schizophrenia. It was noted that these treatments were devices to temporarily alter behavior that had been socially unacceptable. Since Chlorpromazine was safer, easier to administer, and more controllable in its effect and had fewer side effects, it was recommended that it replace insulin coma. Role of electroencephalographic changes in behavioral change As noted in the following section, a direct relation between changes in electroencephalographic delta and behavioral changes in electroshock had been observed in these laboratories. For this reason, a survey of the role of various newer drug agents was undertaken to determine the potential relationship between behavioral change and electroencephalographic effects. Chlorpromazine and promazine are effective agents for the induction of changes in motor patterns of behavior. Concomitant electroencephalographic effects are the induction of delta activity, a desynchronization of the record, and a decrease in the amount of fast activity. Both drugs also induce seizure activity spontaneously in patients who have not had seizures prior to the administration of the drugs, and in whom pre-treatment electroencephalograms have not demonstrated dysrhythmic activity. Reserpine, while inducing a definite parkinsonian syndrome, does not generally induce seizures. At therapeutic levels, the changes in the electroencephalogram are limited to an increase in fast activity. We have not observed delta activity in any patient receiving reserpine. In patients receiving meprobamate, also, delta activity has not been observed. Records consistently demonstrate high-voltage beta activity, similar to barbiturate. Clinically, meprobamate has some effect in �MODE OF ACTION 329 reducing seizure activity. When dosages are suddenly reduced, we have observed spontaneous seizures in 2 subjects. This observation is similar to that noted in animals.3 Electroshock evalution studies In the course of an extensive evaluation of the electroshock process, a direct relationship has been observed between the degree of induced delta activity and the degree of behavioral change.4 We observed that serial records taken during the course of electroshock therapy and measured for quantitative changes in delta activity could serve as a guide to the therapeutic outcome. Of 11 patients who were clinically rated much improved, 10 had high-degree delta records in the third and fourth weeks of treatment, whereas of 7 unimproved patients only 1 had such a record. In a subsequent series,5 these observations were extended in a predictive study. It was suggested by these initial observations that the much improved patients were those in whom high-degree delta activity had been induced early in the course of treatment and sustained. Records taken during the second and third weeks of treatment were assessed. The results in 54 consecutive patients are noted in Table 111. Of the patients who developed high-degree delta activity during the second and third weeks of treatment, 67 per cent were rated much improved, whereas only 30 per cent of the patients without such activity were so rated. TABLE III PATIENTS WITH HIGH DELTA ACTIVITY IN EEG DURING SECOND AND THIRD WEEKS OF TREATMENT EEG Delta Both high (18) One high (16) None high (20) Much Improved 12 (67%) 4 (25%) 6 (30%) Clinical Rating Unimproved Moderately Improved 4 (22%) 8 7 (50%) (35%) ' 2 (11%) 4 (25%) 7 (35%) Delta activity in the electroencephalogram reflects the state of brain function, and is a guide to alterations in that state. To verify the relationship between delta activity and behavioral change, concomitant amobarbital tests for altered brain function6 were done in this series of patients. It was observed that the amobarbital test results were parallel to the electroencephalographic effects.7 Of patients in the initial series who had been rated as much improved, all had positive amobarbital test reactions after the seventh to ninth weeks of treatment and sustained this response. Of the unimproved patients, however, 15 per cent had �PSYCHOPHARMACOLOGY FRONTIERS 330 positive amobarbital responses in the third week and 28 per cent in the fourth week, but these responses were not sustained. A comparison of both electroencephalographic observations and the amobarbital test data, as related to the eventual clinical ratings, is seen in Table IV.5 TABLE IV ’ EEG AND AMOBARBITAL TEST RESULTS DURING SECOND AND THIRD WEEKS OF TREATMENT Much Improved Moderately Improved Unimproved Both positive amobarbital and high EEG delta activity Either positive amobarbital or high EEG delta activity Neither positive amobarbital nor high EEG delta activity Totals It 25 10 3 8 12 5 0 3 11 33 25 19 apparent that the cluster of positive amobarbital tests, high EEG delta activity, and the much improved clinical ratings is a significant one; equally significant is the cluster of negative amobarbital tests, low to moderate EEG delta activity, and a clinical rating of “unimproved.” In the clinical observations in the electroshock study varied behavioral responses were observed. These included the absence of noticeable symptoms with the return of pre-morbid behavior; hypomania, euphoria, and denial; paranoid states with ideas of reference and delusional formation; confusional states with varying degrees of memory disturbance; increased somatic complaints and preoccupations; states of increased panic, excitement, and agitation; and varying degrees of withdrawal and seclusiveness. Similar psychopathologic reactions were observed in schizophrenic patients undergoing either chlorpromazine or insulin coma treatments, or patients with severe manifest anxiety undergoing reserpine therapy. In the electroshock group, the degree of behavioral change was directly related to the degree of alteration in neurophysiologic indices. This direct relationship between neurophysiologic change and behavior was even more clearly manifested in a group of patients treated with subconvulsive therapy. In another control study, 27 subjects received subconvulsive therapy instead of grand mal therapy. The electroencephalo— grams demonstrated either no delta activity or a minimal amount of such activity during the course of treatment. In no patient were moderate or high-degree delta activity records observed. In the amobarbital tests, only 3 patients had positive reactions during treatment, and'in each instance this. occurred only once. Of the 27 subjects no change in sympis �MODE OF ACTION 331' toms or behavior was noted in 23. Nineteen were later referred for a second course of treatment. Of these, grand mal electroshock induced changes in brain function reflected by high-degree delta activity and /or repeated positive amobarbital tests in 14. All 14 showed significant changes in behavior, whereas of the 5 patients in whom physiologic indices showed only minor changes, only 2 showed a definite behavioral change. It is important to note that there was no direct relationship between the physiologic changes and a specific type of behavioral change. There was, however, a direct relationship between the degree of induced physiologic change in brain function and the degree of behavioral change. In a further attempt to determine the relationship between the type of behavioral change and other variables, we have carried out studies on the role of personality in the behavorial response.8 The initial study of the role of personality was devoted to a study of the relation between the characterologic disposition of patients to show denial mechanisms and the clinical results. The relatives of 47 patients were interviewed and denial personality scores were assessed, following a structured interview. Denial scores range from 0 to 25, with a median of 11. The scores were then divided into two groups: scores from 11 to 25 were classed as high denial and those from 0 to 10 as low denial. Of patients with high denial personality scores, 58 per cent were in the much improved group and only 1 patient was in the unimproved group. The ratings of improvement for the patients with low denial personality scores were random, about one-third appearing in each rating category. These studies support the present neurophysiologic adaptive hypothesis of the mode of action of electroshock therapy. This hypothesis notes that alteration in brain function is the central effect of electroshock therapy and is a prerequisite to behavioral change. It also notes that under the conditions of the induced change in brain function, altered patterns of adaptation are expressed. The type of adaptation varies, apparently dependent upon the personality organization. CONCLUSIONS Largely on the basis of these observations, as well as of reports of numerous other observers, the following conclusions regarding the role of physiodynamic therapies in schizophrenia are suggested: (1) None of the present therapeutic regimes, including insulin coma therapy, electroshock therapy, and the newer drug therapies including chlorpromazine, reserpine, meprobamate, and promazine, are specific for schizophrenic illnesses. No evidence has been educed that any of these therapies have altered the basic schizophrenic process. �332 PSYCHOPHARMACOLOGY FRONTIERS (2) Behavorial change in electroshock has been shown to be depend- ent on an alteration in brain function, as evidenced by serial changes in delta activity in the electroencephalogram. Under these conditions, the pattern of behavioral alteration varies markedly, depending on the degree of induced cerebral dysfunction, the personality of the subject, and the environmental situation. (3) The newer drug therapies have effects on brain function in direct proportion "to their ability to alter behavior as determined by clinical observation. The parallel between electroencephalographic change and behavioral change leads to the proposition that the mode of action of newer drug therapies may be similar to that of electroshock therapy; viz., by altering brain function in a nonspecific manner, behavioral changes are induced.9 To the extent that the behavioral alteration is of a kind that is rated as improved by the environment, the drugs are considered satisfactory therapeutic agents. In this regard, it is important to note that improvement ratings are but a special case of behavioral change, dependent on the type of adaptation elicited, the expectation of the therapist, administrator, and family, and the tolerance of the milieu. REFERENCES l. Wachspress, M., Blumberg, A. G., Fink, M., and Miller, J. S. A. Evaluation of high-dose reserpine therapy for relief of anxiety. 1. Hillside Hosp, 5: 67, 1956. Fink, M., Shaw, R., Gross, G. C., and Coleman, F. S. Comparative study of chlorpromazine and insulin coma in therapy of psychosis. ]. A. M. A. In press. 3. Wikler, A. Personal communication. 4. Fink, M., and Kahn, R. L. Relation of EEG delta activity to behavioral redr Arch. A. A. Neural. M. studies. serial electroshock: in quantitative sponse Psychiat., 78: 516, 1957. 5. Fink, M., Kahn, R. L., and Green, M. A. Experimental studies of the electroshock process. Dis. Nerv. System, 19: 113, 1958. 6. Weinstein, E. A., Kahn, R. L., Sugarman, L. A., and Linn, L. Diagnostic use of amobarbital sodium (“Amytal Sodium”) in organic brain disease. Am. ]. Psychiat., 112: 889, 1953. 7. Kahn, R. L., Fink, M., and Weinstein, E. A. Relation of amobarbital test to clinical improvement in electroshock. A. M. A. Arch. Neurol. 69' Psychiat., 76: 2. 23, 1956. Kahn, R. L., and Fink, M. Personality factors in behavioral response to electroshock therapy. Confinia neural. In press. 9. Fink, M. A unified theory of the action of physiodynamic therapies. J. Hillside 8. Hosp, 6: 197, 1957. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alteration of brain function in therapy. In NS Kline (ed.), Psychopharmacology Frontiers. Little, Brown & Co., Boston, 1959: 325-332. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-002-33b-011 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprinted from Psychopharmacology Frontiers. Proceedings of the Psychopharmacology Symposium of the Second International Congress of Psychiatry held in Zurich, Sw1tzerland on September 2-4, 1957. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Boston: Little, Brown and Company Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/96ce3f4b6be961e4eabd7724c9d19da6.pdf a0a4da54e32427732cf5206a7a8e7ac6 PDF Text Text m: 603.29% (f/ 3 mammowmmmwmwm MW“ * m an W8 at mm. mm, mm- mm, am am, L.,I.. m. and u. tho mung a: u:- mrim m Mum Atlantic any, m 31;. 3.958. �’umwuummcmmmmoommm “We! mmsémwwmmmwwmumduymmmu 02-00%de mammuotmhighwltago doltn ants-upon: nativity woolly mm by convulsive tux-spy. may also noted mm the M 91‘an mammary to affoettm Rem mob an tuba “mama with mutant music: afiaou. m reporta by Janinar and W!“ mums W mmmcmquuammnmmmma-o mamummo u an miehonmme with patent MWtfinflW;mdthouMmfim,intumlodfamlmflgatm ofothormmnu. 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For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Effect of anticholinergic compounds on post-convulsive electroencephalogram and behavior. Electroencephalogr Clin Neurophysiol.,10:776, 1958. (abstract). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-002-34a-012 Date A point or period of time associated with an event in the lifecycle of the resource 1958 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource [preprint]. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/ab4087755279fc01b94c0135ed348fc4.pdf b42318ee79fcb2ebd0a6f398dbb0a0b0 PDF Text Text EFFECT OF ANTICHOLINERGIC COMPOUNDS (IN POST CONVULSIVE ELECTROENCEPHALIIGRAM AND BEHAVIOR 0F PSYCHIATRIC PATIENTS MAX FINK, M.D. Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L.I., N.Y. Reprinted from "Electrrrrrephalography and Clinical Neurophysiology Ioumal" Vol. 12, No.2, May 1960. �EFFECT OF ANTICHOLINERGIC COMPOUNDS ON POST CONVULSIVE ELECTROENCEPHALOGRAM AND BEHAVIOR OF PSYCHIATRIC PATIENTS 1 MAX FINK, M.D. Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L.I., N.Y. (Received for publication: March 11, 1959) Demonstrations of the significance of high voltage EEG delta activity in the convulsive therapy process (Roth et al. 1951, 1957; Fink and Kahn 1957) and the report that this delta activity was blocked by the administration of atropine and scopolamine (Ulett and Johnson 1957) provided the basis for these studies. As there were attendant unpleasant systemic effects with the administration of these agents, reports describing diethazine as an antieholinergic compound with potent neurologic but minimal systemic effects (J enkner and Lechner 1955; Lechner 1956) led us to undertake studies similar to those of Ulett and Johnson using this compound (Fink 1958). Observa— tions with diethazine led to the investigation of other experimental anticholinergic agents. This report describes clinical and electroencephalographic observations incident to the intravenous administration of various anticholinergic agents in psychiatric patients at various stages of convulsive therapy and relates the observations to hypotheses concern— ing the mode of action of convulsive therapy and of hallucinogens. Patients have been observed at various stages of the treatment process. The observations were made in the EEG laboratory, using a standard 8 channel EEG recorder and needle electrodes applied in 17 lead placements following Strauss et al. (1952). In each trial, the compound under study was administered intravenously at a set rate per minute until clinical behavior or electrographic changes were observed. The compounds studied have been dietha— zine (Heymans et al. 1949), Win-2299 (Pennes and Hoch 1957), benactyzine (Jacobson 1955), JB-318 and JB-336 (Abood et all. 1958) and atropine. Diethazine was administered at 25 mg. per minute for a total of 175-250 mg. (2.5-5.0 mg/kg.) ; Win-2299 and benactyzine at 0.5 mg. per minute for 2 to 5 mg. (0.02-0.15 mg/kg.) ; and JB-318, JB-336, and atropine at 0.4 mg. per minute for 1.2 to 4.0 mg. (0.01-0.10 mg/kg.). OBSERVATIONS (a) Diethazine. The administration of diethazine in 15 patients prior to convulsive resulted in a decrease in EEG volttherapy SUBJECTS AND METHOD ages an-d a desynchronization of all freThe subjects were 90 psychiatric patients quencies. Prevailing rhythmic patterns bereferred for convulsive therapy. Ages ranged came less pronounced. In some instances, symfrom 18 to 67 years, and diagnoses included metric low voltage 6—7 c/sec. activity appeared schizophrenic reactions and manic-depressive and was most apparent in frontal and anterior and involutional-depressive psychoses. A va— temporal leads (Fink 1958). ried number of subjects were studied for each In 25 patients with varying degrees of induced high voltage delta activity during compound for a total of 107 observations. convulsive therapy (Fink and Kahn 1957), 1Aided, in part, by grants M-927 and MY-2092 there was a significant decrease in voltage and of the National Institute of Mental Health, National in per cent time of slow wave activity. From Institutes of Health, US. Public Health Service. 45 of in frontothe delta cent an average per Atlantic Read at the American EEG Society, occipital leads, there was a reduction to a City, June, 1958. [359] . �MAX FINK 360 mean of 20 per cent. Both random and burst delta activity diminished. Low voltage alpha and beta frequencies became more prominent. The usual increase in per cent time and in voltage of slow wave activity with hyperventilation was no longer apparent. These electrographic effects appeared during drug administration and persisted for 1 to 5 hours (Fink 1958). Concurrent with these electrographic effects, we observed distinctive systemic and complaints of abdominal griping. Such effects were generally less prominent than the electrographic or behavioral. Behaviorally, patients became irritable, restless, tense and excited, and it was difficult to maintain eyelid closure. They complained of feelings of unreality and of tingling, weakness and heaviness of the extremities. Complaints that colors were pale or more intense, halos about lights and changing shadows were accompanied by delusional thoughts about W W W mm W W W W W W W W W W WWWW PRE-DRUG LF-LO WWW/(WWW RF—RO + 40 MINS. AFTER 3.2 mg. WM + 80 MINS. wwwwvuwwmm WWWM wwwmmmw LAT-LF MAM-«Mm RAT-RF LF-RF LPT-LO 0-0 RPT'RO SouVLlsfi- #2016 HH Fig.1 Effect of i.v. Win-2299. Note desynchronization of frequencies after behavioral changes. The initial systemic effects were episodes of coughing and complaints of dryness of the mouth. Skin remained dry and the heart rate increased by 5 to 10 per cent. This increase was rarely noted by the subject, and was not accompanied by precordial distress. There was no change in pupillary size, and constriction in response to light was prompt. There were occasional 3.2 mg. (Female, age 41). their illness, the setting of the test procedure or the examiner ’s identity. (1)) Win-2299. The report by Pennes and Hoch (1957) that Win-2299 induced illusory and hallucinatory states in man, led to this next study. On intravenous administration of Win-2299, both electrographic and behavioral effects similar to diethazine were observed. In 5 patients without EEG slow wave �ANTICHOLINERGIC COMPOUNDS AND POST CONVULSIVE EEG activity, desynchronization of frequencies and a decrease in voltages were noted in four (fig. 1). In 11 patients with high voltage delta activity there was a decrease in amplitude and per cent time of slow wave activity with an increase in the per cent time of alpha and beta frequencies. The mean delta activity dropped from 50 to 23 per cent (fig. 2). Associated with these electrographic effects were clinical patterns of restlessness and excitement, and minimal systemic effects. PaPRE-DRUG 361 rate was unaffected except in patients who became. overtly excited and fearful, in whom tachycardia appeared during this excitement period. Dryness of the mouth was reported only on direct inquiry. (c) Benactyzine. Reports that benactyzine induced EEG desynchronization (Coady and Jewesbury 1956), its anticholinergic nature, and the structural similarity to diethazine and to Win-2299 led to our testing of this compound. Intravenous administration in 12 subjects elicited similar clinical and + 40 MINS. AFTER 2.0 mg. + 60 MINS. LF-LO W WW W” W WW W WWWW Wm Wm M W MW RF- R0 Wm WM RAT-RF WWW WNW LPT-LO 0-0 RPT-RO 50ml I SEC. # 1977 HH Fig. 2 Effect of i.v. Win-2299 on post—convulsive delta activity. Record taken 24 hours after convulsion #8. Note desynchronization of frequencies and persistence after 2.0 mg. (Female, age 51). tients became fearful and tense. Visual illusory sensations were reported and were associated in these subjects with delusional elaborations about their hospital experience. Excitement was accompanied by ideas of reference, and in two subjects, intravenous chlorpromazine was administered to halt this process. These behavioral changes appeared during drug administration or within 10 min, and disappeared within 2 to 3 hours. Systemic effects were slight. There were neither cough nor respiratory distress. Heart electrographic patterns. Both in the well modulated alpha record and in the record with high voltage delta activity, desynchronization was prompt. Delta activity decreased from a mean time of 39 to 16 per cent in 8 subjects (fig. 3, 4). These electrographic patterns were again accompanied by clinical restlessness, irritability and excitement. Artifact-free recording was more difficult. The illusory sensations and delusional thoughts seen with the initial compounds were not noted at these dosage �MAX FIN K 362 levels. Systemic effects were similar to Win2299. activity and clinical somnolence, we administered this anticholinergic agent intravenously in 15 subjects, in dosages of 0.8 to 4.0 mg. (.01-.10 mg/kg.). In 6 subjects without EEG delta activity, there were no changes in EEG pattern during drug administration nor for 10-20 min. thereafter. During a period of lassitu-de, decreased voltages, minimal desynchronization, and an increase in per cent time delta were noted. In subjects with delta activity, there was (d) Piperidylbenzilates. Following recent reports by Abood et al. (1958) that various piperidylbenzilates with measurable anticholinergic activity induced hallucinations in psychiatric subjects, we tested JB-318 and JB— 336 in 24 subjects. The electrographic patterns were identical with the other experimental anticholinergic compounds. Desynchronization of frequencies was noted during W W W W WM W W W WWW WWW WW PRE-DRUG LF-LO + 30 l0 MINS. AFTER |.5 + 50 MINS. MINS. mg. RF-RO LAT-LF RAT-RF LFTRF .. LPT-LO .. "A“... WWW/w WWW/WW 0'0 RPT-RO WM 50ml— WNWMNW‘AMAM. I Fig. SEC. WWW # |922 HH 3 Efftct of i.v. benactyzine. Note persistent decrease in voltages and desynchronization after 1.5 mg. (Female, age 34). the injection or within 15 min. and persisted for one to 4 hours (fig. 5). In each instance in which desynchronization was observed, clinical restlessness, excitement, illusory and hallucinatory activity were noted, and were concurrent with the electrographic changes. In two instances the behavioral changes were halted by the intravenous administration of chlorpromazine. (e) Atropine. Considering the numerous reports that atropine induced EEG slow wave an apparent initial decrease in voltage and per cent time of such activity during the first 10 min. after administration, followed by a return to original values during the period of quietude. In neither period were the changes significant (fig. 6). Systemic effects were prominent during the injection with increased respiratory rate, pallor, dry skin and dry mouth, precordial complaints and an increase in heart rate up to 100 per cent. Subjects became restless and �ANTICHOLINERGIC COMPOUNDS AND POST CONVULSIVE EEG recording became difficult. Within 10 min. these symptoms subsided and the subjects became drowsy and relaxed. 363 atropine under similar experimental condi- tions. These observations can be related to theories of the mode of action of convulsive DISCUSSION therapy; to concepts of the basis of experIn these studies, various experimental imentally induce-d hallucinations; and to recompounds with measurable anticholinergic ports of the effects of atropine on EEG patactivity have been observed to have similar terns. electrographic and behavioral effects. Elec(a) Convulsive therapy process. Earlier trographically, each agent induced a desyn- studies indicated that the development of high PRE-DRUG LF-LO RF-RO LAT-LF W + l0 2 MINS.AFTER MINS. |.5 mg. M +50 MINS. WW Wm «MW—MAW .AWNV'VW W W W WM W W W WW WW RAT-RF LF-RF LPT-LO Wm MWM'W 0-0 WWW/v RPT-RO WW4{)0qu #ZOIB HH Fig.4 Effect of i.v. benactyzine on post-convulsive delta activity. Record taken 24 hours after convulsion # 7. Note desynchronization of frequencies after 1.5 mg. (Female, age 33). chronization of frequencies and a decrease in voltages, which was most prominent in subjects with delta activity following convulsive therapy. Behaviorally, these electrographic patterns were associated with stimulating, excitatory, illusory and hallucinatory activity. To a lesser degree, minimal systemic changes in heart rate, salivation and sweating were noted. These latter systemic effects were more prominent in patients given intravenous voltage slow wave activity was a neurophysiologic correlate of behavioral change in convulsive therapy, and a necessary, though not sufficient, condition for clinical improvement (Fink and Kahn 1957). In summarizing the observations of numerous authors on the relation of acetylcholine metabolism to trauma of the central nervous system and to convulsions (Fink 1958) it was suggested that a biochemical concomitant of the induced EEG slow �MAX FINK 364 WWW WWVWWWW PRE-DRUG LF-LO AFTER 2.4 MG.IV l0 MINUTES AFTER WWW mm WWW WWW W W WWW W PR=|08 PR=96 .18 318- N-ETHYL, 3-PIPERIDYLBENZILATE PR=84 SOuvL—_ # 2|50 HH ISEC. Fig. 5 Effect of JB-318 on post-convulsive delta activity. Record taken 24 hours after convulsion #9. Note desynchronization of frequencies, decreased voltages after 2.4 mg. Cardiac rate shows 10 per cent increase. (Female, age 27). Similar records observed with PRE- DRUG JB—336. AFTER 2.0 MG. IV AFTER 30 MINUTES LAT-LF # 2|90HH HR=78 HR=|50 Fig. 50va__ l 6 SEC. Effect of small doses of i.v. atropine on post-convulsive delta activity. Record taken 24 hours after convulsion #6. Note minimal effect on delta activity and associated increase in heart 2.0 mg., 025 mg/kg.) rate, with persistence. (Male, age 18. Atropine : �ANTICHOLINERGIC COMPOUNDS AND POST CONVULSIVE EEG wave activity was an increase-d level of acetylcholine-cholinesterase activity of the central nervous system. The present observations of alterations in the slow wave activity of convulsive therapy by these experimental anticholinergic compounds are consistent with this suggestion. That the problem is more complex is indicated by reports of compounds with other biochemical activity also affecting slow wave activity in a similar fashion. Amphetamine (Lennox et al. 1951), Mescaline (Merlis and Hunter 1955; Denber 1955), lysergic acid diethylamide (Bente et al. 1957 a, b) and diphenhydramine (Diaz—Guerrero ct al. 1956) also reduce-d post-convulsive slow wave activity. In these reports, such a reduction was accompanied by excitatory and stimulating effects on behavior. These compounds, how— ever, are primarily sympathomimetic and antihistaminic in pharmacologic activity and not anticholinergic. The similar effects of these diverse biochemical agents on electrographic patterns and on clinical behavior may be considered within theoretic constructs of the relation of synaptic activity to behavior as expressed by Marazzi (1953, 1957), Bradley and Elkes (1957), Evarts (1958 a, b), Sherwood (1958) and Woolley (1958). These authors suggest that two types of interacting chemoresponsive receptors exist within the nervous system which are selectively responsive to cholinergic or to adrenergic agents. Where such receptors exist, they exert opposing stimulatory or inhibitory action. Thus, repeated induced convulsions may lead to a change in synaptic cholinergic activity, reflected in surface electrodes as high voltage slow wave activity. Administration of anticholinergic agents may alter synaptic activity, resulting in a decrease in the manifest cortical electrical activity to preconvulsive levels. Administration of sympathomimetic agents may achieve the same electrical effects by increasing the level of adrenergic activity. The manifest slow wave activity, so prominent and so persistent in the post-seizure EEG, may thus be viewed as resulting from a persistent alteration in the synaptic activity of large numbers of cells of the central nervous 365 system. The delicate nature of this balance is seen in the ready reversibility with alerting, time, and the wide variety of pharmacologic agents noted here. While an alteration in synaptic activity may underlie the behavioral changes in convulsive therapy, the mechanism by which such alteration is developed or sustained is unclear. The observation by Aird et al. (1956 a, b, 1958), that an increase in permeability of the blood brain barrier followed repeated induced convulsions suggests one way in which synaptic changes may be mediated. The consistent nature of these neurophysiologic observations makes an exclusively psychologic explanation of the mode of action of convulsive therapy less tenable. These studies are consistent, however, with the neurophysiologic-adaptive view of the convulsive therapy process which suggests that neurophysiologic changes provide the substrate for alterations in all aspects of the subject’s clinical behavior; the type of behavioral alteration being dependent upon the type and degree of neurophysiologic change, the personality of the subject and the expectations and tolerance of the milieu (Weinstein and Kahn 1955; Fink and Kahn 1957; Fink 1957). (b) Neurophysiology of hallucinogenic activity. The effects of anticholinergic compounds-on EEG and behavior may also be related to the understanding of experimental hallucinogenic activity. Each of these experimental compounds induced excitatory behavior, including illusory and hallucinatory phenomena. Here, too, a synaptic model may be applicable. Sympathomimetic agents, as Mescaline, LSD and amphetamine, and anticholinergic agents as those described here, are also potent hallucinogens. A neuropharmacologic basis for such behavior may be characterized as an alteration in the level of synaptic activity in the direction of increased inhibition (decreased transmission) of stimuli. The clinical efficacy of convulsive therapy in modifying hallucinatory activity may lie in alterations at this neurophysiologic level. The effects of such hallucinogenic blocking agents as chlorpromazine and Reserpine on EEG electrical activity are consistent with such a view. Both compounds induce EEG �366 MAX FINK hypersynchrony in man (Bente and Itil 1954, 1958) and block the EEG desynchronization effects of LSD and Mescaline (Schwartz ct al. 1955). Chlorpromazine was found equally potent in aborting the excitatory activity of the experimental anticholinergic compounds in these studies. (0) Relation to atropine. Comparison of the systemic and neurologic effects of experimental anticholinergic compounds with atropine reveals differences in initial focus of action. Experience with atropine at physiologic and toxic levels in man indicate that the predominant effects are focused at peripheral nervous structures. Initial bradycardia, followed by tachycardia, loss of sweating and salivation, pupillary dilation, intestinal relaxation and decreased motility are amongst the effects at low (0.2-1.2 mg.) dosages. At higher dosages (2-5 mg), the neurologic effects of ataxia, irritability, disorientation, and delirium are observed (Goodman and Gilman 1955). In contrast, the experimental anticholinergic agents in dosages sufficient for central nervous system effects manifest little peripheral activity. The central effects are observed early and may continue for extensive the dosage of atropine varied from 0.5 to 7 mg/ kg. — a range roughly comparable to the dosages used in atropine coma therapy (Forrer and Miller 1958) . In the present studies, the EEG effects of low dosages of intravenous atropine (0.01 to 0.10 mg/kg.) were minimal and systemic effects considerable, confirming similar observations by Verdeaux and Marty (1954) and by Danielopolu et al. (1955). The slow wave activity so prominent in animals and man at high dosages of atropine, may not be a manifestation of the initial or direct effects of atropine, but a reflection of a more widespread alteration in body physiology. Thus, while considerable speculation as to central neurophysiology has been based on studies with atropine, such observations provide a special case of anticholinergic effects. The anticholinergic activity established in observations in vitro and in the peripheral nervous system, may not be the effective physiologic activity in the large doses necessary to affect central structures. The experimental compounds, however, provide more suitable agents for the study of central neurophysiologic (anticholinergic) patterns than atropine, as, for example, in a re-evaluation of the studies of craniocerebral trauma and epilepsy. Ward’s (1950) reports of the efficacy of high doses of atropine in altering the clinical manifestations of head trauma indicated that effective doses brought with them severe systemic effects. The failure of atropine and scopolamine to affect epilepsy may be related to the inability of these compounds to reach the central nervous system in adequate quantity. It would seem advisable, therefore, to repeat these studies utilizing such more centrally active anticholinergic compounds as used in the experiments reported here. periods without gastrointestinal, cardiac or pupillary changes. It is within the context of the focus of activity in relation to dosage that the apparent discrepant EEG observations of the effects of atropine (in inducing slow wave activity) and these experimental anticholinergic compounds may be reconciled. Wescoe et al. (1948) administering 1.0 to 3.0 mg/kg. atropine in curarized cats and monkeys and Fun— derburk and Case (1951) using 0.4 to 1.2 mg/ kg. in curarized cats, observed high voltage EEG slow wave activity. Wikler (1952, 1957) reported that 7.2 mg/kg. atropine on SUMMARY unanesthetized, uncurarized dogs produced 1. Experimental anticholinergic comslow similar to wave” sleep. “spindle patterns Rinaldi and Himwich (1955 a, b) reported pounds (diethazine, Win-2299, benactyzine, JB-318 and administered to JB-336), psy0.5 2.0 of doses to that atropine in mg/kg. chiatric patients at various stages of convulin curarized rabbits exaggerated EEG sleep sive associated with: therapy, were of the inhibited and the alerting patterns EEG to peripheral stimuli. Similar observa- (a) desynchronization of EEG rhythms with tions have been reported by Bradley and Elkes a blocking of post-convulsive delta activ(1953) in the conscious cat. In each instance ity ; �ANTICHOLINERGIO COMPOUNDS AND POST CONVULSIVE EEG 367 (a) des effets systémiques de faiblesse musculaire, sécheresse buccale, sécheresse cutanée et tachycardie. Les effets de comportement, électrographiques et systémiques étaient concurrents. 2. Ces observations sont consistentes avec The electrographic, behavioral and systemic la suggestion qu’un concomittant neurophysiologique de la thérapie convulsive soit l’augeffects were concurrent. 2. These observations are consistent with mentation de l’activité cholinergique du systéme nerveux central. the suggestion that a neurophysiologic conco3. Des observations sur le fait que le LSD, mitant of convulsive therapy is an increase in central nervous system cholinergic activity. l’amphétamine, 1e Mescaline, et le diphenhy3. Observations that LSD, amphetamine, dramine — agents sympathicomimétiques et Mescaline and diphenhydramine —- sympatho- antihistaminiques — induisent également une mimetic and antihistaminic agents — also in— désynchronisation EEG, le blocage de l’acti— duce EEG desynchronization, blocking of vité delta post-convulsive et l’activité clinique post convulsive delta activity and clinical excitatoire, soutiennent la suggestion que des excitatory activity support the suggestion that variations de comportement et electrographibehavioral and electrographic patterns may ques puissent étre basées sur des alterations be based on alterations in synaptic activity. de l’activité synaptique. On suggere que l’acIt is suggested that increased synaptic activ- tivité synaptique augmentée (effets cholinerity (cholinergic, sympatholytic effects) is giques, sympatholytiques) soit associée a l’hyassociated with EEG hypersynchronization, persynchronisation EEG, la sé-dation clinique and clinical sedation and euphoria; while de- et l’euphorie; tandis que l’activité synaptique creased synaptic activity (anticholinergic, diminuée (anticholinergique, sympathomimesympathomimetic) is associated with EEG tique) soit associée a la désynchronisation desynchronization and clinical excitatory and EEG et des états cliniques excitatoires et hallucinogéniques. hallucinogenic states. 4. Des observations contradictoires avec 4. Discrepant observations with atropine are related to significant differences in dosage. atropine sont en relation avec des differences Re-assessment of the role of anticholinergic signifi'catives de dosage. Une reevaluation du role d’agents anticholinergiques dans les trau— is seizure and in head states trauma agents matismes craniens et les états comitiauX semsuggested. 5. These observations amplify the neuro- ble étre indiquée. 5. Ces observations amplifient l’hypothese physiologic-adaptive hypothesis of the mode of action of convulsive therapy and of exper- neurophysiologique-adaptive du mode 01 ’action de la thérapie convulsivante et des états halluimental hallucinogenic states. cinogenes expérimentaux. (b) alerting, excitatory behavioral response with illusory, delusional and hallucinatory i-deation; and, (a) systemic effects of muscular weakness, dryness of the mouth, dry skin and tachycardia. RESUME Des composés anticholinergiques eXpérimentauX (diethazine, Win-2299, benactyzine, JB-318 et J 13-336), administrés a des patients psychiatriques a des étapes différentes d’une thérapie convulsivante, étaient associés avec: ZUSAMMENFASSUNG 1. (a) une désynchronisation des rythmes EEG, avec un blocage de l’activité delta postconvulsive; (b) une réponse de comportement excitatoire, vigilante, avec de l’idéation illusoire, délusionnelle et hallucinatoire, et Mischungen von experimentellen anticholinergischen Stoffen (Diethazine, Win2299, Benactyzine, JB-318 und J 13-336) wurden psychiatrischen Patienten verabreicht welche sich in verschiedenen Stadien der konvulsiven Therapie befanden. Hierbei wurde folgendes beobachtet: 1. (a) Eine Desynchronisierung der EEGRhythmen mit Blockierung der postkonvulsiven Delta-Aktivit'at. �MAX FINK 368 (b) Eine Weckreaktion mit erregtem Benehmen, welches mit Illusionen, Halluzinationen und Wahnideen einherging. (c) Allgemeineffekte charakterisiert durch Muskelschwache, Trockenheit des Mundes und der Haut und Tachykar-die. Die elektrographischen- und Allgemeineffekte, sowie die Veranderungen des Benehmens erfolgten gleichzeitig. 2. Diese Beobachtungen stehen nicht in Konflikt mit der Theorie, wonach eine Erhahung der cholinergischen Aktivit'at im zentralen Nervensystem eine neurophysiologische Folgeerscheinung der konvulsiven Therapie darstellt. 3. Die Beobachtungen, dass LSD, Amphetamin, Meskalin und Diphenhydramin sympathomimetische und antihistaminische Stoffe —— ebenfalls die EEG-Desynchronisation herbeifiihren, die postkonvulsive DeltaAktivitat blockieren und die klinische Erregtheit dampfen, unterstiitzen die Annahme, dass elektrographische Veranderungen sowie solche des Benehmens auf Anderungen der synaptischen Aktivit'at zuriickgefiirt werden konnen. Es Wird angenommen, dass eine erh'ohte synaptische Aktivitat (cholinergische, sympathikolytische Effekte) assoziiert ist mit Hypersynchronisierung des EEG’s, mit klinischer Sedation und Euphorie, W'ahrenddem eine verminderte synaptische Aktivit'at (anticholinergische, sympathikomimetische Effekte) assoziiert ist mit Desynchronisierung des EEG und mit klinischen halluzinatorischen Erregungszustanden. 4. Abweichende Beobachtungen mit Atropin stehen mit signifikanten Differenzen in der Dosierung in Beziehung. Die Rolle, welche anticholinergische Stoffe bei Kopftrauma und Anfallszust'anden spielen, sollte erneut in Betracht gezogen werden. 5. Diese Beobachtungen unterstiitzen die neurophysiologische Hypothese fiber die Aktionsart der konvulsiven Therapie und der experimentellen halluzinatorischen Zust'ande. I am grateful for the technical assistance of Mrs. Hannah Mosquera in EEG recording and analyses. Supplies of the various pharmaceuticals were made freely available by Lakeside Laboratories (JB318 and JB—336), Merck Sharpe &Dohme (benactyzine), Sandoz Pharmaceuticals (LSD-25), SterlingWinthrop (Win-2299) and Smith, Kline and French Laboratories (diethazine, chlorpromazine). REFERENCES ABOOD, L. G., OSTFELD, A. M. and BIEL, J. A new group of psychotomimetic agents. Proc. Soc. Exper. Biol. Med., 1958, 97: 483—486. AIRD, R. B. Clinical correlates of electroshock therapy. A.M.A. Arch. Neural. Psychiat, 1958, 79: 633- 639. AIRD, R. B., STRAIT, L. A., PACE, J. W., HRENOFF, M. K. and B‘OWDITCH, S. Neurophysiologic effects of electrically induced convulsions. A.M.A. Arch. Neurol. Psychiat., 1956, ’75: 371-378. BENTE, D. und ITIL, T. Zur Wirkung des Phenothiazinkorpers Megaphen auf das Menschliche Hirnstrombild. Arzneimittelfarschg, 1954, 7: 418-423. BENTE, D. and ITIL, T. A comparison of the action of various phenothiazine compounds on the human EEG. Trans. Int. 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Fizialagicheskiy DANIELOPOLU, Zhurnal SSSR, 1955, 41: 601—611. DENBER, H. C. B. Studies on Mescaline: III. Action in epileptics. Psychiat. Quart, 1955, 29: 433-438. DiAz-GUERRERO, R., FEINSTEIN, R. and GOTTLIEB, J. S. EEG findings following intravenous injection of diphenhydramine hydrochloride (Benadrylr). EEG Clin. Neurophysiol, 1956, 8: 299306. E. V. Neurophysiological correlates of pharmacologically induced behavioral disturbances. Res. Publ. Ass. nerv. ment. Dis., 1958, 36: EVARTS, 347-380. EVARTS, E. V. Chemical bases for psychoses. Chem‘ ical Concepts of Psychases. McDowell, Oblensky Inc., N.Y., 1958, pp. 41-62. FINK, M. A unified theory of the action of physio- dynamic therapies. J. Hillside Hosp, 1957, 6: 197-206. �ANTICHOLINERGIC COMPOUNDS AND POST CONVULSIVE EEG FINK, M. Effect of anticholinergic agent, diethazine, on EEG and behavior: Significance for theory of convulsive therapy. A.M.A. Arch. Neural. Psychiat., 1958, 80: 380-387; and Biological Psychiatry, ed. J. 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Cholinergic mechanism involved in function of mesodiencephalic activating system. A.M.A. Arch. Neural. Psychiat., 1955, 73: 396-402. ROTH. M. Changes in the EEG under barbiturate anesthesia produced by electro-convulsive treatment and their significance for the theory of ECT action. EEG Olin. Neuraphysial., 1951, 3: RINALDI, 261-280. ROTH, M., KAY, D. W. K., SHAW, J. and J. GREEN, Prognosis and Pentathal induced electroencephalographic changes in electroconvulsive treatment. EEG Olin. Neuraphysiol., 1957, .9: 225—237. SCHWARZ, B. E., BICKFORD, R. G. and ROME, H. P. Reversibility of induced psychosis with chlorpromazine. Prac. Maya Olin., 1955, 30: 407-417. SHERWOOD, S. L. Central cerebral chemicals and their relation to psychoses. Chemical Concepts of Psy- chosis. McDowell, Oblensky, N.Y., 1958, 268-276. STRAUSS, H., OSTOW, M. and GREENSTEIN, L. Diag— nostic Electroencephalography, Grune & Stratton, N.Y., 1952. ULETT, G. A. and JOHNSON, M. W. Effect of atropine and scopolamine upon electroencephalographic changes induced by electroconvulsive therapy. EEG Olin. Neurophysiol, 1957, 9: 217—224. VERDEAUX, G. et MARTY, R. Action sur l’électroencé- phalogramme de substances pharmacodynamiques d’intérét clinique. Rev. Neural, 1954, .91: 405-427. WARD, A. Atropine in the treatment of closed head injury. J. Neurosurg., 1950, 7: 398-402. WEINSTEIN, E. A. and KAHN, R. L. Denial, of Illness: Symbolic and Physiological Aspects. C. Thomas, Springfield, 111., 1955. 0., GREEN, R. E., MCNAMARA, B. P. and KR-OP, S. The influence of atropine and scopolamine on the central effects of DFP. J. Phar- WESCOE, W. macol, 1948, .92: 63-72. WIKLER, A. Pharmacologic dissociation of behavior and EEG “sleep patterns” in dogs: morphine, N’allylnormorphine and atropine. Prac. Soc. Exper. Biol. Med., 1952, 79: 261—265. WIKLER, A. The Relation of Psychiatry ta Pharmacology. Wm. Wilkins, Baltimore, 1957. WOOLLEY, D. W. Serotonin in mental disorders. Res. Publ. Ass. nerv. ment. Dis., 1958, 36': 381-400. Reference: FINK, M. Effect of anticholinergic compounds on post convulsive EEG and behavior of psychiatric patients. EEG Olin. Neuraphysial., 1960,12: 359-369. W w IN �ANNOUNCEMENT WEEK—END COURSE IN "EEG AND CLINICAL NEUROPHYSIOLOGY IN PAEDIATRIC PROBLEMS” Institute of Child Health, Hospital for Sick Children, University of London, London, England Saturday, June 18th, 1960 9.45 a.m. Introduction. 10.00 a.m. Electrocorticography During Operations for Partial Epilepsy. 11.15 a.m. Coffee. 11.30 a.m. Motor Function and The Basal Ganglia. 1.00 p.m. Lunch. 2.00 p.m. Behaviour after Cerebral Lesions in Children and Adults. 3.15 p.m. Tea. 3.30 p.m. Diffuse Systems in the Brain: Physiological and Pharmacological Mechanisms. Dr. Otto Magnus, Head EEG Dept, St. Ursule Clinic, Wassenaar and “Meer en Boslk’ ’, Hemsteede, Holland. Dr. John A. V. Bates, Neurological Research Unit (M.R.C.), The National Hospital, Queen Square. Prof. H. L. Teuber and Dr. R. Rudel, Dept. of Psychiatry and Neurology, New York University, Bellevue Medical Centre. Dr. Philip Bradley, Dept. Experimental Psychiatry, University of Birmingham, Hon. Director M.R.C., Neuropharmacology Research Group Sunday, June 19th, 1960 10.00 a.m. Circulatory Arrest. 11.15 a.m. Coffee. 11.30 a.m. The Clinical Physiology of the Lower Motor Neurone. Dr. G. Pampiglione, Dept. Clinical Neurophysiology, Hospital for Sick Children, Lecturer Institute of Child Health, University of London. Dr. J. A. Simpson, Neurology Unit, Northern General Hospital, and University Department of Neurology, Edinburgh. ��,. ,r" . 7/ Editor-imChief E L E C T R O E N C E p H A LO G R A p H Y Montreal Neurological Institute 3801 University Street Montreal 2' Canada AND HERBERT H. JASPER CLINICAL Editorial Assistant Montreal IItlleurological Institute 3801 niversity Street “m“l 2. R' S. SCHWAB . Massachusetts General Hospital Boston 14. Mass” U.S.A. H. FISCHGOLD 9 ans “élP‘FQ‘” . rance l NEUROPHYSIOLOGY PIERRE GLOOR M Associate Editors Clinical and Laboratory Notes can“ d ° . An International )ournal European Office Managing Editors W. STORM VAN LEBUWEN OTTO MAGNUS THE E.E.G. JOURNAL Aid. Electro-Neurologie Academisch Ziekenhuis Leiden, Holland. StreEt Montreal 2' Canada . 3801 univerSity my 6 , 1959 a Technical Notes _H. {WM 3,1111%??? D.lVlSlon o e rca ec romcs College of Medicine Iowa City. Iowa. LI.S.A. F. BUCHTHAL Universitetets Izeurofysiologiske Institut Copen aaen. Denmark _ _ Index and Review of Literature C. E. HENRY Institute of Living 200 Retreat Avenue Hartford, Conn., U.S.A. Dr. Max Fink, Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L. N. Y. Dear Dr. Fink: I., - Effect of Anticholinergic Compounds on Post Behavior of Psychiatric Patients Convulsive I am pleased to inform you that the above manuscript has been reviewed by members of our Editorial Board and recommended for publication with some revision. < .. ”by/finwfilw... l , Re: MS 981 EEG & In the first place, I am sorry to have to ask you to condense the manuscript to about two thirds of its present size, since we have had to institute a more stringent regulation regarding the length of manuscripts, due to an excessive amount of material for publication. I should think that this condensation could well be made in your study by reducing the length of your discussion and trimming up descriptions in places where elaboration of drug action is perhaps not necessary, as such information may well be available in current pharmacological literature. also that you consider alternative hypotheIt is recommended modes and of action. Reference to the work by Aird, other possible see; on Cerebro-vascular Permeability, to be found in the Archives of 1956, the Journal of Nervous and Mental Disease of 1956, the Archives of 1958 and the Journal of Neurosurgery of 1952 might be worthwhile. Your synaptic theory would be stronger if it was not over-emphasized and made clear that it is only a tentative hypotheses throughout, perhaps particularly in the conclusions where it should be quite clear that your statements are hypothetical rather than proven, since the relationship between the EEG patterns and synaptic activity is a very tenuous one and may, at times be inverted. We also would like to have some legends for your illustrations make them to clear and independent of the text. Official organ of the International Federation of Societies for Electroencephalography and Clinical Neurophysiology, Inc. �ELECTROENCEPHALOGRAPHY Editor—in-Chief HERBERT H. JASPER Montreal Neurological Institute 3801 University Street Montreal 2. Canada R. S. SCHWAB Massachusetts General Hospital Boston 14. Mass.. U.S.A. AND C LI N I C A L Editorial Assistant H. FISCHGOLD NEUROPHYSIOLOGY PIERRE GLOOR Montreal Neurological Institute 3801 University Street Montreal 2. Canada H. W. SHIPTON THE EEG. JOURNAL Division of Medical Electronics College of Medicine Iowa City, Iowa. U.S.A. F. BUCHTHAL Universitetets Neurofysiologiske Institut Copenhagen. Denmark 3801 University Street. Montreal 2, Canada Index and Review of Literature EurOpean Office Managing Editors OTTO MAGNUS Afd. Electro-Neurologie Academisch Ziekenhuis Leiden, Holland. 1 rue Lu Cases Paris VII. France Technical Notes An International Iournal W. STORM VAN LEEUWEN Associate Editors Clinical and Laboratory Notes C. E. HENRY Institute of Living 200 Retreat Avenue Hartford, Conn.. U.S.A. _ 2 _ to your illustrations, we compliment you on their clarity and clean presentation; but there is some question as to whether they are all needed to make your points. If you can find some way of reducing their number to enable further condensation of your presentation, it would be adWith regard visable. sorry to cause you this extra trouble with your manusa splendid piece of work; but we feel that due to our own publication problems, and for the benefit of the clarity and conciseness of your presentation, the above alterations would be advisable. cript, which I am is obviously Yours sincerely, / Wt Herbert H. Ja Editor-in-Ch' f e rmrx HHJ/nb Official organ of the International Federation of Societies for Electroencephalography and Clinical Neurophysiology. Inc. �lurch 9, 1959. the Editor, EEG Journal, 3801 University Street, Hentranl, 2, Clnldl. Dear Dr. Jasper: I :1 enclosing a copy of a report entitled Effect of Anticholinargic Compounds on PostOonvulaivc EEG tad Behavior of Psychiatric Patients“ for your consideration for publication in the EEG Journal. Ran: thanks for yam: consideratiun. “The Sincortly yours, m Junk, 31:33 14.». �Hay 20, 1959. Dr. Herbert H. The EEG 3801 Jasper, Editorain-Chier, Journal, University Street, Montreal, 2, censda. Re: as 981 Jasper: I as pleased.to return the enclosed manuscript which has been edited according to your suggestions. I found your comments and reoosnendatiens helpful and have been able to condense the manuscript oonsidersbly. I trust that it will still read intelligibly. Dear Dr. by I have reduced the nnnber of illustrations 1958 the since the tee diethasine deleting cots, report has adequate pictures. I have also taken out one each or the piperidylbensilate and atropine figures, leasing but six figures for the final manuscript. Legends for each of the illustrations are eppended after the rersr~ CBCOEe I had seas difficulty in encespassing the obsersetiens or iird in this report, since he has not attempted a generalisation of nenrophyeiologic change and behavior. As I interpret his studies, he has observed changes in distribution of large molecules in spinal fluid after convulsive therapy. This observation say or say not be consistent with changes in cholinergic, adrenerxio or synaptic relationships but in no wise excludes the concoaitsnt changes suggested by our studies. In any case, I have screed that the synaptic theory has been rather strongly pot and have modified the language considerably, including what I believe is a relevant reference to iird's studies. Except for the hypotheses suggested by Roth and Blett, which I believe are consistent with the suggestions or this report I know or no other systeaatio atteapt to relate nenrophysiologic and behavior changes after convulsive therapy. I would be pleased to include such studies. �Dr. Earhart H. and Jaipur, (Contd) #2 I an grateful for your vary kind caaoidcratioa nest £hut¢htrul criticism. I stunt that this copy a: the unnuseript any aunt with your approv:1. Sincoruly yours, an aran Fink, rm. �Anticholinergic Hellucinogene and Post Convaleive' EEG From and Behavior the Department of Experimental Psychiatry, Hillside Hoepitel, Glen Oaks, L.I., N.I. Aided, in part, by grant M~927 and HY~2092 of the National Institute of Mental Health, National Institutes of Health, 0.8. Public Health Service. Read at the VII: 1/59 - American EEG EEG Society, Atlantic City, June, 1958. �Anticholinergic Hellucinogens and Post Convuleive EEG and Behavior In 1956 Ulett and Johnson ( ) reported that atropine and scopolanine blocked the eppesranee ot the high voltege activity usually induced by convulsive therapy. that the dose of atropine necessary to affect the They EEG delta also noted EEG was such es to be associated with unpleasant systemic effects. Reports by Jenkner compound & Lechner ( ) describing diethaeine es en enticholinergio with potent neurologic but minimal systemic effects led us to undertake studies using this compound ( similar to those of Ulett and Johnson ); and these observations, in turn, led to an investigation of other experimental anticholinergic agents. It is the purpose of this report to describe clinical and electro- encephalographic observations incident to the intravenous administrao tion of various anticholinergic agents in psychiatric patients at verious stages of convulsive therapy and to relate these observations to hypotheses concerning the node of action of convulsive therapy ( ) and of exogenous hellucinogene ( ). �-2SUBJECTS AND METHOD: subjects were consecutive referrals for convulsive Our therapy in an open ward volunhry psychiatric hospital. While varying numbers of subjects have been studied for each compound, subjects in 106 experiments have been essayed. 88 Iron 18 Agesranged to 67 years, and diagnoses include schizophrenic reactions, manioudepressive and involutional depressive psychoses. Patients have been studied at various stages of the treatnent process. EEG The observations were laboratory, using a made standard 8 in acute experiments in the channel EEG recorder and needle electrodes applied in 17 lead placements following Strauss 33_5l ( ). In each experiment, the compound under study was administered intravenously at a set rate per minute, until clinical behavioral or electrographic changes were observed. have been atropine. diethasine, Each is a Win~22§9, The compounds studied benactysine, JB-318, JB-336, and potent enticholinergic agent in vitro. Diethasine (diethylaminoethylwxwdibensoparathiazine), for example, induces nydriasis end hypotension, suppresses salivation and blocks the bradycardia, salivation and seizures of acetylcholine and �-3fluorophclphntc ). ( win-2299 (2-diethylnninoethyl cyclopcnty1-2, thienyl-glycolnte) end benactysine (2-diethy1nninocthy1 benzilnte) are synthetic nnticholinergic agents with potent central neurologic effects nininal peripheral systemic effects and cnd JB~336 two ). Diethazine 175-250 ninnte for ). JBnBlB 2 to of a recent series of synthetic antichclinergic central potency compounds or high total of , (N-ethyl-3~piporidy1benzilatc, X-nethy1o3~piperidy1~ bennilcto) are ( ( was mgm; and high administered at hallucinogenic activity 25 mgm. Win-2299 and benactyzine 5 mgm.; and per minute for a at 0.5 mgm. JB-318, JB~336, and atropine :31. per minute for 1.2 to h.0 mgm. at per O.h �OBSERVATIONS: (a) Diethaeine: As previously reported administration of diethacine in 15 ), the ( patiente prior to convulsive therapy resulted in a decrease in voltages and a deaynchronisation of all frequencies. Prevailing prominent. instances, symmetric In some activity appeared, temporal leede. rhythmic patterns beoane leee most prominent in the The low voltage 6;? cps frontal and anterior alpha frequency fies not altered, but the build-up in voltage and the slower frequencies induced by hyper- ventilation vere blocked (Fig. 1). -Q-‘-Fig. 1 UUUUU Q-flO-u-n--In 25 patients during convulsive therapy, with varying degrees of induced high voltage delta activity significant decrease both in voltage slow wave hSfi neon activity. From an and in 20%. ) there was a per cent time of average per cent tine delta of in the {route-occipital leads, there per cent time or ( was a Both random and reduction to a burst delta �-5- activity diminished became prominent. slow wave activity increase in per cent time and voltage of The on voltage alpha and beta frequencies hyperventilation was no longer apparent. clectrographic effects appeared during drug administration These persisted for and and low one to five hours (Fig. 2). ‘fl’--“---yig. 2 fi‘-‘~“---Concurrent with those electrographic effects, distinctive systemic effect was an and S The observed initial systemic episode of coughing and the occasional spontaneous complaint of dry mouth. by behavioral changes. we to 10 per cent. Skin remained dry and-heart This increase was rate increased rarely associated by pron cordial awareness. Baring the period of observation pupils were not altered, and responded pronptly to light and near vision. were There occasional complaints of abdominal griping. These effects, however, were generally or behavioral. less prominent than the electrographic �-6. Beheviorelly, patients became more irritable and restless. They became tense end excited, end it use difficult to neintein eyelid closure. They complained of feelings of unreslity and of dysthesias of the extremities. Visual illusory phenomena and delusional thoughts about their illness, the setting or the test procedure or the examiner's identity were also reported. were cherecteristic in behavior. chenges in lenguege There sssocieted with this change Syntectic language patterns ( altered in ) were 1 fashion opposite to that previously described for amobarbitel ( ) so node and that verbal denial, minimization, cliches, third person past tense became less prominent. nese of speech, measured by dyadic TTR, The degree of repetitive- decreased )whieh ( eltered opposite to that described for convulsive therapy (b) Win-2299: Reports by Pennes enticholinergic men ( ) compound, Uin~2299, induced led to this next study. 0n that an is ( en ). eXperinentel excitetory states in intravenous edninistretion of 2—5 n3n., both elsctrogrephic end behavioral effects similar to diethesine were observed. In five petients without EEG slow were �-7- ectivity, deeynohroniaetion of frequencies and a decrease in voltages were noted in four (Fig. 3). -‘h‘-----‘ ‘-0-----~~ In 11 patients with high voltage delta activity there wee a decrease in amplitude and per cent time or slow wave activity with an increase in alpha and beta frequencies. The noun cent tine delta activity dropped from (Fig. h). 50% to 23% per ‘—-~..—“--‘ Fig. h -~--~-~-“Associated with these electrographie effects were minimal systemic effects but prominent clinical patterns of restlessness and excitement. Patients became fearful and tense. Visual eeneetione were reported and in three subjects, delusional eleboretiene about their hoepitel experience were prominent. These beheviorel chengee Appeared during drug administration or within ten ninetel, end disappeered, at theee doeege levels, within two to three hours. �-8Reports that beneetyzine induced Benectzzine: (C) deeynchronizeticn ( and ) EEG its structural similarity both to diethanine end Win-2299 led to our testing of this compound. Intrevenoue adminiatretion in 12 subjects elicited similar clinical end electrogrephic patterns. Both in the well modulated alpha record and in the recerd with high voltage delta activity, deeynchronieetion wee prompt. Delta activity decreased from a teen per cent time of 39% to 16% in subjects (Figs. 5, 6). 8 n--fi-¢-----Figs. 5, 6 ”0.“--“u-fi'flfiu- These electrcgraphic patterns were again accompanied by clinical restlessness, irritability tree recording wee here difficult. delusional thoughte seen with the noted et these dceege levels. orienteticn ( wee an excitement. Artifact- The illusory eeneeticne initiel compounds were and not In patients with nenifeet die- end language changes ), however, there end associated with convulsive therepy alerting petterne, as noted with diethezine. and a reversal cf the language �-9(d) Piperioylbensilstesz Following recent reports by Abood ( ) that verious piperidylbensilates both manifested cnticholinerzic activity tested and induced two of hallucinations in psychiatric subjects, these, JB-318 end JB~336 in 2h subjects. we The electrographic patterns were identical to these other experimental Onset of desynchronizetion was during coupounds; injection or within 15 minutes and persisted for one to four hours (Fig. 7, 8). .n...‘..“... Figs. 7, 8 ---0------uIn each instance in which desynchronizetion was observed, restlessness and clinical excitement, illusory and hallucinatory activity iwere noted, and were concurrent with the electrogrsphic changes. In two instances the beheviorel chenges were halted by the subsequent intravenous edninistretion of chlorpronesine. (e) itrogine: Continuing our study of enticholinergic compounds, we administered atropine intravenously inlh subjects, in doseges of 0.8 to h.0 ngn. Systemic effects were prominent during the iniection with increased respiratory rate, pellor, dry skin end dry mouth, precordiel complaints and nerked techycerdie �-10- (Pig. 9). Subjects became restless and fearful and recording became and the difficult. Within ten minutes these symptoms subsided subjects became drowsy and relaxed. In six subjects without delta activity} no change in pattern was seen during drug administration or for minutes thereafter. During the period of voltages and ninisal desynchronisetion was no was EEG 10—20 lassitnde, decreased observed, but there significant difference in per cent tine delta. Fig. 9 -fi.--‘.& In subjects with delta activity, there was an apparent initial decrease in voltage and per cent time of such activity during the first ten minutes after administration, followed by a return to original values during the period of quietude. period were the changes significant (Fig. 10). “-~-“---~ In neither �-11DISGUSSIOH: Various experinentel compounds with measurable enti— cholinergie activity have thus been shown to have similar electrographic and behavioral effects. Electrogrephicslly, each agent induces a desynchronizstion of frequencies and s in decrease Ind voltages, which is most prominent in subjects with delta activity following therapeutically induced convulsions. Beheviorally, these electrogrsphic patterns are associated with stimulating, excitstory, illusory and hallucinatory ectivity. To e lesser degree, nininsl systemic heart rate, sslivetion, sweating letter systenic effects ere and changes in ptpil are noted. more prominent in These patients given intravenous atropine under sinilsr experimental conditions. These observstinns can be relsted to theories of the node of action of convulsive therapy and the basis for the induced slow were activity; to concepts of the besis of experimentally induced hallucinations; and to the conflicting reports of the effects of atropine on nervous ectivity. �-12- (a) Convnlsive therapyuprocees: In earlier studies we indicated that the develcpnent of high voltage slow wave activity was the neurophysiologic correlate of behavioral change in convulsive therapy, and a necessary, though not eufficient, condition for clinical improvement ( ). During the past ten years, numerous authors including Bernstein, Tower and chachern, Ward, Sachs and Huge have reported similarities in the biochenical changes of the central nervous system in convulsive therapy to that seen in crania— cerebral trauna ( ). They observed an increase in cholinergic activity, nanirested by an elevation of free acetylcholine and pseudocholineaterase in the spinal fluid, and associated with high voltage slow wave activity. Sinilar high voltage slow wave activity has been reported after the administration of the cholinesterase blocking agent (di-isoprcpylfluorophoephate),I with attendant increase in cholinergic activity. In addition, the increase in central nervous system cholitergic activity by topical administration of acetylcholine induces high voltage ~ bursts and spike activity ( ). blocking of the behavioral and electrographic effects of convulsive therapy by the antichelinergic actiyity of atropine and scopolanine (Ulett and Johnson) are replicated by these observations on diethazine, Win-2299, benactyzine and the piperidylbensilates. The potent anticholinergic activity or The cent!!! each of these compounds (with apparent predominant locus or activity in the central nervous system) supports the �suggestions that the biochenioal basis for the induced activity of convulsive therapy results slow wave from an increased level of central acetylcholine~cholinestereos activity; While these observations demonstrate that anti— choliuergic compounds are effective in reducing slow activity, reports of other compounds with have also appeared. ( ), nescaline similar effects Agents such as anphetanine (Bensedrine) ), lysergic Acid diethylanide“ ( wave and diphenhydrasine (Benedryl) convulsive slow wave ectivity. ( ) ( ) also reduce poet~ These compounds are primarily synpathoniuetio and antihistaminic in pharmacologio aytivity, yet each has excitstory and stimulating effects ( and , , , ). The on behavior relations of these various anticholinergic synpathoninetic agents say be related within constructs of synaptic activity. observations have been confirmed in this laboratory. Intravenous adainistration of So~1oo genus LSD in subjects withoutldelta activity induced EEG desynchronisation one to two hours after administration. In subjects with delta activity there is a marked reduction of delta with the re-essertion of proainont, high voltage alpha frequencies. These �~1h- In a study or the effects or various agents on the EEG and the behavior of unaneethetised cats with chronic implanted electrodes, Bradley and llkes ( ) postulsted the existence of two, or possibly three, types of interacting chenoreeponsive receptors within the central nervous system: cholinergie, nonucholinergic susceptible to anphetaeine, nonucholinergic susceptible to Harassi and Hart pathways in the on evoked ( ) LSD eXplondng and tryptaminie derivatives. intercortical (transcellosal) cat, described the effects of various potentials on end oonpounds direct electrical stinulation. They postulated the presence or two chenoreceptive potentialities of the synapse - cholinergic and edrenergic - with opposing stimulatory and inhibitory ectien. been described by Hoolley ( Similar constructs have ), Evarts ( ( ) and Sherwood ). According to these models, the administration of snticholinerzic agents, or of sympathoninetic agents, results in equivalent synaptic electrical effects, and nresnnebly, similar electrogrsphic and snpethnine, nescaline end behavioral effects. LSD Thus adrenaline, inhibit the level of electrical �-15- activity at synapses as effectively as the blocking or inactivation of acetylcholine by atropine end other enti~ cholinergic compounds. In the light of these scggesticns, the present eXperinents permit a mere specific hypothesis regarding the phernacclcgic basis cf the convulsive therapy process. Repeated induced convulsions lead to an increase in the synaptic or xyxplttl cholinergic activity which voltage slow wave activity.; electrical activity (and of is reflected in surface electrodes level ) as angnented high Administration at anticholinergic agents reduces the level of synaptic activity, resulting in a decrease in the manifest cortical electrical activity to precenvulsive levels. may also achieve the Administration or synpathcmisetic agents same electrical effects, not by eltering the level of cholinergic activity but, by increasing the level of adrenergic activity. The nsnirest slow wave prominent and so persistent in the waking state ( ) nay thus be viewed as a EEG activity, so or the pcst~seisure persistent alteretion in synaptic transmission activity or large numbers of cells of the �central nervous system. is seen in the ready ( ) and The delicate nature or this balance reversibility with alerting ( ), tine the wide variety of pharmacologic agents noted here. Repeated induced convulsions may thus be described as a device to create biochemical changes in the brain for their resulting behavioral effects. view a Such/formulation that convulsive therapy is process ( a is consistent with the nonuspecifio therapeutic ). the initial suggestion ( ) basis for the convulsive therapy process that the pharaaeologio may lie in an alteration in acetylcholine-oholinesterase relationshipsban thus be focused on the alteration in the level of synaptic activity. In this regard, the observation that diphenhydranine, primarily an anti-histaminic agent, also reduces slow induced convulsions ( ), and the wave activity of observations by Sachs ( ) that increased amounts or serotinin appear in the spinal fluid after convulsions suggest that this image in convulsive therapy is oversimplified. ’ 0; synaptie activity Further studies or the effects or various drugs on the postcseiaure electrical ‘ �activity are warranted. (b) Iearophyeiolggy or hallucinogenic These EEG activity; observations of anticholinergic compounds delta activity also related to concepts of eXperinental may be hallucinogenic activity. Each of these compounds induced excitatory behavior including illusory and Here, too, synaptic models phenomena.* on hallucinatory may be applicable. Synpathoninetic egents, ae mesoaline, LSD, and amphetamine, and anticholinergic agents as those described here, are equally potent hallucinogens. i necrophareacologic basis for such behavior nay be characterised as an alteration in the level of synaptic activity in the direction of increased inhibition (decreased transmission) of stimuli. The clinical efficacy hallucinatory activity biochemical level. ester: ( The may of convulcite therapy in modifying thus In the doses used, higher dosage ( A in alterations at this effects or hallucinogenic blocking agents ), as chlorpronarine for benactysine. lie and reserpine, on EEG electrical hallucinatory phenomena were not observed report of such activity was reported at ). �~18~ ectivity are consistent with EEG hypersynchrony in non effects of LSD end LSD and such a View. ), block the ( nesculine ), ( and Both compounds induce EEG desynchronizetion in animal studies, block neeceline behavioral and electrographic effects ); ( Chlorpronaoine was found equally potent in abutting the excitatory activity of these experimental anticholinergics in these studies. (c) Relation to atropine: Comparison of the oystenic and central effects or these experimental anticholinergic conponnda with atropine reveals significant differences. Extensive experience with atropine at physiologic end toxic levels in men indicate that the predominant Initial effects are focused at peripheral nervous structures. bradycnrdia, followed by marked tachycardia, loss of sweating and salivation, papillary dilation, intestinal relaxation and decreased motility are amongst the effects at physiologic (O.2~l.2) dodagee. At higher dosages (2-5 mg), the central nervous irritability, disorientation, oyeton effects of ataxia, delirinn ( may be observed ( ), anonnta ranging Iron ). In the atropine 32 to 212 some end studies 33:. injected intra- �.19nuacularly into psychiatric petiente resulted in the following ( sequence )t ”There is an induction period or 15 to minutes 20 after adninietretion characterised by restlessness, occasionally mild exoitenent, confusion, and at times nausea and vomiting. This proceeds, smoothly and predictably, to muscular inooordinetion, ataxia, weakness, vertigo and difficulty in articulation. An acute brain syndrome with memory disturbance, disorientation, elouded consciousness, illusions and most frequently visual hallucinations vergee into delirium come... ' Thus and rapidly proceeds to central nervous system effects are preoedodhnd accompanied by marked peripheral effects. In contrast, these experimental enticholinergic agents, in equivalent dosage ranges, manifest and lurked central. The are observed early and effecto may on little peripheral effects the central nervous system continue for extensive periods and in higher dosages with minimal peripheral nervous effects. It ie within this context of central tarsus peripheral predominant sets or activity that the apparent discrepant EEG observations of the etteete of atropine (in inducing elow wave �.20- activity) these experimental enticholinergic compounds and be reconciled. The variable EEG effects, like the verieble behavioral effects are dose related. adminietering l~3 mg/Kg may Weeeae exist 33‘3l ( ) atropine in curarized cats and monkeys using O.h to 1.2 mg/kg in curerized and Funderburk and Case ( ) cats, produced high voltage slow wave activity. Wikler ( ) reported that 7.2 mg/kg atropine in unanosthetized, ancnrarized patterns strikingly similar to dogs produced "epindle slow wave" sleep. 'Rinaldi and Himwioh ( ) reported that atropine in doeee of 0.5 to 2.0'mg/kg in cnrarized rabbits exaggerated patterns and inhibited the electing of the EEG EEG sleep to various peripheral stimuli. _Sinilar observations have been observed by Bradley and Bikes ( ) in the conscious oat. In each instance the dosage of atropine varied from 0.5 g 3 mg/kg- a range roughly comparable to the massive dosages need in atropine coma therapy. Yet what of the electrographie eitects in lower In our observations, the EEG effects of dosage? low dosages of intravenous atropine (006‘ .06 ng/kg) were minimal. Similar obeervatione have been reported by Danielopelie, Guirgee end Drooen �021-: ( ) who specifically releted the effects to dosage level. EEG with high doeeges of atropine (h-B ng/kg) in rabbits einiler high voltage nixed slow and feet (21-30 ope) activity was observed, while with low deeegee (2h~.8 ng/kg) the original rapid rhythms remained unehenged. These authors thus suggested ! flat atropinegs effects were multiple end doee determined, and related the observations to similar findings with regerd to EEG heart rate. Denielopelu atropine slow down ( ( observed that small doses of cardiac rhythm nine while larger doses cenee eexeklteiien acceleration. been confirmed ) These obeervetiene have recently ). Thus, while oonsidereble speculation as to central neurophysiology he: been related to observations with atropine, these observations provide e special case of atropine effects. The entiohelinergic activity, so prominently established in observations in vitroI end in the peripheral nervoue system, may not be the effective physiologic activity in the large doses neeeeee y to reach central structure. It is poeeible that the experimentel entichelinergic compounds used in the present studies �-22protfie more suitable experimental tools fer the elucidation of central neurophysiologic nativity than atropine. In part, these differences may be related to difference- in etrnctnrel chemistry. Each of these experimental cenponnde contain a tertiary canine linkage, while atropine (and ecopolemine) quaternary centnin a qxxtx:xznx linkage. Such differences may be clearly observed in the structure~ectivity relationships or the piperidyl- bennilatee ). ( While Hwnethyl-B-piperidylbenzilete and Nsethyla 3-piperidxlbeneilate have potent enticholinergic and hallucinogenic potency, Hedinethyl~3~piperidylbeneilete - the quaternary conpennd - has considerable in vitro anticholinergic activity, and no hallucinogenic property. The significance of tertiary amine linkage for central neurophysiolcgic effect: he: been repeatedly affirmed by numerous observers, and neat recently by Pennel Denber; ( ), Theee e Hake ( ) and Plodnerk ( ). structure~aetivity relations lend theneelves to re-eveluation or studies or creniccerebrel trenne Ward's ( ) ( and epilepsy. reports orfithe efficacy of high doses of etrepine in altering the clinical manifestations of head trauma indicated ), �-23- that effective dose: brought with Thu them severe systemic effects. failure of the oxtohaive studies a: the efficacy or atropinc and soopalunine in epilepsy ( ) any be related to : failure of these quaternary compounds to reach the central nervous syntax in adequate quantity. It would noun advisable, therefore, to, ropoat those studies utilizing such more potent, more centrally specific, antieholinorgic canpaunds as used in the eXporixonts reported here. �lj MS 981 W Mel 3;..." EFFECT OF ANTICHOLINERGIC COMPOUNDS EEG AND BEHAVIOR OF Max (Received ON POST CONVULSIVE PSYCHIATRIC PATIENTS Fink M.D. for publication: march 11, 1959) v v-u-u. From the Department of Experimental Psychiatry, Hillside Hospital, L.I., Glen Oaks, Aided, in Institute N.Y. M-927 and MY-2092 of the National Health, National Institutes of Health, by grants part, Mental of U.S. Public Health Service. Read at the American W-EEG 3§5357k? EEG Society, Atlantic City, June, 1958. �MS 981 ANTICHOLINERGIC COMPOUNDS AND POST CONVULSIVE EEG �Effect of Anticholinergic EEG and Behavior of Compounds on Post Convulsive Psychiatric Patients Mcsfl—vsflswfi kg 76.: gagifisignificance of high voltage EEG delta activity in the convulsive therapy process (Roth gt_gl, 1951, 1957; report that this delta activity was blocked by the administration of-eniiehnlinersic ealfiifiiaa atropine and scopolamine (Ulett and Johnson, 1957) provided the basis for these studies. As there were attendant unpleasant systemic effects with the administration of these agents, reports describing diethazine as an anticholinergic Fink and Kahn, 1957) and the with potent neurologic but minimal systemic effects (Jenkner and Lechner, 1955; Lechner, 1956) led us to undertake studies similar to those of Ulett and Johnson using this compound (Fink, 1958). “@bservations with compound diethazine led to the investigation of other experimental anticholinergic agents. This report describes clinical and electroencephalographic observations incident to the intravenous administration of various anticholinergic agents in psychiatric patients at various stages of convulsive therapy and relates the observations to hypotheses concerning the mode of action of convulsive therapy and of hallucinogens. �SUBJECTS AND METHOD: subjects were ninety psychiatric patients referred for convulsive therapy. Ages ranged from 18 to 67 years, and diagnoses included amcaai-t!=s£ schizophrenic The reactions‘ and manic-depressive and involutional—depressive varied number of subjects were studied for each compound for a total of 107 observations. Patients have been observed at various stages of the treatment process. The observations were made in the EEG laboratory, using a standard 8 channel EEG recorder and needle electrodes applied in 17 lead placements following Strauss gt_§l (1952). In each trial, the compound under study was administered intravenously at a set rate per minute until clinical behavior or electrographic changes were observed «a -'w ‘M psychoses. Www'” mam. "4”,...“ A." A Hm , ‘5 was”“My HM A r-m new M, -J:,M-,_.m,..\. "was... “A...“ i, ,1“. The ine, JB3l8 JB~336, and atrOpine.{ Each is a potent “p' a: icholinergic agent in vitro. Diethazine (lgflgéwdaetfiyl- \\ ‘H‘benact v. __~ ‘ (2-diethylamipdéthyl fignzilate) are synthetic anticholinergic '- 3‘ .h u k‘ ‘ ‘ �W [M fiW/émgw (m w 1,?de //h)1 (Maw (WW. a /¢‘¢¢) ’ f flux-322.497“ f E (W . 7’6’33“ wit/4&4, xiJ'C) 7 I (W fig?) 17”} M .7313”: W �agents with potent neurologic effects and minimal peripheral P’w ‘nwV""' systemic effects W JB- 318 and JB~336(N~et§gl~3flwiperidylbenzilafe N-methyl-~3two of a new series of syntfiébiq piperidylbenzilatafl (Pennes and Hocn%wl9§7?“§:c9bson, 1955) """ ‘m‘,’ anticholiHErgic compounds w'th a»? éfimm‘ distinct hallucinogenic 1958). et a1, g Diethazine administered at _activity __ ’ total (Abood was mac?“ 25 mg per minute for 2.5-5.0 mg/kg); Win-2299 and mg per minute for 2 to 5 mg (0.020.15 mg/kg); and JB-318, JB-336, and atropine at O.h mg per minute for 1.2 to h.o mg (0.0l~0.10 mg/kg). of 175-250 benactyzine at 0.5 a mg ( �OBSERVATIONS: administration of diethazine in fifteen patients prior to convulsive therapy resulted in a decrease in EEG voltages and a desynchronization of all frequencies,€¥$§3;=;$§8%. Prevailing rhythmic (a) Diethazine: patterns became The less pronounced. In symmetric low voltage 6-? cps most apparent in W frontal and some activity appeared and was _ (F3416 anterior temporal leads. ammmmmwmmm~.w fequencyas not send, ”Mm“ Thz“‘;“i”;“n. instances, ,, .1. >u-L—‘7‘? mm»- ,.... .14.“ mm“. We they”; In twenty~five patients with varying degrees of induced high voltage delta activity during convulsive therapy (Fink and Kahn, 1957), there was a significant decrease in voltage and in per cent time of slow wave activity. From an average-pal—Icnt-ttne delta of h5% in the front-occipital leads, there was a reduction to a mean uggzggntntine of 20%. Both random and burst delta activity voltage alpha and beta frequencies became more prominent. The usual increase in per cent time and in voltage of slow wave activity with hyperventilation sans-no diminished. Low 51, \} "it; 2’ lfJ?e>» �-5longer apparent. These electrographic effects appeared during drug administration and persisted for one to five hours Mfifl (Fun/t} xqs’f) Concurrent with these electrographic effects, we observed distinctive systemic and behavioral changes. The initial systemic effects were episodes of coughing and complaints of dryness of the mouth. Skin remained dry and the heart rate increased by S to 10 per cent. This increase was rarely noted by the subject, and was not accompanied by ,n» precordial distress. -9ar&ng—tho—peried~e£w- , Gems/haflhv observationnfihere was no change in pupillary size, and their response to light was prompt. There were occasional complaints of abdominal griping. Ihfiégweffects were generally less prominent than the electrographic or behavioral. Behaviorally, patients became irritable, restless, tense and excited, and it was difficult to maintain eyelid closure. They complained of feelings of unreality and of tingling, weakness and heaviness of the extremities. Complaints that colors were pale or more intense, halos about lights and changing shadows were accompanied by delusional thoughts about their illness, the setting of the test procedure or the examiner's identity.4p . AM �-7(b) Win-2299: The report by Pennes and Koch (1957) that Win-2299r—aaother_axparamoatalwaatieholinergée~eempound1 induced illusory and hallucinatory states in man, led to this next study. 0n intravenous administration of Win-2299, both electrographic and behavioral effects similar to diethazine were observed. In five patients without EEG slow wave activity, desynchronization of frequencies a decrease in and voltages were noted in four;éi§igggg; {Vfgf / ), In eleven patients with high voltage delta activity there was a decrease in amplitude and per cent time of slow wave activity with an increase in the per cent time of alpha and beta frequencies. dropped from 50% to 23% The mean pea—eoat—tine (Fig.1;3. Fig.3 delta activity 3" Associated with these electrographic effects were clinical patterns of restlessness and excitement, and effects. Patients became fearful and tense. Visual illusory sensations were reported and were minimal systemic associated in these subjects with delusional elaborations �-3about their hospital experience. Excitement was accompanied by ideas of reference, and in two subjects, intravenous chlorpromazine was administered to halt this process. These behavioral changes appeared during drug administration or within ten minutes, and disappeared within two to three hours. effects were slight. There were neither cough nor respiratory distress. Heart rate was unaffected except in patients who became overtly excited Systemic fearful, in and whom excitement period. on ' tachycardia appeared during this Dryness of the mouth was reported only direct inquiry. (c) Benactyzine: Reports that benactyzine induced EEG desynchronization (Coady and Jewesbury, 1956), its anticholinergic nature, and the structural similarity to diethazine and to Win-2299 led to our testing of this compound. Intravenous administration in 12 subjects elicited similar clinical and electrographic patterns. Both in the well modulated alpha record and in the record with high voltage delta activity, desynchronization was prompt. Delta activity decreased in 8 subjects from a mean pti—OUI$ time of Wfifi/d} 39% to 16% �-9These electrographic patterns were again accompanied clinical restlessness, irritability and excitement. Artifact-free recording was more difficult. The illusory by sensations and delusional thoughts seen with the initial compounds were not noted at these dosage levels. Systemic effects were similar to Win-2299. (d) Piperidylbenzilates: Following recent reports by Abcod et a1 (1958) that various piperidylbenzilates with measurable anticholinergic activity induced hallucina- tions in paychiatric subjects, we tested JB-318 and JB-336 in 2h subjects. The electrographic patterns were identical with the other experimental anticholinergic compounds. —¥he— ur ng e njection or Waffles ync hroniza ti onA? ?- duufdtvthhfhfl within 15 minutes and persisted for one to four hours (Fig. 5: t). ‘ , Figs. 5f In each instance in which desynchronization was observed, clinical restlessness, excitement, illusory and hallucinatory activity were noted, and were concurrent with the electrographic changes. In two instances the behavioral changes were halted by the intravenous administration of chlorpromazine. �-10Considering the numerous reports (e) Atropine: that atropine induced EEG slow wave activity and clinical somnolence, we administered this anticholinergic agent intravenously in 15 subjects, in dosages of 0.8 to h.0 In six subjects without EEG delta mg (.01-.10 mg/kg). activity, there were no changes in EEG pattern during drug administration nor for 10-20 minutes thereafter. During a period of lassitude, decreased voltages, minimal desynchronization, and an increase in per cent time delta were noted. In subjects with delta activity, there was an apparent initial decrease in voltage and per cent time of such activity during the first ten minutes after administration, followed by a return to original values during the period of quietude. was» In neither period (@3925) were the changes significanta �-11- Systemic effects were prominent during the injection with increased respiratory rate, pallor, dry skin and dry mouth, precordial complaints and an increase in heart rate up to 100%. Subjects became restless and recording became difficult. Within ten minutes these symptoms subsided and the subjects became drowsy and relaxed. �-12- arious experimental compounds with measurable anticholinergic activity have been observed to have similar electrographic and behavioral effectsignmthnsematudiOOVM Electrographically, each agent induced a desynchronization of frecuencies and a decrease in voltages, which was most prominent in subjects with delta activity following convulsive therapy. Behaviorally, these electrographic patterns were associated with stimulating, excitatory, lesser degree, minimal systemic changes in heart rate, salivation and sweating were noted. These latter systemic effects were more prominent in patients given intravenous atropine under similar experimental conditions. These observations can be related to theories of the mode of action of convulsive therapy;and-ofirthevastS“fvr' illusory and hallucinatory activity. ‘thauaadnoedfiaiew—wamowaewévttyj To a to concepts of the basis of experimentally induced hallucinations; and to.thv reports of the effects of atropine on EEG patterns. (a) Convulsive therapy process: Earlier studies indicated that the development of high voltage slow wave activity was 4:; neurophysiologic correlate of behavioral change in convulsive therapy, and a necessary, though not sufficient, condition for clinical improvement (Fink and Kahn, 1957). In summarizing the observations of numerous �-13the relation of acetylcholine metabolism to 1;” 4o $vuuna andAconvulsions (Fink, central nervous system Ckxcxnurnsd'éjf 5L biochemical bootseinn the the 1958) it was suggested that induced EEG slow wave activity lay-fin an increased level of acetylcholine-cholinesterase activity of the central authors on nervous system. in the slow wave 1? present observations of tin alterations_ activity of convulsive therapy by these The experimental anticholinergic compounds are consistent with this suggestion. is indicated by reports of compounds with other biochemical activity also affecting slow wave activity in a similar fashion. Amphetamine That the problemis more complex gt_§l, 1951), mescaline (Merlis and Hunter, 1955; ‘Ib (Bente gt_§1, %§?b§i$ 1955), lysergic acid diethylamide ”iuuéig,snd diphenhydramine (Diaz-Guerrero et a1,1956) also reduced post-convulsive slow wave activity. In these reports, such a reduction was accompanied by excitatory and stimulating effects on behavior. These compounds, however, are primarily sympathomimetic and antihistaminic in pharmacologic activity and not anticholinergic. The similar effects of these diverse biochemical agents on electrographic patterns and amuauibusfi be behavior may rat-ind within theoretic on clinical (Lennox «K2~Kssrsr'6247 ‘fitfiix “fi’ constructs of synaptic activity;r— mm w The existence oftwo, or possibly three, Mypee cf interact~ 'AQ/ 1. m.“- ing chemo~re§pofisive receptors withinthd‘central ner::gg,system �/ (I W24: L M7? 5 ,7 v M/ ’46; MW w- M} Arm/a; Ail/”M Wag .- f �“Jamal-un- h awmh'auu: gnaw“WWW WU“we ' lead to a change in synaptic cholinergic activityywhésh—és— reflected:h11llhsurface electrodes as augusntsd high voltage slow wave activity. Administration of anticholinergic agenggijltenfl'synaptic activity, resulting in a decrease in the manifest cortical electrical activity to preconvulsive levels. Administration of sympathomimetic agents 3f-lg-‘Leja-‘fiieve/ the same electrical effectsr-s-s-t-by—ns4tssang—tha—1saol—sfrehoiénsrgss—sstinitanbat by increasing the level of adrenergic activity. The manifest slow wave A activity, so prominent and so persistent in thsffi::;ng£§;:& -ss«the—pust-setzure-statej may thus be viewed as tho resulttnf persistent alteration in the synaptic tssssméssésn activity of large numbers of cells of the central nervous system. The delicate nature of this balance is seen in the ready reversibility with alerting, time, and the wide ~qflra variety of pharmacologic agents.nntsdwhaner-m~m~"~"“ ’jifi/ér\:;> The consistent nature of these neurophysiologic observations all. makes an exclusively psychologic explanation of the mode of action of convulsive therapy less tenable. These studies are consistent, however, with the neurophysiologic-adaptive view of the convulsive therapy process which suggests that neurophysiOlogic chanazMs provide the substrate for alterations in all aspects of cligical behavior} fg’h" �Ma . ,W‘ w, .M Won/7w AC ,W W hyLWM MWMWM'W“ W 5 I414} 2‘5 Maxwu 4; ’ :73? (/ija; Z; W Wag a, WM7£ ILL-«44.1“ 04”), MLIMK W; ”W MW; “4344: a' WM W I a; a. L « �-17- we, of~the—oabaeetp"{fln type of behavioral alteration ts fisvwig dependent upon the type and degree of neurOphysiologic change, the personality of the subject and the expectations and tolerance of the milieu (Weinstein and Kahn, 1955; Fink and Kahn, 1957; Fink, 1957). (b) Neurophysiology of hallucinogenic activity: The effects of anticholinergic compounds on EEG and behavior may also be related to the understanding of experimental hallucinogenic activity. Each of these/tzzgfunds induced illusory excitatory behavior, including 4L phenomena. m Here, too, the synaptic and hallucinatory model] may be applicable. Sympathomimetic agents, as mescaline, LSD and described amphetamine, and anticholinergic agents as those here, are 01-‘3iv potent hallucinogens. A neuropharmacologic basis for such behavior may be characterized as an alteration in the level of synaptic activity in the direction of increased inhibition (decreased transmission) of stimuli. ‘The clinical efficacy of convulsive therapy in modifying hallucinatory activity may lie in alterations at this neurophysiologic level. . The effects of such hallucino- genic blocking agents as chlorpromazine and reserpine on EEG electrical activity are consistent with such a view. Both compounds induce EEG hypersynchrony in man (Bente and Itil, 19Sh, 1958) and block the EEG desynchronization effects of LSD and mescaline (Schwarz et al, 1955). �-19Chlorpromazine was found equally potent in aborting the excitatory activity of the experimental anticholinergic compounds in these studies. (0) Relation to atropine: Comparison of the systemic and neurologic effects of eXperimental anticholinergic with atropine reveals signi£ieaat differences.«av ax/Aaf compounds {pH/95 s:%bé§i£3§§§§2::ence with atropine at physiologic and toxic levels in man indicate that the predominant effects are focused at peripheral nervous structures. Initial bradycardia, followed,by tachycardia, loss of sweating and salivation, pupillary dilation, intestinal relaxation and decreased motility are amongst the effects at low (0.2-1.2 mg) dosages. At higher dosages (2-5 mg), the neurologic effects and delirium are of ataxia, irritability, disorientation, Mgr...“ observed (Goodman and Gilman, 1955). In atrop' e coma therapy, 7amounts ranging from 32 to 212 g injected int amuscularly into psychiat ic patients resul s in the fell wing sequence (Forrer and Miller, 1958): "Th re is an induc ion period of 15 to 20 minufes after adminis ration charactkrized by V mm:Wm..- ! 2 I . Jonfusion, and . restlessnessg ceaselonally mil excitement, at times naufca and rarely vo ting. This p oceeds, smoothly and predictably, to muscular coordination, ataxia, weakness, vertigo and ifficulty in artffulation. An cute brain syndrome wit. memory dis turbanhe, disorienta ion, clouded illusions and mtst frequently kisual hallucinaconsciousnesf, tions mergesa into delirium and§.:;rapid1y proceehs to coma. ..." I ‘ I ’ ; �-20.. Thus/central nervous system effects arevprecededwwv accompanied by marked peripheral effects?” contrast, the experimental anticholinergic agents in dosages sufficient for central nervous system effects manifest little peripheral activity. The central effects are observed early and may continue for extensive periods without gastrointestinal, cardiac or pupillary changes. It is within the context of the focus of activity and w. -din relation to dosage that the apparent discrepant EEG observations of the effects of atropine (in inducing slow wave activity) and these experimental anticholinergic In reconciled. Wescoe gt_al (l9h8) administering 1.0 to 3.0 mg/kg atropine in curarized cats and monkeys and Funderburk and Case (1951) using O.h to 1.2 mg/kg in curarized cats, observed high voltage EEG slow wave activity. Wikler (1952, 1957) reported that 7.2 mg/kg atropine on unanesthetized, uncurarized dogs produced "spindle slow wave" patterns at-ihiugiy similar to sleep. Rinaldi and Himwich (1955a, b) reported that atropine in doses of 0.5 to 2.0 mg/kg in curarized rabbits exaggerated EEG sleep patterns and inhibited the alerting of the EEG to unit-l: peripheral stimuli. Similar observations have been reported by compounds may be Bradley and Elkes (1953) in the conscious cat. In each instance the dosage of atropine varied from 0.5 to 7 mg/kg - a range roughly comparable to the dosages used in atropine (me'w‘ Md: We’rfrfg. “ma therapy! �: M 4% 1mg,» Jyyzmw f)”; r gag“; m mflfl/w 1:; @c‘jf jaw/(4,4,2... W a; 351,, fgflzfl, �-21'éoueraduuage? Auéf In thelzn;tudies, the ‘g’ flfimal EEG effects of low dosages of intravenous atropine (0.01 to 0.10 mg/kg) were minimalaasfi CMMHKM éfi, ifikbfi iconfirming similar observations by Verdeaux anglflgrfizw (195h) and by Danielopolu et al (1955)., Danielopolu et a1” Wmmwflwawmqum specifically related the EEG effects to dosage levelvfw” ith high dosages of atropine in rabbits ( h to flffig/kg) . W wa‘ianMu-‘rm‘m. -W«m««uw~w ~w-wwmw~wmmw .; m W. ..,..-..g., , m ,u . swan-bani" .twmi-mc”1; ~11.»- . man. ; they observed similar high voltage mixed slofifand fast activity, while with low dosage (.Zh t9 id mg/kg) the original apid rhythms remained hgphanged. These authors It fy~”' thus sugges d that atropinetg effects were multiple and“ related the EEG ob rvationgxtg similar findings with rega dfitfi heart rate. Danie ported earlier that s 11 doses of atropinesloqed cardiac rhythms while/larger dose caused acceleration. These dose determine ’ and cardiac observations have recentlyxbeen confirmed (Morton 232;; ‘ Thus, while considerable speculation as to central neurophysiology has been based on studies with atropine, té§LL——— special case of anticholinergic effects. The anticholinergic activity,—eo—pnonéaeatky established in observations in vitro and in the peripheral nervous system, may not be the effective physiologic activity in the large doses necessary to affect central such observations provide a �.. 2 2 - Th3’2xperimental compounds z:::=zm—the~preeontm the flflfigw provide more structures. s-‘bu-d‘éoo flow/M)“: udtuoédubéon of suitablewe} Wfor central neurophysiologic (anticholinergic) patterns than atropine] M, #AMcuu/eml AM» In part, these physiologic differences may be re to differences in structural chemistry. Each of the experimental compounds contains a tertiary amine linka e, while atropine contains a quaternary linkage. The e fect of structure on in vivo pharmacology may be clea y observed in the structure-activity relationships of e piperidyl- benzilates (Abood 22.21:.1953)' While -methyl-3-piperidylbenzilate and N-ethyl-B-piperidy enzilate have potent anticholinergic and hallucinoge \c-potency, N—dimethyl-B-piperidylbenzilate - the quate ary compound - has considerable in vitro anticholinergic tivity but no hallucinogenic property. nd Hoch (1957), Denber (1958), Naka (1958) and Flodmark i (1958). f_ _-‘_ , f - . in.a re-evaluation 05‘studies ,_”4 , 1 7 ,. _éwr of craniocerebral trauma and epilepsy. Ward's (1950) reports of the efficacy of high doses of atropine in altering the clinical manifestations of head trauma indicated that effective doses brought with �-23- effects. The failure of atropine to affect epilepsy may be related to the them severe systemic and scopolamine inability of these quota-unis compounds to reach the central nervous system in adequate quantity. It would seem advisable, therefore, to repeat these studies utilizing ardfiuf such mere-paten%7~more centrally speeésée..anticholinergic , compounds as used in the experiments reported here. �'Zh' SUMMARY: 1. EXperimental anticholinergic compounds (diethazine, Win-2299, benactyzine, JB-318 and JB—336), administered to psychiatric patients at various stages of convulsive therapy, were associated with: (a) desynchronization of EEG rhythms with a blocking of post-convulsive delta activity; (b) alerting, excitatory behavioral reaponse with illusory, delusional and hallucinatory ideation; and, (c) systemic effects of muscular weakness, dryness of the mouth, dry skin and tachycardia. electrographic behavioral and systemic effects were The concurrent. that an fl; 2. observations are consistent with the suggestion “faxmufaui These We!) thug,” ” ' of convulsive therapy'iilllllr.4fl increase in central nervous system cholinergic activity. 3. Observations that LSD, amphetamine, mescaline and diphenhydramine - synpathomimetic and also induce desynchronization, blocking of post convulsive EEG delta activity antihistaminic agents - and clinical excitatory activity support the suggestion that bUth-hhu behavioral and electrographic based on alterations in synaptic activity,, sis Patterns Increased synaptic activity (cholinergic, sympatholytic effects) we ,4 �-25- hypersynchronization, and clinical sedation and euphoria; while decreased synaptic activity (anticholinergic, sympathomimetic) is associated with EEG desynchronization and clinical excitatory and hallucinogenic is associated with EEG states. Discrepant observations with the-entéehottnergifi agent? atropine are related to significant differences inrfiéfvfifygw’ h. .thawnantzalMnenuensmsaatanmaiflactsmofimhighudeaagamainapinefl Re-assessment in_man_maxanataha4nninanil¥_anaiahnlinargis. of the role of anticholinergic agents in head trauma and seizure states is suggested. 5. These observations amplify the neurophysiologicadaptive hypothesis of the mode of action of convulsive therapy and of experimental hallucinogenic states. �ACKNOWLEDGEMENT: I Hannah {Efl grateful for the technical assistance of Mrs. Mosquera in EEG recording and analyses; and—to— am Supplies of the various pharmaceuticals were made freely available by Lakeside Laboratories (JB-318 and JB-336), Merck Sharpe & Dohme (benactyzine), Sandoz Pharmaceuticals (LSD-25), Sterling—Winthrop (Win-2299) and Smith, Kline & French Laboratories (diethazine, chlorpromazine) �:f/ébétp/g 04M¢MW71M£04¢ W, 2: wow f/éétdi./g.7 JAM/47 7249.; ’9‘” M MW «044ml. W,- m; {fJZ/ E.- 37I-370‘ �-27Abood, L.G., W4} “E:ZLE:D Ostfeld, A.M. and Biel, J. new group of A psychotomimetic agents. Proc. Soc. Exper. Biol. Med., 1958’ 21: hq'é‘h86o Bente, D. and Itil, T. Zfir Wirkung des Phenothiazinkorpers Megaphen auf dasuMehschliche Hirnstrombild. Arzneimittelforsch§:“l95h, Z: h18-h23. Bente, D. and Itil, T. A comparison of the action of various phenothiazine compounds on the human EEG. Trans. Int. Cong. of NeurgpsychOpharm., 1958, (in press). Itil, Electroencephalographic studies concerning the action of LSD-25. EEG Clin. Bente, D., T. and Schmid, E.E. Neuroghysiol., 1957, 2: Bente, D., Itil, 359 (abst.). T. and Schmid, E. E. Elektroencephalon graphische Studien zur Wirkungsweise des LSD-25. Psychiat. et Neurol., 1958, $25: 273-28h. Bradley, P.B. and Elkes, J. The effect of atropine, hyoscyamine, physostigmine and neostigmine on the electrical activity of the brain of the conscious cat. J. thsiol., 1953, lfig: 1h_-15; Bradley, P.B. and Elkes, J. The effects of some drugs on the electrical activity of the brain. Brain, 1957, g9: 77-117. Coady, A. and Jewesbury, E.C. A clinical trial of benactyzine hydro<3hlcride ("Suavitil") as a‘physical relaxant. Brit. Med. Jour., 1956, l: h85-h87. �-2&- Danielopolu, D., Giurgea, C. and Drocon, G. Electroencephalographic study of the non specific pharmacodynamics of the stimulatory effect of atropine on the cerebral cortex. ” Fiziologicheskiy Zhurnal SSSR, 1955, El: 60l~611. Denber, H.C.B. Studies on mescaline: III. Action in epileptics. Psychiat. Quart., 1955, 32: h33-u38. 9.,see;4a;é:§;fs;ag"inasced stgtgg”.gsembiagg“..tur.11y occuring MW psychoses,‘mgM ~jrbpicDrugs. Elseviar, / r Amsterdam. 1957, 263S Diaz-Guerrero, R., Feinstein, R. and Gottlieb, J. S. EEG findings following intravenous injection of diphenhydramine hydrochloride (Benadrylr). EEG Clin Neuro— ‘ 7 Evarts, E.V. Neurophysiological correlates of pharmacologically induced behavioral disturbances. Res. Publ. Ass. Nerv. Ment. Evarts, E.V. Dis., 1958, 2§:3b7-380. Chemical bases for psychoses. Concepts of Psychoses. 1958, Fink, M. A Chemical McDowell, Oblensky Inc., N.Y. hl-62. unified theory of the action of physiodynamic therapies. J. Hillside Hosp., 1957, g: 197-206. Fink, M. Effect of anticholinergic agent, diethazine, on behavior: Significance for theory of convulsive therapy. A.M.A. Arch. Neurol. & Psychiat., 1958, EEG and 29: 380-387; M Wflifi‘f‘féy A2u&“x dad Akhaifin, za37.,/ff4: £1.J./Ita4u/t-W‘Wfi fifi¢’{7¢£ �-29Fink, Relation of electroencephalographic delta activity to behavioral response in electroshock. M. and Kahn, R.L. A.M.A. Arch. Fink,mu. and Neurol. Jarre, J. & Psychiat., 1957, Drug induced changes 1Q: 516-525. in interviEW“‘ patterns.iiconf”“onoFsychodynamic Aspects of Neuro- leptic ‘‘‘‘‘‘ ) FloemargE S. ,afiines ed. J. Sarwer-Foner (in press). effect of some tertiary andwgnatornary QEggs, The EEG Clin. Neuro~ activity. “MM“MW 753 (abst. ). 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A.M.A. Arch. Neurol. & Psychiat., 1955, 12: 396-h02. Roth, the EEG under barbiturate anesthesia produced by electro-convulsive treatment and their significance for the theory of ECT action. §§§_ Clin. Neurophzsiol., 1951, 2: 261-280. M. Changes in Roth, M., Kay, D.W.K., Shaw, J. and Green, J. Prognosis pentothal induced electroencephalographic changes in electroconvulsive treatment. EEG Clin. Neuro- and �-32Schwarz, R.E., Bickford, R.G. and Rome, H.P. Reversibility of induced psychosis with chlorpromazine. Mega 2522. Clin., 1955, 29: h07-h17. Central cerebral chemicals and their relation to psychoses. Chemical Concepts of Sherwood, S.L. Pszchosis. McDowell, Oblensky, N.Y., 1958,v268-276. Strauss, H., Ostow, M. and Greenstein, L. Diagnostic Electroencephalography, prune Ulett, Stratton, N.Y., 1952. & Effect of atropine and scopolamine upon electroencephalographic changes induced by electroconvulsive therapy. EEG Clin. G. A. and Johnson, M.W. Neurophzsiol., 1957, 2: 217-22h. 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Woolley, D.W. Serotonin in mental disorders. Res. Publ. Ass. Nerv. Ment. Dis., 1958, 2g: 381-h00. Wm. �On this sheet please prepare for publication in BIOLOGICAL ABSTRACTS a typewritten (double spaced) abstract of your paper and attach it to your corrected proof. Since proof cannot be furnished, check your abstract critically—especially the citation, scientific names, formulas, chemicals, and technical terms. An abstract should be an informative digest of the significant content and conclusions of the paper, not a mere description. It should be intelligible in itself, without reference to the original, but is not intended to substitute for it. It should be brief (preferably less than 3% of the original), written in whole sentences, not telegraphic phrases. For directions, please see the reverse. Sample Citation: DOE, JOHN J. (U. Commonwealth, Capitol City), and RICHARD ROE. Metabolism of phosphorus in rats. Jour. Pest Control Res. 37(4): 152-165. 1957. Detach here and return lower portion only �A GUIDE FOR THE PREPARATION OF ABSTRACTS CONTENT—Include: 1. Name of organism, and objective of the study. 2. Materials, manner of use, or route of administration, principal findings, and results. 3. New techniques, their uses and qualities. 4. New apparatus, its intended use, and if commercially available, name and address of its manufacturer. 5. New or verified data of permanent value, e.g., absorption spectra, chromosome numbers, constants, mathematical or chemical formulae. 6. New genera of animals/ plants, new classifications, new distribution records. (For systematic data, see below.) ,7. New theories, new interpretations, evaluations, if possible; if not, reference to them. ‘ -Omit: Information contained in the title. 2. Additions, corrections, or any information not contained in the original published paper. 1. FOR SYSTEMATIC PAPERS—Additional instructions. FORM: 1. Write the name of a subgenus, genus, or any supergeneric taxon, if old, in small letters with a capital initial; if new, all in capitals. The name of a species, subspecies, variety, or form is never capitalized. 2. Alwa rs underline the name of a genus, subgenus, s ecies, su species, variety, and form: with a straight ' e if old, with a wavy line if new. No other group name is ever underlined. Write the name of a new combination of a species from one genus to another) transfer ‘ (e5: a straight line under the old and a wavy line under the new or shifted part, followed by the basonym and its author in parentheses. CONTENT: Be alert to information other than the formal, strictly taxonomic and nomenclatural. Summarize or men— tion new data in any biologic field—life history, morphology, biogeography, cytology, ecolo , evolution. (Nontaxonomists welcome such information. NEW TAXA. Omit detailed descriptions, long synonymies and ~ �DEC 7'5 3.959 m, x. (mm. Hume-1. mm m, a. 1.). mm or MWo W m m. W on Wu But EEG mum- and 101. mm mummrm mm (cu-mum. win-2299‘. administer“ to mum-'10 patent- flung, are «minted with n blocking Wtua Fatima. . JB~318 and 38-1336). Wu of of. with! It various «mutation a: mm, than at EEG rhythm pelt—amid” delta wtivity; darting, mum-y illusory. donning: and mnucinatory mum; and attacks of Ins-mm mimosa, drynosa of the mouth, dry akin md can— halyard“. The cloemgraphic, behaviml and manic offsets behavioral We mt.The“ mom. with m ' Mmtiam suggest. that. a «mimosa: film is an 1mm in mtml mama “timers What at convulsive dim Mastic” that LSD, «momma, 30mm and aynpumm and awakening agomm -. also mam EEG deaymhnoniuum, blocking of post «mun delta activity and clinical Quinton? nativity support. the suggestion hand on that behavioral and durum in mm scum“ mug activity ehctmgnphie panama any be It is suggest“ that. increased (ahelinorzia, mamas atom) 1: associated mm EEG and cumin}. mum and euphoria while Mmud Widen, �‘_ W", . ”-77 .V . ,. . . ,, .. .. w. . ..‘Vr._.wum“.mmm————__——_q‘_ 02¢ mm activity (autumn-31¢, metie) is associated filth Em WWfian and clinical .33th and WWW: cum. Wampum; observations with atropine are round to significant hmmmnt a: the role of mtichonmme agents in head tram md «ism auto-n in mggaltad. no” chain-tum mpnfy the mmyhyaiologimfinptin Wham at the m or motion of cmlsiv. thorny and of ”puma hallucinogenic out». Mfume” in damage. �HS 981 33130? 0! ANTIGBOLINERGIG GOHPGUIDS OI P03? GOHVULSIVE EEG AID BEHAVIOR OF PSIGEIATRIG PATIENTS nux Fink H.D. (Rocoivod for publication: larch 11, 1959) Iron tho Departnont of Exporinonttl Psychiatry, Hillaid. Ronpitnl, Glon Oaks, L.I., 3.1. purt, by grant. H-927 and 31-2092 at the Nationtl Mental Hotlth, lutionul Institutes of Health, 3.8. Public Konlth Serviel. Icad at tho Alcricun EEG fiocioty, Atlantic City, June, 1958. Aided, 1n Institute of 11: 5/59 �HS 981 AlfialflLIlElGIG GOHPOUIDS AID POST GOIVULSIVE EEG �Ettact or Anticholinargie Compounds on Post Convulaiva EEG and Bohavior at Psychiatric Patients BIG Daaanatrationa or the aignificanea or high voltage dolta activity in the gonvulsive therapy procaaa (Roth w, this delta activity report that was blocked by the adniniatration or atropina and acopolanina (Ulatt and Johnaon, 1957) provided the basis for than. studioa. A: there were attendant nnplaaaant ayatoaic effects with the adniniatration of than: agents, report: describing diethalina as an antiehalin~ crgic compound with potent neurologic but minimal systolic affects (Janknor and Lcehnar, 19553 Laehnar, 1956) led an to undartaka studio: similar to those of Blott and Johuaon using this coapound (link, 1958). aboarvationa with diathasine lad to the invaatigation of othar experimental anticholinargic 1951, 1957; Fink and Kahn, 1957) and thc agonta. report daaeribac clinical and olactrooncaphalo» graphiu observations ineidant to the intravenous adniniatration at various anticholinarzie agent: in psychiatric patients at various stage: of convulsive therapy and relates the obaarvationa Thia to hypotheaaa eonaerning tho and. or action a! canvulaivc therapy and of hallucinogcna. �SEBJEGTS LIE KETKODi subjects were ninety psychiatric patients referred for convulsive theraoy. ages ranged from 18 to 67 years, and diagnoeee included schizophrenia reactions end nanio-deoroeaive end involutiona1~depreaeive peyohoeeo. a varied number of eubjeote were etudied for eaoh oonpoond for a total of 107 observations. Patients have been obeerved at variooe etagea or the treatment prooeee. The obeervatione were made in the EEG laboratory, using a standard 8 channel EEG recorder and noodle oleotrodee applied in 17 lead placements following Streuee £t_2; (1952). In eeoh trial, the compound under study we: administered intravenously at a set rato per uinnte until clinical behavior or electrogrephio changes were The obeerved. The compounds et a1, 19h9), studied have been diethezine (Reynane Win-2299 (Pennee and Hooh, 1957), benactyoine (Jacobeon, 1955). JB~318 end JB~336 (Abood ££_5;, 1958) end atropine. Diethaoine was administered at 25 mg per minute for a total or 175-250 I: (3.5-5.9 nelkg); w1n~2299 and bonaotyeine at 0.5 mg per ainute for 2 to 5 e3 (0.02~0.15 eg/kg)3 and JB~318, JB~336, and atropine et O.h mg per minute for 1.2 to h.0 mg (0.01~0.10 mg/kg). �OBSERVATIOHSa- (a) Diethaeine: administration of diethaeine in fifteen patients prior to convulsive therapy reaultea in a decrease in EEG voltages and a deeynchronieaticn of all trequenciee. Prevailing rhythmic patterne becane leee pro» nuanced. In acne inatanoee, symmetric low voltage 6-7 epa activity appeared and wee aoet apparent in frontal and anterior temporal leade (gink, 1958). In twentyative patiente with varying degreee of induced high voltage delta activity during convulsive therapy (rink and Kahn, 1957), there was a significant decreaae in voltage and in per cent tine of aloe wave activity. Iron an average delta or hSS in the trontnoeeipital leade, there was a reduction to a mean of 201. Both render and beret delta activity dininiehed. Low voltage alpha and beta frequencies became more prominent. The usual increase in per cent tine and in voltage or slow wave activity with hyperventilation was no'lenger apparent. Theee electrographic effects appeared during drug administration and pereieted for one to five houra (link, 1958). The . Concurrent.vi}h these electregraphic effecte, we cbeerved dietinctive eyetemic and behavioral changes. The initial eyetenie effects were episodes of coughing and complaints of dryneee of the mouth. Skin reaained dry and the heart rate increased by 5 to 10 per cent. this increase �-5- rarely noted by the preoordial'dietraea. not aoconpahied There was no change in papillary by sine, and constriction in response to light wan prompt. There were occasional oozplainte or abdominal griping. Such effects were generally less prominent than the electrographio or behavioral. was eubja ot, and was lehaviorally, patients hooano irritable, restless, tense and excited, and it was difficult to maintain eyelid closure. they oonplained or feelings of unreality and or tingling, weakneee and heavineea or the extremities. Oonplainte that color: were pale or more intenea, halos about lights and changing shadows were accompanied by delusional thoughts about their illness, the setting of the test procedure or the axaainer'e identity. (h) that Win—2229: Win-2299 induced The report illusory by Pennee and Hoch (1957) hallucinatory states in intravenone aaniniatration and led to this next etudy. 0n o: win-2299. both electrographic and behavioral attests einilar to diethaeine were obaerved. In five patients without EEG aloe wave activity, deeynohronisatien of frequencies and a deoreaee in voltagee were noted in four (Fig.1). “QC“.-.‘-- man, fig. 1 In eleven patiohto with high voltage delta activity there was a decrease in amplitude and per oent time of slow wave activity with an increase in the par cent tine of alpha and �.5beta trequcnciee. tc 235 (Fig. 2). The neen delte ectivity dropped tron Fig. 50$ 2 ,ieeccietcd with these clectrcgrephic effecte were clinicel patterns of reetlceeceee end excitement, end minimal eyetcuic effecte. Petiente becene teertul end tense. Vieuel illuecry eeueeticne were reported end were ececcieted in theee eubjecte with deleeicnel elebcreticne about their hospital experience. Excitenent yea ecccnpenied by ideas of reference, end in two chjecte, intrevencue chlcrprcnesine wee edainietered to halt this process. Theee behevicrel chengee eppeered during drug eduinietreticn or within ten minutes, end disappeared within two to three hcnre. systenic effects were alight. there were neither cough nor rcepiretcry dietrccc. Scert rete wee unettected except in petieate who becene overtly excited and teertcl, in vhcn techycerdie eppeered during thie excitement peried; Dryneee cf the ecuth wee repcrted only on direct inquiry. (c) Benectieine: Reports that bonectyeine induced EEG deeynchrcniseticn (Ccedy end Jeweebury, 1956), its enti~ chclinerzic nature, end the etrccturel cinilerity to dietheeine and to Win-2299 led to our touting ct thin ccnpcund. Intrevencne edninietreticn in 12 subjects elicited similar clinical and electrcgrephic petterne. Bath in the well ncduleted elphe record and in the reccrd with high vcltege delte ectivity, deeynchrcnieeticn wee prompt. Dclte ectivity decreased trcn - �.5a mean time of 391 to 165 in 8 Fig-t, These electroxraphic by subjects (Fig. 3, h). 3, h~ patterns were ngnin acconpuniod clinical roctlenlneol, irrittbility and oxeitcmont. Artifactwrree recording was nor; difficult.. the illusory sensitionl ind dblunional thoughts a¢en with the initinl aénpounds were hot notad at then. dongs. luvtla. Syatcnie effects wore niuilar to Win-229?. ‘ (d) Piparigylbanzilatoa: Following racont reports by Ahead 33_§; (1958) that various pipcridylbcnailatca with nynaurxblo antichoiincrgie activity induced hallucinations in psyehintrie subjects, we taut-d JB~318 and JB~336 in 2h vubjoets. Thu olectrogrnphic'pntterns wort identical with the other experihonttl antiehulinorgia compounds. Dosynchrenination of troquancios wan noted during the injectian or within 15-minute: and pornistod tar due tp {our hanrs (Pig. 5). O’Qflflfiflw Fig. 5 In each inataneq in whieh duaynchronixation was obaarvad,‘ ainicnl restlolancau, excitcnont, illunary and hallucinatory activity were acted, and were eonuurrant with the nloetrographie changes. In two inatuneoa the behaviornl changoa wore haltcd by tho intravonoua administration or chlerprenasino. , �-7-(c) Atronins: Considering the numerous reports that atropine_indnced EEG elow wave activity and clinical eonnolence, we adninistered this anticholinergic agent intravenously in 15 aanecte, in dosages of 0.8 to h.0 as (.01~.1o ng/kg). In six snbjecte without EEG delta activity, there were no changes in EEG pattern during drug administration nor for 10-20 minutes theratter.. During a period of laseitude, decreased voltages, minimal desynchronication, and an increase in per cent tine'delta were noted. In subjects with delta activity, there nae an apparent initial decrease in voltage and per cent tine or each activity during the first ten ninutes after adainistration, followed by a return to original values during the period of quietode. In neither period were the changes significant,: (31:. 6). fi Fig. 6 systemic effects were prominent during the injection with increased respiratory rate, pallor, dry skin and dry precordial complaints increase in heart rate up to 10oz. Subjects became restless and recording became difficult. Within ten ninntes these symptoms subsided and the subjects became drowey and relaxed. mouth, and an �-8DESGU$SION3 In those studies, varione experimental compounds with neaenrable anticholinorgic activity have been obeerved to have similar electrosrephic and behavioral effecte.' Electrographically, each agent induced a doeynchronination of frequencies and a decrease in voltages, which was most prominent in cubjocte with delta activity following convulsive therapy. Behaviorally, theee electrographic patterns were aceociated with stimulating, excitatcry, illusory and hallucinatory activity. To a leeeer degree, ainiaal oysteaic changes in heart rate, eelivetion and eweating were noted. Theeo latter eyeteaic cffccte were lore prominent in patiente given intravenous atropine under einilar experimental conditione. Thceo obecrvatione can be related to theories of the node of action of convnleive therapy; to concepts of the basic of experimentally induced hallucinatione; and to roporte of tho effocte of atropine on EEG patterns. (a) Convaleivo thcrggy process: Earlier etndieo indicated that the development of high voltage slow wave activity wee a nenrophyeiologic correlate of behavioral changc in convulsive therapy, and a necessary, though not sufficient, condition for clinical improvement (Pink and Kuhn, 1957). In enanarieing the obeervationc of nuaerone authors on the relation of acetylchcline metabolic: to trauma of the central nervous eycten and to convnleione (Pink, 1958) it wee enggeeted that a biocheaical concoaitant of the induced EEG �.9. alov wove ootivity to. an increased level or acotyicholinoo‘ oholinootorooo activity of tho central nervous system. Tho . pro-ant oboorvations of altorotiono 1n the slow wave activity at oonvnloivo thorapy by that. oxporiuontal antioholinorgic compounds or. oonaiatont with this suggestion. That tho problon 13 not. complex is indicated by reports or oonpoundn with other biochemical activity alto ottocting clot wave nativity in o aililor faahion. Alphotnnino (Lonoox‘:1_g;, 1951), nonoalioo (Karlia and Router. 19553 Dunbar, 1955), lyoorgio acid diothylonido (Dante gg_g;, 1957 a,b) and diphonhydranino (Bios-Guerrero £3;=;, 1956) olso reduced post-convulsive slow wave activity. In these reports, such a reduction vac aooonpnniod by excitntory nod stinuloting effects on bohtvior. Those conponndo, hovovor, are prinarily oynpathoninotio and antihistoninio in pharfiaoologio activity and not antioholinorgie; 81n113r_oftocto of those divoroo bioohomical ngontt on olootrographio patterns and on cliniool behavior may be oonoidorod within thoorotio oooatruota of the relation of synaptic ootivity to behavior on oxproauod by Harolsi (1953, 1957), Brndloy and Blkool(1957), Evarts (1958 .,b), Sherwood Tho thono author: nnzgoot thot tvo ohonoroopon-ivo roooptorl oxiot within (1958) and Hoolloy (1958). typos or interootiog the nervous oyston which or. Iolootively roopoouivo to oholioorgio or to udrenorgio agonto. whore ouch rocoptorl oxilt, they oxort oppoaiog ntinolotory or inhibitory ootioo. �-10Thus, repeeted induced oeuvuleione mey lead to e choose in eyneptio eholiaergio activity, reflected in surface electrodes on high voltage slew wove activity. Administration or enticholinergio egente may alter eyneptie nativity, resulting in e decrease in the manifest aortioel electrioel eotivity to preoenvuleivo levels. Adeinietretion of eyupethoeinetio egente eey eohievo the gene electrical effects by inoreeeing the level of edrenergie activity. The neoiteet elov weve activity, so proninent end so pereietent in the poet~eeisure 328, any thne be vieved ee resulting from n persistent elteretion in the synaptic activity of large hunters of cello of the control rnervone eyeten. The delicate netnre or this balance is seen in the reedy reversibility with alerting, tine, and the wide variety of phernnoologio agents noted here. While an alteretion in synaptic activity may underlie the behavioral changes in coovulsive therapy, the neoheniel elteration is developed or eueteinod is uncleer. The obeervation by iird gt~gl‘(l956 e,b, 1958), that an inoreeee in permeability of the blood brain barrier followed‘ by which such repeeted indooed convulsion: euggeeta one sz in which synoptic ehengee eey be mediated. coneietent neture or these neurophysiolozio observation: nekee en exclusively payehologic explenetion e: the node or action of convulsive therapy lees teneble. These etudiee ere ooneietent, however, with the neurunxmyeiologio~‘ adoptive view or the convulsive therepy preoeee whioh eugzeete The �«11 an that nenrcphyeielcgic chengee provide the enbetrate for alterations in all aepecte cf the enbject'e clinical behavior; the type or behavieral eitereticn being dependent upon the type and degree of neurophyeiclcgic change, the personality or the eubject and the expectations and tolerance of the milieu (Weinetein and Kahn, 1955) link and Kahn, 1957; Pink, 1957). (b) leurcphyeialegy c: hallucinczenic activity: The effects of antichelinergic ccnpcnnde on EEG and behavior nay alec be related to the underetandinz or experinental hellucin» ct theee experinental ccnpcunde induced excitatery behavior, including illneery and hallucinatory phenomena. Here, tee, a synaptic nedel any be applicable. cgenic activity. Each sympathceinetic agente, ae neecaline, LSD and anphetanine, and anticheiinergic agente ea thcee described here, are alee potent hallucinogene. i necropharnacelcgic basis for each behavior nay be characterised ae an alteration in the level or eynaptic activity in the direction of increased inhibition (decreeeed tranenieeicn) or etincli. The clinical efficacy of ccnvnleive therapy in modifying hallucinatcry activity nay lie in alterations at thie nenro~ physiologic level, The effects or ench hallucinogenic blocking agents ae chlcrprenacine and rceerpine on EEG electricl activity are ccneietent with each a View. Both ccnponnde induce EEG hypereynchreny in nan (Bente and 339 deaynchrcnicaticn effects of 1955). Chlorpromazine was Itil, 195k. 1958} and b10¢k thd neeceline (Schware gt_3;, found equally potent in aborting the LSD and �-12. exoitatory activity of the experimental anticholinergic coupouoda in these etudiea. (c) Relation to atropine: Goapariaon or the eyetenic land neurologio effects of experimental anticholioergie compounds with atropine reveals ditterencea in initial focus of action, Exoerienco with atropine at physiologic and toxic levela in nan indicate that the prodoainant effects are :ocuaed at peripheral nervooe ctroctnroa. Initial bradycardia, followed by tachycardia, lose or creating and ealivaticn, papillary dilation, intestinal relaxation and decreased motility are. aaonget the effects at low (0.2-1.2'ug) dooagoa. At higher doaagea (ans :3), the neurolggic effects of ataxia, irritability, disorientation, and delirium are observed (Goodlla and Gilnan, 1955). ‘ In contrast, the experimental anticholinergic agents in doaegoo sufficient for central nervous system effects manifest little peripheral activity. The central effects are observed early and may continue for exteneive periods without gaetro~ intentinal, cardiac or pupillery changes. It ie within the context of the tocue or activity in relation to dosage that the apparent discrepant EEG observations or the effects or atropine (in inducing aloe wave activity) and the-e experimental antioholinergic coapounda nay be reconciled. I weecee 33_g; (19h8) administering 1.0 to 3.0 ag/kg atropine in curariadd cata and monkeys and funderbuzk and Ceae (1951) using 0.h to 1.2 ag/kg in curarised cata, observed high voltage EEG �.13.. aloe wave activity. Hitler (1952, 1957) reported that 7;! Ig/kg atropine on unaneethetiaed, uncurarieed deg: produced "spindle slow wave” patterns eiuilar t6 sleep.) Rinaldi and 'Hinwich (1955a, b) reported that atropine in doses of 0.5 to 2.0 mg/kg in curarized rabbits exaggerated EEG sleep patterns and inhibited the alerting or the EEG to peripheral stimuli. Sinilar observations have been reported by Bradley and Elkee (1953) in the cenecione cat. In each instance the doeage at atrepine varied tree 0.5 ta 7 ng/kg . a range roughly eoeparable te the deaagea need in atropine coma therapy (Ferret and Miller, ; 1958). In the present etudiee, the EEG effects at low deeagee of intravenous atropine (6.01 to 0.10 mg/kg) were minimal and systemic éfteete censiderable,cenriraing einilar observations by Verdeaux and Hartylfl95h) and by Danielepalu g§_3; (1955). the slow wave activify an prominent in animals and man at high doeazea at atropine, may not be a manifestation of the initial or direct effects at atropine, but a reflection of a more widespread alteration in body yhieialogy. Thee, while eeneiderable epeeulatien aa ta central neurophysiology has been based on studiee with atreyine, each abeervatione provide a epecial'caee at anticholinergic affects. the anticholinergic activity eetabliehed in observation: in vitro and in the peripheral nervous eyitee, may net be the effective physiologic activity in the large deaea necessary to affect centraldr‘cturee, rhe experimental cenpounde, however, provide mere euitahle �“15- for thu study of cantrnl nturaphysiologic (tnticholinargic) patterns thnn stropine, as, for oxunplc, 1a a ra~ovu1uut1an or the studio: at ertnieeorcbral trauaa :nd dpilcpay. Wtrd'l (1950)'r¢p¢rtl or the otticney a: high do... of atrepino in altering the clinical n‘n1£0ltatienl of hoad trnuau indicutod that effective dose: brought with than Invor¢ systolic ortoctl. the tntluro of ntgopino and scopolnninc to affect cpilcpny any be rolatod to th; inability agontn that. to rcgah thu cintral norvoua system in tdnquato quanlty. It would stun ndviugblo, thoroforo, to rcpuat that. Studio: utilising inch fiorc ccntrnlly active of eoupounda anticholinargic hora. compound; 18 used in the oxporimonta rapartud �-15SUHNARI: _ 1. Experinontsl natiohclincrgic compounds (dicthntinc, .Win«2299. bannctysino, JB~318 and JB~336), adainintorcd to paychiutric patients nt variant stcgcs c: convulsive therapy, wcro aascciated tith: (a) dcnynchrcniunticn of EEG rhythm: with a blocking of paltnccnvulcivo delta activity! (b) alurtina, cxcitatcry bahtvicral rolpcnao with illnlcry, delusional and hallucinatory idonticng and, (c) systemic Ottocts of muscular Icahn-cs, dryncun of thc month, dry skin cad tcchycardia. 2h. oltctrcgraphic bohavicral and systemic nrfncts were ccn~ current. 2. Thou. obscrvnticna are consist-at with tho auggonticn thut a nourcphysiclczic ccnconitant or convulsive therapy is ca incroulo in contral norvcul Iynton cholinorgic activity. Obscrvctionn that LSD, anphotuninc, nouculinc and diphonhydranino - tynpnthouinctic tad antihiatnninic agents . 31:0 induco BEG dcnynchrcniuaticn, blocking of part convullivc 3. doltn activity an; clinicsl cxcitntcry activity cuppcrt‘thc luggcsticn thut behavioral and clectrographic patterns may be bclud on altcrcticns in syntptic activity. )It is nuggclt that incrca-od synaptic activity (cholinorgic, aynpnthclytic ctructa) in calccintod with EEG hypornynchrcnisaticn, Aka clinicul �~16~ Itdgtion and ourhoria; whilo dtcrtasod synaptic activity (untieholinorgie, uynpathoninottc) is associated with EEG doayuchronization and clinical Ixeitatory and hulluainocanic stutou. nascrcpunt obscrvatiana with gtropinu art rulattd ta significant difroruncca 1n doaagc. Ronaasoaununt or tub h. rain or anticholinorcic taunts state: 1n hild truunt 3nd noisurn luggoatod. 5. These obaurvations amplify the neurophysioloxtcw tdaptivo hypothonia a: the and. at tcticn or convulsive thcrupy and of experinontnl hallucinogenic Itaton. 18 �-17“ AGKEOULBDG§§§§ga I u: gr‘totul far the tcchnicul auuiutanee of Bra. Etnnnh fibuquorn in recording and nnulyaoa. Supplici ot‘tho various pharnncauticals were and. froely availtblc by Lake-1d. Laboratories (JD-318 and JB-336), Herck sharps & Donna (bounctyzinc); Sand»: Pharnnconticaln (nan-25). Sturlingwmthrup (win-2299) sud Smith, x11" und Preach Lnboratorica (ditthnsino, chlarpronastna). EEG �-18REFEREIOEB Ahead, L.G., Oottuld, A.H. and 31.1, J. A now group of psyohotominutic agonta. Proc. Soc. Expor. Biol. 804., 1958, 21: h83~h86. 11rd, 3.3. c11.1..1 oorrolnton o: clootroahook thorapy. 5:5:5: Arch. laurel. & quohiat., 1958, 12; 633-639. Lira, 3.8., Strait, L.A., Puoc, J.W., Hronott, 3.x. and Bowditch, 8. Neurophysiologic ottootn of olootrioolly induood convulsions. A.n.;. Aroh. lourol. & Pglghiot., 1956, 15: 371-»3'28. Dante; D. and Itil, T. Zur Hirknng do: Phonothiuninkorporo out do: Honaohlicho Hirnatronbild. Arsnoinittoltoroogg, 195k, 1} h18~h23. Bantu, D. and Itila I. A conporilon of tho action of various nogaphon phonothhsino compounds on tho human EEG. Trans. Int. Gong. of Houroagycggzyarm., 1958, (in gross). lonto, 9., 1%11, I. and Schnid, 3.3.. Eloctrouncophalographtc atndioo ooncorning the action or LSD-25. lourozhzliol., Bonto, D., I Itil, !. EEG Olin. 1957, 2} 359 (ubo£.) and Schnid, 3.x. Eloktrooncopholoo graphilcho studion our Wirkungauoiuo do: L8D~25. ggyohiut. at louro1., 1958, £25: 273~28h. Bradloy, P.B. and Bikes, J. the ottoct of atropine, hyosoynnine, phyooottgnino and noosttguino on the oleotriool ontivity of tho broin of the conscious cutoo J. thl1o1., 1953, ggga 1h~15. �‘19Bradley, P.B. and Bikes, J. effects of drugs on the electricel activity of the brain. gggég, 1957, fig:' The some * 77~117. 3.0. A clinical trial of benectysine hydrochloride ('8uev1t11') as e phyeiael relexent. gggg. andy, 1. end Jewesbnby, Hed. ‘Ben1e10pelu, Jean, 1956, y 1.85—1.87. 9., Giurgee, c. end Brocan, G. Eleotroencephele~ grephic study at the,non~epoeitic phernecedynenice of the etimnlnigry effect at etrnpine on ths corebrel cortex. Iiiieégggcheekly Zhurnel 8858,'1955. g5: 601~611. Defiber, 3.6.3. Stud1ee on neecelinec III. letien 1n epileptice. 3933.,1955, 29: h33~h38. mm. Die.2~auerrero, R., re1nete1n, R. and eettlieb, J. a. EEG finding: following intrevenoue injection of d1phenhydramine hydrachloride (Benadrylr). Ema. Olin. Beure» 2n;.1.1., 1956, g; 299-306. Everte, E.V. Heurophysiologicel correlates of pherueeologicelly induced behavioral disturbencee. Ree. Publ. lee. xerv. .uent. 91... 1958, 29: 3h7-38o. Everte, 3.7. Chemical bases for peyohoeee. Chenicel Conceggg e! Pezphoeee. XuBovell, Dbleneky Inc., H.!. 1958, k1~62. link, a. A unified theery of the ection or phyeiodyuenic y therapies. J. Hilleide leep.. 1957. g; 197-206. l1nk, K. Efreet e: entichelinergic egent, dietheeine, an EEG and behevier: 81¢n1t1cence for theory at convulsive therapy. I 1.3.1. laurel. a Peyehiet., 1958, 80: 380~3873 end Biologicel Peyvhiet_z, ed. J. neeeernen, Grune & Stretton I. 3., Arch. 1959’ 1811*19he �-20- rink, Rnlation or olectrocncophnlogrqphic delta activity ta bohuvioral rulponao in aloctrolheck. H. and Kuhn, R.L. A.H.A. Arch. tartar, a. lourol. and 3111:», J.J. & szuhint., 1957, 13} 516~525. Atropiuo cont: A‘Ionatic therapy in psychiatry. Lu. J. quehint., 1958, $35; h55~£58. rundcrburk, w.n. 1nd Onto, !.J. rho affect of ntropino an cortical pot-ntiuln. EEG Olin. lburophlniel. 1951, g: 213~223. L.8. and Gilnnn, A. Pharmacolqlgcll Basin of Thorazcntieu. Kacxillan, I.!. 1955. Hoynans,.c., Establo, J.J. and dc Bonncvnanx, 3.6. sir 1: Boodnan, I - pharmacologio d0 11 phonothiaz1ny1-oth71d10thylnninc (2987 R.P.). Arch. Int. Pharmacofizg; 19h9, 12; 123-138. Ito: ltd spacitik virkning p: contruluorvoayltonot. g‘plkritt far Lqugg, 1955, 3E2: Jacobson, E. Susvitil, at nyt ' 11h7~1151. Jonknor, 1.2. tad Lochnor, a. Th0 offset or diparoel on tho olcctrooncophnlogran in tho nnrnul Inhaoct und in than. with corobral iguana. BEG Olin. lenrophyniol., 1955. 1; ' 303-305. Lochnor, the influence or naticholinorgic drugs on the EEG Clin. EEG at rcchnt OIOIId crtniccrobral injuries. lourenhyliol., 1956, g. 71h'71§.' a. 0n Lonnox, H.A., Ruck, 1.0. :nd Gutornnn, B. The the postuoloctroshock lourozhza1a1., 1951, g: 63~69. boas-aria. on oft-ct EEG. EEG of 0113. �-21. 'Hereeei, A.$.- Sene indicetiene e: oerebrel hnnerel necheniene. science, 1953, 1;81 367-370. lereeei, A.8. Etteete ;;“peycheten1eet1c druxe eynepeee. Egyehotrepie Bragg. on cerebrel Eleevier, Aneterden, 1957, 283~28h. Herlie, 3. end Hunter, 7. Studies en eeecelinee II. Electra. eneephelegren in echieephreniee. fezghiet. 93ert., 1955, Pennee, 8.3. mum”. end neck, P.H. Peychetonimetice, clinicel end theoretical eeneideretiene: Hernine, w1n~2299 end leiline. Amer. J. Pelehiet., 1957, ;;3: 887~892. Rineldi, 7. end ninwich, 3.3. Alerting repeneee end ectione or etrepine end chelinergic drnge. A.H.A. Areh. Neural. end Rineldi, I. Pezehiet., 1955, 12: 387-395. Cholinergie nechenien involved in functien of neeodieneephelic ectiveting eyeten. ena ninwieh, H.E. leurel. e Peychiet., 1955. 1;: 396-h02. 3. Chengee 1n the nu unau- bubttnrete mu...“ produced by electroaeonvuleive treetnent end their significance fer the theory or E0! eetien. BEG clin. leureghzeiel., 1951, 3: 261-280. A.H.A. Arch. Roth, 30th, l., D.W.l., Sher, J. end Green, J.‘ Pregneeie end pentethel induced.electroencephelegrephie changes in Key, electreeenvemlve treeteent. E36 6113. leereggzg}el. 1957, 2: 225-237. �a22- 3.2., Bicktord, 3.0. Schwarn, and Rona, H.P. inducod psycho-it with ohlorpronasino. 1955. 2Q; h07oh17. Bhorvood, 3.x. Contrul oorohrol ohoniools dud Rovoroihility or Proc. Hiya Clin.. their rolation to paychonol. chonioal Gonoopto or £329hoaiu. xenowoll, Oblonlky, 3.2., 1958, 268~276. Btrnuol, 3., Ootov, H. and are-nutoin, L. Diagnostic Electroonccpholggrtphz, Gruno & Strntton, R.I., 1952. Vlott, 6.1. and Johanna, u.w. Ettoct o! ntropino and acopolonino upon alootrooncophalogrnphio changos induced by olootroconvulaivo thorapy. EEG Olin. lonrophzgiol., 1957,‘2: 217-22h. a. and Harty, R.‘ Action our l'oloctroonoopholocronno do ouhstancol phnrnacodynauiquoo d'intorot cliniquo. Vordoaux, Rev. Word, A. lourol., 195k, 2;:‘hosuh27. Atropino in the troatnont of cloood hood injury. J. lourouur‘., 1950,‘ls 398-h02. Uninstoin, 3.A. ond Kuhn, R.L. Doniol of Illness: aznholie and_phyoio1o§ict1 oqpooto. c. rhonal, Springfield, 111., 1955. Roscoe, nonunora, B.P. and Krop, 8. Tho influonco of atropine and aeopolonino on tho control ottooto of 91?. J. Phnrnaeo1., 19h8, 23: 63~72. w.c., Groom, E.B. Uiklor, A. Pharnocologic dissociation of behavior and EEG ”sloop pattorns' in dogs: morphine, l'nllylnornorphino and atropine. Ptoc. Soc. up». 31.31. 14“., 1952, 12: 261-265. �«~23. the 1.1915593 or P£Ich1utrl to thaaoLg‘z. Wu. Wilkins, Bathe", 1957. Woollcy, BAY. Scrotum”: in maul disorders. Ru. Pub]... Hitler, A. A". new. Hunt. 913., 1953, 29 381-4400. �aasaaaa '13. 1a Effiflt or :1 313.1299. was. anuyuchraaiiattua a! troqucaatnu nXtur 3.! 3:. (Fig.1.. 88' kl). 11:. 3. Efrhet at 1' Reward satin 31n~2299 an pottueoavu131Vt 2h hoard dulta :ettvtiy: artor aouvulsiau #8. flat. dauznchrinilatioa at tvcguuueaou and yursiniana. nttor 2.0 is. ("l‘l’fi ago 51). ‘ attooz a: It nuuuutwtaaot uni. perutntaut apero¢ac 1n rol‘agu: and duawachviatnntsaa art-r 1.5 It. (Filtllg “. 3’4). Ettoct at 1V aunuotrtfin- an yaatuoauvulatvo.doltt nottvaty. accord tokua 2£ hctru arch: cauvuzntau I7. lot. tetrachruntnttton or {toquuuclco urtor 1.5 ug. (tumult. It! 3)). 9“. 5. . Rttcat I: Jimfllfi an yout~¢¢uvulliau Rigord takun 2% hour: ¢¢I%& tttnr cunrulttan #9. nativity: lat. duarunhroattttiua a: Irvquuuotnn, fineronagd rulingslttar !.h It. eur‘taa vita 330'! 101 tuartalt. (vaunlo. ago :7). 5&l11lr run-van thwarted math £I~336. �’1‘. 6. ”net or «$11 «Inn 62 I? “up“. an ”anemia" «In «an». nun mm: 2!; hour. um amass.» #6. 30%: man an.“ an delta “tint: and ”min“ menu. in heart an, with partition“. (mo. :3. “mam . 2.0 In. «025 Int/u). 18. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Effect of antichlolinergic compounds on post convulsive electroencephalogram and behavior of psychiatric patients. Electroencephalogr Clin Neurophysiol. 1960 May; 12:359-69. 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FINK Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Long Island, N. Y. (U.S.A.) Recent studies have presented data supporting a neurophysiologic—adaptive View of the convulsive therapy process“: 15. This hypothesis holds that the clinical efficacy of repeated induced convulsions is dependent upon the induction of a persistent alteration in cerebral function, which provides the milieu for changes in the subject’s inter— action with the environment. In these studies the best index of neurophysiologic change has been those aspects of cerebral function reflected by 8 activity in the electroencephalogramS—lo. The efficacy of newer psychopharmaceuticals in altering psychotic behavior patterns led to the suggestion of a similar hypothesis for the mode of action of these agents“, and to studies of the relationship and specificity of altered behavioral patterns to neurophysiologic change as reflected in electroencephalography. This report summarizes some of the experimental data observed in on—going tests of this hypo— thesis. ‘ SUBJECTS AND METHODS We have studied consecutive patients, suffering from depressive psychoses, agitated and excited schizophrenic states and severe psychoneurotic disorders, referred for physiodynamic therapies (convulsive, psychotropic drug, insulin coma) in a voluntary, open—ward, psychiatric hospital. Serial electroencephalograms were taken prior to, Aided, in part, by grants M-927 and MY—2092, National Institute of Mental Health, National Institutes of Health, U.S.P.H.S., and Bristol, Wyeth and Smith, Kline and French Laboratories. * References p. 446 . �M. FINK 442 during and after the course of therapy. In addition, at various stages of the treatment As done. convulsive both studies chlorand were acute experimental program promazine therapies elicit varying degrees of EEG slow wave activity, these acute observations have been made in two groups of subjects: those without slow wave activity, and those with diffuse slow wave (HSD, LSD) or burst and slow wave (BSD) activity”. Observations have been made in the EEG laboratory. Following a routine bipolar EEG recording, an unstructured psychiatric interview was tape—recorded. Under continuous EEG recording, medication was administered intravenously at a set rate until EEG or behavioral effects were observed. Following the injection the interview was repeated and recorded. Periods of EEG recording and interview recording were alternated for the duration of the drug activity. Behavioral evaluations have been based both on clinical descriptions by the participants (subject, physician and technician) and analyses of changes in language patterns12:14. Electroencephalograms were measured for shifts in dominant frequencies, and changes in voltage, modulation, and per cent time of or, {3 and 8 frequency bands. The psychopharmacologic agents were administered orally for extended periods in clinical trials, and intravenously in the acute experimental trials (Table I). Dosage for each compound varied, but in each instance sufficient medication has been given to achieve clinical behavioral effects. TABLE I PSYCHOPHARMACOLOGIC AGENTS STUDIED (Oral and intravenous) Chlorpromazine Prom azine Triflupromazine Perphenazine * Reserpine Iproniazid ** Deanola ** Amobarbital ** Thiopental Atropine Diethazine Amphetamine Methamphetamine Meprobamate * ** LSD—2 5b ** Win—22996 ** J B—3 I 8d J B-336e ** Benactyzine Dimethylaminoethanoll". b Lysergic acid diethylamide. 0 2-Diethylaminoethyl cyclopentyl (2-thieny1) glycolatel“. d N—Ethyl—3-piperidy1 benzilatel. e N-Methy1-3—piperidyl benzilatel. a * Oral only. H Intravenous only. OBSERVATIONS (a) Electroencephalographic Four broad types of EEG patterns may be identified according to the characteristics of frequency shift and synchronization‘l: References 35. 446. �443 INVESTIGATONS IN NORMAL HUMAN SUBJECTS I) Increase in slow wave activity and in synchrony; Increase in synchrony without frequency shift; 3) Increase in fast wave activity and in synchrony; 4) Desynchronization and frequency irregularity. Examples of each are seen in Figs. 1—4. During convulsive therapy, an increase in slow wave activity and synchrony is manifests. With drug administration similar changes in frequency spectrum and in synchrony can be observed. Such changes include an augmentation of the slow wave activity8 or a marked decrease in such activity with desynchronization of frequencies? .Of the psychopharmaceuticals tested in acute experiments an increase in synchrony With or Without an increase in slow Wave activity has been observed for chlorpromazine, promazine, and triflupromazine. Barbiturates regularly induce an increase in fast activity With an increase in synchrony, While amphetamine and 2) W W W MW W WWW WWW |600 PER DAY 3 MONTHS IZOO MG PER DAY 2 MONTHS PRE-DRUG LAT—LF MG WWW/WWW , LPT-LO ‘ 0-0 RPT-RO JWVWWMMNMM it 2049 HH 4* 2143 HH 2l95 50M— ISEC HH Fig. I. Chlorpromazine, oral (male, age I 5). 800 - PRE-DRUG MG | ‘WWW ' PER DAY MONTH wwwwvwwwmmwm LAT'LF AFTER 350 MG LAT-LF RAT-RF RAT-RF \ LF-RF ’ LF-RF W LPT‘LO LPT-LO NWWMMWM WWWNWWWWMWWVI o-o “MIN/WWW . MAM/WM wmwm |9|5 # |962 SOle—l RPT-RO a: W W W W mm PRE-DRUG HH - SEC HH Fig. 2. Chlorpromazine, oral (female, age 34). www—fiu o-o M‘WVWM WWW , Ill/WWW RPT-RO 5°VV‘—_|SEC #0 2'51 HH Fig. 3. Amobarbital, intravenous (male, age 31). methamphetamine increase fast activity Without increased synchrony. Desynchronization of frequencies is prominent after diethazine, LSD-25, Win-2299, JB-3I8, JB-336, and benactyzine. Refeyences p. 446. �M. FINK 444 In subjects with post—convulsive 3 activity, acute administration of chlorpromazine, promazine, triflupromazine, amobarbital and pentothal increased the per W W ,W W W» PRE-bRUG LF-LO WWW _ MIN + 80 MIN wWWM-NMWNM Rf-RO LAT-LP + 40 AFTER 3.2 mg .. RAT-RF LPT-LO . I 0-0 “WW“M‘M‘WW“ RPT-RO WWWW WW WW | SEC #ZOISIHH Fig. 4. Win-2299, intravenous (female, age 41). cent time and voltage of slow wave activity. Decrease in voltage and per cent time of slow wave activity is seen with LSD-25, benactyzine, Win—2299, JB-3I8, JB-336 and diethazine5’ 6. Similar electrographic patterns are noted in chronic oral administration of these compounds. Chlorpromazine, promazine, high doses of reserpine and occasionally perphenazine elicit increased synchronization and a shift of frequencies to the 8 range. Increased synchronization without frequency shift is occasionally observed with iproniazid. Increased high voltage fast activity is observed with meprobamate and barbiturates. Oral administration of LSD-25 and benactyzine induces EEG desynchronization with an increase in fast frequencies. (6) Behavioral Initial studies of convulsive therapy noted that behavioral change was dependent upon the development of synchronous slow wave activitys. Prominent among the associated behavioral effects were sedation, tranquillization and euphoria in agitated, depressed subjects, and a decrease in somatization, paranoid ideation, hallucinations and delusions in schizophrenic and excited subjects. Increasing agitation, paranoid ideation and panic were observed in less than IO 0/0 of the subjects. Similar behavioral relationships were prominent with these psychopharmacologic agents. In acute experiments, administration of chlorpromazine, promazine and triflupromazine was associated with increasing sedation, drowsiness, denial and euphoria, decreasing agitation, panic, excitement and delusional and hallucinatory activity, and minimization and displacement of symptoms. Sedation, euphoria, denial and minimization were similarly associated with amobarbital. Administration of amphetamine and methamphetamine resulted in behavioral alerting, hypomania, excitement, and increased motor activity. Similar increased alerting, excitement, tension and panic were observed after benactyzine. In addition to these patterns, illusory sensations and hallucinatory, delusional and paranoid ideation were observed with diethazine, LSD-25, Win-2299, JB—3I8, and J 13-336- References {3. 446. �INVESTIGATIONS IN NORMAL HUMAN SUBJECTS 445 Equally prominent with the behavioral changes were alterations in patterns of language. Previous studies of convulsive therapy had indicated that specific syntactic language patterns (as in the use of the third person mode, past and future tense, dis— placement, minimization, denial, clichés, and cryptic remarks) increased with increasing neurophysiologic change”. These language patterns were further exaggerated by intravenous amobarbita114’15. In the present studies, chlorpromazine, triflupromazine and iproniazid increased these language patterns. Diethazine, LSD—25, Win-2299, and benactyzine decreased and reversed these language patterns, increasing the use of the present tense, first person mode, and somatization7. Relation of behavioral and electrographic observations The electrographic patterns Were consistently altered concurrently with behavioral changes both in the acute and chronic administration studies. Tranquillization, euphoria, sedation and minimization of symptoms were commonly associated with increased EEG synchronization and shift of frequencies to the delta range. Agitation, tension, panic, excitement, illusions and hallucinations were associated with a desynchronization of frequencies. Similar patterns were demonstrated in subjects with prior 8 activity. Agents that tended to synchronize frequencies, as chlorpromazine and barbiturates, augmented the per cent time 8 activity and enhanced clinical patterns, while agents that desynchronized frequencies, as diethane, LSD—25 and benactyzine, minimized the clinical effects ascribed to repeated convulsions5-7. (0)} DISCUSSION These observations are consistent with the neurophysiologic—adaptive hypothesis of the mode of action of the newer psychopharmaceuticals“. This hypothesis states that the clinical efficacy of psychotropic drugs is dependent upon the induction of a per— sistent alteration in cerebral function which provides the milieu for changes in the subjects’ interaction with the environment. The variety of neurophysiologic patterns induced by these agents is in contrast to the limited patterns resulting from convulsive therapy and thus provides amplification of the original hypothesis. It is evident from these studies that the type of neurophysiologic alteration induced, as reflected in EEG synchrony and frequency patterns, is related to specific types of behavioral adaptation. With increasing synchrony and a shift to the 8 frequency spectrum, tranquillization, sedation and decreased agitation become prominent, while desynchronization and a shift to [3 frequencies are associated with excitement, illusions and delusional ideation. These studies are also consistent with numerous reports of the neurophysiologic effects of these compoundsm’ll’ 13:19:21, and specifically support and amplify those of WIKLER who concluded, in his studies of morphine and mescaline, that “regardless of the nature of the drug administered, shifts in the pattern of the electroencephalogram in the direction of desynchronization occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness”2°. This hypothesis, and the electrographic measure of neurophysiologic change, lends itself to application in the assay of new psychotropic drugs“, the rational References p. 446. �446 M. FINK application of pharmacotherapy7, and as a basis for further experimental study of neurophysiologic—behaviora1 relationships in psychiatry. ACKNOWLEDGEMENT We are grateful for the cooperation of the following laboratories who made supplies of the various psychopharmaceuticals freely available: Ciba Pharmaceutical Prods. (reserpine), Lakeside Laboratories (JB—318, 336), Eli Lilly & Co. (amobarbital), Merck, Sharpe & Dohme (benactyzine), Riker Laboratories (deanol), Roche Laboratories (iproniazid), Sandoz Pharmaceuticals (LSD-25), Schering Corp. (perphenazine), Smith, Kline & French Laboratories (chlorpromazine, diethazine), E. R. Squibb & Sons (triflupromazine), Winthrop Laboratories (Win—2299), Wyeth Laboratories (promazine, meprobamate) . REFERENCES 1 L. G. ABOOD, A. M. OSTFELD AND J. BIEL, Proc. Soc. Exptl. Biol. Med., 97 (1958) 483. 2 3 4 5 6 7 K. ANDERMANN, Med. ]. Australia, 2 (1957) 1. P. B. BRADLEY AND J. ELKES, Brain, 80 (1957) 77. M. FINK, ]. Hillside Hosp, 6 (1957) 197. M. FINK, A.M.A. Arch. Neurol. Psychiat., 80 (1958) 380. M. FINK, Electroencephalog. and Clin. Neurophysiol., IO (1958) 776. M. F INK, J. JAFFE AND R. L. KAHN, Drug—induced changes in interview patterns: linguistic and neurophysiologic indices, in J. SARWER-FONER, The Dynamics of Psychiatric Drug Therapy, Springfield, Ill. 8 M. FINK AND R. L. KAHN, A.M.A. Arch. Neurol. Psychiat., 78 (1957) 516. 9 M. FINK, R. L. KAHN AND M. A. GREEN, Diseases of Nervous System, 19 (1958) 113. 10 M. FINK, R. L. KAHN AND H. KORIN, Proc. Intern. Congr. Neurol. Sci, 1957, Brussels, in the press. 11 S. GARATTINI AND V. GHETTI, Psychotropic Drugs, Elsevier, Amsterdam, 1957. 12 J. JAFFE, ]. Hillside Hosp, 6 (1957) 207. 13 R. S. JORGENSEN AND M. H. WULFF, Electroencephalog. and Clin. Neurophysiol., 10 (1958) 325. 14 R. L. KAHN AND M. FINK, in P. HOCH AND J. ZUBIN, Psychopathology of Communication, Grune & Stratton, New York, 1958, p. 126. 15 R. L. KAHN, M. FINK AND E. A. WEINSTEIN, A.M.A. Arch. Neurol. Psychiat., 76 (1956) 23. 13 H. PENNES AND P. HOCH, Am. Psychiat., 113 (1957) 887. ]. 17 C. C. PFEIFFER et al., Science, 126 (1957) 610. 13 H. STRAUSS, M. OSTOW AND L. GREENSTEIN, Diagnostic Electroencephalography, Grune & Stratton, New York, 1952. 19 G. VERDEAUX AND R. MARTY, Rev. neurol., 91 (1954) 405. 20 A. WIKLER, Nervous Mental Disease, 120 (1954) 157. ]. 21 D. L. WINFIELD AND G. H. AIVAZIAN, Electroencephalog. and Clin. Neurophysiol., 10 (1958) 575. C. C. THOMAS, Printed in The Netherlands �EEG and Behavioral Effects of Psychopharmacologic Agents Max From Fink MOD. the Department of Ekperimental Psychiatry, Hillside Heapital, Glen Oaks, L010, NIY. Institute of Mental in part, by grants III-927 and MY—2092 , National Health, National Institutes of Health, U.S.P.H.S., and Bristol, Smith, Kline Aided, French and Wyeth Laboratories. Read at the Collegian Internationale Neuro-Psychophamacologicum, September 12, 1958. IV:9-3-53 Rune, and �EEG and Behavioral Effects of ggzchophgrmacologic Aggnts Recent studies have presented data supporting a neurophysiologica adaptive view of the convulsive therapy process (1, 2). This hypothesis holds that the clinical efficacy of repeated induced convulsions is dependent upon the induction of a persistent alteration in cerebral function, which provides the milieu for changes in the subject's interaction with the environment. In these studies the best index of neuroplnrsiologic change has been those aspects of cerebral function reflected by delta activity in the electroencephalogram (3 ,h,5). efficacy of newer psychopharmaceuticals in altering psychotic behavior patterns led to the suggestion of a similar hypothesis for the mode of action of these agents (2), and to studies of the relationship The and specificity of altered behavioral patterns to neurophysiologjc as reflected in electroencephalogram. experimental data observed in ongoing SUBJECTS AND We change This report smunarizes some of the tests of this hypothesis. MODS: patients, suffering from depressive excited schizophrenic states and severe psycho- have studied consecutive psychoses, agitated and neurotic disorders, referred for physiodynamic therapies (convulsive, psychotropic drug, insulin coma) in a voluntary, open-wand, psychiatric hospital. Serial electroencephalograms were taken prior to, during and sitar the course of therapy. In addition, at various stages of the treatment and program acute experimental studies were done. As both convulsive chlorpromazine therapies elicit varying degrees of EEG slow wave activity, �.2these acute observations have been made in without slow wave activity, and those with diffuse s1 or burst EEG w wave (HSD, LSD) activity (6). and leW'WaVB (BSD) Observations have been bipolar of subjects: those two groups in the made laboratory. Following a routine EEG recording, an unstructured psychiatric interview recorded. Under continuous EE‘3 intravenously at a set rate until was recording, medication was administered EEG or behavioral effects were observed. Following the injection the interview was repeated and recorded. EEG drug tape- Periods of recording and interview recording were alternated for the duration of activity. Behavioral evaluations have been based both on clinical descriptions by the participants (subject, physician changes in language patterns and technician) and analyses of (7,8). Electroencephalograms were measured for shifts in dominant frequencies, and changes in voltage, modulation, and per cent time of alpha, beta and delta frequency bands. The psychopharmacologic agents were administered periods in clinical trials (Table I). trials, Dosage and intravenously for each compound orally for extended in the acute experimental varied, but in each instance sufficient medication has been given to achieve clinical behavioral effects. �I TABLE PSYCHOPHARMAGOIDGIC AGENTS STUDIED (Oral and Intravenous) chlorpromazine amobarbital atropine ** promazine thiopenzal ** diethazine ** LSD-25 triflupromazine (b) " perphenazine amphetamine Win~2299 reserpine* methamphetamine JB-318 (c) (d) ** JB—336 (e) iproniazid deanol (a) meprobamate ** * benactyzine a. dimethylaminoethanol (9 ) b. lysergic acid diethylamide c. 2-d1ethylaminoethyl cyclopentyl (2-thieny1) glycolate (10) d. n~ethyl-3~p1peridy1benzilate (11) e. n-methyl—B—p1peridy1benzilate (11) * oral only ** intravenous only ** �OBSERVATIONS: (a) Electroencephalographic: patterns, observed on acute drug be identifieci according to the characteristics Four broad types of administration, of frequency may shift EEG and synchronization (2): activity in synchrony; 1) Increase in slow 2) Increase in synchrony without frequency shift; 3) Increase in wave fast wave activity and and h) Desynchronization and frequency Examples of each are seen in figures l-h. -0- ---”-“-U- u -- Fig. 1, 2, 3, ,4 in synchrony; irregularity. �-5 During convulsive therapy, an increase in slow wave synchrony is manifest. (Fig.5) ‘iith Fig. activity and drug administration similar changes 5 -------in frequency spectrum and in synchrony are observed (Figs. 6, 7). Figs. 6 7 0f the psychophnrmaceuticals tested in acute experiments in synchrony with Sr without an increase in observed for chlorpromazine, promazine regularly induced an increase and slow wave triflupromazine. in fast activity with an prominent after diethazine, increase activity has been Barbiturates increase in synchrony, while amphetamine and methamphetamine increased without increased synchrony. an fast activity Desynchronization of frequencies was LSD-25, Win-2299, JB-BlB, JB-336 and benactyzine. In subjects with post-convulsive delta activity, acute administration of chlorpromazine, promazine, triflupromazine, amobarbital and pentothal increased the per cent time and voltage of slow wave activity. Decrease in voltage and per cent time of slow wave activity was seen with LSD-25, benactysine, Win-2299, JB-318, JB~336, and diethazine (12-13). Similar electrographic patterns administration of these compounds. were noted in chronic oral Chlorpromazine, promazine, high do$s of reserpine and occasionally perphenazine elicited increased synchronization and a shift of frequencies to the delta range. Increased �.6synchronization without frequency shift was occasionally observed with iproniazid. Increased high voltage fast activity was observed with meprobamate and barbiturates. benactyzine induced EEG Oral administration of LSD-25 and desynchronization with an increase in fast frequencies. (b2 Behavioral: Initial studies of convulsive therapy noted that behavioral change was dependent upon the development of synchronous slow wave (3). Prominent among tranquillization activity the associated behavioral effects were sedation, and euphoria in agitated, depressed subjects, and a decrease in somatization, paranoid ideation, hallucinations and delusions in schizophrenic ideation and excited subjects. Increasing agitation, paranoid and panic were observed in less than Similar behavioral relationships pharmacologic agents. 10% of the subjects. were prominent with these psycho~ In acute experiments, administration of chlorpromazine, promazine and triflupromazine was associated with increasing sedation, drowsiness, denial and euphoria, decreasing agitation, panic, excitement and delusional and hallucinatory activity, and minimization and displacement of symptoms. Sedation, euphoria, denial and minimization were similarly associated with amobarbital. Administration of amphetamine and methamphetamine resulted in behavioral alerting, hypomania, excitement, and increased motor activity. Similar increased alerting, excitement, tension and panic were observed after benactyzine. In addition to these patterns, illusory sensations and hallucinatory, delusional diethazine, and paranoid ideation LSD-25, Win-2299, JB-318 and JB—336. were observed with �-7Equally prominent with the behavioral changes were alterations in patterns of language. Previous studies of convulsive therapy had indicated that specific syntactic language patterns (as in the use of the third person mode, past and future tense, displacement, minimization, denial, cliches, and cryptic remarks) increased with increasing neurophysiologic change (7). These language patterns were further exaggerated by intravenous amobarbital (l, 7). In the present studies, chlorpromazine, triflupromazine and iproniazid increased these language patterns. Diethazine, LSD-25, Win-2299, and benactyzine decreased and reversed these language patterns, increasing the use of the present tense, first person mode, and somatization (1h). (0) Relation of Behavioral The and Electrqgraphic Observations: electrographic patterns were consistently altered concurrently with behavioral changes both in the acute and chronic administration studies. Tranquillization, euphoria, sedation.and minimization of symptoms were commonly synchronization and associated with increased EEG shift of frequencies to the delta range. Agitation, tension, panic, excitement, illusions and hallucinations were associated with a desynchronization of frequencies. Similar patterns were demonstrated in subjects with prior delta activity. Agents that tended to synchronize frequencies, as chlorpromazine and barbiturates, augmented the per cent time delta activity and enhanced clinical patterns, while agents that desynchroniaed frequencies, as diethazine, LSD-2S and benactyzine, minimized the clinical effects ascribed to repeated convulsions (12, 13, 1h). �-8DISCUSSION: These observations are consistent with the neurophysiologic-adaptive hypothesis of the mode of action of the newer psychopharmaceuticals (2). is This hypothesis states that the clinical efficacy of psychotropic drugs persistent/alteration in cerebral function which provides the milieu for changes in the subjects' interaction with the dependent upon the induction of a variety of neurophysiologic patterns induced by these agents is in contrast to the limited patterns resulting from convulsive therapy and thus provide amplification of the original hypothesis. It is environment. The evident from these studies that the type of neurophysiologic alteration induced, as reflected in EEG synchrony and frequency to specific types of behavioral adaptation. a With patterns, is related increasing synchrony shift to the delta frequency spectrum, tranquillization, sedation and and decreased agitation become prominent, while desynchronization and a shift to beta frequencies are associated with excitement, illusions and delusional ' ideation. These studies are also consistent with numerous reports of the neuroand physiologic effects of these compounds (15-20), and specifically support amplify those of Wikler who concluded, in his studies of morphine and mescaline, that "regardless of the nature of the drug administered, shifts in the pattern of the electroencephalogram in the direction of desynchroniza- tion occurred in association with anxiety, hallucinations, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness" (21). This hypothesis, and the electrographic measure of neurophysiologic change, lends itself to application in the assay of the rational application of pharmacotherapy (lb), new psychotropic drugs and as a (2% basis for further experimental study of neurophysiologic-behavioral relationships in psychiatry. �SUMMKRI AND CONCLUSIONS: The relation between electroencephalographic change and behavioral response was determined on acute and chronic administration of a variety of psychopharmacologic agents in voluntary, openoward, psychiatric patients. EEG patterns were classed according to effects on synchrony and frequency patterns. Behavioral and language pattern changes were noted as concurrent with Agents EEG response. that induced an alteration in neurophysiology manifest as increased synchrony and frequency slowing in EEG were associated with behavioral sedation, tranquillity, and minimization of symptoms. Increased synchrony and increased frequency were associated with sedation, euphoria, hypomania and decreased somatization. Desynchronization of frequencies was accompanied by increasing agitation, excitement, somatization, illusory phenomena and and hallucinatory delusional ideation. The neurophysiologiccadaptive hypothesis of the psychotropic drugs is supported; mode of action of and the value of electroencephalography in the behavioral assay of these agents is suggested. �-10REFERENCES and Weinstein, E.A.: Relation of Amobarbital Test to Clinical Improvement in Electrashack, A.M.A. Arch. Neural. & Psychiat. 1Q: 23-29, 1956. l. Kahn, R.L. , Fink, 2. Fink, 3. Fink, h. Fink, M., Kahn, R.L. and Green, M.A.: Experimental Studies of the Electroshock Process, Dis. Nerv. . 12: 113-118, 1958. M.: A M. Unified Theory of the Action of Physiodynamic Therapies, J. Hillside Hosp. é: 197-206, 1957. Balatian of EEG Delta Activity to Behavioral Response in ElectraShock: Quantitative Serial Studies, A.M.A. Arch. Neural. & Psychiat. 1.8.: 516-525, 1957. M. and Kahn, R.L.: a Fink, , Kahn, R.L. and Karin, H.: Relation of Tests of Altered Brain Function to Behavioral Change Following Induced Convulsions, Prac. Int. Cong. Neural. Sci,, 1957, Brussels, (in press). M. Strauss, , Ostaw, ography, Grune H. Kahn, R.L. and M. & and Greenstein, L.: Diagnostic Electroencephal- Stratton, N.Y., 1952. Fink, M. : Changes in Language During Electroshock and Therapy, in Psychopathalgg of Comunication eds. Hoch, P. Zubin, J., Grune & Stratton, NJ. 1958, 33-139. Jai‘fe, J .: An J. Hillside Hosp. é: 207-215, 1957. - Pfeiffer, C.C. et a1.: Stimulant Effect of 2 - dimethylaminoethanal _12__§: 610-611, views, 9. 10. Objective Study of Communication in Psychiatric Inter- Precursor of Brain Acetylcholine, Science Pogsible 19 7. Pennes, H. and Hach, P.: Psychatomimetics, Clinical and Theoretical Considerations, Amer. J. Psychiatn 113: 887-892, 1957. Abaod, L.G., Osti‘ield, A.M. and Biel, J.: mimetic Agents, Proc. Soc. Exp. Biol. A New Group of Psychoto- Med. 21: h83-h86, 1958. Effect of Anti-Cholinergic Agent, Diethazine, on ER} and 12. Fink, 13. Fink, M.: Effect of Anti-Cholinergic Compounds an Post-convulsive EEG and Behavior, EEG. Clin. Neurophysiol. (in press). 14.: Behavior: Significance for Theory of Convulsive Therapy, A.M.A. Arch. Neural. & Psychiat; (in press). �-11.. REFERENCES Fink, M. and Jaffe, J.: Drug Induced Changes in Interview Patterns: and Neurophysiologic Indices, in Conference on amic A ects of Neurole tic D 3, ed. 3. Sarwer- Linguistic P chc oner in press . 150 Verdeaux, G. and Marty, R.: Action sur L'Electroencephalogramme de Substances Pharmacodynamiques D'interet Clinique, Rev. Neurol. ............._.. 2;: 1.05-4.27, 195a. 16. Andermann, K.: Electroencephalographic Evidence of Personality Change Produced by Ataractic Drugs in Mentally Disturbed 17. Bradley, P.B. and Elkes, J.: The Effects of Some Drugs on Electrical Activity of the Brain, Brain, g9: 77-117, the 1957. 18. Garattini, S. 19. Jorgensen, R.S. and wulff, M.H.: The Effect of Orally Administered Chlorpromazine on the Electroencephalogram of Man, EEG. Clin. ' and Ghetti, V., Amsterdam, .1957. eds.: Psychotropic Drugs, Elsevier, Neuroghysiol. 39: 325-329, 1958. 20. Winfield, D.L. and Aivazian, G.H.: EEG. Changes Associated with Sparine Therapy, EEG. Clin Neurophysiol. $9: 575, Inégnsive 19 . Wikler, A.: Clinical and Electroencephalographic Studies on the Effects of Mescaline, N-allynormorphine and.Morphine inLMan, J. Nerv. Ment. Dis. 120: 157-175, 19Sh. �-12.. FIGURES 1. Chlorpromazine, oral (male, age 15). 2. Chlorpromazine, oral (female, age 3b). 3. Amobarbital, intravenous (male, age 31). Win-2299, intravenous (female, age bl). flectroconmllsive Therapy (female, age 55). Amobarbital, intravenous (female, age 36). Win-2299, intravenous (female, age 51). �ACKNOWEDGEMENT are grateful for the cooperation of the following laboratories who made supplies of the various psychopharmaceuticals We fully available: Ciba Pharmaceutical Prods. (reserpine), Lakeside Laboratories (JB—318, 336), Eli Lilly 8: Co. (amobarbital), Merck Sharpe 8c Dohme (benactyzine), Riker Laboratories (Deanol), Roche Laboratories (iproniazid), Sandoz Pharmaceuticals (LSD-25), Schering Corp. (perphenazine), Smith, Kline 8: French Laboratories (chlorpromazine, diethazine), E.R. Squibb & Sons (triflupromazine), Winthrop Laboratories (Win-2299) and Wyeth Laboratories (promazine, meprobamate ) . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource EEG and behavioral effects of psychopharmacologic agents. In P. B. Bradley, P. Deniker, and C. Radouco-Thomas (eds.), Neuro-Psychopharmacology. Elsevier, Amsterdam, 1959, 1: 441-46. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-37b-003 Date A point or period of time associated with an event in the lifecycle of the resource 1959 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint and [preprint]. Reprint from Neuro-Psychopharrnacology Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/e014a6afb9c7514b91c71748685499ca.pdf 9f4aefec5e8c130c970f3538c3603299 PDF Text Text ELECTROENCEPHALOGRAPHIC AND BEHAVIORAL EFFECTS OF TOFRANIL Max Fink, M.D. Reprinted from “CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL” Volume 4 Special Supplement, 1959 McGill University Conference on Depression and Allied States, Montreal, March 19-21, 1959 �ELECTROENCEPHALOGRAPHIC AND BEHAVIORAL EFFECTS OF TOFRKNIL MAX FINK* With the rapid increase in the number of potential psychopharmaceuticals, the need for screening technics has become more acute. In studies of the electro— graphic patterns of convulsive therapy, the hypothesis evolved that behavioral changes induced by new compounds could be related to their neurophysiologic effects as reflected by the type and degree of electrographic change (1, 2). This suggestion followed a similar one by Wikler (3) who stated that “regardless of the nature of the drug administered, shifts in the pattern of the electroencephalogram in the direction ofdesynchronization occurred in association with anxiety, hallucina— tions, fantasies, illusions or tremors, and in the direction of synchronization with euphoria, relaxation or drowsiness.” Studies with various psychotropics (4) and anticholinergic hallucinogens (5, 6) supported such a relationship. It is the purpose of this preliminary report to describe initial behavioral and electrographic observa— tions with Tofranil'l, a new psychopharmaceutical, and to relate these observations to the neurophysiologic—adaptive hypothesis of the mode of action of physiodynamic therapies (1). Methods Two types of studies were undertaken in an open—ward, voluntary hospitalized population. In 28 acute experiments, consecutive patients referred for physiodynamic therapies were tested in the EEG laboratory at various stages of treat— ment. Tofranil solution (10 mg/ml) was administered intravenously at a set rate (1 ml/4O sec.) until electrographic or behavioral changes became prominent, for a total of 40—125 mg (0.5—mg/kg). Behavioral observation and electrographic record— ing continued for one to three hours. A second group of 16 patients manifesting depressive, withdrawn or retarded behavior were referred by their therapists for pharmacotherapy. The patients received daily oral Tofranil, 75—250 mg. Behavioral observations and EEG recordings were made prior to and during treatment. Patients ranged in age from 17 to 58, and were diagnosed as suffering from schizophrenia, manic-depressive and involutional depressive psychoses, and psychoneuroses. ' Observations I. dcute Studies: On acute administration, there was an initial restlessness, associated with dizziness, dry mouth, “faintness,” nausea, and on four occasions, vomiting. These symptoms persisted for 10—20 minutes, and were accompanied by lassitude, heaviness of the extremities and eventual drowsiness. Heart rate was un— changed or slowed. Subsequently, subjects were relaxed, quiet and disinclined to activity, even when returned to their ward. The electrographic patterns accompanying these behavioral changes were initiated by a gradual decrease in voltages during the injection. By ten minutes, the per cent time alpha and mean alpha voltage had been halved. In four patients with moderate amounts of beta activity, such activity increased in voltage and low behavioral with association lassitude, time. minutes, By in cent twenty per voltage (to 50 microvolts) random theta frequencies (5-7 cps) appeared (Figures 1 and 2). *Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L.I., N.Y. Aided in part by grants M-927 and MY-2092 of the National Institute of Mental Health, National Institutes of Health, U.S. Public Health Service; and by a grant from Geigy Pharmaceuticals. The technical assistance of Mrs. Hannah Mosquera in EEG recording is gratefully acknowledged. ’rTrade Mark. �Special Supplement pre-d rug WWW WWW LF-LO 8167 DEPRESSION AND ALLIED STATES W W after 75 mg after 30 minutes WNW RF-RO wWWv«w¢wanMV‘ I‘VWW LAT-LF RAT-RF k/\_Jl/L,Ah/L JL/\,JA/A,_JL/\, =72 #2638Hh WW W WWW HR after 45 minutes HR 50 Mv|—_l SEC. =74 HR =72 1 Fig. 1 Effect of intravenous Tofrinil on EEG delta (female, aged 46) pre—drug LF-LO «wwNWVHMWwNmN RF-RO WWW LAT-LF W W after 100 mg after 30 minutes hv after 30 minutes “NV“WJWWWWVVV¢ UWMerVkmeV4 WWW WWW RAT-RF LF-RF LPT-LO 0-0 EKG plvltul HR=84 #2138HH W MymMA/VW-WVN MWVWVWMN‘ HR=108 50/.1vl—__J 1 Fig. 2 HR=84 SEC. Effect of intravenous Tofrinil on EEG delta (male, aged 37) HR=9O �8168 Vol. 4, 1959 CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL In six records with post—convulsive delta activity, there was a marked decrease in voltages and per cent time of slow wave activity. These electrographic patterns persisted for half—an-hour to two hours (Figure 3). There was considerable individual variability in the EEG response. In patients who received 100 mg or more of Tofranil, EEG and behavioral changes were Observed in all but three. In six patients, dosage Of Tofranil less than 50 mg were not associated with either EEG or behavioral changes. 2. Chronic fldministmtion Studies: Sixteen patients, manifesting depressive symptoms with varying degrees of insomnia, anorexia, withdrawal, and agitation, have received Tofranil medication for four weeks or longer. Medication was given in oral divided doses of 100—250 mg per day. Behavioral changes generally appeared during the second and were maximal during the third week of treatment. LF-lO after 100 mg pre-drug W W WW W W WWW RF-RO RAT-RF LF-RF . LPT-LO 0-0 #2348 after 30 minutes after 15 minutes iv HR=86 HR=84 ,_~,\_M, amw HR=75 50 uv HR=72 l_ 1 __ SEC. _J Fig. 3 Effect Of Tofranil on EEG delta (female, aged 41: 24 hours post convulsion no. 7) The most prominent behavioral adaptation was euphoric denial, which was noted in eight patients. The depressive attitude was nO longer apparent. They participated more fully in ward activities, complained less of somatic symptoms, and denied, minimized or displaced their illness on inquiry. Agitation decreased, and complaints of insomnia became less. It became increasingly difficult to discuss significant life relationships as the patients pressed for an early discharge from the hospital. In three patients somatization and restlessness increased, and depressive affect persisted. In two of these, restlessness, insomnia and vomiting led to cessation of therapy. Sweating increased in most patients, but became a focus of attention in these subjects. NO change in symptoms were noted in five patients after four weeks of therapy. While no serious complications of therapy were noted, nausea, increased sweating, vomiting, dryness Of the mouth, restlessness and excitement, and increasing �Special Supplement DEPRESSION AND ALLIED STATES $169 insomnia were reported. These were prominent early in therapy, and except for the vomiting and restlessness, did not limit the treatment. In three subjects medica— tion was initially administered parenterally without untoward effects. Abnormal motor patterns and seizures were not noted in these patients at these dosages. Electrographic studies on chronic administration showed minimal changes. Voltages became lower and record modulation became poorer. Well—defined fast activity became more prominent, and in four subjects low-voltage theta (5—7 cps) activity was noted. Discussion These observations indicate that Tofranil is an active central nervous system agent in man, both on oral and intravenous administration. The neurophysiologic effects are manifest electrographically as desynchronization of rhythms and a shift-in frequency spectrum to the slower range. In depressed retarded subjects, Tofrinil administration is associated with such behavioral changes as decreased depressive affect with increased participation in ward activities, increased use of denial patterns (7) and occasional excitement. In comparison to our previous experience with other physiodynamic therapies, the behavioral and electrographic patterns of Tofranil are most like those seen with central anticholinergic agents. We observed desynchronization of frequencies, with an increase in theta activity, to be prominent with experimental anticholinergic compounds such as diethazine and benactyzine* (5, 6). In those studies, electro— graphic desynchronization was associated with behavioral alerting, excitement and illusory and hallucinatory activity. On Tofranil administration, similar electrographic patterns of desynchronization were observed, accompanied by euphoria and increased ward participation. While we have not observed hallucinatory activity at our dosage ranges, Lehmann (it a]. (9) have reported hallucinations and hypomanic excitement in 7 of 84 patients receiving Tofra‘mil. In earlier reports, Wikler (3, 10) suggested that the electrographic patterns of synchronization and desynchronization reflected neuron systems distinct from those neuron systems subserving such functions as ‘sensation,’ ‘ideation’ and ‘level of awareness.’ While these systems were frequently interlocked, dissociation between EEG pattern and behavior was observable under a variety of drug—induced states. In our earlier studies we were impressed that the electrographic and behavioral patterns seen after induced convulsions, anticholinergic compounds and phreno— tropic agents were directly related. On acute administration of Tofranil, however, electrographic desynchronization was associated with clinical sedation. These studies are consistent with Wikler’s suggestion. These observations permit the classification of the neuropharmacologic activity of Tofrinil in the central nervous system as predominantly anticholinergic. However, we have noted aspects of the electrographic and behavioral patterns reminis— cent of increased cholinergic activity. These include the electrographic shift to slower frequencies and sedative, euphoriant behavioral effects. Such observations suggest that there may also be an effective degree of central cholinergic activity. Summary Intravenous administration of Tofranil in 28 voluntary, open—ward psychiatric patients elicited electrographic patterns of desynchronization and an increase of theta rhythms, associated with behavioral alerting, relaxation and lassitude. Chronic administration of oral Tofrinil in 16 depressed and retarded psychiatric subjects elicited behavioral adaptations of euphoric denial in eight, restlessness 'A recent report by Abood and Meduna (8) relates the behavioral. improvement in depressed patients with a new central anticholinergic agent which has Similar electrographic patterns. J B-329, H ” �8170 CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL Vol.4,1959 and somatization in three and no change in five. During the fifth week of adminis— tration, electrographic desynchronization was manifest. It is concluded that Tofranil is an active central nervous system agent, with a Spectrum of activity most like experimental anticholinergic hallucinogens. The theoretic significance for neurophysiologic-behavioral constructs is briefly discussed. Résumé Nous avons étudié la relation existant entre les efiets du Tofrinil sur le com— portement et sur le tracé électrographique, chez des patients atteints de psychoses aigués ou chroniques. Mét/zode Cas aigus: les patients retenus étaient examinés avant le traitement physioin— celui—ci. Tofranil Le de administré était stades divers ainsi en qu’a dynamique, jections intraveineuses d’une solution a 10 mg/ml, jusqu’a un total de 40—125 mg (0,5_2,5 mg/kg), concurremment avec des examens électro—encé—phalographiques. Cas chroniques: des patients présentant de la depression et un ralentissement du comportement étaient mis a la dose de 75—250 mg de Tofrz'mil par jour. Les examens encéphalographiques et du comportement étaient effectués avant le début du traitement, et a intervalles d’une semaine au cours de celui—ci. Observations 1° Cas aigus a) Comportement: au cours de l’administration du medicament, sur 28 cas, nous avons noté des nausées, des vertiges et de la faiblesse. Quatre fois des vomissements sont survenus. Le rythme cardiaque est demeuré inchangé, ou s’est ralenti. En 10 minutes ces symptOmes diminuaient d’intensité et les patients se détendaient. b) Electro-mcéphalogmmme: pendant le traitement, il y a eu une diminution du voltage dans toutes les fréquences. En 10 minutes le pourcentage de temps alpha baissait et les voltages tombaient a la moitié de leurs valeurs initiales. Chez les sujets a activité béta (4 cas), celle—ci devenait plus importante. Au bout de 20 5—7 de lentes ondes des minutes, cps, atteignant 50 microvolts, apparaissaient ici et la. Dans les enregistrements avec activité delta postconvulsive (6 cas) nous avons noté une baisse marquee des voltages et des pourcentages de temps danS l’activité des ondes lentes. Ces tracés électrographiques persistaient pendant M-Z heures. 2° Cas chroniques a) Comporz‘emem: seize sujets ont été observes a ce jour. Les effets~initiaux de la medication furent des nausées, deS vomissements, de l’agitation et de l’excita— tion, une exagération de l’insomnie et une transpiration tres augmentée dont se plaignaient les malades. Le traitement a été interrompu dans deux cas avec agita— tion. Des 13 autres sujets, 6 ont vu leurs symptOmeS de depression S’amender et ont pu reprendre une plus grande activité; ils ont pu étre renvoyés chez euX, ou ont été prévus pour un prochain licenciement. Les autres n’ont guere présenté de chan— a la soumis été n’ont leurs thérapeutique que pendant dans symptOmes, ou gements un temps trop court. &) Electra—encéphdlogmmme: Les enregistrements obtenus pendant 1e traite— ment n’ont montré que peu de modifications. Leur modulation était appauvrie et leurs voltages abaissés. Une activité rapide bien caractérisée a pris de l’impor— 5—7 de a bas activité noté voltage 4 malades chez une cps. nous avons tance; Conclusion: 1° Chez les psychopathes, les effets electrographiques du Tofrinil sont une Ces a tracés has lentes d’ondes activité voltage. suivie une désynchronisation, par a alors ressemblent les traités, et dans chroniques moins cas prédominants sont ceux que l’on Obtient avec la benactyzine. ' �Special Supplement DEPRESSION AND ALLIED STATES 2° En ce qui concerne le comportement, nous constatons une $171 augmentation de la motilité, un changement dans l’humeur et un malade plus éveillé. 3° Ces observations concordent avec les hypotheses neuro—physiologico—adaptatives expliquant 1e mode d’action des traitements physiodynamiques des psychoses. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Fink, M.: Hillside Hosp. J. 6:197, 1957. Fink, M.: Alteration of brain function in therapy, in Kline, N. S.: Psychopharmacology frontiers, Boston, Little, Brown, 1959, pp. 325-333. Wilder, A.: J. Nerv. & Ment. Dis. 120:157, 1954. Fink, M.: EEG and behavioral effects of psychopharmacologic agents. Read at 1st International Congress of Neuro—psycho—pharmacology, Rome, September 1958. In press. Fink, M.: A. M. A. Arch. Neurol. 8: Psychiat. 80:380, 1958. Fink, M.: Electroencephalog. 8t Clin. Neurophysiol. 10:776, 1958. Weinstein, E. A., and Kahn, R. L.: Denial of illness: symbolic and physiological aspects, Springfield, 111., C. C. Thomas, 1955. 'Abood, L. G., and Meduna, L. J.: J. Nerv. & Ment. Dis. 127:546, 1958. Lehmann, H., Cahn, C. H., and de Verteuil, R.: Canad. Psychiat. A. J. 3:155, 1958. Wikler, A.: Proc. Soc. Exper. Biol. & Med. 79:26], 1952. General discussion from the floor (summarized) The question was asked whether administration of a large dose of Tofranil once a day would not be as effective as multiple dosage. This would of course be a tremendous saving in the time of the nurses involved. In answer it was stated that Tofrénil is best given not in one large daily dose but in a series of small doses such as 2 tablets t.i.d. It was also brought out that Tofranil has a tremendous influence on transference phenomena and that these can be analyzed in dreams and symbolisms. While such observa— tions have been made, definitive results must await an extensive study. Another discussant asked what is the difference between the effect of barbiturates and anticholin— ergic drugs on the EEG. One discussant felt that the EEG was a poor tool, since it could be modified in only two ways, synchronization or desynchronization, and firm conclusions should not be drawn from such changes. He therefore felt that analogies between diethazine and Tofrénil were dubious and that nausea was not a specific effect of Tofranil. He wondered if EEG changes would always exist in the absence of nausea, and felt it important to correlate EEG changes with clinical changes. In replying to these comments, Dr. Fink stated that he considered Tofrfinil an anticholinergic drug because of its similarity to other anticholinergic drugs in regard to its EEG patterns. Dr. Fink recalled that Dr. Sigg’s paper had also indicated that Tofrfinil was an anticholinergic drug. Many anticholinergic compounds appear to have rather specific central effects, and some are also experimental hallucinogens. In his experience, barbiturates produce not desynchronization, but rather synchronization. This becomes clear if the factors of dosage and time are considered. Thus the initial effect is hypersynchronization; if the drug is continued, sleep is of course produced and the initial effect disappears. The author replied to the criticism of his use of EEG. He agreed that it is a poor tool in many respects, but that it is possible to analyze EEG records for synchronization, desynchronization and fre uency shifts. One obtains different patterns with different agents even in the same patient. Dr. Fink explained that he was making a long—term study, and hoped that more conclusive data could be offered at a later time. ��’*” EEG uni nahtviernl striat: .2 nu nah, Torranil 3...». * 2h: rulltion hotvtcu thc filcetragrcphie and behaviortl «Itcctt at retranil in velunthry paychintrie pationtt wan datarnincd in taut. and thrsnic ntudioa. _ Kathodnr latto: Ganaaeutiva patiants rcturrod for phytiodynunic thtrupiol ttntod not: prior to and at yariatu itngal Of therapy. With 330 rocordinc, retruail nelution (10 ng/oc) was adminintorud intruvanouuly for I total of h0~125 I; (0.S~2.5 ng/ks). chronic: Pttiontp annitslting duprctuivo tad rotnrdod bchlvior aura plnoud an rogiucua o: 7S~2oe lg renunil daily. EEG oxnniuntionn and hchuyiornl obsothtiaus war. and. prior to and It weekly int-yttla during troutncnt. Oblarvntianus 1. Acute Stadielt a. Buhfiyiora Baring drug zduiniltrutiou in 25 albjoata, 3.13033, EIuIIncoo in! Ionknoan wort rcpcrtud. Viniting ocearrcd an tour oecaaicnc. fictrt rgto was Inshtngod, tr nluvcd. In 1&3 Iinutca, th... aynptoun were 103:, und puticnta war. roluxod. b. EEG: During ndninistrttion thtrc was a dccruuuc in yoltagc a: all trcquonans. By tan minuttu, thc par cant tint alpha ducronsed, lad valtngea were halt at thc initial values. In pationts with sodurnto anonntn of but. uctiyity (h), auch activity hocuno morc yroxincnt. fly taunty mintha, slow It?! nativity of k-7 apt, up to 50 uiarovclta upponrnd, rundouly. In roenrd: with poat~eenvulaiva daltg activity (6), thert in a nurkcd docrotio in voltngcn and in par tent tin. of claw wave nativity. tutu: electraartphic pattcrn: pcraictcd far 2. Chrunia I studioat _Bchnvi¢rn i. rittouu patient: hay. 2 hours.\ boon under ebccrvutiou to data. -Iai -n a van a at nodicntian inaludod nanaou (a) vaulting (a), roatlouuuocn lad axaitantnt (2), insomnin oxaggorntod (35, And aonplainta o: oxacstivo uwiating (11). In tha tun pationtn with roitlsasnoal, nedic;~. tit» at: diaoontinund. a: the thirtaon pntionts, nix Innitcttni In 3110'iatiun or symptoms a: doprnulion with incronnad pnrtiaipation in activitics, Ind hava Bean dilahargad or rccaunoudcd tar diuehnrga. Th: rcaaiuing buy. nhaun littlc engage in a tan. (3) at thcrapy ht! baan patitntl udniniltorud for too thort a ptriod (hgfp 3:. mm: In neat-d. «ht-sin“ during hottmnt, tiniaul change: taro obIcrvoa. fieduiation a: rucordu was poortr with lcwor yoltncct. H011 dutinod rant activity bee... not. proninont; tad in tour subject. 10v waltago 5~7 cps activity VI! noted. conclusion. Ll Sloetrozrtphic extactn o: Totrunil in payehiutriu patiuntc are thus: of duayuehroniantion, tullowod by law voltngo slaw wtva nativity. * Iron thc Duplrtuant at magazinpnttl Payehintry, nilluidc Rhapital, glig ggk" L010 301% �.2th¢to pattorna arc 1.0: proninnnt an chrcnie udntnintrntiau, tad rononblo that. or bnunctynin0¢ 2) Dihtviornl offset: arc that; of alurtiuc, Iced ch¢n¢a and inurilnnd motility. «autistant with fiha nauraphyszolagtau :Athivu hypathuntu at :h: act. at action or physiodyuania thcrupion 3) Thnss abaorvution¢ nae of paychoucu. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Electroencephalographic and behavioral effects of tofranil. Can Psychiatr Assoc J. 1959;4(Suppl):166-71. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-38a-004 Date A point or period of time associated with an event in the lifecycle of the resource 1959 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint from CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL Volume 4 Special Supplement, 1959 McGill University Conference on Depression and Allied States, Montreal, March 19-21, 1959 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/0a74924969c48b97fad064f4d827441c.pdf e33e0604bf1a53d201e8e551507b5084 PDF Text Text Founded in 1887 by G. STANuIY HALL OFFPRINTED FROM THE AMERICAN JOURNAL OF PSYCHOLOGY EDITED BY KARL M. DALLENBACH UNIVERSITY OF TEXAS AND M. E. BITTERMAN BRYN MAWR COLLEGE E. B. NEWMAN HARVARD UNIVERSITY WITH THE COOPERATION OF E. G. BORING, Harvard University; W. K. ESTES, Indiana University; J. P. GUILFORD, University of Southern California; HARRY HBLSON, University of Texas; E. R. HILGARD, Stanford University; FRANCIS W. IRWIN, University of Pennsylvania; G. L. KREEZER, Washington University; D. G. MARQUIS, Social Science Research Council; GEORGE A. MILLER, Harvard University; W. B. PILLSBURY, University of Michigan; LEO PosTMAN, University of California; W. C. H. PRENTICE, Swarthmore College; T. A. RYAN, Cornell University. THE ROLE OF SET IN THE PERCEPTION OF ‘SIMULTANEOUS TACTILE STIMULI By HYMAN KORIN and MAX FINK, Glenn Oaks, Long Island September, 1959, Vol. LXXII pp. 384—392 Published b The American Journal of Psychology. Department of sychology, University of Texas, Austin. Tex. �Founded in 1887 by G. STANLEY HALL OFFPRINTED FROM THE AMERICAN JOURNAL OF PSYCHOLOGY EDITED BY KARL M. DALLENBACH UNIVERSITY OF TEXAS AND M. E. BITTERMAN BRYN MAWR COLLEGE E. B. NEWMAN HARVARD UNIVERSITY WITH THE COOPERATION OF E. G. BORING, Harvard University; W. K. ESTES, Indiana University; j. P. University of Southern California; HARRY HELSON, University of Texas; E. R. HILGARD, Stanford University; FRANCIS W. IRWIN, University of Pennsylvania; G. L. KREEZER, Washington University; D. G. MARQUIS, Social Science Research Council; GEORGE A. MILLER, Harvard University; W. B. PILLSBURY, University of Michigan; LEO POSTMAN, University of California; W. C. H. PRENTICE, Swarthmore College; T. A. RYAN, Cornell University. GUILFORD, THE ROLE OF SET IN THE PERCEPTION OF SIMULTANEOUS TACTILE STIMULI By HYMAN KORIN and MAX FINK, Glenn Oaks, Long Island September, 1959, Vol. LXXII pp. 384-392 Published by The American Journal of Psychology, Department of Psychology. University of Texas, Austin, Tex. �THE ROLE OF SET IN THE PERCEPTION OF SIMULTANEOUS TACTILE STIMULI By HYMAN KORIN and MAX FINK, Glenn Oaks, Long Island The influential role of ‘mental set’ in determining a subject’s response to a perceptual task has been well documented.] In studies of the perception of simultaneous, tactile stimuli, various patterns of response have been observed which seemed to be the result of a set induced by suggestion. This investigation was undertaken to determine the relation between different conditions of ‘set’ and the frequency and type of perceptual error elicited in tests with simultaneous, tactile stimuli. Recently the advantages of the simultaneous stimulation of different body-parts in tests of tactile perception have been stressed.2 Simultaneous stimulation may elicit perceptual errors under conditions in which successive single stimulations are correctly perceived. When two stimuli are applied to body-parts at the same time, only one stimulus may be reported —an error referred to as 'extinction’; or one stimulus may be perceived correctly and the other mislocalized—an error called 'displacement.’ Occasionally, if a single stimulus is interspersed in the testing-sequence, it may be reported correctly, but an additional, extraneous stimulus may also be reported—an error of ‘confabulation.’ Such errors of extinction, displacement, and confabulation are significantly increased in patients with brain dysfunction. When errors of extinction and displacement occur, they are elicited in a consistent pattern. Thus, on stimulation of the hand and face, the stimulus to the face is usually reported correctly, while that to the hand is mislocalized or not reported. By testing various combinations of bodyparts, an ‘order of dominance’ may be determined in which stimuli to the face and genital areas are most often perceived and those to the hand are for publication September 23, 1958. From the Department of Experimental Psychiatry, Hillside Hospital, Glenn Oaks, Long Island, New York and aided in part by Grant M-927, National Institute of Health, US. Public Health Service. 1]. J. Gibson, A critical review of the concept of set in contemporary experimental psychology, Pryc/aol. 32111., 38, 1941, 781—817; Robert Leeper, Cognitive processes, in S. S. Stevens (ed), Handbook of Evperimeoto] Psychology, 1951, 730-757. 2M. B. Bender, Disorder: in Perception, 1952; M. B. Bender, M. A. Green, and Max Fink, Patterns of perceptual organization with simultaneous stimuli, A.M.A. Arc/a. Neural. é Put/riot, 72, 1954, 233-255; Fink, Green and Bender, The facehand test as a diagnostic sign of organic mental syndrome, Neurol., 2, 1952, 46-58. * Received 384 �SIMULTANEOUS TACTILE STIMULI 385 least often perceived. Between these extremes, stimuli to the shoulder, foot, buttock, breast, back, thigh and abdomen are perceived in a gradient.3 Theories involving factors of rostral dominance,‘ maturation,“ inattention,6 and inherent body-image,7 have been advanced to explain the organization of these perceptual patterns, but no one theory has adequately explained all the facts. We have ascribed significance to the relative intensity of the stimuli and the thresholdvalue in the frequency and the pattern of the 'extinction’ error, when electrical stimuli are applied at threshold and suprathreshold intensities.8 The present study was undertaken to assess the relation between ‘set’ induced by suggestion and errors of 'confabulation’ and 'displacement.’ The specific problem studied is whether an 'inquiry’ into the testing pro— cedure is significantly related to the frequency and type of these errors. Since these errors are most prominent in $5 with cerebral dysfunction, patients undergoing convulsive and subconvulsive therapies were studied. Subjects. The 55 were 61 consecutive psychotic patients referred for electroconvulsive therapy. Their ages ranged between 21—67 yr., mean age being 46 yr. Thirtyseven of them received convulsive therapy; 14 first received subconvulsive therapy and then convulsive therapy; and 10 received subconvulsive therapy alone. The 55 were selected for convulsive or subconvulsive treatment on a random basis by the supervising psychiatrist. Procedure. Two model S-4B Grass square-wave stimulators were synchronized to deliver either single or simultaneous electrical stimuli. An isolation unit was connected with each stimulator to eliminate artifacts and the Output was visually monitored by an oscilloscope. A switch-box was inserted in the circuit to permit independent selection of the various parts of the body. The active and indifferent electrodes for each part were small 3fig-in. steel disks, placed l-in. apart and secured with tape. Bentonite electrode paste was rubbed into the skin of each area before the electrodes were applied. The patient was placed on a couch in a relaxed and supine position. To alleviate undue anxiety, the nature of the testing was described. It was emphasized that a slight tap-like sensation would be felt. The electrodes were then placed on (a) the dorsum of the hands, (b) the mandibular area of both cheeks, and (c) the medial aspect of the calves of the legs. aBender, Green, and Fink, op. .cit., 253-255. 4R. Cohn, On certain aspects of the sensory organization of the human brain: I. A study in rostral dominance as determined by ipsilateral simultaneous stimulation, ]. new. mem‘. Dis., 113, 1951, 471-484; II. A study in rostral dominance in chil1, 1951, 110-122. Neurol., dren, 5 Louis Linn, Some developmental aspects of the body image, Int. ]. Pryc/ooanol., 36, 1955, 1-7. 6Macdonald Critchley, The phenomenon of tactile inattention with specific references to pariental lesions, Brain, 72, 1949, 538-561. 7Bender, op. cit., 77-88. 8 Hyman Korin and Max Fink, Role of stimulus intensity in perception of simultaneous electrical cutaneous stimuli, I. Hillside H0511, 6, 1957, 241-250 �386 KORIN AND FINK Thresholds for the various body-parts were first determined. At a frequency of 0.3 cycles per sec. and a pulse-duration of 50 m.sec., the voltage was increased in uniform increments of 5 v. to the hands and 1 v. to the cheeks every 6.7 sec. (2 pulses) until 5 perceived 100% of the stimulations. After a 10-sec. interval, voltages were decreased until the sensation was no longer reported. After another 10sec. interval, voltages were increased by 1 v. every 6 sec. until the patient again reported 100% of the stimulations. This reading was considered the minimal voltage required to produce threshold-sensation. After thresholds were determined, testing with a random series of 4 single and 6 double simultaneous stimulations followed. The body parts tested were the right hand and left cheek (heterologous stimulation) and the right cheek and the left cheek (homologous stimulation). Stimuli were applied either simultaneously or to one part singly, in a mixed order, for 10 trials. The order of presentation of the heterologous and homologous stimulation was alternated. Failure to report the interspersed single stimuli served as an index that the perceptual threshold had changed. At such times the threshold was again determined, and the 10 test-trials were repeated. Threshold changes, however, occurred infrequently during testing. The patients were tested in two groups: an ‘inquiry' group and a 'no-inqury’ group. The ‘inquiry’ group, consisting of 24 convulsive and 9 subconvulsive 55, was asked the question ”anywhere else?" after each response to a stimulation. No question was asked of the 'no-inquiry’ group, which consisted of 27 convulsive and 15 subconvulsive $5. (The total number of Ss exceeds 61, since 1 S in the 'inquiry’ group and 13 Ss in the ‘no-inquiry’ group were included both in the convulsive and the subconvulsive series.) Electroencephalograms were obtained weekly, on a day following a treatment. These records were quantitatively measured for the degree of induced slow-wave (delta) activity.9 Both the convulsive and the subconvulsive treatments were administered three times weekly on alternative days. Remltr: (1) Errors of confabulation. A response was scored as a confabulation if two stimuli were reported when only a single stimulus was applied. The observations are noted in Table I. In the 'inquiry’ group, confabulatory errors were elicted before treatment from both types of Ss—convulsive and subconvulsive. During treatment, the mean error increased from 0.08 to 0.72 among the ‘convulsive’ Ss and from 0.22 to 0.70 among the ‘subconvulsive’ ones. After treatment, the mean number of confabulations persisted in the ‘subconvulsive’ 55 (1.00) but declined in the ‘convulsive’ ones (0.10); the difference 0.90 being significant at better than the 5% level.10 In the 'no-inquiry’ 9Max Fink and R. L. Kahn, Relation of EEG delta activity to behavioral response in electroshock: Quantitative serial studies, A.M.A. Arc/9. Neural. <5 Psytbidt., 78, 1957, 516-525. 1” The Mann-Whitney ‘U'-test was used to test the significance of these data and those that follow as the scores were not drawn from a normally distributed population. Since the 'U'-test is based on rank-order of the scores, the differences between means are only grossly related to level of significance. �387 SIMULTANEOUS TACTILE STIMULI group, few confabulations occurred at any interval of testing for either the convulsive or the subconvulsive 55. Before treatment, the subconvulsive, ‘inquiry’ 55 made significantly more confabulatory errors than the subconvulsive, ‘no-inquiry’ 55. In a comparison of the ‘inquiry and ‘no-inquiry’ procedures during treatment, the differences were significant both in the convulsive and subconvulsive groups of $5. The differences during treatment are based on the substantial increase in the number of confabulations of the ‘inquiry’ group. After treatment, the confabulations of the convulsive, ‘inquiry’ group decreased to the pretreatment level, and the differences between the convulsive, 'inquiry’ and ‘no-inquiry’ groups were not significant. Though the mean TABLE I MEAN NUMBER ERRORS 0P CONFABULATION No inquiry Inquiry Period convul’ subr convul. sive (N: 24) Pretreatment Treatment Post’treatment * p<o.os; .08 .72 . 10 (N= 9) . 22 .70 I .oo Tp<o.o3; ——————— convul’ subr convul. sive (N: 27) (N: 15) o .11 . 06 o .05 —-— Diff. between inquiry and no! —— inquiry convul’ subr sive convul. .08 .22: .61]L . o4 .65T — Diff. between convulsive and subconvulsive —— inquiry n0r inquiry . 14 .02 . 90* 0 .06 — Ip<o.01. number of errors of the subconvulsive, 'inquiry’ 55 increased after treatment, a comparison between the ‘inquiry’ and 'no-inquiry’ subconvulsive 55 could not be made. Data were not obtained after treatment from the subconvulsive ‘no-inquiry’ 55 because they were transferred to convulsive treatment and were not available for testing. (2) Error; of dirplacement. A response was scored as a displacement if the locus of one of two stimuli was reported correctly and the other incorrectly. Displacements were rarely elicited from the Ss in any of the groups (Table II). The mean number of displacements tended to increase during treatment for the convulsive 55, but the differences from the pretreatment period lack significance. ( 3 ) Error: of extinction. An error was scored as an extinction if only one of two simultaneously applied stimuli was reported. The difference in the number of errors of extinction between the ‘inquiry’ and ‘no-inquiry’ groups was not significant at any period during the course of therapy both for the convulsive and subconvulsive 55 (Table III). During treatment, the mean number of extinctions decreased in all groups. At this period, �388 KORIN AND FINK the difference between the convulsive and subconvulsive, 'inquiry’ 55 was significant. After treatment the errors of all the groups decreased further. (-4) Errors of confaémlatz'on and change: in EEG. An analysis was made of the number of confabulatory errors elicited in convulsive Ss in relation to the degree of electroencephalographic change. ‘Inquiry’ $3 with high degrees of delta activity made significantly more confabulatory errors than inquiry patients with moderate and low degrees of delta activity (Table IV), while few errors were reported by the ‘no-inquiry’ Ss regardless of the change in the EEG. The mean scores of the moderate and low EEG among the ‘inquiry’ 55 was similar to the mean scores of the ‘no-inquiry' ones. N0 EEG slow-wave activity or low degrees of such activity occurred in TABLE II MEAN NUMBER ERRORS Post—treatment * DISPLACEMENT Convulsive Period* Pretreatment Treatment or inquiry . o6 . 09 . 08 Subconvulsive no’inquiry - . 07 . IO . 02 inquiry o .02 . 06 nOrinquiry 0 .01 o Inter! and intrargroup differences are not significant at any period. the subconvulsive 55. As had been indicated, however, the number of confabulatory errors of the subconvulsive group increased significantly during and after treatment. This increase resulted from increasing confabulatory errors in four of the nine patients. Dircmrz'on. Errors of displacement, confabulation, and extinction are elicited when sequences of multiple and single tactile stimuli are applied to various parts of the body. In clinical tests with touch stimulation, these errors are most prominent in patients with cerebral disease.11 Theories which have been advanced to account for the occurrence of such errors have therefore emphasized endogenous factors involving the central nervous system. Numerous studies of the role of set in perception indicate, nevertheless, that the frequency and type of response to a perceptual task may be markedly altered by the immediate aspects of a situation.12 In this study the stimulus-situation has been varied to bring about differing conditions of mental set. The endogenous factors have not, however, been 11Pink, Green, and Bender, op. cit., 46-58. 12Leeper, op. cit, 752-757; Max Pollack, W. S. Battersby, and M. B. Bender, Tachistoscopic identification of contours in patients with brain damage, I. romp. playriol. Pry/301., 50, 1957, 220-227. �389 SIMULTANEO US TACTILE STIMULI neglected and the relation between the effects of diflerent degrees of brain dysfunction has also been determined. In the course of convulsive therapy a marked increase in the number of confabulatory errors is brought about by the ES query: “anywhere else?” which followed every stimulation. Of the convulsive 55 who were asked this question, confabulations were elicited primarily in the group with high degrees of EEG slow-wave activity (marked cerebral dysfuncTABLE III MEAN NUMBER ERRORS 0F EXTINCTION Period Inquiry ———————-——— convul— sive Pretreatment Treatment Postvtreatment * subr convul. (N: 24) (N: 9) I6 2.03 1.37 I . 67 1.14 2. .89 Diff. between No inquiry ————— convulv sive (N= 27) 2. 76 1.71 1.44 sub convul. (N: 15') inquiry and n0vinquiry -——-—~—convulr subv vulsive convul. 2. 37 1.27 —— .60 .32 .07 .70 \ .13 — Diff. between convulsive and subconvulsive N0 inquiry .49 .39 .89* .44 — .48 inquiry p<o.os. TABLE IV RELATION BETWEEN EEG DELTA ACTIVITY AND MEAN NUMBER OF CONFABULATORY ERRORS Degree of Delta activity Group inquiry no inquiry .81 .10 high moderatealow Diff. Signif. (N= 9) (N=2I) .19 (N= 10) .07 (N: 6) .62 .03 p<0.05 N.S. tion) and not in the group with low and moderate degrees (minimal cerebral dysfunction). The importance of the inquiry is emphasized by the consideration that, regardless of changes in the EEG, there was little tendency for confabulatory errors to occur among the convulsive 55 when no inquiry was made. Thus both inquiry and high degrees of EEG delta activity provided the milieu favorable to evoking confabulatory errors in the c0nvulsive therapy 55. Subconvulsive 35 present a different picture. Although virtually no delta activity is induced by subconvulsive therapy, the number of confabulatory errors of four of the nine subconvulsive Ss queried increased substantially during the treatment. Furthermore, while the confabulatory errors of these four subconvulsive Ss persisted and even increased following the course of therapy, the errors of the convulsive Ss queried, in contrast, decreased to the pretreatment level. Patterns of reversible error manifested �390 KORIN AND FINK by convulsive 55 have been reported in the various studies of the effects of electroshock on different types of mental functioning.13 It was expected, however, that confabulations would not be elicited in subconvulsive $5 at is cerebral that earlier observations of view dysfunction in period, any not induced in these patients.14 An explanation for the differences between the ‘convulsive’ and subc0nvulsive ‘inquiry’ 55 is that their therapies had differing effects on the factor of practice. In 'convulsive’ 55, treatment diminished the practiceeffect, including those both with low and high degrees of slow-wave EEG activity. For each test-interval, it was as if the ‘convulsive’ 55 were starting anew. Under these conditions, only $5 with high EEG delta activity manifested a confabulatory set within a single test-period. After the course of therapy, with the disappearance of the delta activity, convulsive 35 were performing at the pretreatment-level. In the ‘subconvulsive’ $5, the set established in the pretreatment-interval was reinforced during each test-period during treatment. Thus the subconvulsive S 5 made even more confabulatory errors after treatment. The results for the subconvulsive group of 55 indicate that certain of them Such brain-function. of alteration without make an errors confabulatory may 53 are apparently influenced by the E and may be described as being suggestible or acquiescent. The failure of the convulsive $5 to establish a set which persisted for prolonged intervals of time, as did the subconvulsive SS, sugS’s If convulsive from effect derived for the basis therapy. a therapeutic gests such mental set, an interpretation as a pathological, regarded are symptoms is particularly appropriate. From the point of view of concepts of mental set, the effect of induced convulsions is to bring about a disruption of maladaptive patterns of behavior. The number of displacement-errors remained the same regardless of whether an inquiry was made. These errors occurred much less frequently than confabulations. During treatment, approximately 30% of the convulsive $5 of both the ‘inquiry’ and ‘no inquiry’ groups responded with at least one displacement. This finding compares closely with the results of 33% with displacements obtained in a study of a similar population of Hyman Korin, Max Fink, and S. Kwalwasser, Relation of changes in memory and learning to improvement in electroshock. Conf. Neurol., 16, 1956, 88-96; Max Fink, R. L. Kahn. and Hyman Korin, Effects of diffuse altered brain function on XV C(mf. of Pryc/ool. Proceed, 1958, 238—239. perception. 1“ Fink, Kahn, and Green, Experimental studies of the electroshock process, Dir. New. $315., 19, 1958, 113-118. ’3 �SIMULTANEOUS TACTILE STIMULI 391 electroshock Ss in which touch-stimuli were applied by the clinical method. Errors of displacement are not a prominent type of error in an electroshock population. With regard to errors of extinction, differences were not significant between the ‘inquiry’ and ‘no inquiry’ groups. The high number of errors of extinction before treatment and the subsequent decrease in errors during treatment, noted in this study, is in contrast to the results obtained with clinical tactile techniques. If clinical methods are used, few errors of extinction are elicited before treatment and there is a marked increase in error during treatment. The results obtained in this study are probably related to the initial difliculty experienced by Ss in perceiving electrical stimuli at threshold and the rapid adaptation to the technique in further testing. These factors play a greater role than the changes induced by the treatment. In initial studies with threshold electrical stimuli, it was believed that a more sensitive test of changes in brain-function than the clinical tactile method could be devised.15 For clinical purposes, however, the perceptual patterns obtained with electrical stimulation lack sufficient discriminability as indices of brain dysfunction. In part, the deficiencies of the method may be ascribed to the necessity for using fixed electrodes and limitations in switching arrangements at threshold. For clinical testing, therefore, simultaneous tactile stimuli applied rapidly in a varied sequence remains the best index of altered brain function.1‘6 Summary and conclmiom. This study of the perception of simultaneously applied tactile stimuli was undertaken to determine the relation between the frequency of perceptual errors to the inquiry made by E. The relations among inquiry, perceptual response, and the degree of brain dysfunction were also considered. In the test-procedure, the threshold (100% point) for square-wave electrical stimuli applied to the hand and cheek of 61 psychiatric patients was determined. Sequences of two simultaneous and single stimuli were applied in a mixed order for the hand and cheek (heterologous stimulation) and both cheeks (homologous stimulation). Heterologous and homologous trials were alternated for each patient. For one group, an inquiry was made following each response to a stimulation, while in a second 15 16 217. Fink, Green, and Bender, op. (13., 46-58. Green and Fink, Standardization of the face-hand test, Neurology, 4, 1954, 211- �392 KORIN AND FINK convulsive 55 treated either made. or The by were was no inquiry group, subconvulsive courses of therapy, at three times a week for 12—20 applications. There was a significant relationship between the frequency of confabulatory errors and the inquiry (suggestion-induced set’) in both convulsive and subconvulsive patients. The confabulatory tendencies of these patients, however, differed greatly. Although the errors for both increased during treatment, errors decreased after treatment for the convulsive differfurther. increased The subconvulsive but in the errors group group, ences between 'inquiry’ and 'no inquiry’ groups with regard to errors of extinction or displacement were insignificant. In 'convulsive-inquiry’ 55, the confabulatory errors of those with high degrees of EEG slow-wave activity were significantly more frequent than those with a low or moderate degrees of slow wave activity. The results of this study lead to the following conclusions: (1) In tests with simultaneous electrical tactile stimuli the number of confabulatory errors is related to an induced set suggested by ES inquiry. (2 ) The number of confabultory errors is increased in $5 with braindysfunction in relation to an inquiry, but may also be induced in patients without brain-dysfunction who are acquiescent and susceptible to suggestion. (3) The frequency of errors of displacement or extinction is not related to the ‘inquiry’ procedure. ��”era Role of Stimulus Intensity in Perception of Simultaneous Tactile Stimuli Hyman Karin, H!» on. and max From ELY. fink, MOD. the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, Aided by Institute 10-9 ’57 of the National Institute of Mental Health, National of Health, 11.5. Public Health Service. grant M—927 .M/J- I 44/ f7 �III: Role of Stimulus 10/9/57 Intensity in Perception of Simultaneous Tactile Stimuli and his coIn the course of the extensive investigations by Bender stimuli, workers (1, 2, 3,) into the perception of multiple simultaneous of two stimuli the pattern of failure of subjects to accurately report one Since led to a concept of an "order of dominance" in cutaneous perception. dominance to biologic and then, the relationShip of the observed pattern of been the subject of psychiatric concepts of body image and body scheme has considerable speculation (h, 7, 8, 1h). The interrelationship of body areas was initially clearly demonstrated was noted in simultaneous tactile tests of face and hand (2) in which it that the stimuli to the hand were frequently not reported or mislocalized. inference These phenomena of "extinction" and "displacement“ led to the that cheek area stimuli were "dominant" to reports, Bender, Pink inance for and Green (3, 10, tactile stimuli in ll, fell stimuli. In subsequent 12) described a pattern of dom- which the face and the primary genital areas were the most perceptive or dominant body dominant; and the shoulder, hand areas; the hand was the foot, buttock, breast, back, thigh, between these extremes in a mild gradient. least and abdomen These observations were made were most in normal adults and children and psychiatric patients, but the major portion clearly discerned in patients with brain disease. Indeed, of the data relates to a group of patients with severe diffuse brain dys- function under observation in a general psychiatric hospital. Bender, The basis for these phenomena is unclear. In their review, Green and Fink (3), after considering hypotheses ascribing significance to and neurophysiologic anatomic, psychophysiologic, genetic, environmental �i "no one theory‘adequately explains the organization factors, conclude that of .2- this pattern. Learning and maturation are probably factors, but appears to be mostly inherent." brain disease and normal young it (h, 5), in studies of patients with Cohn children, emphasized the rostral order of significance to "an ontogenetic or phylogenetic thalamic residue in the sensory organization of the human brain." He noted specifically, also, that this pattern was primarily associated with "the dominance and ascribed over-all sentient function of the brain." A elaboration of a maturational more extensive and developmental explanation of the order of dominance was proposed by Linn (1h). Taking the infantile patterns of sucking and feeding as a model, Linn ascribes primitiveness in the development of the body image; the dominant role of the genital area to the intensity of pleasurable sensation that the infant elicits from masturbation; and the subordinate position face dominance to role as an exploring and tension-relieving appendage holds second place in awareness to its stimulation of the more of the hand to it wherein exciting A its its mouth and genitalia. neurophysiologic view was advanced by Critchley (6, 7), who after expressing a preference for the term "tactile inattention" instead of "extinction," emphasized the rostral order of dominance. He stated that "strong stimulation of the healthy side suppresses the attentuated sensations on the impaired side," patients is probably no more than an which may be demonstrated besides the tactile - that "tactile inattention in parietal and concluded instance of local neglect or disregard, at times in many other spheres of consciousness whether motor, visual or spatial." �.3... A psychophysiologic explanation workers (10, 11), who found no tactile threshold for was eschewed by Bender and relation between the order of touch or pin prick. (8), however, insisted that these patterns an overcome by were only apparent when They hand stimulus by a stimulus four stimuli to the hand. dominance and Denny-Brown, Meyer and Horenstein alteration or loss of two-point discrimination. that the extinction of the his co- The dominance there was further demonstrated to the leg could be of the cheek to the hand could not, however, be altered by ten stimuli to the hand. following data further emphasizes psychophysiologic factors. These The studies represent the initial report of the technic of simultaneous hand of tactile stimulation tests to the alteration in brain function induced measurment of the In the course of of an investigation into the application problem of by electroshock therapy. this study electrical stimuli were applied to the cheek and psychiatric patients. Stimuli were either at threshold or supra- threshold levels. Two (a) aspects of the data are presented: The effect of alteration of relative strength of stimulus in the order of dominance (b) :3va JECTS The on face-hand tests; and Relation of perceptual thresholds to the order of dominance. ms I-‘IETHOD: subjects were electroshock therapy. mean age was 3h consecutive psychiatric patients referred for The range of their ages was between 21 and 65 and the h5. Eleven patients were diagnosed as involutional melancholia, thirteen as manic-depressive, depressed, eight as schizophrenia,and two as psychoneurosis mixed type. All testing was done prior to a course of electro- �.11.. shock therapy and no patient had clinical or EEG evidence of altered brain function. Two model S—hB Grass squareswave stimulators were synchronized to deliver either single or unit was connected was monitored two simultaneous electrical stimuli. to each stimulator to eliminate artifacts visually by an oscilloscope. A An isolation and the output switch bdx inserted in the circuit permitted independent selection of the various body parts. An active and an indifferent electrode required for each body part were small 3/8" steel discs placed 1" apart and secured with tape. Bentonite electrode paste (Medcraft) was rubbed into the skin of each area before the electrodes were applied. patient was placed on a couch in a relaxed and supine pbsiticn.. To alleviate undue anxiety the nature of the testing was described. It was emphasized that only a slight tap-like sensation would be felt. The electrodes The were then placed on (1) the dorsum of the hands, (2) the mandibular area of both cheeks and (3) the medial calf area of the legs. In the testing procedure, thresholds for the various first determined. At 50 body parts were a frequency of .3 cycles/second, and a pulse duration of milliseconds, the voltage was increased in uniform time increments of .67 seconds (2 pulses) monitored from the oscilloscope, ceived 100 percent of the stimuli. Increments of hand and increments of 1 5 until the subject pervolts were applied to the volt to the cheeks. After a ten second interval, until sensation disappeared.' After another ten second interval, the voltage was gradually increased by 1 volt each 6 seconds until the patient reported 100 percent of the stimuli again. This reading was the voltage was decreased considered the minimal voltage required to produce threshold sensation. �-5- and After the thresholds were determined, testing with a series of single double simultaneous stimuli followed. The body parts tested were the right and hand and left left cheek (heterologous stimulation) and the cheek homologous stimulation). taneously or one part singly in a Both mixed order parts right cheek were stimulated simul- for ten trials for each of the iollowing conditions:(l) threshold (2) suprathreshold (10 percent above the threshold), (3) one body part at suprathreshold and the other at threshold and (h) the reverse (3). The order of presentation of conditions (1) and (2) for conditions (3) was alternated for different subjects and (h). Similarly the order of presentation of the heterologous logous stimulation was and the same was done and homo- alternated. Single stimuli were introduced as a control. Failure to report the single stimulus indicated that the threshold had changed. occurred, stimulation was increased until a and 10 new threshold When this change was determined trails were started anew. RESULTS: A. Threshold Values. The threshold stimulation for perception cheeks and legs. (Table for the hands, was determined I). TABLE Mean Thresholds and I Standard Deviations of Body Parts Right Hand Hand Left Right Left 7.85 29.25 22.35 2h.50 19.52 h.86 1h.88 '13.60 13.99 Left Cheek Cheek Threshold (volts) 6.76 Standard Deviation h.h7 Mean Right Leg Leg ' 13.6h �~6The threshold values for the hands and legs are 3 to h times higher than the thresholds for the cheeks. While the threshold values in the legs are less than in the hands, these differences lack statistical significance. Variability of the threshold is considerably greater in the hands and legs, than in the cheeks. There is virtually no overlapping of thresholds, however, where the cheeks and the hands are concerned. B. Extinction Patterns: difference between the The or the left number of extinctions of the right cheek on stimulation of both parts with hand either threshold or suprathreshold stimuli was not significant (Table II). Also, when both cheeks were stimulated with either threshold or suprathreshold stimuli, there were no differences in the number of extinctionszhzeach cheek . (Table III). In contrast to these observations, stimulating one body part with a suprathreshold stimulus and the other at threshold, resulted in a significant increase in the failure to report the body part stimulated at threshold. Thus the cheek was dominant over the hand, or the hand was dominant over the cheek depending on the body part to which the stronger stimulus was applied (Table II). Altering the relative strength of the stimuli applied to the cheeks resulted in a similar predictable change in the pattern of dominance (Table III). Further analysis of the data in Table II indicates that the hand was dominant over the cheek with greater mean frequency (2.08) than the cheek was dominant over the hand (1.0h) for the threshold - suprathreshold condition. This tendency is also evident at suprathreshold. If it is considerefi when both that the parts were stimulated mean threshold for the hands �mua mama mmbn mmma nwmmw eUHmmwowa mmeOWmmw ma mmuo m& ma mcwuwdwwmmwowa mfi mum mum ofimmw oummw fin pa mcmumwuwmmuowm mcvumdunmmuowa efiflmmUowa awnmmwowa Kama counudwoum ow .wm m.wo H.0m zwmb H.ww nummw mxdwunawoum ow mxaqudMosm afiammwowo om saws ow H.wm .mm .mm abwbm mum H.mm cummw -mma mmuo HH madusodwoum mun mcwwpdwummwowa mmum mow v.0: m.om .m4 .OH <muwwnm dwwwmwmuom mwwe:Hdeou z.m. wAAuow vAnuow 2.m. mwmswwwombom �Emma abomw Hmwfi wear wumue wows avummuowm drummvown ma mcwuwawuwmwowm mchm&UHmmwowm owmmw ofimmw numGWm owwmwm ma ma QUGmW mum mw ma ma grammwowa meU& mum mcvum: awnmmuowm on .om .wm .Hm .ww saws nonmwdHOUm Hmwd mxwucnduoam Kama Qummw ow mxauuodwoum awwmmwowm on ow 3mm: avwbm H.mm .H# .w4 .rw mum mumwfi . mxwwannwoum md woaw.nwmme owmmw mcwumauammUowo won <muewum H.mm .mm .Hm .om wanmuwuom mdwstwmawou u‘AmoH v_Auom z.m. z.m. mumsuwwnmbnm HHH - �-7- is approximately 30 volts, while for the the difference in incidence of extinction stimulation was set at ten percent may be explained. above the threshold stimulus was therefore increased by 3 is cheeks the threshold volts 7 volts, Suprathreshold value. The hand and the face stimulus by only increase, although proportionately equivalent, appears to have given greater relative strength to the hand 1 volt above the threshold value. Such an stimulus. C. Incidence of Extinction: Regardless of pattern, the mean total of the number of extinctions heterologous body parts were stimulated at threshold than when these parts were stimulated with suprathreshold stimuli (Table IV). For these same conditions of stimulation the differences between the mean was greater number of when extinctions obtained on homologous stimulation of the cheeks lack statistical significance but the results are in the direction that a greater number of extinctions occur when two body which indicate parts are stimulated at threshold (Table IV). The failure to obtain a significant difference in the latter instance is partly due to the fact that relatively few extinctions are elicited total when homologous number of parts are stimulated. These findings on the extinctions are in agreement with previous observations (2). �2. TABLE Mean IV of Combined Number of extinctions For Varying Conditions of Threshold and Suprathreshold Both Parts at Threshold A - Cheek B — Band A - Left B - Right % Cheek Cheek Both Parts SuprathreShold 3.11 1.63 .85 .56 Differences between the at mean number of % Stimuli A B - SuprathreShold - Threshold A B 1.68 1.31 extinctions at threshold - Threshold — 2oh3 1.10 and the other three conditions of stimulation are significant for the cheek and hand but are insignificant for both cheeks. SupraThreshold �-8DISCUSSION: pattern of extinction following stimulation.with threshold and suprathreshold stimuli has been determined. In contrast to the findings The of Bender, link and Green (2), face stimuli were not reported more frequently than hand stimuli when either simultaneous threShold or suprathreshold stimuli were applied. Under these conditions, neverthless, it is clear that the pattern.of extinction for any the body parts can be readily altered by stimulus varying the relative strength of the stimuli. Thus,a suprathreshold applied to the hand tends to obscure a threshold stimulus applied to the cheek and when these stimuli intensities are reversed, the cheek tends to obscure the hand. Theories which hold that dominance of the cheek over the hand is due to an inherent factor, perceived body image, rostral dominance, developmental principle, or a learned factor, are not supported by these observations. If any of these been elicited factors were involved, a pattern of face when dominance should have the hand and cheek were stimulated with equivalent stimuli at threshold and suprathreshold intensities. Although, more recently, Bender (3) has advanced an inherent factor theory, he previously attributed the extinction phenomenon to differences in the thresholds of the various body parts and to the intensity of the stimulation used (1), strength of the The finding. in this study, that differences in the simu taneous stimuli can supports a stimulus intensity hypothesis. alter the pattern By of extinction inference, differences in threshold also play a significant role. That an intense stimulus elsewhere could raise the pain threshold as This much as 35% has been denonstrated by Hardy, Wolf and Goodell (13). �-9:- effect of a relatively intense stimulus on the threshold of another stimulus has also been found by investigators using other stimuli (8, 9). The problem still remains, however, how it is that a pattern of dominance, particularly of the hierarchy determined by Bender and his coworkers, may be elicited when presumably equivalent stimuli are applied by touch of hand. The results of this study suggest an explanation. Stimuli of differing intensities are required to elicit a threshold sensation for various body parts. ’Uhen these stimuli are increased 10 percent, the resultant stimuli are proportional and are perceived as equivalent. In contrast, in clinically touching two body parts, the stimuli are disproportionate relative to the threshold value although approximately of equal intensity in their application. differences in threShold for the hand and cheek, the tactile to the cheek stimulus/is proportionately more above the threshold than the stimulus to the hand. Thus the cheek is perceived more frequently than the hand stimulus and Because of the has been considered "dominant." A threshold hypothesis was rejected (3) on the basis that the thresholds for pressure and pain do not strictly corre5pond to the dominance order elicited by the double simultaneous stimulation tests. Most difficult to reconcile is Von Frey's finding that the pressure threshold obtained by Von Frey (16) of the glans penis, which is second in dominance rank only to the cheek in tested, is 111 grams per square millimeter; While the hand, whichzislll least dominant, is only 12 grams per a group of ten body parts the threshold of square millimeter. Unfortunately, thresholds in the genital area for male and female have seldom been determined. Von Frey's list of thresholds (16) is based on a single subject. His more detailed observations (17), however, indicate that �.10- is virtually there no pressure sense the perception of pain, warmth, and in the glans penis or clitoris, although cold is well developed. It is quite with touch possible that the punctate pressure threshold does not correlate there the genital area is concerned but that instead some other sense or combination of senses Thresholds and is involved. for the dorsum of the hand and the cheek obtained by Von Frey other investigators indicate that the cheek is considerably more sensitive in agreement with the thresholds obtained in this study. In a recent study of thresholds at various body sites Sigel than the hand. These findings are dorsum of the (15) reported that "leg areas including thigh and ankle, also definite tendency for higher thresholds. Scalp, The anterior chest temple, forehead and face tended to have lower thresholds. lower thresholds. arm and anterior wrist areas showed a tendency for and hands and the palm showed a upper Neck areas, ment there Bender and abdomen and upper back showed no is no disagreement with definite trend." In this state- the order of dominance as determined by his coworkers. the experimental results obtained here, it is proposed that the may dominance hierarchy elicited under the conditions of simultaneous testing of the be explained in rational terms on the basis of the relative strength From stimuli and the area stimulus theoretic constructs:n threshold, without the invocation of other �-llSUM-JURY: Using square wave the hands, cheeks, and electrical stimuli, the threshold for perception in calves were detennined in 3h psychiatric patients. Simultaneous stimuli were applied in random sequence to combinations of cheek and hand and both cheeks, at threshold, suprathreshold and combinations of threshold and suprathreshold intensities. MWSmmmmwsmmwdmcrfimhwmwswmmmwddmmmwwm the differences between the number of extinctions in either part were NOT significant. With stimuli of unequal intensity, however, (one stimulus at threshold and one suprathreshold) there was a significant increase in the failure to report the threshold stimulus. The total number of extinctions is greater with threshold, than with suprathreshold stimuli; ans greater in heterologous than in homologous patterns of stimulation. LOPELEQ-‘Pist The tests may clinically observed order of dominance in simultaneous tactile he explained by psychophysiological phenomena without resort to theoretic constructs. Differences in the hireshold of perception in various body parts provide the basis for the observed pattern of errors on simultaneous tactile tests at suprathreshold levels, �Biblio ranhv 1. W“ Bender, M;B. (1952): Disorders in Perception Sprin Bender, HgB., Fink, M; and Green, M.A. (1951): Patterns in Perception Tests of Face on Simultaneous field, Illinois. and Hand, A.M.A: Arch. Neurol. & Psychiat. éé} 355-362. 3. Bender, H.B., Green, H.A. and Fink, M. (l95h): Patterns of Perceptual Organization with Simultaneous Stimuli, EgyChiat., Neurol. n lg: 233-255. Cohn, R. (1951): On Certain Aspects of Human A.M.A. Arch. Brain: A the Sensory Organization of the Study in Rostral Dominance as Determined by Ipsilateral Simultaneous Stimulation, J. Nerv: Ment. Dis. 113: h71~h8h. S. Cohn, R. (1951): On Certain Aspects of Sensory Organization of the Brain: II — Human A Study in Rostral Dominance in Children, Neuroloav, 1; 119-122. Critchley, n. (1953): Critchley, M. The Parietal Lobes, a Go. (19h9): Phenomenon of Tactile Inattention with Special Reference to Earietal Lesions. Denny-Brown, London: Edward Arnold 3., Meyer, J.S: grain, 12: 538-561. and Horenstein, S. (1952): The Significance of Perceptual Rivalry Resulting from Parietal Lesion, grain, 15; h33~h7la 9. Dunoker, K. (1937): Some Preliminary Exneriments on the Mutual Influence of Seine, Psychpl. Forsdh, g1: 311-326. 10. Fink, M. and Bender, H.E. (1953): Perception of Simultaneous Stimuli in Normal ChilCren, 1-Ieurologq, ;: 27~3h. Tactile �Bibliograghv 11. Fink, H., Green, M.A. and Bender, M.D. (1953): Perception of Simultaneous Tactile Stimuli by Mentally Defective Subjects, gig. , Q1: . LLB-449 12. Fink, M., Green, M.A. and Bender, M.B. J. Merv. & Ment. (l952):The Face-Hand Test as a Diagnostic Sign of Organic Mental 85ndrome, Neurologz, g; hé-SB. 13. Haroy, J.D., wolf, H.S. and Goodall, H. (19h0): Studies on Pain. New Method for measuring Pain Threshold: Observations Summation of Pain, J. Clin. Invest., l2: on A Spatial 6&9-658. Linn, L. (1955): Some Developmental Aspects of the Body Image, 223! J. Eszchoana1., 2g; 1-7. Sigel, H. (1952): Cutaneous Sensory Threshold Frequency Squareédave Current: Site II. - The Stimulation with High Relationship of and Skin Diseases to the Seesory Threshold, Body J. Invest. Derm., lg: hh7-h51. 16. Von Frey, E. (189M): Beitrage zur Physiologie des Schmerzinns, Egg. Sachs. Ges. 17. diss., Von Frey, M. (1895): gé: 185-196 and 283-296. Beitrege znr sinnephysiologie Haut, Ber. Sachs. 99g. ‘L;iss., £2: 166-18u. �Karin: Amer. J. Psychol. VI: 8-12-58 Role of Suggestion-Induced Set in the Perception of Simultaneous Tactile Stimuli Hyman Korin.fh.D. and max Fink M.D. From the Department of Experimental Paychiatry, Hillside Hospital, Glen Oaks, L.I., (in part) by grant 14-927 of the National Institute of Mental Health, National Institutes of Health, U.S. Public Health Service. Read at the Eastern PSydhological AsSOCiation, Philadelphia, April 11, 1958. Aided N.Y. �Role of Suggestion-Induced Set in the Perception of Simultaneous Tactile Stimuli influential role of "mental set" in determining subject response to a perceptual task has been well documented (1). In studies of the The perception of simultaneous tactile stimuli, various patterns of response were observed which seemed to be the result of "suggestion-induced set." This investigation was undertaken, to determine the different conditions of "set" relation between and the frequency and type of perceptual error elicited in tests with simultaneous stimuli. Recently the advantages of the simultaneous stimulation of body parts in tactile perceptual tests has been stressed (2). simultaneous stimulation may elicit The technique of perceptual errors under conditions in which successive single stimuli are correctly perceived. 'are applied to body parts at the same time, for example, only may be reported - may be perceived correctly and the other'mislocalized an error referred to as "extinction"; or "displacement." Uccasionally, if testing sequence, these stimuli - stimuli two stimulus one one stimulus error called single stimuli are interspersed in the may be an correctly reported, but an additional, extraneous stimulus, (referred to as a "confabulation") Such ‘When errors of extinction, displacement, may also and confabulation are be reported. significantly increased in patients with brain dysfunction. 1. R. Leeper, Cognitive processes, in 5.5. Stevens, Handbook of Experimental Psychology, 1951. 2. M. B. Bender, Disorders in Perception, 1952; Bender, Patterns of perceptual organization with simultaneous stimuli; A.M.A. Arch. Neurgl. & Psychiat. M.A. Green and M. Fink, 1g: 195h, 233-255; Fink, Green and Bender. The face hand test as a diagnostic sign of organic mental syndrome, Neurcl. g: 1952, h6—58. �.2errors of extinction and diaplacement occur, they are elicited in a consistent pattern. Thus, on stimulation of the hand and face, the stimulus to the face is usually reported correctly while that to the hand When is mislocalized or not reported. parts, an "order of and testing various combinations of dominance" may be described genital areas are often perceived. By in which body stimuli to the face most often perceived and those to the hand are least stimuli to the shoulder, foot, are perceived in a gradient (3). Between these extremes, buttock, breast, back, thigh and abdomen Theories inyolving factors of rostral dominance (h), maturation (S), inattention (6), and inherent body image (7) have been advanced to explain the organization of these perceptual patterns, but no one theory has adequately explained all the facts. Previously (8) we have ascribed significance to the relative intensity of the stimuli and the threshold value in the frequency and the pattern of the "extinction" error, when electrical stimuli are applied 3. Bender, h. Green and Fink, 02. cit., 233-255. certain aspects of the sensory organization of the brain. I: A study in rostral dominance as determined by ipsilateral simultaneous stimulation, g, Nerv. Ment. Dis. Eli: 1951, h7l-h8h; II: A study in rostral dominance in children, 32339;. I, 1951, 110-122. R. Cohn, On human S. Linn, Louis: Some developnental aspects of the body images, Int. Jour. Psychoanal. 2gp 1955, 1-7. 6. Critchley, The phenomena of tactile inattention with specific references to parietal lesions, Brain 1;, l9h9, 538-561. M. _ 7. Rnder, 8. Op. Cite, 77-88. Fink, Role of stimulus intensity in perception of simultaneous electrical cutaneous stimuli, J. Hillside Hosp. H. Korin and M. Q, 1957, 2&1-250. �.3threshold and suprathreshold intensities. The present study was undertaken to assess the-relation between "suggestion-induced set" and errors of confaoulaticn and diSplacement. The Specific problem studied is whether in the testing procedure is significantly related to the frequency and type of these errors. Since these errors are most prominent an "inquiry" in Subjects with cerebral dysfunction, patients undergoing convulsive and subconvulsive therapies were studied. Subjects: The subjects were 61 consecutive psychotic electroconvulsive therapy. patients referred for Their ages ranged between 21 and 67 and the ho. Thirty-seven patients received convulsive therapy, While fourteen first received subconvulsive therapy and then were transferred to mean age was convulsive therapy. Ten patients were treated with subconvulsive therapy only. Patients were selected for the convulsive or subconvulsive treatment on a random basis by the supervising psychiatrist. �Procedure: Two model S-hB Grass squaredwave stimulators were synchronized to deliver either single or simultaneous electrical stimuli. An isolation unit was connected with each stimulator to eliminate artifacts and the output was visually monitored by an oscilloscope. A switch box was inserted in the circuit to permit independent selection of the various body parts. The active and indifferent electrodes for each body part were small 3/8" steel discs, placed 1" apart and secured with tape. Bentonite electrode paste was rubbed into the skin of each area before the electrodes were applied. The patient was placed on a couch in a relaxed and supine position. alleviate undue anxiety the nature of the testing was described. It was emphasized that a slight tap-like sensation.would be felt. The electrodes To were then placed on (a) the dorsum of the hands, (b) the mandibular area of both cheeks and (c) the medial aspect of the calves of the legs. Thresholds for the various body parts were first determined. At a frequency of .3 cycles per second and a pulse duration of the voltage was increased in SO millbeccnds, uniform increments of five volts to the hands volt to the cheeks every 6.7 seconds (2 pulses) until the subject perceived 100 per cent of the stimuli. After a ten second interval, voltages and One were decreased second until the sensation was no longer interval, voltages were increased patient again reported 100 by 1 reported. After another ten volt every 6 seconds per cent of the stimuli. This reading until the was considered the minimal voltage required to produce threshold sensation. After thresholds h single were were determined, and 6 double simultaneous the right hand and left testing with a random stimuli followed. In body series of parts tested cheek (heterologous stimulation) and the right �-scheek and left cheek (homologous stimulation). Stimuli were applied either simultaneously or to one part singly, in a mixed order for ten trials (Table homologous I). The order of presentation of the heterologous and stimulation was alternated. TABLE I Failure to report the interSpersed single stimuli served as an index that the perceptual threshold had changed. Such a change occurred infrequently, and at these times the threShold was again determined, and the 10 testing trials were repeated. patients were tested in The "no-inquiry" group. The and nine'subconvulsive two groups: an "inquiry" group and a "inquiry“ group, consisting of 2h convulsive subjects, was asked the question-"anywhere after each responseto a stimulation. No question "no-inquiry" group, which consisted of 27 convulsive and was asked else" of the 15 suboonvulsive patients. This total exceeds 61, since one patient in the inquiry group and thirteen in the no-inquiry group were included both in the convulsive and the subconvulsive series. Electroencephalograms were obtained day following a treatment. in each patient weekly These records were quantitatively for the degree of induced leW'wave (delta) activity (9). on the meaSured Both the convulsive and the subconvulsive treatments were administered three times weekly on alternate days. 9. Pink and R.L. Kahn, Relation of EEG delta activity to behavioral reSponse in electroshock: Quantitative serial studies, A.M.A. Arch. Neurol. & Psychiat. 78 M. 1957: 516‘525 o �TABLE I Order of Presentation of Stimuli Right Hand Left Cheek Right Cheek Left Cheek 'Right hand-Left cheek Right cheek Right hand Right cheekéLeft cheek Left cheek Left cheek Right hand-Left cheek Right cheek Right hand-Left cheek Right cheek-Left cheek Left cheek Right cheek-Left cheek Right hand-Left cheek Left cheek Right hand Right cheek-Left cheek Right hand-Left cheek Right cheek Right hand-Left cheek Right cheek-Left cheek �“HW1 Results: A. two Confabulation Error: stimuli were reported A reaponse was scored as a confabulation when only a single stimulus was applied. if The II. observations are noted in Table TmBLE Convulsive vs Subconvulsive: II Confabulatory errors were elicited pretreatment both in the convulsive and the subconvulsive patients. During treatment the errors increased with approximately the same frequency. The in the convulsive treated patients and from .22 to .70 in the subconvulsive treated patients. Post-treatment, mean error increased from .08 to .72 however, the mean number of confabuLations persisted in the subconvulsive patients (1.00) but declined in the convulsive patients (.10). The difference in number of errors between the convulsive and subconvulsive groups is significant post-treatment, but not in either the pretreatment or treatment periods. In the no-inquiry group few confabulations occurred at any interval of testing for either the convulsive or the subccnvulsive patients. Inquiry vs No-Inquiry: While the differences in the mean number of errors reported by the subconvulsive and the convulsive patients lacks 'significance pretreatment, that between the subconvulsive inquiry differed significantly from the subconvulsive no-inquiry patients. During treatment the number df confabulations increased, and this difference in a comparison of the inquiry and is significant the no-inquiry procedures, both in the convulsive and subconvulsive groups. These differences during the treatment interval are based on the of the inquiry group. substantial increase in the number of confabulations �Hangs». Wmdgmgmfi womduagmggd Ex» % dwm awm mmdm * .1. 6 u w .8. .8. .8 A A km .8 Zn»: conqspmw<m A Huncwnw Foo mum mumswwwomsom. .8 moouwm. .8 .mm .E o 2% mucoouafiwmw<w 3M55L23H¢3m% duo awm mm¢m ac: .8 swwow zaps zug oon<deH<m mwwwmwmsomm domd zusvoa zongncwuw mowwoz. AHNV n cwwtmmu swm .om 0 ow zuwm Hpmnm mscoonqswmw<m Iml mwbnm HH smmsm mvuPHmm oouwmcspmdwob awn muw ad: we onww .8 wome .3 .0m Hunmwuq. oouafiwqum ZonHunnMHw Upwwmwmbom «ama wuwowm .3. wm mou mwommpw % dmmma u .0m .3 Hupswflw. ZouHunswww dwawmuobom mzwoqachqum mwmbwmwombom HmHmdma on 5. is Hmbw ac wow enamw Hm4mH .8 * éwmmm ow om .8 .E Hunzwaw wawmambom mayooudcpmw<m oon<¢wqumu mguooudcwqum oos<sHmH4m. - u .oo o zoquncwuw uwwmmambnm �-9After the course of therapy, the confabulations of the convulsive inquiry patients decreased to the pretreatment level, between the convulsive inquiry and no-inquiry groups not significant. In contrast, the mean number and differences at this time were of errors of the subconvulsive inquiry patients increased. Data for the post-treatment subconvulsive no-inquiry group was not available as these patients to convulsive treatment A and were not were usually transferred available for post-treatment tests. comparison between the inquiry and no-inquiry subconvulsive patients post-treatment cannot be made. B. Displacement Error: one of two stimuli was reported A reSponse was scored as a displacement correctly and the other was if mislocalized. rarely elicited in any of the greups (Table III). of displacements tended to be greater, however, during Displacements were The mean number treatment for the convulsive patients but the differences from the pretreatment interval lack significance. �—10‘TABLE mean Number III of Digplacement Errors Convulsive No-Inqyiry Inquiry Subconvulsive No-Inquiry Inquiry Pretreatment .06 .07 0 Treatment .09 .10 .02 .01 Post-Treatment .08 .02 .06 0 Inter and intra group differences are not significant 0 at any interval. �-llC. Extinction Error: An error one of two simultaneously applied stimuli extinction error between the inquiry at any scored as an "extinction" was reported. was if only difference in The and no-inquiry groups was not significant interval during the course of therapy both for the convulsive and subconvulsive patients (Table IV). During treatment, the mean number of extinctions decreased in all groups. this interval, the difference At between the convulsive and subconvulsive inquiry patients was Postetreatment the errors of D. Confabulation number Error all and significant. the groups decreased further. EEG Change; An analysis was made of the of confabulation errors elicited in convulsive patients in relation Inquiry patients with high to the degree of encephalographic change. degrees of delta activity made significantly more confabulation errors than inquiry patients with moderate and low degrees of delta activity. (Table V), while few errors were reported in the no-inquiry patients regardless of the degree of and low EEG inquiry groups EEG was change. The mean similar to the score of the moderate mean scores of the no-inquiry ‘ patients. No EEG slow wave subconvulsive activity or patients. number of confabulation significantly during low degrees of such occurred activity/in the However, as had previously been indicated, the errors of the subconvulsive group increased and after treatment. increasing confabulation errors in four This increase resulted from of the nine Pqu-u-u-Iu-o-O-u ‘- patients. �eaflsma Wmfimfifia womdlawmmdsmuw H.w< PS who 2n»: ooudswmwdm .x. annwnw 6A. .mw FE ”7% zuw mfidaobdspmwdo 00“ :wms H.rr ffi mid Zamq ZdSUmH oosagHmH<m ow zoquncHHw wabm I VB PS spun mdeHOdHob zuHm mscoos<¢wmw<w H< muaoum .ON .3 .8 Huncwuwu oon<cwmw<m ZOIHsnsHHw mHHmmHmbnm ZOIHSQsHHwHsnzwnw. t .S .3 wawmnmuom mcvaon<cwmw<m . bHHonmbom mzvooudcwmw<m .rw .mw .5 oosdswquou Hangwaq * I .E .3 uwmwmwmbow mcvoob<¢wmw<m zongnsqu aoadcwmwdm. �.13.. TABLE V Relation Between Degree of EEG-Delta Activity and Number of Confabulation Errors Mean Degree of Delta Activity High Mean Number Confabulation Errors ) ) ) Inquiry No Inquiry .81 (N.=9) .10 (N=21) Mederete-Low Difference .19 (Halo) .62 .07 (N=b) .03 Significance p 4 .05 N.S. �Discussion: elicited Displacement, confabulation and extinction errors are sequences of multiple and single tactile stimuli are applied to tests with touch stimulation, these errors are In clinical when body parts. most prominent in patients with cerebral disease (10). Theories Which have been advanced to account for the occurrence of such errors have therefore emphasized endogenous factors involving the central nervous system. That the fre- quency and type of response to a perceptual task may be markedly altered by the immediate aspects of a situation is indicated by the numerous studies of the role of set in perception (11). In this study the stimulus situation has been varied to bring about differing conditions of mental set. factors have not been neglected, and the relation between the effects of different degrees of brain dysfunction has also been However, the endogenous determined. In the course of convulsive therapy a marked increase in the number of confabulation errors is brought about by the examiner's query of "anywhere else?" following each stimulation. of the convulsive patients who were asked the question, confabulations were elicited primarily inthe group with high degrees of EEG 81 w wave activity (marked cerebral dysfunction) and not in the group with low and moderate degrees (minimal cerebral dysfunction). The importance of the inquiry is thus enphasized by the consideration that activity, there was little tendency for confabulation errors to occur in convulsive patients when no inquiry was regardless of changes in EEG 10. Fink, Green and Bender, op. 11. Leeper, op. M. Pollack, cit., - cit. , 146-58. . .S. Battersby and M.B.Bender, Tachistoscopic identification of contours in patients with brain damage, J. Comp. Physiol. Bszghol. g9, 1957, 220-227. made. �.15Thus both inquiry and high degrees of EEG delta activity provided the milieu faVOrable to evoking confabulatory errors. patients present a different picture. Although, virtually delta activity is induced by subconvulsive therapy, the number of Subconvulsive no confabulation errors of four of the nine subconvulsive patients queried increased substantially during the treatment. Furthermore, While the confabulation errors of these subconvulsive patients persisted and even increased following the course of flierapy, those of the convulsive patients queried, in contrast, decreased to the pretreatment level. Patterns of reversible decrement manifested by convulsive patients has been reported WW studies of the effects of electroShock in the of mental functioning (12). However, it was on different types expected that confabulations elicited in subconvulsive patients at any interval, in.view of earlier observations that cerebral dysfunction is not induced in these would not be patients (13). An explanation for the differences between the convulsive and convulsive inquiry patients is that their therapies had differing sub— effects- the practice factor. In convulsive patients, treatment diminished the practice effect in all subjects, including those both with low and high on degrees of slow wave activity. Fbr each test interval, it was as if the 12. H.Korin, M. Fink and S. Kwalwasser, Relation of changes in memory and learning to ercts improvement in electroshock, lg, 1956, 88-96; M. Fink, R.L. Kahn andon of diffuse altered brain function of Psychol. Proceed., 1958, 238-239. EE’Conf. perception, Conf. Neural. 13. Fink, R.L. Kahn and M.A. Green, Experimental Studies of the electroshock process, Dis. Nerv. 528. 12, 1958, M. 113-118. �-16convulsive patients were starting anew. patients with high EEG Under these conditions only delta activity manifested a confabulatory set within a single test period. After the course of therapy, with the disappearance of the delta activity, convulsive patients were performing at the pretreatment level. In the subconvulsive patients, the set established in the pretreatment interval test period during treatment. more confebulatory The may make Such was re-enforced during each Thus the subconvulsive patients made even errors post-treatment. results for the subconvulsive group indicate that certain patients confabulation errors without an alteration of brain function. patients are apparently influenced as being suggestible or acquiescent. by the examiner and may be described The failure of the convulsive patients .to establish a set which persisted for prolonged intervals of time as did the subconvulsive patients suggests a basis for the therapeutic effect derived from convulsive therapy. ‘If the symptoms of the patient are interpretation is particularly appropriate. From the point of view of concepts of mental set, the effect of induced convulsions is to bring about a disruption of maladaptive patterns regarded as a pathologic mental set, such an of behavior. The number of displacement errors remained the whether an inquiry was made. than confabulations. same regardless of errors occurred much During treatment approximately 30% patients of both the inquiry These less frequently of the convulsive and no-inquiry groups responded with one diaplacement. This finding compares at least closely with the results of 33% with displacements obtained in a study of a similar population of electroshock patients in which touch stimuli were applied by the 1h. M. Fink, unpublished data. clinical method (1h) �Displacement errors are not a prominent type of error in an electroShock pepulation. With regard to the extinction error, differences were not significant between inquiry and no-inquiry groups. The high number of extinction errors pretreatment and the subsequent decrease in errors during treatment, in this study, is in contrast If clinical-tactile to the results obtained with clinical tactile techniques. extinction errors are elicited increase in error during treatment. The methods are used, few is a marked results obtained in this Study are probably related to the initial difficulty experienced by the patient in perceiving electrical stimuli at threshold pretreatment and there the rapid adaptation to the technique in further testing. play a greater role than the changes induced by the treatment. and In that a initial studies Bore with threShold electrical stimuli, it These factors was believed sensitive test of changes in brain function than the clinical- for clinical purposes the perceptual patterns obtained with electrical stimulation lack sufficient tactile method (15) could be devised. however, discriminability as indices of brain dysfunction. In part, the deficiences of the method may be ascribed to the necessity for using fixed electrodes and limitations in switching arrangements at threshold. For clinical . testing, therefore, simultaneous tactile stimuli applied rapidly in varied sequence remains the best index= of altered brain function (16). 15. Fink, Green.and Bender, gghgit,, h6-58 16. M. Green and M. Fink, Standardization of the face-hand test, Neurology, h l95h, 211-217. �-18.. Summary: tactile This study of the perception of simultaneously applied stimuli was undertaken to determine the relation between the frequency of perceptual errors to the inquiry made by the examiner. The relation between inquiry, perceptual response and the degree of brain dysfunction was also considered. In the test procedure, the threshold (100 per cent point) for square wave electrical stimuli, applied to the patients was applied and in a mixed order to both cheeks trials made determined. Sequences of was two simultaneous and for the hand (homologous were alternated hand and cheek of 61 psychiatric single stimuli and cheek (heterogenous stimulation) stimulation) Heterologous and for each patient. For one group, an homologous inquiry was following each reSponse to a stimulation, while in a second group, Patients were treated either-by convulsive or subconvulsive courses of therapy, at three times per-week for 12-20 applications. no inquiry was made. There errors significant relationdhip between the frequency of confabulation the inquiry ("suggestion-induced set") in both convulsive and Was and subconVulsive a patients.v However, the confabulatory tendencies of these patients differed. Although the errors for both increased during treatment, errors decreased post-treatment for the convulsive group, but in the subconvulsive group errors increased inquiry errors further. differences between and no-inquiry groups with regard to were extinction or displacement insignificant. £:;.convulsive-inquiry patients, the confabulatory errors of patients with high degrees of more frequent than those of wave The activity. slow-wave patients with a low activity were significantly or moderate degrees of slow �.19- Conclusions: tests with simultaneous electrical tactile stimuli the number of Confabulatory errors is related to an induced set suggested uy the In examiner' s inquiry. The number of confabulatory errors is increased in patients with brain dysfunction in relation to an inquiry, but may also in patientS'without brain dysfunction.who are acquiescent be induced and susceptible to suggestion. The frequency of displacement or extinction errors to the inquiry procedure. is not related � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource The Role of set in the perception of simultaneous tactile stimuli. Amer J Psychol. 72:384-392. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-40-006 Date A point or period of time associated with an event in the lifecycle of the resource 1959 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource [Preprint] and offprint. 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ROTHLIN (Editor), Neuro-Psychopharmacology, Vol. 2 (1961), Proceedings of the 2nd International Meeting of the Collegium Internationale Neuro-Psychopharmacologicum, Basle 1960 From the Discussion to the First Symposium: THE PROBLEM OF ANTAGONISTS TO PSYCHOTROPIC DRUGS MAX FINK Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, N. Y. (U.S.A.) ’ It has been a privilege and a pleasure to read and to listen to the reports by Drs. and DENBER. These authors have approached the problem of antagonists to psychotropic drugs from different vantage points: Dr. GADDUM that of the pharma— cologist — theoretician, assessing general issues; and Dr. DENBER, the experimental clinician with a specific problem exemplifying a theoretic principle. Dr. GADDUM essayed a broad classification of drug antagonisms emphasizing c0mpetitive inhibition. While studies of this concept have a likelihood of clarifying our GADDUM References p. 32. �DISCUSSION 31 knowledge of drug action, there was little that could be specified at present. This View, founded on extensive experience, suggests that a critical appraisal is necessary of the and of relation theories serotonin, fanciful the 5—hydroxytryptophan recent on many amine oxidases, amongst others, to human psychoses. If I interpret Dr. GADDUM’s review correctly, he is describing basic postulates which must be satisfied before drug antagonisms are established, and such establishment is requisite to the determination of the site of action of such interactions. Dr. GADDUM notes, that for the determination of competitive inhibition, four considerations must be fulfilled, i.e.: I. control drugs are not inhibited; 2. antagonistic actions are demonstrable at several sites or systems; 3. dose relationships are systematic; and 4. agents have a common chemical grouping. To these I would also add, that for such determinations of competitive inhibition to have significance for human psycho—pharmacology, the antagonisms should not be based on work limited to a single animal species, but should be demonstrated in man. Dr. DENBER has approached the problem from a specific experiment — the meas— urement of changes in various blood chemical elements and gross clinical behavior in chronic relapsing psychotic subjects. These patients were studied before and after intravenous mescaline followed by a variety of phenothiazine agents administered as “antagonists”. Dr. DENBER confirmed his earlier studies that various phenothiazine derivatives, excepting diethazine, are effective in modifying mescaline clinical affects; and that such effects are related to the halogenation of the chemical ring structure. Parenthetically, we can confirm the observation that diethazine is not an antagonist for hallucinogens, for in our studies diethazine induced illusory states and EEG desynchronization in psychiatric patients, similar to mescalinel. The biochemical data indicates the wide range of behaviors altered by these broad acting agents. Like his earlier studies on the changes in the EEG, and the observations from others of the blocking of induced psychotomimetic effects as measured in frame— theoretic from be this data must a analyzed etc., mood, perception, language, work of the relevance, or imputed causal relations, of such observations to clinical behavior. No such framework is given and the assumed connection between these blood changes and clinical behavior is obscure. Indeed, Dr. DENBER concludes that: “In all probability, the reactions observed represent part of a total body response to a stress-. . Assuming this conclusion is a reasonable working hypothesis, we are taxed by the problem of critical experiments to elucidate the body response to psychotomimetic and psychotropic agents. In this task we are faced by a number of monumental problems, and it is here that Dr. GADDUM’S principles and Dr. DENBER’S experiments approach a common base, albeit tenuous. For what Dr. GADDUM fails to indicate in his principles are the significant behaviors to be studied; while Dr. DENBER selects be— interactive clinical of and —~that blood of behavior global chemistry two aspects havior — as dependent variables. It is the selection of significant experimental variables and their quantification that represents a central problem of human psychopharmacologic research today. Assuming that the laws of human interpersonal behavior are the goals of our studies, and that psychopharmacology represents one aspect of the modification of human References 12. 32. �FIRST SYMPOSIUM 32 interpersonal behavior, what evidence is there that any single aspect of task behavior is correlated with changes in interpersonal behavior induced by drugs? I am troubled by the fact that innumerable investigations have selected a single or few variables on the biochemical level and correlated these with a single or few variables on the behavioral level, the selection of which is not designed to elucidate a theoretic framework but rather based on a vague personal notion. Thus, investigator after investigator selects pole climbing, bar pressing, conditioned avoidance, jiggle cage movement, etc. as single variables in a wide range of animal studies; and rating scales, self—ratings, psychomotor tasks, EEG, blood pressure, and many others in human studies as single significant variables. Few studies assess the relevance of these tasks for the prediction of the direction or efficacy of drug effects on interpersonal behavior. Other significant problems include that of generalizing from non—psychopathic populations to our understanding of disordered human behavior. A sub—aspect of this problem is the generalization from one psychopathic population to another without fully taking into account such population factors as genetic predisposition, early organic traumata, varying acculturation processess and sociologic status upon population characteristics. These aspects may so alter the observations obtained with a specific pharmacologic agent as to give varying, and occasionally opposite results when similar studies are done in different settings. Some years ago, Dr. ABRAHAM WIKLER outlined the problem facing experimental psychopharmacologistsZ. In assessing the relation of psychopharmacology to experimental psychiatry, he recommended: “In psychiatry we need more properly controlled studies on the comparative effects of a variety of drugs, on the behavior of varied, but selected, homogeneous groups of subjects, under varied but standardized experimental conditions, and with varied but specified activities of the observer.” In this I concur and commend it to the Collegium as the most logical beginning to the resolution of the problems of antagonists to psychotropic agents. REFERENCES 1 2 M. FINK, Effect of anticholinergic agent, Diethazine on EEG and behavior: significance for theory of convulsive therapy. A .M.A. Arch. Neurol. Psychiat, 80 (1958) 380. A. WIKLER, The Relation of Psychiatry to Pharmacology, Williams & Wilkins, Baltimore, Md., I957- Printed in‘ The Netherlands �‘ w33;; érn‘msmfi‘ ’1angmgemam: $§i~wgfl .91»: ~' ‘iWMem 423d mmhm: maximmmvmfi .: {Err thwxsfisw 9mm: fim téfim, , . . 1 . Mamiew. > �D First I I S C U 3 8 Synponiun TH! PROBLBH'OF ANTAGOHISTS lax 713k, ~ 0 l 0.1.H.P. TO PSYCKOTROPIC DRUGS H.D. Pro. tho Depart-ant o! Bxporinontal Psychintry, Billlido Hoapitnl, clan Oaks l.!. July hth, 1960, 3:310, Switaorland �It listen has been a privilege and a pleasure to read and to to the reports by Drs. Gaddun and Denber. These authors have approached the problem or antagonists to psychotropic drugs from different vantage points Dr. Gaddna that or the pharmacologist - theoretician, assess~ ing general issues; and Dr. Denber, the experimental-clinician with a specific problen exeaplitying a theoretic principle. — Dr. Gaddnn essayed a breed classification of drug antagonisns emphasising conpetitive inhibition. While studies of this concept have a likelihood of clarifying our knowledge of drug action, there was little that could be specified at present. This view, founded on extensive experience, suggests that a critical appraisal is necessary d’the nany recent fanciful theories on the relation of serotonin, S—hydroxytryptephan and anine oxidases, alongst others, to huaan psychoses. It I interpret Dr. Gaddun's review correctly, he is describing basic postulates which must be satisfied before drug antagonisns are established, and such establishnent is requisite to the deternination of the site of action or such interactions. Dr. Oaddna notes, that for the determination of competitive inhibition, four considerations nuet be fulfilled: i.e.: (1) control drugs are not inhibited; (2) antagonistic actions sre demonstrable at several sites or systems; �To (3) dose rslaticnships are systoaaticg and (h) agonts hsvs a con-on cboaical grouping. that would for ouch dotorsinatioos of thoss I also add, coapotitivo inhibition to have significance for huaan psycho~ pharmacology, tho antagodsus should not be basod on work bo doaonstrablo should but aniacl a to spacios, single liaitod in san. Dr. Donbor has approacbad tho probloa Iron a spocitic oxpariaont - tho aoasursaont of changoa in various blood ohsaical closonta and gross clinical behavior in chronic rolapsiog psychotic and intravonous botoro Thoso studiod attor scro patioots subjects. aoscalino followed by a varicty of phonothiasino agonts adaioistorod so *antsgonists'. Dr. Donbor contirsod his oarlior studios that various phonothiosino dorivativos, oxcspting diothasino, aro ottoctivo in soditying aoscalins clinical atrocts; and that such ottocts arc rolatod to tho halogonation of tho choaical ring structuro. Paronthotically, so can contira tho cbsorvation that diothasino is not an antagonist for hallucinogons, for in our studios diotbasino iodacod illusory stats: and EEG dosynchronisatioc in psychiatric potiouts, aioilar to aoscalino (1). Tbs biochoaicsl data indicatos tho aids songs of bohaviors altorod by thoso broad acting scouts. Liko his oarlior studios? on tho changos in tho EEG, and tho cbsorvations from othors of tho blocking of indccod psychctoaiaotic ottocts as Ioascrod in bo snot data analysod this languago, aood, porcopticc, otc., �-3Iron a theoretic fraaevork of the relevance, or iapcted cancel relatione, of anch obeervationa to clinical behaviour. No Inch fraaevork ia given and the aeauaed connection between these blood changee and clinical behavior in ebecnre. Indeed, Dr. Denber that: "In all probability, the reactione obaerved repreeent part or a total body reaponee to a atreaa- ...' leenaing thie conclnaion ie a reaeonable working hypo-» theeie, we are taxed by the problea of critical experiaente concludee to elucidate the body reeponee to peyohotoaiaetic and paychetropic agent. In thia teak we are faced by a nnaber of aonnaental probleae, and it ie here that Dr. Gaddna'e principlee and Dr. Denber’a experiaenta approach a coaeon baae, albeit tennoce. For what Dr. Gaddna taile to indicate in hie principlee are the eignificant behaviore to be atodied; while Dr. Denber eelecte two aapecta of behavior - that of blood cheaietry and global clinical interactive behavior - aa dependent variables. It in the eelection or significant experiaental variablee and their quantification that repreeente a central problea o: hnaan peyohopharaacologic reeearch today. ieanaing that the lava o: hnaan interpereonal behavior are the goale or our etndiee, and that paychopharnacology repreeenta one aepect of the aodification or hnaan interperaonal behavior, what evidence ie there that any single aepect of teak behavior is correlated with ehangee in interpereonal behavior induced by drugs? �-1... I on troubled by the tent thet innnnereble investicetione heve eelected e eingle or ten veriehlee on the bieeheeioel level end correleted theee with e eincle or ten verieblee on the behevierel level, the eelectien or which ie not deeigncd to elncidete e theoretic freeeeork but rether beeed on e vogue pereenel notion. Thne, inveetigetor efter inveetigetor eelecte pole cliebing, her preeeing, conditioned evoidence, Jigcle cege leveeent, etc. ee eingle veriehlee in e wide reuse of enieel etndiee; end retina ecelec, eelt-retinge, peyohoeotor teeke, EEO, blood preeenre, end eeny othere in hneen etndiee ee single eixnificent verieblee. rev etndiee eeeeee the relevence of these teeke tor the prediction of the direction or etficecy o8 drug ettecte on interpereonel behevior. Other eigniticent prohleee include thet o: generelieing tree non-peyohopethio populetione to our underetending of dieordered hneen behevior. e eobaeepect of this problee is the generelieetien free one peychopethic populetion to enother without ench eccount into populetion rectore ee genetic teking telly prediepoeition, eerly orgenic tredeete, verying eccnlturetion proceeeee end eociologio etetne upon popnletion cherecterietice.» Theee eepeote eey eo elter the oheervetione chteined with e epecifio phereeoologic egeet ee to give verying, end oceeeionelly opposite reenlte when eieiler etndiee ere done in different settings. �-5Solo yoara ago, Dr. Ahrahaa Hiklor ootlinod tho prohloa In aoooooiog (2). paychopharacologiato oxporiaontal facing tho relation of poyohopharoacology to oxporioontal psychiatry, ho roconaondods 'Iu poychiatry Io nood noro properly controllod otndioo on tho oooparativo ottocto of a variety of drogo, on tho behavior of variod, hot ooloctod, hologonoooo groups or ouhaooto, undor variod hot otandardiaod oxporiaontal conditiono, and with variod but opocitiod activitioa of tho oboorvor.’ In this I concur, and connond it to tho collogiuo an the aoot logical hoaiuning to tho roaolution of tho prohloao of antagoniota to psychotropic agonto. �1. link, n: Effect at Antieholinergic Agent, Dietheeine3on EEG end Behavior: Significance fer Theory of Convaleive Therapy. .§_o_ 2. "‘ AHA Arch. figural. a Pezehiet. 380‘387, 1958. Hitler, A: The Relation of Pezphiatrz to Phernecologzl In. Wilkins, Beltinere, 1957. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Problems of antagonists to psychotropic drugs, 30-2 (Discussion, Neuropsychologic response patterns of some psychotropic drugs). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-51-017 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint and [preprint]. Reprint from: E.ROTHLIN (Editor), Neuro-Psychopharmacology, Vol. 2 (1961), Proceedings of the 2nd International Meeting of the Collegium Internationale Neuro-Psychopharmacologicum, Basle 1960 From the Discussion to the First Symposium: THE PROBLEM OF ANTAGONISTS TO PSYCHOTROPIC DRUGS Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/c1a1aa6de811d0a1630b2188051d512d.pdf a467aa19b75ccf3c7353e27cd875e8ef PDF Text Text M. FINK From the Department of Experimental Psychiatry, Hillside Hospital 7 Glen Oaks (N. Y.) Meeting on the Techniques for the Study of Psychotropic Drugs Bologna 1960 DISCUSSION OF THE REPORT OF Prof. MARCEL MONNIER Reprinted from the: of Acta of the International Meeting on the Techniques for the Study Psychotropic Drugs» - Bologna June 26-27th 1960 « MODENA —>SOCIETA TIPOGRAFICA MODENESE �Dr. Monnier‘s excellent review presents a vivid picture of neurophysiologic techniques in the study of drug effects. From monosyna‘ptic and poly— synaptic to organismic patterns the methods of study appear rich in promise. One phase of these studies, that of cortical EEG analysis, has been of considerable interest to our laboratory, Changes in EEG patterns induced by pharmacologic agents are generally considered to be poorly related to changes in clinical behavior. Yet, from the extensive experience with anesthetics, alcohol. sedatives and convulsants, and the theoretical views ascribing to brain function a central role in conscious behavior we would expect that psychotropic drugs may also have significant electrographic behavioral relations. The difficulties in such studies lie in inter—species differences in physiologic response, the range of inter-individual and intra—individual variability in both neurophysiologic and behavioral parameters, and the wide variety of events which must be measured to obtain a reasonable image of mammalian interactive behavior. A further difficulty has been a lack of reasonable theo— retic models of brain function-behavioral interrelations. Recent suggestions, however, may be helpful, including the synaptic models of Marrazz‘i (l) amongst others; the brain stem models of Magoun, as elaborated by Hi‘mwich (2): and the general neuro‘physiovloglic~adaptive views of Wlikler (3), Weinstein (4‘) and our laboratory (5). In 1954. Wikler (6) stated that drugs that alter human behavior in the direction of EEG desynchronization are associated with behavioral excite— ment. alertness, illusory sensations, and hallucinations; while drugs which induce EEG synchronization, with or without increased slowing, are associa— ted with sedation. tranquillization and decreased excitement. In our studies in psychiatric patients, this hypothesis has been substantiated. The following compounds administered in physiologic dosage ranges have been shown to decrease synchronization of the EEG: mescaline, LSD—25, amphetamine; anticholinergics as diethazine, benactyzine. JB—318, JB-336; and local anesthe— tics as cocaine, procaine, and lidocaine. The following agents increase synchronization of the EEG: barbiturates, chlorpromazine and similar pheno— thiazines. meprobamate, and anesthetics as ether, chloroform. etc. In addi— — tion, various compounds without significant clinical behavioral efi'ects have been studied, including phenyltoloxamine, WY-3149 and deanol - and these have inconsistent or indefinable EEG effects. In these studies we have observed. however, that the continuum of synchronization-desynchronization is an oversimplified generalization. In our present view, two other EE‘G pattern changes have assumed considerable prominence. One is a shift of dominant frequencies either to the slow (theta or delta) or the fast (beta) ranges; and the second, the presence of such figures .as burts, spikes or spindling. These latter two patterns were significant in �2 describing the EEG behavioral relations of imipramine (7). Examples of these paterns may he found in publications from this laboratory and elsewhere (8. 9, 10, 11). It is our impression, therefore_ that further EEG analyses of new compounds in man is indeed warranted. We would suggest that the number of quantification procedures be extended to include, in addition to frequency analysis, the techniques of topographic analysis, chronologic analysis - and these techniques may be augmented by computer techniques of summating evoked potentials. In studies of drug effects. not only is it important to define neurophysiologic parameters, but the behavioral parameters are equally significant. The equation of change in rates of animal pole-climbing. bar pressing or jiggleand is inaccurate and excitation human with tranquillization movement cage inappropriate. There is no evidence that such tasks in experimental animals and of to interaction physicians human in significance related to changes are psychologists. Indeed, if one impression dominates the session today, it is that the behaviors studied by pharmacologists are not the behaviors of inte— rest to the clinicians. Further study of the relations between the laboratory tasks highlighted today and human behavioral measures are needed. In this regard multivariate pattern analyses of behavior and the newer applied psycholinguistic techniques may be helpful in defining the changes in human behavior patterns. In conclusions. I wish to reenforce Dr. Monnier’s review, and indicate that increased attention to EEG analyses may be profitable in understanding the mode of action and the significant differences and similarities in psycho— pharmacologic agents. REFERENCES 1) 2) 3) 4) 5) 6) 7) 8) Marrazzi A. S., Science 118, 367 (1953). Himwich 11., Rinaldi F., Brain Mechanism and Drug Action, 115-44 C. C. Thomas, Springfield, 1957. Wikler A., The Relation of Psychiatry to Pharmacology. Wm. Wilkins, Baltimore, 1957. Weinstein E. A., and Kahn R. L., Denial of Illness: Symbolic and Physiological Aspects. C. Thomas, Springfield, Ill. 1955. Fink M., A Unified Theory of the Action of Physiodynamic Therapies. J. Hillside Hospital 6, 197 (1957) Wikler A., J. Nerv. Ment. Dis., 120, 157 (1954). Fink M., Canad. Psych. Assoc. J. 4, 1668 (1959). Fink M., Neuro-Psychopharmacology, ed. Bradley, P., Elsevier, Amsterdam, 441446, 1960. 9) Kink M., EEG. Clin. Neurophysicl. 12, 359 (1960). 110) Verdeaux G., Marty R., Rev. Neurol., 91, 405 (1954). 11) Bradley P. D., Elkes J., Brain. 80, 77 (1957). ��� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource EEG techniques in study of psychotropic drugs. Acta of the International Meeting on the Techniques for the Study of Psychotropic Drugs, Bologna, 1960. Societa Tipografica Modenese, Modena, 1961: 3pp. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-55-021 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource DISCUSSION OF THE REPORT OF Prof. MARCEL MONNIER. Reprinted from the: Acta of the International Meeting on the Techniques for the Study of Psychotropic Drugs, Bologna June 26-27th 1960 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/07a3d1b2eec1cf62891da3ff4c4049c8.pdf f5bf70eb575371f639319602e2837d97 PDF Text Text EXPERIMENTAL PSYCHIATRIC RESEARCH AT HILLSIDE Review and Prospect MAX FINK, M.D. Reprinted from JOURNAL OF THE HILLSIDE HOSPITAL Volume X ° Nos. 3-4 ° July-Oct. 1961 �EXPERIMENTAL PSYCHIATRIC RESEARCH AT HILLSIDE Review and Prospect MAX FINK, MD. The dedication of Hillside Hospital as a Research Institute has been a dream of many of its students—a dream that may achieve realization in this decade. Dr. Tarachow was an early proponent of this view; and both in his sponsorship of the Journal, and in his encouragement of research studies, he presaged this development. He was also the inadvertent sire of the research studies in experimental psychiatry. While I was a resident in psychiatry in 1952, we collaborated in a study of the relation of the early separation of child from a parent to the adult choice of neurosis. Reviewing the hospital records of five previous years we concluded that there was, indeed, a relation—— neurotic patients with obsessional neuroses had a significantly, greater incidence of separation than patients with hysterical neuroses (2). This report was the beginning of the patient population studies described here. Since 1954 the various programs in experimental psychiatry have been devoted to an understanding of the mode of action of the psy- chiatric therapies of the hospital. The techniques have been adapted from descriptive and dynamic psychiatry, neuropsychology, electroencephalography, linguistics, pharmacology, and sociology. This report reviews these studies and presents support for the creation of a Research Institute at Hillside. PAST STUDIES In our early studies of convulsive therapy, instituted with the 1 From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, N. Y. The studies reported here have been aided by the Board of Directors Research Fund; the National Institute of Mental Health (Grants M-927; MY-2092,-27l5, -4798; MF-12,033); Foundations Fund for Research in Psychiatry (FFRP 56-151); Kaufmann, and Dazian Foundations; and numerous pharmaceutical concerns including Geigy, Bristol, Wyeth and Smith, Kline 8c French Laboratories. 159 �160 MAX FINK aid of a grant award of the National Institute of Mental Health, evaluations of patient improvement were shown to be dependent both on changes in brain function and on psychological factors. As our understanding of convulsive therapy developed, a general neurophysiologic-adaptive view of somatic therapies emerged (6). A change in brain function was seen as a necessary condition for behavioral change, with the type of change varying, depending upon psychological and sociological characteristics of the subject (22, 25). Thus, the mode of action was not seen as either “organic” or “psychological” but rather as the interaction of neurophysiological changes and individual patterns of response and behavior. This hypothesis was sustained in studies of convulsive and in sulin coma therapies (21, 22); and the mode of action of the new psychotropic agents was expressed within this hypothesis. It was suggested that psychotropic drugs would be effective to the extent that persistent changes in brain function were induced; and that the type of behavioral response would be related to the type of brain change, and to individual premorbid psychologic (personality) patterns (6, 28, 40). Convulsive Therapy Process: Seeking a measure of altered neurophysiological change that was sensitive and suitable for repeated retests, various measures were studied including changes in the face-hand test (1, 10, 13, 35), memory tests (17, 35), amount of slow-wave activity in the EEG (16, 23) and confabulatory and denial language patterns after amobarbital (3, 15). The latter two, EEG and amobarbital tests, were the most sensitive indices of change in convulsive therapy subjects. In one experiment, clinical ratings of improvement were correlated with high degrees of change in these indices (15, 16). These observations were tested in a double-blind study in which patients referred for electroshock were randomly assigned to either convulsive or subconvulsive therapy. High degrees of electrographic slow-wave activity and positive amobarbital tests were observed only in the convulsive group; improvement rates were significantly higher in this group, and when subconvulsive subjects were retreated by convulsive applications, the improvement rate was similar to the convulsive group (22). In subconvulsive applications, considerable electric current passes between the electrodes. It was postulated that the therapeutic agent was not the total electrical current per se, but the “all or none” quality manifested by the grand-ma] seizure (9, 23, 42). The signifi1. �EXPERIMENTAL PSYCHIATRIC RESEARCH 16] cance of the grand-mal seizure was examined in a comparative study of the inhalant convulsant, hexafluorodiethylether (Indoklon), and electrically induced seizures. Similar degrees of electrographic change, improvement rates, types of behavioral adaptations, and changes in neuropsychological task behavior were observed in both the inhalant and in the electrically treated groups (49). However, not all subjects manifesting high degrees of physiological change were evaluated as “improved.” In a descriptive typologic study, five adaptive modes were described, empirically termed “eu— phoric,” “hypomanic,” “somatization,” “paranoid-withdrawal," and “panic.” While the first two patterns were rated as “much improved,” the latter two were seen as “unimproved" or “worse” (50). In studies of psychological variables, it was reported that patients rated “much improved” and “recovered” frequently manifested personality patterns akin to the explicit verbal denial personality type (37). These patients expressed the “language of denial” more frequently than unimproved subjects, exhibiting such aspects as explicit. denial, minimization, displacement and clichés (27). Other psychological indices also related to favorable outcome included high F Scale score (42), Rorschach determinants of color, absent movement and absent form-color (30, 45), and low educational achievement and foreign birth (31). 2. Anticholinergz'c Compounds and Convulsive Therapy: Seek-ing a way to augment the degree of postconvulsive EEG slow-waveactivity, an anticholinergic compound diethazine, was given intravenously at various stages of the convulsive therapy process (20, 24).. Unexpectedly, diethazine caused an immediate and sustained de-crease in EEG slowing, which was associated with marked changes. in language and mood. In patients with denial language patterns. (27), these could no longer be elicited. Instead of euphoria and wellbeing, the subjects became irritable, anxious, and complaining. In‘ subjects prior to convulsive or drug therapy, diethazine induced, ex-citement, tension, anxiety, and illusory sensations. Subsequent studies with other central anticholinergic compounds" and sympathomimetic hallucinogens showed behavior and electrographic patterns similar to diethazine. These observations led to the suggestion that an increase in the cholinergic activity of the central nervous system was the biochemical basis for the convulsive therapy process (38). Psychotropic Drugs and EEG: Following these studies, the: neurophysiological changes induced by drugs were testedwithinan. 3. �162 MAX FINK acute experimental-EEG setting. It was observed that phenothiazines induced EEG synchronization and a shifting of the frequency spectrum to the slow frequencies; meprobamate and barbiturates, an increased synchronization and a shift of the spectrum to fast frequencies; reserpine, an increased slowing with synchronization at low dosages, and desynchronization at higher levels (18, 26, 28, 40). Imipramine induced desynchronization with a shift of frequencies to the slow bands (33, 34). Each active psychotropic compound was thus shown to have a characteristic frequency pattern. Various other experimental compounds were also tested, and for these no consistent electrographic pattern was recorded. These compounds have since been shown to have either no or very limited clinical psychotropic activity. The absence of behavioral change with these compounds lent further support to the assumption that brain change is a necessary condition for the action of psychotropic drugs. These observations suggested that psychopharmacological agents provide a means for eliciting various types of altered brain function in contrast to the single pattern following convulsive therapy. Furthermore, the type of neurophysiological alteration, as reflected in EEG synchrony and frequency patterns, was found to be related to specified types of behavioral adaptation. The advantage of EEG techniques for the assay of new psychotropic agents and the technical merits of electronic frequency analysis were assayed and described (47, 52). 4. Insulin Coma Therapy: In our insulin coma studies we con- firmed earlier observations that persistent alterations of brain function were related to prolonged coma and spontaneous seizures; and saw in this relationship support for a neurophysiologic-adaptive hypothesis. With the availability of the new psychotropic agent chlorpromazine, a controlled chlorpromazine-insulin coma study was undertaken in September, 1955. As patients were referred for insulin coma they were randomly assigned to courses of either oral chlorpromazine for at least three months in doses adjusted to fall short of toxicity; or insulin coma, induced by a standard technique at least fifty times in each patient. While a number of minor differences were noted in comparing the two therapies, the results at time of discharge showed no statistical difference in the effectiveness of both treatments. Neither treatment seemed to affect the basic schizophrenic process, but chlorpromazine had the advantage of being safer, easier to administer, and better suited to long-term management (21). Concurrently, following the suggestion by the Creedmoor workers that �EXPERIMENTAL PSYCHIATRIC RESEARCH 163 divided insulin doses were superior to single insulin doses, Blumberg and Laderman (39) essayed this problem and demonstrated no significant merit to the multiple-dose technique. (In 1958, following the general confirmation of these observations, insulin coma therapy was discontinued at Hillside). 5. Neuropsychology: Various psychophysical tests were adapted from neuropsychology, where their significance in brain-damaged subjects had been demonstrated. The early studies assessed these tasks as indices of altered brain function (35), and measured the range of performances of psychiatric patients, who are generally assumed not to be brain-damaged. Thus, memory function was assessed on immediate recall, after various interpolated learning tasks (17, 35), as well as during convulsive therapy (17). Tactile perceptual tasks were first examined in the clinical population (1). Later, with more sensitive electrical tactile stimuli, Korin (10) observed the range of thresholds in different body parts, the changes with altered brain function (10), and the influence of set (instruction) on performance (36). We also studied the perception of embedded geometric figures (43), tachistoscopic presentation of embedded color figures (55), perception of the visual upright (55), critical flicker frequency (49), and interference in reading time by delayed auditory feedback (55). For each task, the degree of decrement in task performance was found to be positively correlated with the amount of EEG slowing. Following treatment completion, with the return of physiological indices to pretreatment levels, performance in these psychological tasks also returned to pretreatment levels, or higher—a betterment of performance ascribed to practice effect. Concurrently, assessment of various psychological measures as indices predictive of behavioral change during convulsive and drug therapies led to studies of the Rorschach determinants (30, 45), California F Scale scores (30, 42), language patterns after amobarbital (27), denial scores on interview (37), and the perception of the visual upright and auditory feedback (55). 6. Psycholinguistics: Concurrent with the syntactic language studies (27), analyses of other language patterns were undertaken, both in a search for more objective indices of behavioral change and to gain experience in the technical problems of tape analysis for psychotherapy research. An index of variability in the vocabulary of speech, the type-token ratio (TTR) of consecutive samples of dyadic speech, was extensively studied (7,41, 44, 46, 56, 57). In convulsive therapy patients, significant changes in TTR mean �164 MAX FINK and standard deviations were related both to the degree of induced EEG slow-wave activity and to syntactic language patterns obtained in independent structured interviews. It was noted that speech became more repetitive (lowered mean TTR) and more variable in consecutive samples (41). In interviews before and after the intravenous administration of centrally active agents, similar changes were observed. Agents which produced predominant synchronization patterns on the EEG were related to a decrease in mean TTR and an increase in the standard deviation of scores, while desynchronizing compounds elicited greater variability in speech patterns and decrease in variability of consecutive scores (44). Other language measures studied included distress-relief quotients, self-reference, and alterations in tense and person. It was suggested that these psycholinguistic measures are useful techniques for the operational analyses of physiological and psychological effects of psychopharmacological agents (44, 46). 7. Brain Damage and Schizophrenia: Following his studies at Ittleson Center, Pollack reviewed the relationship between age of hospitalization, intellectual functioning and prognosis in schizophrenic children and adults. He noted that initial hospitalization in childhood and adolescence was related to I. Q. scores in the subnor— mal range, deviant performance on psychomotor tasks, and more frequent ratings of “unimproved” at hospital discharge than was initial hospitalization as an adult. The early and insidious onset of the behavioral syndrome “schizophrenia” was thus related to brain dysfunction (54). Findings suggest that different subgroups of schizophrenia may be classified on the basis of neuropsychological deviancy. 8. Sociological Studies: Considerable interest in the family organization to which discharged patients were returning, the relation of social factors to choice and results of psychiatric treatment, and the specific problem of the relation of these factors to treatment referral patterns led to a series of population studies. In one study (8), education, age, place of birth, and score on the California F Scale were significantly related to the type of therapy received and the utilization of adjunctive hospital services. In a second study (3]), duration of hospitalization, discharge evaluation, and diagnosis were related to the same social factors, while in a study of patient refusal of ECT, similar relationships were observed (51). These observations suggested a comparative interinstitution study, and among three hospitals the relationships between social class and other demographic variables (age, sex, education) to the clinical �EXPERIMENTAL PSYCHIATRIC RESEARCH 165 variables of patient classification (diagnosis), duration of hospitalization, selection of therapy, and discharge evaluation have been assessed. Three teaching institutions were selected in which all therapies are equally available to all patients—Menninger Foundation Hospital (upper-class, Protestant), Massachusetts Mental Health Center (lowerclass, Catholic), and Hillside Hospital (middle-class, Jewish). In such a comparison we have found the differences in designations of treatment, diagnosis, and discharge evaluation so marked as to make comparisons difficult. While many relationships between social variables and clinical variables were observed in each hospital, no social variable was found related to the clinical variables in every hospital (53). In an outpatient department study, sex, age, and marital status were found to be related to the acceptance and rejection of patients and failure to complete the application process (55). These observations in population samples led to concurrent studies of staff attitudes in the selection of therapy (ll, 12). In a series of ward observation studies, Kaplan and Lefkowits indicated the significant role of staff attitudes (especially nursing personnel) in the referral for subjects for somatic therapies, and in the transfer of patients from one ward to another. (To study the influence of stafi attitude on patient selection for drug therapy, we requested one ward be designated as a “no-movement” unit. This was adopted in September, 1959 and shortly thereafter by the whole hospital.) PRESENT STUDIES During the period of the convulsive therapy studies, many new psychotropic compounds were assessed clinically (5, 21), electrographically (34, 40, 48), and psychophysically (48). The present psychopharmacology evaluation program, based on these studies, was designed to answer the following questions: 1. Is there a relation between measurable alteration in brain function and behavioral change with psychotropic drugs on chronic administration? 2. Are there pretreatment clusters of psychiatric, physiological, and psychological variables which are related to the type of behavioral adaptation? 3. Are such clusters related to the type and degree of physiologi- cal change? As an initial approximation, a double-blind, fixed dosage, ran- �166 MAX FINK dom assignment drug study was undertaken. Based on our clinical experiences three types of compounds were selected on the basis of their EEG patterns. In this study, 203 subjects were referred, and 149 have completed the testing program, from October, 1959 to July, 1961. l. Behavioral Change: In a survey of the behavioral adaptations of patients receiving various psychotropic compounds during 195859, a behavioral typology based on the treatment response and on pretreatment psychiatric profiles was developed (55). In the present study, the typologies are being tested, and various measures of behavioral change studied, including therapist ratings, self-ratings, and various ward observation scales. 2. Neuropsychology: Psychological tasks have been viewed both as indices of behavioral change and as predictive guides in convulsive therapy. Each of these tasks and a selected group of motor tasks are now being assessed for both their capacity to reveal change with various drugs and their capacity to predict change with the drugs in. this program (48). 3. Electroencephalography: In the convulsive therapy studies, the degree of EEG slowing was measured by counting the consecutive waves in selected samples (16). When the more subtle changes of drug effects are studied, it is necessary to apply less tedious techniques (48), and electronic frequency analysis was introduced in August, 1959. By measurement of the pen deflection for various frequencies from 3 to 33 cps in ten-second epochs, rapid measurement of apparently small changes in total activity and frequency spectra are obtained (52). Other physiological variables studied in this program include the response of EEG to intravenous chlorpromazine, blood pressure response to mecholyl, the EKG, radioactive iodine uptake, and analyses of various blood and urine elements. 4. Data Analysis: To analyze the data generated in this study, we have sought the aid of complex statistical methods and computational facilities. Analyses of covariance, correlation matrices, factor analyses, and discriminant function analyses are computations now in progress with these data at the NIMH Psychopharmacology Service Center’s Biometric Laboratory in Washington. THE NEXT STEPS Favored by a national research climate and a cooperative hospital staff, these studies have proceeded vigorously. The assets for research in this setting have been great—a selected, intelligent patient popula- �EXPERIMENTAL PSYCHIATRIC RESEARCH 167 tion resident from six to twelve months, without individual economic limitation of hospital stay; a sophisticated administration tolerant of controlled studies; and approval of a Board of Directors who desire “research” as an institutional function. As Dr. Lewis Robbins noted in his first hospital report in 1959, a specialty hospital can make little impact on the mental illness problems of the community by treatment alone. The successful treatment of 350 patients a year is but little comfort to the 40,000 resident patients in the state hospitals of Long Island. Nor will the annual training of twenty or thirty physicians in the arts of psychotherapy do much to help these unfortunates or the many thousands of ambulatory mentally ill resident in the nation. No, a therapeutic goal alone is salutary but inadequate to our needs. As he proposed, the answer may lie in the dedication of a “research hospital,” as it is here that a specialty hospital can truly excel. The charter has been written in the Board’s assertion of research as a hospital goal. With the assets of an exemplary therapeutic facility, such rededication can provide the stimulus for the continuous study of the cause of mental illness and of methods of therapy. Such dedication would provide the stimulus for comparative and controlled assessments of different therapeutic techniques. Continued study is urgently required of the selection of patients for various therapies; the application and mode of action of the therapies; and the role of social and milieu factors in supporting the effects of our ther- apies. Assessments require a meaningful classification of subjects. The behavioral variables alone, which are the basis of our present diagnostic schemata, are unsatisfactory. Study is urgently required of the applicability of social and demographic variables; psychological task performance profiles; typologies based on behavioral response to defined stresses or drugs; and physiological reactivity measures. Such classifications are also essential for any biochemical, physiological, or evaluative study to provide homogeneous samples and comparable controls. Assessments also require meaningful indices of evaluating change. Present global “improvement” ratings and socialization measures are inadequate. Whether the intervening variable be milieu therapy, psychotherapy, drug therapy, or time, the criteria of behavioral change require definition. The applicability of rating scales, language tasks, self-ratings, psychophysical change scores, family assessments, etc., require study and evaluation. Recent studies of psychotic subjects have provided the suggestion �MAX FINK 168 that there is a neurologic factor in a group of the schizophrenias. The high incidence of electrographic and neurologic dysfunction, the lack of behavioral response to all therapies, and the relentless course of the illness suggest an “organic” involvement in this cluster. Such a substrate must be clearly sought by the application of biochemical, neurophysiological, and epidemiological techniques to various clus- ters of young psychotic subjects. These are broader views of some of the questions studied in the programs in experimental psychiatry of the past seven years. These programs, and the contemporary projects in biochemistry and in medicine, provide models of bootstrap studies undertaken with limited support. A dedication of Hillside Hospital as a Research Institute will provide the needed focus and impetus for the scientific and humanitarian forces of the community to join in a common endeavor to resolve the problems of the mentally ill. Acknowledgment: Participants in these programs include the present members of the Department of Experimental Psychiatry: Ira Belmont, Martin A. Green, Abraham Kaplan, Eric Karp, Donald F. Klein, John C. Kramer, Max Pollack, and Arthur Willner. Former associates included Karl Andermann, Joseph Jaffe, Robert L. Kahn, Hyman Korin, George Krauthamer, Nathaniel Siegel; and Research Fellows Barre Alan, Fred Coleman, Harold Esecover, Stanley Friedman, Henry J. Lefkowits, and Robert Shaw. The cooperation of Arnold G. Blumberg of the Department of Medicine in the present program is gratefully acknowledged. The reports listed here are the result of the collaboration of these workers and the professional staffs of the hospital who gave unstintingly of their time and their good-will. REFERENCES' (1) This Journal, 1:21, 1952; (2) ibid., 2:67, 1953; (3) ibid., 4:3, 1955; (4) ibid., 4:134, 1955; (5) ibid., 5:67, 1956; (6) ibid., 6:197, 1957; (7) ibid., 6:207, 1957; (8) ibid., 6:216, 1957; (9) ibid., 6:229, 1957; (10) ibid., 6:241, 1957. This Journal, 10:84, 1961; (12) ibid., 10:97, 1961; (13) Neurology, 4:211, 1954; (14) Arch. Neurol., Psychiat., 72:233, 1954; (15) ibid., 76:23, 1956; (16) ibid.‘, 78:516, 1957; (17) Conf. Neurol., 16:88, 1956; (18) EEG Clin. Neurophysiol.,9:180, 1957; (19) ibid., 10:162. 1958; (20) ibid., 10:207, 1958. (21) J. Am. Med. Assn., 166:1846, 1958; (22) Dis. Nero. Sys., 19:113, 1958; (23) ibid., 19:227, 1958; (24) Arch. Neurol., Psychiat., 80:380, 1958; (25) ibid., 80:73, 1958; (26) Neurology, 8:682, 1958; (27) Psychopathology of Commum'cation, New York: Grune 8c Stratton, 126, 1958; (28) Psychopharmacology Frontiers, New York: Little, Brown, 325, 1959; (29) Proc. XV Int. Cong. Psychol., North Holland Publ., 238, 1959; (30) J. Nerv. Ment. Dis., 1281243, (11) 1959. (31) Arch. Gen. Psychiat., 1:565, 1959; (32) EEG Clin. Neurophysiol., 11:398, �EXPERIMENTAL PSYCHIATRIC RESEARCH (41) (51) 169 1959; (33) ibid., 12:243, 1960; (34) Canad. Psychiat. Assn. 1., 4:166S, 1959; (35) Proc. Int. Cong. Neurol. Sci., Pergamon, 613, 1959; (36) Am. J. Psychol., 72:384. 1959; (37) J. Neuropsychiat., 1:45, 1959; (38) EEG Clin. Neurophysiol., 12:359, 1960; (39) Am. J. Psychiat., 116:839, 1960; (40) Neuro-Psychopharmacol., 1:441, Elsevier, 1960. J. Nerv. Ment. Dis, 130:235, 1960; (42) ibid., 130:187, 1960; (43) Arch. Neurol., 2:547, 1960; (44) Dynamics of Psychiatric Drug Therapy, Springfield: Thomas, 29, 1960; (45) ]. Neuropsychiat., 1:242, 1960; (46) Am. J. Psychother., 15:46, 1961; (47) Neuro-Psychopharmacol., 2:30, Elsevier, 1961 ; (48) ibid., 2:381, 1961; (49) Arch. Gen. Psychiat., 4:259, 1961; (50) ibid., 5:30, 1961. J. New. Ment. Dis., 132:153, 1961 ; (52) Medicina Experimentalis (in press); (54) Arch. Gen. Psychiat., (53) VA Conf. Psychopharmacology (in press); 2:652, 1960; (55) Unpublished manuscript; (56) Psychiatry, 21:249, 1958; (57) Comparative Psycholinguistic Analysis of Two Psychotherapeutic Interviews. New York: Int. Univ. Press, 1961. ' Due to the length of this Bibliography, it is presented in an abbreviated form. ��IIPRIIIBIIAL PBIGIIATEIO 13831303 A! IILLBIBI noiiow and Proapoct HI: Pink, 3.9. Iron tho Dopsriuont of Export-cutnl Psychin$ry, 31113160 Hospittl, clan Oaks, L.I., 1.!. 2h. Itud1fil roportod hart hi1. baa: ntdud hr tho Board Dir-ctoro Research Fund; thc lttiannl Instituto or I: Honttl nutlth (Grants l-927; I!-2092,-2715,-h7983 nr~12,033); POIndationl Fund for honoureh 1: Psychiatry (373? 56-151); xuutnan§, tad Dalian fantastical; and lustrou- pharnao ooutionl cost-rap tncIudinx 60131, Briatbl, Wrath and Snith, K1130 a Iroach Lnboratorioa. 1': 10/1/61 �Exporinontol Poyohtotrio Rooooroh ot Htlloido lovtov ood Proopoot tho dodtoottou of 3111-14. Boopttol oo o Rooooreh Inotttoto boo boon o drooo o! nony or 1to otudooto - o drool that nay oohiovo rooliootion in thin dooodo.< Dr. 3. toroohov woo on oorly propoooot of thio vtow, ood both in hto oponoorohip of tho Joorool, ond to his onooorozonont or rooooreh otldtoo, ho prooosod thio dovolopuoot. no woo oloo tho toodvortoot oiro at tho rooooroh otodtoo 1n oxporioontol poyohtotry. “halo 1 woo o rootdoot 1n poyohtotry to 1952, no oolloborotod in o otudy or tho ro~ lotion of tho oorlr ooporotsoo of child tron o ohotoo tho poroot to odolt of uoorooto. notion13¢ tho hoopttol rooordo o: ttvo proviomoyyooro no oonolodod thot thoro woo, todood, o rolotioo nourotto pottooto with otooooionol oouroooo hod oigoitxoootly xrootor tooxdoooo o: ooporotioo thou potiooto with hyotoriool oonroooo (a). rhto roport woo tho boctooinc of tho potioot popolottoo otodxoo dooorabod horo. stnoo 19Sh tho vortooo progrooo 1o exportoontol poyohiotry hooo boon dovotod to on ondorotoodtog of tho undo o: o U �.2.- antioo of tho poyehiatric thoropioo of tho hoopitol. rho tochniquoo hovo boon odoptod tron doooriptivo ood dylooio payohiotry, oouropoyoholou, olootroonoopholonophy, linguiotiuo, phoroooology, ood sociology. Ihio roport roviowo thooo otudioo ond prooooto support for tho erootion or o nooooroh lootitoto ot lilloido. PIS! SIFDIBS In our early ttudioo or oonvoloivo thoropy, inotitotod with tho oid o: o grout oword of tho Iotionol Institoto o: nontoi Roolth, ovoluotioal o: potioot iaprovonont woro ohown to to dopoodont both on choocoo in broio function ond on poyoholociool tootoro. AI our Indorotondioz of oonvoloivo thoropy dovolopod, o gonorol nooropnyoioloxio~ odoptivo viow'o: ooIotio thoropioo ooorgod (6). i cholgo in brain function woo oooo oo o noooooory condition for hohoviorol ohonuo, with tho typo or chooco, houovor, voryiu; dogoadin; upon poyoholocicol oud oooio— logiool chorooto'iotioo ox tho outjoot (22,25). thou, tho oodo o: ootioo woo not too: oo oithor “orgooie' or ”prlyoholouinl' but rotbor oo tho iotoroction or non-ophyoiologiool chooaoo nod individual pottoroo o: rooponoo oud bohovior. fhio hynothooio ' woo oootoiood in otodioo or convulsivo old insulin oono thoropioo (21,22); and tho oodo or action of tho now psychotropic oconto woo ozprooood within thin �.3. payohoiropic'drugn that It would bu urinativo to tho uxtnn‘ thu‘ pcrllutcnt ehgugon k.— fiypo or tho tad induncd; that brain Inuation ugro in hnvtoral reopens. would bu rolntcd to tn. iypo o: br¢1a hypothosta. wan unggun‘od chnnga, and to individual pro-norb1d psychologie (par-caulitr) vtttnrns (6,28,ho). consu1;1v3 thcrngz Draco-s: Soaking a noncaro of gltorcd nourOphgstoleglogl «hangs that w:- annuitivo 1. tnitnblo for rcpol#od rutolta, various nan-urns wort studigd inpludinx chanson in tho ts¢o~hand tout (1,10,13,35), nanory tout; (17,35), anoant .1 slow utvn activity 1» tit :30 (16,23) tld contnbulatory and duaial languago pfit‘Orll attur nuebarbitul (3,15). an. llttor two, EBB und unubnrbittl touts, Hit. tbs nest oonlttlvo indie.- o: chaulc 1a convulnivo thgrtpy subjects. In on. uxpcrincnt, clinical rating: a: taprcvcfiont var. carrolatod wi‘h high 6.320.! of chungo in than. indicol (15,16). 2)... oblcrvutlon: wore touted 1n n doublo-bltnd study in which p;titntl tutorrod tor oloctroahock worn rindauly ‘3313306 to oithor convulsivo cr anhconvnlsivu and . therapy. nigh dour-on o£_oltetrogrnphic Ilcw wave :otivity and pastfiivg nnfibarbttnl tout: warn obsorvod only 13 the convulaivc group3~1nprovcutnt titan were algntticuntly highQr in this group, and whnn subconvn1I1Vt aubjccto var. retransod by convulnsvo applications, (he tnprovogout rat. way 31:31.: to tho ooarulstvo ureup (22). �.3. In sibeonvuluivo applications, nousidornblo oloatric current pgaau: botwugn the cleatrudou. It wan pontulntod that tho ihcrapoustc tguut was nut tin $Otl1 olootrt¢:1 current, r so, but_thu ":11 or nonn' quali$7 llhiftl‘td by tho crana 331 Ittluro (9,23,h2). 2h. Itcniriounao o: tut [rand 3:1 .oisuro was «an-$306 in n ounparuttv. study of sh. 13ha1:nt oonvulutut, lnxaflnnrodiothylathnr (Indckloa), :nd clnotrtotlly inducad soituroa. 81:11:: dour... ct olcatrtcrnphao chango, improvuuunt rat‘s, typo. or bohnviornl ndtptntionn, Ind ohnnxcn in Inuropcychnltgiotl talk hchavior war. ohocrvod 1n bush tho inhalant And in tho alcctraa;117 tronfiod crouy: (k9). Kuvonr, not ‘11 Iibaootl auntie-ting high dccroo: or phyttolbgiaal thugs. var. avnluttcd .3 “improved“. I: n doncrtp‘tvo typologia Ifindy,_£1vo .dnptivn aldol war. dusoribod, cupirxcslly torund “ouphorto', ”hypunnaic‘, "nmuuuon', 'mmnld-wtthdravnl', Vial. ‘h. strut tun pattcrnn ltttcr worn ratcd and ”pan“ . an 'uuoh inprovnd', var. loan as 'undnpruvod' or “war-0' (So). In utudloa at plynholoaicnl varinblou, it was ruportod that pationtn ratod “much inpravcd’ $36 'rocovorod' troquently nanitultnd parloatlttw pattern: :kin t. tho explicit vurbal dcntnl parnonnlity type (37). 2h... pattoutn cxproslod tho ”innauago a: 6.3151“ nor. troguontly than uninprov‘d aubjoctl, antibiting such asp-oil a: tho two �-5- explicit deeiel, einieieetiee, dieyleeeeeet eed oliehee (27). Other perchelexieel indieee else releted te fevereble eeteeee included high I fleele eeere (ha). nereeheeh deternieente ex eeler, ebeent eeveeeet eed ebeeet rereneier (30,h5), eed lee edueetieael eehieveeent eed rereice birth (31). 2. Aetiohelieer ie cenmeuede end Geeveleive There seeking e we: te enceeet the degree at peet-eeevuleive EEG e10? were eetivity, en eetiehelieergie deepened dietheeine, wee given intreveueeely e. verioue etegee or the ceavuleive therepy preeeee (20,2h)Q Unexpectedly, dietheeiee eeeeed en ieeediete end eeeteined deareeee in EEG elewiec, ehieh wee eeeeeieted with eerked cheagee in lengeeae end need. In petieete with deeiel leeteege petterne (21), theee oeuid no longer be elicited. Ineteed e! eupherie eed well 'heing, the subjects beoeee'irriteble, enxieus end coepleiuinn. In eebjeote prior to convulsive or drug therepy, dietheeine induced exeiteeent, teeeiee, eexidty end illeeery eeeeetieee. Subeeqeeet-etediee with ether centrel entiehelinergie cenpeeede end eyepethenieetie helleeieegeee ehewed behevier end electregrephic petteree eieiler to dietheeiee. the-e ebeervetieee led te the eeaxeetien thet ee ieereeee ie the ehelieergic eetivity at the eentrel eerveee eyetee wee the bieoheeieel beeie to: the eenveleive therepy preceee (38). �-6Iad‘filat Fallowing thtli Itudiou, tn. neurophyliolosic‘l august: induond by drugwar! touted within a. acito oxporiadnt.1 EEG Iotttng. It run obitrvod Butt phnuothinuianu induced BIG synchronxuuticn and a Ihittlnc at tun Iroqunncy spectrum to tbs slew Iroqunuotons taprobannfic and barbituratoa, tn agar-1:04 lynchruatagsgon ;nd a ahttt of thy spectrum to tact troquaauiau; rosorptnu, an iuaruatod slowing with uynohrcn3. ?a tutttoa at chair: is ,r law dontgua, gnd doqynohronitasion IIVOII (18,26,28,ho). at hiahur Iazprnliao induced douynchronination with a sun .1 trauma to the now bud: (33,310. Each ‘otivu psychotrnpia compound wgu #hu: about to ant. a charactnriatic trnqnoacy patturn. Vtriouo 9th.: axpcrtncafisl coipounda wort also tantad and tar than.. no noafiistcnt ulcotrogruphic pattart was rooordod. In... ounpuinds bl?! Gino. boon nhawa to have dittor no ¢r vary limitad clinical psychotropic :ctivity. rho .bIOflei of bahaviurul chins. with than. coupoundo loot turthor uupport Sc tho anlunptton that 32.1: chnnco is a accosstry condition far the nefiion of puyehntrOptc drugs. 2h... obncrvnfisons auccoattd thnt psychophgrnncou 10310.1 tannin provide a noun: icr niioitin; vnriou- typgs or altarod brain function in coltrnst to tho $13319 pattcrn following canvalniva tharupy. furthermora, tn. type a: luurophrliolocionl altorution, an rallcotod in EEG Iyuohrcay �.1and traqucncy patfiorns, val round rcln‘cd to 0’0011106 a: bohnvicrul adaptation. 2h: ndvnntazu 0: £80 toohnancs to: tho ‘Icay at new psychotrOpic taunt. sad types fihy toohntcnl tarts: or aloo‘rontu Iroquanoy tally-t- «or. unnarcd and dolcrihod (£7.52). h. Insulin can: fhnragz: In our inluliu can: studies we ocuttrnod anrlaor observations that porutntout alfiorntiona or brain tunottom were taint-d to prolonsud «one and upcntanaonu nuilnrou; and tau in this rolntioanhtp suppert for n nitroplyltologtc~ndapttvo hwpothontl. With thc grailnbtlitr 01 ‘h. ncv psychotropic asant chlnrprunasinn, a ountrollod?chlorprunaltao Insult: can; atudy was undartnkon in Sop‘anbgr 1955‘ AI patiaata war. rotorrod for insulin aim: tun: get: rundonly unsignod fin couraos or nithor oral chlorprcualino for at IQlIt 3 months in dosoa adJuIt-d #0 1111 short of toxicity; or'tnnultn cans, induoud by s uuhmd «chateau at last» so was 1: «ch pattont. Vh110 a uI-bur or ulnar distoroncou worn noted in comparing the two thgrnpigs, thn results at tile or dicohtrac chewed no stutilfitonl ditrorcnco in tho offsettVQBQnI at both traatncntl. loithnr troutunat £00.06 to affect tn. bantc nonsquhrcnto procons, but chlorpro-asino had tn. advantagot boing 3:202, tacit: to adniniator, lad hotter suited so long torn unnnzunont (21). concurrontly, following the 0“goutton by £ha Or-odnoqr worker. thtt dividod insulin �.3. doooa woro aofiorior to olaglo insulin doooo, Bloabor; and Ladoroao oooayod thin probloo and donorotratod no significant oorit to tho oulttplo dooo toohoiquo (19). (lo 1958. £91 ral courtroa too at hooo oboorvotiono tho a , 5. floor woro adaptod oho :' Various poychaphyoloal tooto tron oooropoyoholozy, whoro thoir signitioaooo to brain da-agod onbdocto had boon dononotratod. 1h. oarly otodioo aooooood thooo took: on lodlcoo a: altorod brain rotation (35), aod ooaaurod tho ranzo of portornaocoo or poyohtotrlc patiooto, who oro conorally aooonad not to to brolo dana‘od. Into, looory function woo aooooood on inoodiato roooll, artor vorlouo tutorpolatod loorninc tooko (11,35), aa roll ao aorta: coorulolvo thorapy (1?). rootilo porooptoal tooko voro tirot oxaninod to tho clioioal population (1). Lator, with ooro oonoitivo eloctrioal tootilo otlaoli, Karin oboorvod tho raafio o1 throoholdo 1a dittoroot body parto (10), tho ohaogoo with altorod . brain function (10) and tho inflooooo or oot (inotrootloo) on porforaanoo (36). Ho also studied tho porooption o: ooboddod gooootrio figuroo (h3), toohiotoooopio prooootatloo o1 ooboddod color rigoroo (55), porooptloo of tho vzoual oprlsht (55). orltlool illokor froqaoocr (h?) and 1ntor~ toroooo 1n roadtag tioo by dolayod auditory toodbaok (55). For oooh took, tho dogroo of dooroaoat 1» took portoroaooo �-9- gastttvaly oarralatad with tha anoint at 386 aldwtas. Folluuina troatnoat couplattan, with an. rota»: at partialoatoal tadtaaa ta pre-traatlaat lavala, partaraauoa in thaaa paychalagioal tanks also rataraad to prautraataant lavala, or tight: -.a battaraanfi a: partoraaaoa aacribad to practiaa afract. waa found $0 be concurrautly, aaaaaanant or varioua payoholaxtcal aaaauraa an indicaa pradictiva or behavioral «hang. daring convulsive and drug tharaptaa lad to studiaa of the Rorschach datarninanta (30,h5). calitornia F Seala nonra(30;h2), languaco pattern. attar atobarbital (21), daatal acarae an antarviaw (3:) and tha paroapttan of tho visual upright and auditory taadback (55). 6. razehalég‘uiattoa: concurrant with an: syntactic studio: languaua (27), analyaaa of othar languaga pattaraa warn andartakan, boat 1: a aaarch tor aura objective xadiaaa a: bahavtaral chaaua and to gain oxparianca in the taehnioal pwablana of tapa aaalyaia tar payahatharapy research. La . influx of variability in the vocabulary of apaaoh, tha typo- tokaa-ratio (if!) of eonaacufiavo Iaaplaa of dyadic apaaoh, wu “unholy atudiod (1,h1,hh.h6,56). In convulsiv. aharapy patxanta, aigaiftoant chanson 1n TIE naan hué standard daviationa war. ralatnd bofih to the dagraa or iadaaad 280 slow wave activity and to ayniactic �~10- lcnlicsc puitarnl abicincd in indcpcndcnt tircotnrcd intnrvicvn. It was cocoa that uptick bola-o norrepetitive (lav-rod not: III) an! acre varinblo in colaocntiVb cunplc: (kl). In intnrviowl infur- nnd cttor tho intravenous administration or ccntrclly active agents. ainiIcr chanson war. ohlcrvcd. input: which produced prcdo-iaact synchronisation pattorun on tho EEO ware rclctod to a docrctso in «can 1!! cad an incronno in flu: smdcrd duration or ...m. while «synchronising ccapcuada clicitod groatcr variability in cpccch pcticruc and dccrocnc in variabilifir at consecutivu acorn: (hh). 0thcr 1:33:53. Iltlflrlfl atndicd included diatrclc~rclict quoticntc, colt-rotoroncc, and altar:ticnc in till. cad patina. It VIC snag-ntod that than. paychcliuguictic accsuro- arc usctnl techniqnoc for thc operational caclyscl c: phyniolcgical and psychological uttcctc or psychopharnncclcgiccl cgcnta (hh,h6). 7. ling; B‘llli gud Schinaghrcgil: rollcwiug his ' Itudicl at Ittlsccn Ccntnr, PoIlnck ruvicwod th. rclcticnu chip bctwcon can 9! hospitaliscfiicn, intollcctucl tunationils and prognosis in cchincphrcnic childron ind nttad that initiil bagpitalilltica cdclta. H: in childhood cad Idoloaccncc was rclatcd to I.Q. secret in tko cubncrncl tango, dcvicnt pcrxcrnancc on psychanctcr ttlkfl, and nor. �.11; troqasat ratings or 'uaiaprsvsd” ai hospital discharge than was initial haspihaliaaiioa as as adult. rho aarly sad insidious sasst st iha hahsvisral syndrsss “sohissphrsaia‘ was ihas rslatsd to brain dysfunction (5?). Findings saggsai that say ha olsssitiod on davianoy. diffsrsat suhrroaoo s: aohisophrsoia tho basis at asarspsyohslogioal in Considarahlo iotorssi Studios: aooiols‘ioal tho family organisation to vhioh disohargsd patisnhs ohoios‘ wars rotsraing, tho ralatioa a: social factors to sad rssults o: pevohiatrio irsaiaaat, and ihs spaoifio prohlaa of tho ralatioa at thasa factors to irsatasot rorsrral paiisras lad to a ssrisa of population studios. Ia oas study (8), soaoatiao, ago, plaoa at birth and soars on tho California I seals wars significantly rslaisd to tho hypo or thorapy rsasirsd ass tho utilisation of adaaaotivs hospiial ssrviosa. In a ascend study (31), darstioa or hospitalisation, dischargs avaluaiioo and diagnosis wars rslatsd to tho sans social factors, whila in a study of patisht rafuaal of BOT, sitilar relationships wars ohsarvad (51). Thass ohssrvations suggastad a_conparativs and tho three among hospitals study, min-institution batwssn othsr demographic social class and rslationahips 8. ‘ variables (ago, sax, sdooatioo) to tho clinical variablos �.12. at patanat cltulixtcttscn (ataanonal), auruttoa o: inapttuln tuttton. soloctiqn or thornpy and dtuohnrgu uvaluntion 5.1. 3.0: unlocuod. Into. touching tuntttuttolu were :11 thortptcc arc oqaa11y avatlnblo to I11 pntiontl, - nonnincor Foundation Hospital (uppor-clusc, .Protoctant), uttsaohuontta ncntnl lualth Contor (loverclnll, Cathnlic) ind £111.16. Boaptttl (niddlo-claul, Jow1ah). In hack a canytrtton w. turn round tho dittorcaoul 1n duotgnntiona of trontnnnt, diagnoliu tad dtuehargo cvnluatton so dafforbnt an to ugh. nonpartnean difficult. Vhtla III: rolttionnhtpu tatvton Iodill varinblon 1nd 91131c31 Virilbltl var. oblarvad in each heapitnl, to 1001.1 variablo was fauna rclstcd to thc clinical variablo. 1- "01-7 hospital (53?. In an Out-Pattont Departnont utndy, sex, 8‘. 3nd narttallatata: var. found to ho rc1atod to tho acceptancand roawetion at patttuts tad fuilnr. to couplcto tho upplionttuu pIOGOII (5h), that. abatrvnt1¢nl 1; population Ianploa 10d ta coa— current Itmdios or start attituia: 1: tin Iolootion at thorapy (11,12). In a aortas o: ward obnorvation studiol; Kaplun and Lotkawttn indientsd tho significant :01. or otntt attitudes (oupocta11y turning porcannol) in thc rerorrgl tor lubaostn for lunatic thtrcp1on, and in tho tranutcr at pztiontl tron out ward to unothur. It stud. Icloctod ' 1n whaen �-13. fit. tn£1u ca .1 :finxt attitndo t1§n$ soloattoa for drag thorngz, w. g33u03$nd can ward be dontgagtnd an a "ago-avnusas' unit. 2):! van ndagtad in 8:233:34: 1259 and an shor‘lz fihornuttqr 3: the whole hangatul.) mum 8E1“ buriug *ho parioa at the convullivc thsrupy studios, man: nun psychotropic 00:90:36: were attained clinically (5,21) alootrographzgally (3h,h0,h8) ‘fid psychophrttcnllr .(aa). rho pro-ant payehophntuncology cvaluattoa progrta, b;sod on ‘hoao u§udion, was designed in gnaw-r tbs follow- ing'qunltions: I 1. fiber. ; rclntion botvooa COIII9I§XI &lt.rlttga in brcin function tad bahaviurnl Chtflflfl with psychotrOpic drug: on circuic :d-intstrntton? Ar. that. prb-troatnoat cluttcrl of plyohtatric, phy1101031ca1 and psycho- logiotl variablnl which are rolatod to ‘ho flypc at bohnvtoral adaptation? Arc ouch olultcro rclntad to thy typo and dogroo or physiolextcll chango? LI an iatt1;1 upprqxin&t19n, a doubln-blznd, fixed detach, vandal aunt‘s-ant drug study was undartakcn. Blood on our c1131ca1 cxporicaenl throo tIpCI a: compound: var. �Du. oolootod on tho boots o: thotr EEO pottoroo. 1: thin otody, 293 onhjooto woro rotoirod old 1&9 hovo oonplotod tho touting progron, tron ootohor 1959 to July 1951. 1. lohoviorol Chog‘oa In o ourvoy of tho bohoviorol Adoptotioao o: potiouto roooivin; voraoao poyohotropto compounds during 1958-59, o bohoviorol typology boood on tho arootnont rooponoo one on pro-trootnont poyohiotrto protiloo dovolopod (55). In tho pro-out otndy,tho typoloatoo oro botng tootod, old various oooouroo of bohoviorol choogo otodtod, inolnd1n‘ thoropiot ratings, coll-ratingo old various word ohoorvotaoo oooloo. woo 2. ggnr o cholo : Psychological tooko hnvo boon viovod both on indiooo of bohoviorol chonuo and on prodietivo goidoo to convulntvo thoropy. Koch o: thooo tooko and o oolootod group or uotor tooko oro now bozo; oooooood for both thoir oopoaity to rovool ohongo with voriouo drug: ood thotr oopooity to prodiot ohongo with tho drugs to this -pro.ron (hB). 3. Blootrooooogholg‘goggln In tho ooovuloivo thoropy ' otodiot, tho dogroo of slowing woo loooorod by counting tho oonoooutivo wovoo in oolootod oonploo (16). whoa tho noro oubtlo ohongoo or drug ottooto are studied, 1a noooooory to opplr loot todiouo tochniquoo (ha), ond EEG it olootronio froquonoy ontlyoio woo introdocod in August, 1959. I: nooourouont of tho pon dotlootioo for voriouo �.15- ' sooosd is_ton opoois, ropid trsqssssiss tron to nosslrsnsat or oppsrsstly sssll ohsncss is total activity and trout-soy upsets: or. sttsisod.(52). ethos physiological vsristlos stadiod in this 3 33 bps yrogron include tho rooponso of 830 to istrsvsnoos chloru ~pro-suns, blood prosaoro rospouso to nooholyl, tho EKG, radioactive iodine optsko, and saslysss or various blood tad urine olsnsnta. h. hots Ansgzgisx rs onslrso tho dots goosrotsd in this otndy, as hsvs sovxtt tho aid or complex ststisti- colon-thud: and computational tsuilitios. Analyses or notorious, osaj‘rslstioo ”trio", factor analyses and disorisintst function onslrsoo ore connotations new in prouross with this dots at tho III? Psychophsrnsoology aortic. contsr's Biolstris Laboratory in Washington. Ill-l!!! STEPS Favorsd by s notional rososroh ' clissto and s ooopor- stivo hospital staff, thsso studio; hows proooodod vigorously. Rho ssssts for rososroh is.this sotting hi7. toss arsst ~— s solsctsd, intslligont pstisst popnlstiou rssinsnt from six to twolvo months, without individual economic linitstios of hospital stay; a sophistiostsd sdninistrstioa tolorsst or controlled studios; sud spprovsl o: s 30:26 or Birootors who dosirs 'rssosroh' as on institutional function. �~16- eeted 1n hie tiret heepitel repert 1a 1959, e epeetelty heepitel eee eeke little tepeet en the eeetel illeeee prehieee er the seeeehtty by treet— eent elehe. the eeeeeeetel treeteent e: 350 petteate e contort to the h0,000 reeident petteete in but little yeer 1n the etrte heepzltele a: La; Ieleed. I» will the eeeeel treieie. or twenty er thirty phveieieee in the erte e: peyehetherepy do exeh to help theee untertnnetee or the reeident 111 theeeende of in the mentally enbnletery nee: eetiee. he, e therepeetle [eel eleee 1e eelutfiry bet teedeqeete to ear neede. he he prepeeed, the eeewer eey lie in the deeieetiee or 'reeeereh heepttel”, ee it 1e here thet e epeeielty heepttel eee truly excel. the eherter hee been written in the neerd'e eeeertlee er reeeereh ee e heepttel ceel. with the eeeete or en exeeplery therepeette teeility, each rededteetlee eee previde the etieelee tor the centieeeue ether 9! the eeeeee er mental zlheeee end at eethode e1 therepy. Seek dedicatiee ueeld provide the etteulee tor cenperetive and controlled eeeeeeeeete e: dittereet therepeette teehniquee. Centteeed etudy 1e urgently required of the eeleettee e: petseete ter verieee therepiee; the epplieeteee end eede er eetlee e: the therepiee; end the role of eeetel end ntltee :eetere in euppertte; the exteete Le Dr. Levin hehhtee & �.17- o: oar tharaptol. tubjoctl. the hohavioral Vtrtnblou OIOII, which are tin halt: a: on: profiont ditcznltso Ichtnstn, arc taunts-raotcry. at:dy is urgtntly requirod at tho upyltonbtlltr a! aootnl tad dulnarnphtc i:riab1¢a; paybholoutcal t:§k pcrfornancu protilun; twpologinc bnaod ca b-havxoral response to dozinnd Itroaaun or drug.; and physiologicall roactivity measures. such olaantticatioan arc also oniéntial for any biochemical, phyainlogioal or tvnlunttvo study to pravado ha-nzonous 33:91.! and campgrablo outrun. ‘ Alloa§nantu tlnd requsro moaningtul indtcoo of evaluating 05833.. Pros-at global 'tnpro.uncnt“ rating: tad loeaalitttton noctur-n arfi inadequate. Whathor tho 'iatorvuuing variablo bu nilihn thnrnpy, psychothnrapy, sino,‘§héleri£irii at bohhvioril chant. max... «anti-.1»; in.” 3592;131:1511”: a: rung-«1n, drug therapy 0r ' ladguaao #:028, idlt€r££1n3n,wpsyohéphyatéal"ch:n¢cVaéufca. . family CUIOIIIO§$I5I2E2- raqniru study :33 cviilatién; Roount attains of p¢y§hottc hubjoeta has proiidcdv tho succession thit thfirs in a notrolosic factor 1a.: group a: eh: ichisophroainn. The h1¢h tacidoneo er citatro"graphic and aauroloxie éysiunetian, the 153k or behavioral Vidnficulc to all thoripiol, and tut rclontlcna course a: �-18 o illncts nascent: involvontut in thin clustcr. Such a substrate aunt bo-olourly sought by tho app11egt19n of biochemical, nourophyniolegioal and opia daiiologionl toehuiquu to Vitus elation or you; pcyohutio hubgccta. 5: Eh. quontiona broador or 110:. than. arc son. Ittdiud in thc prosrtlz in cxyurimontul psychiatry ot-tho pant aovan yéura. than. programs, and the cantonporury projaots-in hiaahuniatry and in medicino, providc nod-1s It hootuatrgp studios andor;lkon with linitod uupport. ‘A dodieltion at lilllidOIHinitll as a ncaonrch Institutc I111 providc tho neodca £96“. and impetus for tha Iciontltia and hunnnitcriun forces at the oonnnntty to Join in a connea endeavor to roaclva the problems or the tantally £11. fiho 1n “orznn1¢* �LGRROUIOG‘OIIi‘ Participanfil in than. procraua inalndo thprouont ac-bcru a: fih- Dopartnnnt or Expnrtnoutnl tuyohiatry: Its lalnoat, acrtln A. Orton, thrthna Iaplnu, Brio Karp, Beunld 1. £1.13, Joha 0. truncr. an: Pollack and Arthur 33113.3. turner associntad includod Kurl tuner-nun, Joseph 4:230, lobart L. Kahn, Hyman Koran, Goircu Kruathunor, ln£h3n101 81.3.1; and angry J. Lorkauats, untold Intonvur, lid ntrrc Alan. It. couporn$1on 0! Arnold a. Blunborc ot~ Bopartaont of Hodictnn in the protont program in srqtntully the ropor‘s liltod horn are the roault at tun collnboratian of this. tartar. and fit. prutoastonll atQtta a: $h| h0upita1.vha an?! unnttnttnxly or tuttr tin. acknuwlodgnd. and that: nooduw111. �W J. innum- mug. 3:21, 1. was, 67, 1956; 6. 1953; 3. 3. 1955; ha 1952; 93.59201, My 1951; 10. £535.21.» aggmh, man, 53339229, 33539216. 7. 1957; 9. 1951; wgaév. 2. 1951; 1955; 5. 19575 gnu“ 12. 1961; and 35;: 33:81:, J. gag. 13. ”surfing, £3211, 195k; 1!... Arch. Home)... 16. 1956; 15. 195!“ 33311923, 353 3:233, 11. 91, 1961: and. ”an“. 13.516, 1951; can. gut. . 33:88, 11. human-.101. 3:180. 1957! 19. 10:207, 1958; 21. 22. 91!. 21;. Arch. and. Im. haul. 733, 19583 ' Jon. “or. M Ann. 1956; 18. no 011:. 32:162. 1953; 20.3113 }_6_§:18h6, 1958; 23. 3333.21221, 1958; 25. 1958; and £9: £33380, . cg ’E‘L‘E 26. Iowa. 33682, 1958; 21. Pazohoutholqz 323. 323113. 1958; w. at Gal-Inna», Brno & Suntan, 126, 1958; 28. PatchesGo. 1959; 325, a Iron Luna, , zbnrnuohg nation, 29. Pros. xv 139. can. Pulp»)... lath fioluud Pthln 238, 1959: 30. 3921.3, 1959. 31. Arch. 00:. PI:«but. $3565, 1959; 32. Egg cm. lam-gm“ . M 531668. 1959: 35- Pros. 33:398. 1959; 33. 6256. Porch. Luna. .1. 0.3.. Install. 501., Forum, 613, 31;. Plzchn . 133381;, 19595 31. J. 1959; 300911011. 35.2w. 36. 1960.: I“. nor. J. 11155, 1959-; �38. Ila 3113. "‘£32Ez.1.13 $30359, 1969; 39. Aunt. J. Plzdhzut. ;;§t839, 19601 ho. lonro~rozghgzhurnneologzll: n(‘) kl. Jeur. Harv. Rant. 31-. $§91235, 1960; ha. ibid $293187, 1960) h}. Arch. H.353 . 3.5h7. 1960; bk. nganien or Puyuhintrio Brag rhorugl, $9, 0.8. rhonnl, 19603 £5. 3. retrogjzoh. $3252, 1960; hé. 130:. J. Pazchuthor. $3; h7. Intro-tszghaghuguncolagz‘gc30, Elsovicr, 19613 hB. than 3:381, 1961: M9. Azeh Gan. rqzuhil . 5:259, 1961; 50. thid 2130, 1961. 56, 19611 ' orv. Rant. 91.. £2gn153, 19613 52. 535:, taint Eggorinontalcs (in prosl)£ 53. '5 can :wggvahogharuneo » (1n 5h. 890111 pro-I): 2‘; Inn‘s; (in prose); SS. Bupub~ lishoa §anulcript3 56. Pszohiltrz 3;:2h9, IQSB; 5?. Arch Gen. Paychiat. 23652, 1960. 51. Jour. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Experimental psychiatric research at Hillside: review and prospect. J Hillside Hosp. 10:15969. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-57-023 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint and [preprint]. Reprint from JOURNAL OF THE HILLSIDE HOSPITAL Volume X Nos. 3-4 July-Oct. 1961 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/dcb2d198f268393b586365e8e34503d8.pdf f1412cf3717181597ffc25684c3fe518 PDF Text Text PREDICTION OF INDIVIDUAL PATIENT RESPONSE TO CONVULSIVE'THERAPY 1/ e i - i e ' . <-- Max Fink, M. D. l - E -ku'xs‘b The prediction of response to treatment is a necessary daily task of medical practitioners, who, after a process of clustering the symptoms and signs of illness of a patient, select a treatment regimen most likely to effect a salutary change in the patient. Where the classification of the disease is established by definitive criteria in syphilis. diabeas tes or malaria - the physician's problem is simplified. Where classification is not based on definitive criteria, as in heart disease, or mental disease - the physician's is problem complex. for he must resort to the recognition of pattern based on his individual experiSuch classification is not readily validated, and in the absence of specified external ence. criteria, errors in grouping for therapeutic purposes are frequent. ' wv'h"'" ‘ ' In the instanCes where remedies are established by their effectiveness. as in syphilis, or bacterial infections, or avitaminosis - treatment selection is readily defined. Where remedies are non-specific, as in the treatment of mental illness by environmental manipulation, psychotherapy and various physiodynamic therapies, the problem is complicatcd, not only by the non-specificity of treatment but by the probability that potentially effective therapies are applied to potentially responding and potentially nonresponding pop- -...-....'..-.-....-..—”.y—--—- ,.. ulations. The problem is further complicated b y a lack of evaluative criteria of salutary Various change. approximations are in use, as symptom rating scales, social adaptational measures, patient self-ratings, and changes in target symptoms. These indices are gencrally too broad, too inclusive and too non-specific to be useful. For example, in the target symptom approach, the assumption that anxiety in neurotic phobic, neurotic depressed, or paranoid schizophrenic subjects are equivalent processes is not valid. in Depression various subjects is no more the same phenomenon than is the fever in t mania or lung abscess. c . ' There are, therefore, three aspects to the problem of predicting individual patient response to therapy: the specification of populations (patient selection); the selection of therapy; and the specification and evaluation of behavioral change. These will be aspects described with reference to the convulsive therapy evaluation of the Hillside programs Hospital as studied during .the past seven years. Hillside Hospital is a voluntary, nonprofit, community supported institution in New York City. In these studies, the patients were referred specifically for convulsive therapy by staff psychiatrists to the special somatic treatment unit which was responsible for all somatic treatments at the hospital. .. ' I I mvvv’ ! . ' ; ~<~u .‘-~v- “tn“ a. ' ,,..~..‘..-.... i Observing the usual mixed group of subjects referred for convulsive thera py, we recorded a variety of behavioral adaptive patterns at the times when subjects had received the number of treatments sufficient to i nduce neurophysiological The changes. patterns ineluded euphoria, hypomania, denial, and minimization; loss and increased memory complaining; increased fearfulness, agitation and excitement; and withdrawal, paranoid and delusional ideation. In assessing these patterns, that of euphoria, denial hypomania. and minimization was prominently associated with clinical ratings of much improved and recovered. We termed this adaptive mode "euphoric-hypomanic" and set this as the criteria for the behavioral change which we would like to predict (l). \r I N. Y. ..~: “ Since treatment selection was defined by the institution, our studies focused initially the definition of parameters of change. 1/ From the De partment of Experimental ‘- aw.- 'V.¢§“-.~ Methods on ...._.-.,-..-,',.-»--—s.- Psychiatry, Hillside Hospital, Glen Oaks, L.I a. Aided, in part, by grants M-927 and MY¥Z715 of the National Institute of Mental Health, U.S. Public Health Service. 317 __W_ -_.. ”_.u' ‘U .—:r.. U..- ‘ �(and be therefore this show adaptive pattern to To determine the population prone terms usual diagnostic or the eschewed symp. we recovered) and rated as much improved these studies behavior. During of We measurable aspects more and sought tom check list. the termed which we neuroconvulsive-therapy process the of had develOped a concept a device to as convulsions seen are repeated view. In this (2). view physiologic-adaptive behavioral function brain adap. altered of such conditions the Under alter brain function. attitudinal and factors. sociocultural Thus, individual personality, based on tations emerge indices. attitude and predictive as personality we sought measures of pre-treatment defined that the we studies these had completed we after it was For the most part, of "much clinical ratings the earlier tables these on that "euphoric-denial" pattern, so with this be to equated be. View. in and our reported are, improved" and "recovered" are havioral pattern. Results Earlier of language patterns. was assessment Our first 3. Lan ua e measures. with brain dysfunction that patients demonstrated had (3) Kah and n Weinstein studies by after confabulation and intra. disorientation of denial, changes had characteristic language language these that same observed we study electroshock In one venous amobarbital. those that noted We patient. also of treatments. numbers with increasing changes occurred those not while recovered, evaluated as the ones showing these language changes were content A analysis linguistic unimproved. rated as generally exhibiting the changes were disminimization. denial. be to explicit the in study showed the language patterns rated of tense, of change third use comments, person, cryptic cliches, evasion, placement, (4). with question a and responding withdrawal, qualification, elecafter showed these who patterns language the subjects It seemed probable that treatment before such to . using patterns who have propensity a the be ones troshock would tested therefore. We. test. provocative some by changes if we could elicit the language adinterview, structured short in a questions each patient before electroshock by asking then and repeated and nystagmus. slurred speech until was there amobarbital ministered after amoof changes number language the for the We scored answers the questions (3). barbital (4). We noted a relation between the number of pretreatment language pattern changesthe during manifested clinically of changes number language the to following amobarbital between, also relationship a there was 1'). Furthermore. (Table of treatment week fourth imof much clinical ratings and term short changes the number of pre-treatment language proved and recovered (Table 2). TABLE 1 TO RESPONSE LANGUAGE PRETREATMENT BETWEEN RELATION AND CHANGES CLINICAL AND SODIUM AMOBARBITAL WITHDRAWAL DURING TREATMENT Three or more clinical language patterns“. Pretreatment response to amobarbital sodium pretreatment response to amobarbital sodium No *x2 +x2 318 4. 26; p< . 05. 6. as; p< . 01. Withdrawal reactions to amobarbital sodium: The scorn denial sc< We 1 cal rating score and �TABLE 2 “""“ RELATION OF PRETREATMENT LANGUAGE CHANGES WITH AMOBARBITAL SODIUM TO EVENTUAL CLINICAL RESPONSE V: «vs Change with amobarbital sodium‘I Much Improved 19 -~..-,..’. 68% .-.~.e. .. Moderately Improved _,_ ‘91- _ Unimproved *x2- 10. 30; P < .01 y-a-M-...‘;N -——vr-- b. Famil Interviews. Our second assessment was a denial personality As inventory. patients were referred for convulsive therapy, we interviewed a relative in an unstruc- exploratory interview. The questions were designed to determine the degree to which the patient approximated the explicit verbal described personality type Weinstein by and Kahn (3). On fifteen items, patients were scored on three a scale of l point and 2. 0, The scores were ranked and divided in half - those in the half termed were upper "high denial score" and those in the lower half, as "low denial score" (5). tured, vvvu—n- .vw- . . w».- w— v .AW observed a significant relationship between the denial score and short term clinical ratings (Table 3), In addition. there was a significant between relationship the denial score and the number of clinical language changes during treatment (Table 4). We . -pv TABLE .- 3 ..1..—. RELATION OF DENIAL PERSONALITY TO CLINICAL RESPONSE TO ELECTROSHOCK 'Much Improved Personality Score - ,ewv. .w-vv- Moderately Improved ,V, l4 s 7 u-....r.»-v 21 T,-..,'.«..fl_~. —.s.-—.— .--.-.. TABLE 4 RELATION OF DENIAL PERSONALITY SCORES TO CLINICAL LANGUAGE CHANGES DURING TREATMENT Personality Scores 11-25 (2.0) 0-10 (20) Number Language Changes 8 l7 ‘ 12 3 * . 319 �We the did Rorschach. was task Another not essayed Determinants. Rorschach c. look upon this test in the usual interpretive manner. but scored the number and patterns of Rorschach determinants following the schemata of Klopfcr and Kelley (6). It was observed that ratings of much improved and recovered were associated with the following Rorschach criteria; absent human movement (M). absent form color (PC). few responses, high form percentage (F ). presence of color (C) and color form (GP) or absence of all color. and low shading response. One schedule is reproduced in Figure l (7)- FIGURE 1 RELATION OF RORSCHACH PATTERN TO CLINICAL RESPONSE TO EST °/° NO M, no c M,CF AND [3 MUCH IMPROVED NO M, a\ MODERATELY IMPROVED AND no M,.cF/c M, NO c F6 AND M, FC UNIMPROVED. d. California F Scale. Still another attitudinal task is the California F Scale. This is the which to 10 subject statements of global of uncritical,’ series consists a task simple asked to express the extent of his agreement or disagreement. High scores reflect high agreement, and low scores, high disagreement (8). There was a significant correlation between high F scores and favorable clinical and (9,10) studies factors social out realso carried In we addition, 5). (Table ratings ported that favorable outcome was associated with few years of education. foreign'birth. and older age. ' » TABLE 5 RELATION OF SOCIAL FACTORS TO DISCHARGE RATINGS IN CONVULSIVE THERAPY . Recovered Much Improved Improved and Unimproved 320 Mean F Score 53.1 Mean Age Mean Years Education 7- 50 9. 4 / 10.6 12. 3 Foreign Born ‘ 35 17 �Conclusion summary, we have observed that a variety of pre-treatment measurable aspects of behavior, usually described as personality variables, are associated with the develop— ment of the euphoric-hypomanic adaptive pattern in convulsive therapy and are rated as much improved or recovered in our setting. These variables have been defined in language patterns, denial scores on family interviews, perceptual style reflected in the Rorschach. California F Scale measure of attitude, and the social variables of age, educational level, and birthplace. These personality and social variables provide the perceptual and attitudinal bases for the adaptive changes which occur under the conditions of altered brain function induced by repeated convulsions. Absence of these personality traits, in the presence ,of equivalent degrees of brain function leads to other adaptive patterns, usually rated as "improved" or "unimproved. " and not to the euphoric-hypomanic mode. In The same theoretical model of the neurophysiologic - adaptive interactional hypothesis is applicable to drug therapy (2, ll). We would suggest that different agents are psychopharmaceutically useful to the extent that brain function is altered systematically. These can be measured by the electroencephalogram, although not exclusively. Under the conditions of persistent altered brain function, changes in adaptation will occur, dependent on pre-treatment personality variables. These can be specified, and studies now in progress at Hillside Hospital are assessing this model for various psychotropic agents. References (1) Pink. M. and Kahn, R. L. : Patterns of Behavioral Change and Improvement in Convulsive Therapy. AMA Arch. Gen. Psychiat. (in press). (2) Fink, M. : A Unified Theory of the Action of Physiodynamic Therapies". J. Hillside (3) Weinstein, E.A. and Kahn, R. L. : Denial of Illness: Smbolic and Physiological Aspects, Springfield, Ill. C. C. Thomas, 1955. (4) Kahn, R. L. and Fink. M.: Changes in Language During Electroshock Therapy. Psycho atholo of Communication, Ed. Hoch. P. and Zubin. J., Grune & Stratton 1958, pp. l26-139. (5) Kahn, R. L. and Fink, M. : Personality Factors in Behavioral Response to Electroshock Therapy. J. Neuropsych. 545-49. 1959. (6) Klopfer. (7) Kahn, R. L. and Fink, M. : Prognostic Value of Rorschach Criteria in Clinical Response to Convulsive Therapy. J. Neuropsych. _1_: 242-245, 1960. (8) Kahn, R. L. , Pollack, M. , and Fink, M. : Social Attitude (California F Scale) and Convulsive Therapy. Jour. Nerv. Ment. Dis. L351: 187-192, 1960. (9) Kahn, R. L. , Pollack, M. and Fink. M. : Social Factors in Selection of Therapy in a Voluntary Mental Hospital. J. Hillside Hosp. 2: Zl6-228. I957. (10) Kahn, R. L. , Pollack, M. and Fink, M. : Sociopsychologic Aspects of Psychiatric Treatment in a Voluntary Mental Hospital: Duration of Hospitalization. Discharge Ratings and Diagnosis. AMA Arch. Gen. Psychia . l_: 565-574. 1959. 1942. (ll) Fink, B._ and Kelley, D.: The Rorschach Technique. New York, World Book Co. . EEG and Behavioral Effects of Psychopharmacologic Agents. NeuroPsychopharmacology. ed. Bradley. P. . Elsevier, Amsterdam, 441-446. 1960. M. : DR. LASKY: .,- Thank you Dr. Fink. Do members of the panel have any questions or comments? 'r~ r- ”‘5 | 321 ”.“wnpm‘. �DR. KLERMAN: I Max, you presented with a fair amount of specificity, the personality and social fac. tors which characterize the patient. Iwas disappointed in that the other half of your neuro-adaptive scheme was left unspecified. Namely, is there any specificity in the alter. ation of brain function that is as predictive as these specific social and persouality factors? ‘ . patien1 adapta to tree will nc brain are co convul nnl, tt that hi . DR. PINK: answer to that is that we do have considerable specificity for the various treatments that we use. If I might have Figure 2. This Figure will show that we did use electroencephalographic measures. We were rating the EEG changes according to criteria which we called high degree-slow wave activity. This index could be specified and quantified. After determining which records were "high degree" slow wave activity, we were able to go back and look at the patients who had shown the much improved category, the moderately improved and the unimproved. It is apparent that of the patients who were in the much improved group, about 90% of the records of that group had shown high degrees of EEG change during the third. and fourth weeks of treatment. It is also clear that the pa. tient's who were "unimproved" did not show the high degrees of EEG change. We interpret these data to indicate that unless a patient has a high degree of EEG change he will not .show behavioral change. It is necessary to have changes in brain function and it is under the conditions of the brain change that adaptive change will ocdur. The type of adaptive change depends on these personality variables. In drug therapy we have other EEG patterns which can also be specified. I think the change 'shock. - DR ' L I schalk comm much crude with tl ' DR. F FIGURE 2 I . h. r . >‘ ,._ o—MUCH IMPROVED (u) E ..... moo IMPRovsom g S 3O ‘ - DR. 7 _ umumoveom (3 spe cif tional being . ‘ has s‘c UJ LL] as 0 0 $ DR. F LL! I reflec know \ “I": atric 6 5 u these more our e1 ber of E: we do much eupho: being: 2% if ‘ ' 4'6 7'9 “242 NUMBER OF TREATMENTS statin: . behavj which . . DR. KLERMAN. Is one difference between this kind of physiologic measure and the other measures in that they occupy different type predictive factor? Would you say here that unless the patient has this characteristic, EEG changes, he will not subsequently develop behavior and adaptive changes but can you predict before the treatment in any physiologic way whether or not a given patient will manifest these characteristic delta wave changes 7 In other words there is a difference between a predictive variable that you described as existing or .. characteristic with the patient prior to his exposure to the treatment and a predictive variable that says he must experience a certain kind of change under the influence of the so- matic therapy. 322 : ‘ - this a‘ $323: - ation This i ‘ :fifhfi hospit e ducai �PINK: I think what you are asking is whether we can predict the physiologic response of the patient. I think we can, although this is much more difficult than predicting the behavioral adaptation. We still do not know what the determinants are or how to measure them prior to treatment, to predict whether a person will or will not show a drug response or will or will not show a physiologic response. The question is not one of a sequence, where altered brain function comes first and then the subjects involuntarily adapt to it. These processess arc concurrent. At the time that brain function is changing under the influence of repeated convulsions or under the influence of repeated doses of drugs, the perceptual, the attitudinal, the conceptual and all the other aspects of patient behavior are undergoing change so that his whole view of life and his response to his environment is changed. The kind of change he shows depends on his pretreatment propensities, as we tried to show on electroshock. DR. ‘\ x v w -« ~ .rv-w--. "a... mv‘vo—‘w “ o...— DR. LASKY: 01-- - Dr. Fink, we'll ask another question or two. They are short ones. think Dr. Gottschalk and I have something rather similar in mind. Now, the one I had was--Could you comment On your criterion. You used a three level over-all clinical rating of recovery, much improved and improved. Now the question that comes to my mind is why use such a crude criterion when you are using rather quantitative measures as predicters and ties in with that, of course, what (ices this criterion mean that a man is "improved" 7 I DR. ”on mu w-wfinwvr'Vb-‘M FINK: Dr. Gottschalk, do you want to ask something ? w-vfimnmm DR. GOTTSCHALK: Well, I had a somewhat similar question, but I have focused on something a bit more specific than that--As whether Dr. Fink had any idea why those people with lower educational levels tended to have more improvement, was this possibly because of the goals being less as compared say to persons with higher educational levels, then of course this has some relationship to the question about the criterion for improvement. 'r-v-q—vruwm.“ - ‘ a ‘ Wm DR. ‘w FINK: .5 we‘rv .. think that both these questions are crucial ones.. I tried to indicate that our slides reflect early aspects of our studies. At the time that we did these first studies, we did not know what we were using as the eventual criterion of behavioral change. We used psychiatric ratings much as everybody else. This criterion was fairly effective. In the course of these studies, we learned that there were different behavioral modes, and these seem a more meaningful criterion. We are now in the process of assessing patients going through our electroshock program, trying to predict these various modes. Unfortunately, the number of patients referred for electroshock in 1960-61 has dropped off precipitously, so that we do not have a large enough sample. But, the statement of the slides on recovered and much improved reflects, ‘as we look back in our data, those patients who showed the euphoric-hypomanic adaptation. That adaptation can be characterized by a feeling of wellbeing; an attitude on the ward of being fine; dressing up, and participating; and on inquiry stating they are no longer sick or depressed and that there is nothing wrong with me. Such" behavioral changes are the ones that psychiatrists rate as much improved. In our hospital, which is psychodynamically oriented, there are a number of psychiatrists who have seen this adaptation and have said that this is not improvement, but explicit denial is a psy— chotic adaptation. There is, therefore, a problem of evaluating what we mean by much improvedor unimproved. The question about educational level is also related. The evaluation of "much improved" is dependent on the psychiatrist's or the evaluater's attitude. This is one of the reasons why the use of much improved characterizations across hospitals is almost impossible. We tried to show this yesterday in Dr. Pollack's report of our tri-hospital study where discharge ratings did not have the same meaning in the various hospitals. The educational level is important because. there is something about being well educated in the American culture which does not lend itself to the use of the, gross denial I , r‘tV‘W‘WW' mq— v'fT'V-a run-"Vera nrw— m. u~—WWWW—w—wm~n» l—"r'" le‘fp ”r" «- -m .» 1‘ i l t i l i V ‘323 i i i i �\Q institution is this in and reour them, we see as cultures ive The more primit response. who have and in may Europe who born were flected in the people in the older age group the adaptation use or such can people that in Europe, life sustained their early processes American Our younger. intelligent, denial. more verbal do use the adaptation of explicit born girls and boys just don't use gross denial. the for I on use apologize must and. is poor very The use of improved categorization The next studies. started our the we is that way the slides, but Ihad to use it because reflect will but an have not will that. two hence, series of slides, hopefully a year or that have teased think we which we predictors the" hope we Then adaptive mode typology. differences. those in demonstrating effective be will out using improving categories in ap procedure by investi; In or pharmacol lucidly, tc jsctive es; of familia: able dosa; 'age level not associ experimer pipradr‘ol tect: 47 ju : DR. LASKY: who A. 'Gottschalk. Louis Dr. is next Our speaker Fink. Thank you very much, Dr. Cinof Psychiatry. the Department at Coordinator Research and is Associate Professor to Individual Pay. Response is "Measuring his of title The paper cinnati General Hospital. Free-Associative) Behavior (or Verbal and Method a Introspective an choactive Drugs by Method. " Dr. Gottschalk. Fron the indivic a seconda: by pipradz themselve able to wo one thing themselve duced stin 1 AN BY DRUGS PSYCHOACTIVE TO RESPONSES INDIVIDUAL MEASURING INTROSPECTIVE METHOD AND A VERBAL BEHAVIOR (0R F REE-ASSOCIATIVE) METHOD 1] of accomp] , ‘ Louis A. Gottschalk, M. D. Introduction is a redrugs to psychoactive and individual idiosyncratic responses the Measuring of study and The systematic serious search area of increasing interest to investigators. the fact that the collective effect of such phenomena is made difficult and compounded by and the unique that time the at same the psychoactive drug has to be accurately measured for accounted plausibly whenever possible, and, observed individual effect is being validly at some level of organization. individual the for and accounting of measuring, Approaches to this problem detecting, and methof the Some principal ingenious. been have many drugs to psychoactive response different with major of to of patients a drug administration groups The ods have been: l) suband of behavioral different for patterns psychiatric nosological syndromes and looking psychoneuroschizophrenia, the , category, to diagnostic e.g. jective reactions according 1929; 1953; Bensheim, and 1952 and Pennes, sis, etc., (Beringer, 1927; Hoch, Cattell, of of the relationship Z) determination The 1960). Weinstein, 1953 and 1954; Kornetsky, beor profiles with different personality associated to a drug varying individual reSponses by measured etc. --as hysteria, depression, extraversion, havioral patterns--such as, and (Kornetsky evaluations clinical psychiatric various psychologic inventories or tests or individof the The 3) 1958). assessment a1. 1955; Laverty. , Humphries, 1957; Lasagna, et of defear such a conflict, as, with psychodynamic a ual reactions to a drug associated different The investigation'of 4) 1957). pendence (Gottschalk, et a1. , 1956; Sarwer-Foner, Kurland. 1955; and 1950 1956; et a1., Wolf, and 1955 a1. et . reactions to placebos (Beecher, the hence and effect placebo sometime of powerful the 1960), which provide an indication individual placebo component of the reaction to a drug. of Medicine. of College Cincinnati, of University the Department Psychiatry. 1/ From from (MY-1055) research in grant a by These investigations have been supported part and Welfare. Education of Health. Mental of Health, Department the National Institute 324 The i the individ about the i very devia ple and 1e: tive drugs character cannot, ho rically we] drug addic individual major psy¢ The pharmacol I assessing 1960, 1961‘ measuring perimenta situation subject to 1 investigatl The verba the only 1': of ‘speech The relia’: the scales eral or ty: been devel s chizophr ‘ �lfifilt$1ll at Indxvtiaaz Pattau$ nutpunua $0 etuvuzntvu rhnrtpy Ill! Flak, Rafi. .: Impurinuntnl Payuhattry, fvun tho nlylr§ncnfi #10! MC. ‘31., 'gta tad-i, 1: port, Hillttan Ibupitnl. 0: tin luttcuul Ilnl%h aurvict. by graafin uaytv nai 31.:115 Instittfio of Haiti} Icalth. v.3. PuBISa Proaoatnd gt ti: 6%; annual V.A. lcuoaroh atatcrtutc, 1': 8/13/61 �rouponio 1n n nonalu fivtatuunt to prudxutlaa o; it: IOdIOIl yrsctatxynorn, at». 31%.: a vary «£517 ttak arupttat ind stuns o: illnoua o: grants. 0: alxnfiurtug :: ti. a putatut, atlact I trtttuon‘ raglan: moat likely $0 otttcfi was». tho tho in ‘8ango clanuitlcttioa unlutnry pntiunt. : of it: ‘13.... :- estabISshcd by antlnitavc 091%.r1a an in typhtlis, 61:50:03 or malaria th¢=phyutotua'u vrohlcn in usnplitatd. whit. clacnttiaa‘taa 1: not b!!!‘ on definittvu . ~ disoutc Inutul thGlittil, tr phynictun's yrobluu 1. uonvlex, tar ha aunt raaovt tn the raeocaittca or pattcrn bssod on his 1361114311 cxyurtanao. Inch olunutrteu‘lon 1. act readily *alldntcd, and in the thuunc- at apccttlsd axtorunl oritoria, 09?!!! in grouwinu to: thsrtpcutta pnrpoaon urc trcqncut. In it. anatanoon Ihlfi rI-caion at. iatubliahod by thuir artistIVInoal, a: in nyphtllo, at hscturzgl tntnottoaa, 0r nvttuasaontu - £rnutncnt 0.100%10n 1: ro&4117 tortacd. what. raunélun up! una~:poottta; n: in the tralCanat if uantnl 311:... by .nvirulnnuttl nuntpulttiun, pnyuhcthurnpy nae vnrlcun phyvluayuuntc thcrapioo, ta. problan 1: Gain placntod, an: only by tun unwoupoattlctty Qt trcntnnufi Eat 37 the probability that pntuutiilly'urtccttvo thornpiou and to mapltsd pct¢at13113 nun. ratpaufillg petuntltlly Ir. r.upond£ag populttiouo. the problnu :- further ocuylioutcd by a Ina! or cvaltatavc crasorsu or aslutnrr «bingo. Variou- uppromintu $1.». 33¢ in a... nu uyuptan tutti: uculni. 3001.1 ari‘«r£s, an 1: heart �.m, Idtp‘ltttnil atannrnt, putiant ¢¢It~rntiu¢a, sud ihtfifll! in strait nynptonu. $31.: 13d1¢¢5 art :cnurllly tlu b?ill. to. incluntvt Out to. non-nyueitzo t; h. utctil. for CIIIDIO, in it. tar¢1t I’lptdn apprauoh, tn; anaunp‘lun that anxiety 1n noarofilt phattc, ufiuro£1n daprcscod, a: paranoid naiinoyhruuiu lthtItfl at. ugutvnloat arousaaOI 1: nit valid. napvtasinn In various «ataoota a: nu I02¢ tan tuna phanoncnuu thug a. ‘3. first in fiukcratlonis, ynluuoatt tr its: drastic. nipacto to tin protlou this! nra. thuruttrc, flirt. of proiitilu: inltvadafil pattant rtuponac to thcrt’yg it. upocsttctttun it purulgtxlu- (pataoat '01-.tAcu); tan talotttuu at fihnrayyy and tho Ipuuartaatioa and cvgllatiua o: bohnvlurul :Inugo. That. guy-etc Itll bu actortbod with rttarcaua in the cauvulalvu thavuyy tvnlnation prvcrtun a! fit. tillaldt laivitdl an ctudtid during thc pnu$ IUVUI gusts. 111131;. Ritalin: it a thgntary, nonwprutxt. eon-natty anppcrtod 1ac$1tatzon 1n luv flirt 63". In that. tuanatomy "no Mum mu gum. a. nun» vulutvu thirty: by afint! pnythsstrtuts to the 19001.1 nu-nfito trastnnat :318 tits) at; roapaanthlu tor all tauntic sysataaut: at tic httpstul. mm: 513:. trantntnt coluctsca our cfimdaou or changn. initially tbcgacq III it datinod by thy Incitinttou. fit. dofiuttilm at ynvunatnvc �n53.» antarctic 5h: tunul atatd group a! Iuhstétu rcfttrfifi um tOOIrdId a itriuty at iuhiriaral ounvnlntvo tharnpy, it: udapttva pgtturnu 3t tho ‘tnnn when nuhsacto had roeoivtd .thc 383509 of troltnnntu Initiatont t0 induct naurtphyiiolocicul antagoa. 1h. pattarun 13011614 cughnriu, hypauuuit. X00. and tauranuad couwltiaw lnfi scumry aiuiniaatsan; atrial, 1am; inoraAI-d tourtulncuo, ugitutian and clattancnt; and withdrawn}, ptranatd and dnluntuual iauattau. In nsnassing than: unitarul, that at nuphartt. hyvonuuat. dupini and 3131315551.» van aroniutntly agitaatiod 81th clinical rattan: 01 Inch inprtvnd uni rnoovcrud. Ha tarnnd this snaptavo and. 'Ilphnriauhapouunxc' as! not fits. as $8. arifioraa (or tic hohtviornl Ihlnli thick at until 11:. ‘0 prodlat (I). in fiatarnino ‘hc p¢pultfitln 9:03. to that thin tdqptlvc puttura (and thorotura by ritad II 3:33 iuprcvui and r'covurcd) an uaahauud fin; Ic‘ul dingaantnu torn: or taught unrc honourabla anyocta at activiuw. Duran; thou. utuaica v. had dcvtlupad a stucopt or in. convultlvu-thornpy'praaist think an tarnnd tin nouruphrsiaiocismudapttva vita (a). In thin vicu, rnpoatad «intuitions urn lCfin a: u dgvtat to alto: brain truatiuug Undur it. atadttann: or tank llifirifi brush taxation h¢hsv1tva1 uasptttionn nuwtga tuned on indivtautl partuntltty, lactacultural and attitudtuul rin$pra. raga. an tomcat unalarna at prcatruasnnut pavnannltty «a: attitndn an pradtttlvu symptoa chock tadiait. liut, mad �.4... It: fit: unit part, It ran nttnr u. ind uolpldtud this. siuasot tint um cosine! tau ‘U‘Qhfitifihltfilil’ pgttaru. :0 ihtfi on than. tahlnu fit: ourltnr «lininal ratings 0: 'umuh auyrwvoafi and *rwcvvared' urn 20903104 and cit. in car vicw, it b: tqnztnd witk than bohmvtnrcl gust-ru- I a ; u: A. Ina-11w Langfiaga nannuran at: tarst gurus-nan! was of imaging. patt‘rnu. and“: by minute» and mm (3) m cum-tuna that pl‘tlfl‘l with basin dyml‘acttQI had churaatortatit lancuucu chanson u: tout-1. diaovtuntttlun and cuatnbulntsou it‘.’ iatruvuacnn an OhOOrVIO tint tnnbnrblfiax. In an. c1¢¢Qr9Ihntk study thcnu a... ltuculcc chtngns uacurrna It‘s 1302.531»; nuubnr3 at fiata‘luu‘a. Ho Ill. fitted tint that. ya‘toatu ohiuttgl‘hosc luncu;go chanson war. in. and. ovalultci an vucovnrtd, title than. nut annihitlag the .chnlgta tutu guncrully tutti an unimprovaa. A lingutnttc soatalt‘iathatu ahavud tbs languagu pntfiarna rntca in :3. Iiifly in he uxpllett £03131, Ianilisn£t¢u, dtuplacuutnfi, CVttiuu, clichcu, crypttu ocuanutc, II. of ttlrd purcun, lhlnxt or tonne, withdrtuul. qunlltiaatiun, :nd roupondxug with 3 citation (h). Xi aaauct probahzu that $3: Iuhsuotc It. august thin. Inusutcu puttcrnc utter aluo‘rcchuok vuuld be the fill any but! u prnpauatty to I‘tflg itch 9I$itlil burst. truatHOQt �.5g' II tait. 12 00:13 olacit sh. laacuago «haunt. by nous prcvcau£1vo no, uhurgtovo. tou‘od 0:0h putanut tutors ulnafircshank by acting qncstloan in t abort a‘rtttnrla intOtvtiu, Idntaiafiartd unohnrbtfial uu‘xl that: In: Ilnrr-d apo¢ah lad ayatngnnn, and #305 rtpuated tho quca‘iout (3). we luarcd tbs Innunrn {pr tho u‘ubur at luagulgc chanson altar mu»! alficd 0:). at u rolatlln butv.uu the ntnbgr or pru~ $I¢utuuai language puttnru chi-go: following :noharbttul ta £hn mutate a: luugnnao chtngcs Ianttuu£ad 311310311: during tn. fourth rock 0: tran‘nout (Tunic I). Furtharnnro, that. can :13. $ rolationohxp httfllfln tn. nuibcr or protrottlout linguoco chanson and about torn clinics: rating: find rtcovorod (tabla 11). or Inch ingrowcd fi‘-‘ .. O“ 40“ ‘ rabltu I, I! 3. ltully Iatorvituw : dautnl p¢raoa31tty rotorrcd it: touvulttvo thnrnpy, Our accond aunnolnnat at; savvniory. In patients worn no tltnrvinuod a ruxttlvu an an uanructurod, caploratorr £n$orvicu. fun qunatton: var! 60313306 ta actarline the vhtci 303:3. to tic pat10u% .pariualutcd tbs axpllost vvrbul plrsonnlity typc duccribol I7 “biacttin Ind tab» (3). an titties itnna, patients were t£09¢4 on & throa point tall. at o, 1 ‘nd 2. 1h. IIOFDI nur- rgnkod and �.75. dividcd in half . thlil in tho app»: htlt cur. taruod 'hxzh Junta: tact.“ and thtst an ‘3. lava: h:1!, us '10! innit! it!!!“ (5). aigaittulut rulutleulhip butauon tin short torn eliutcul rating: (table 111). no abacrvoa a dcnial ntoru and In afidation. chart was a siguztiuuut rulntsonshiy untrue» ‘hn «tutu! IOOIO and it. illhlr or clinical langunso GICIIOI daring £routunu$ (tabla It). D--“m““--‘ 215190 121, IV ..¢..~........ c. lartchnah nutcruanuntu Anothur task cunnyue In: in: lornchtch. 80 did u.% look uyou that tout in thc It!!! inturprctivo nuancr, hat scarce tho IIIbCf and pattcrnt a: Iorlchloh eatcruauv unfit following in. unhonstn 0! 110990: find tollty (6). It III Obaorvcd fihnt vstinga or tank improvud and rucovurad wort tauoain£od with the tailoring Inraohaoh crituric; thaini lunan havonunt (I), ubuuat for: 001.: (re), tut raupauuua. high for: ptroautnco (30), proscuco at atlor (6) Ind 0010: turn (or) if «haunt. a: .11 oolnr, 10' thufliug rulpcntt. can Iahudulo 1: rugrodtco‘ Inblo 1 {7).’ and fihlo V -Wd 1n �.7. a. culitoruia I aetistill anoint! attitudinal tint in tho caiitoruin r 80.1.. this ailpln tank eon-int: at n 0:21.: at 10 unoriiiaai, global sintonnntc to which in. Inbaoct in Ilkod to otprocl the cairn: of his agrcoaont or dinnarcosemi. list .3090. rotioct high tarocnnnt, and low amoroa, hick iiungrtclant (a). that. VII I liguiticuni curt-iniita hair... high r snort. and taverahio clinical rutinga (tail. '1). In addiiion, u. .1:- curriod out toainl factor. Italian (9.10) and roperiod ihai tavorahlo antenna val aaaociuicd with for yuaro or adiaution. tor-inn birth, und .16.: ago. -‘....” Tfiblt VI GQlCEVSIOls In Cilllfy, no but. oboorvcd this a varinty of pr.trottnaat lauuurabia aspect: at b-havior, unually douoribod .3 porooanlitw varinfiina, it. nauociniad with tho devoIOpr nant at tho ouphorieahypolnnio aduptivo pittcrn in unavainivo ihcrnpy and Ir. rated in luck inprcvod u: r-oovorod in our uniting. in... variuklou havo boon auxin-d in language pittorna, Gemini 30.9.. on 2:311: int-trio's, puroapiuni styl- rotlooicd in the nor-chuck, culitorain Sonia nannurn or nttitudc, and in. social variabiao 0: :30, educational 10701, and hirihvluca. r �“as this: permanality and utoitl vurtuhlnu yravtdu tha ptrauptutl and attitudinal bacon tar tug tdnptiva cunngon whiwh oaaur undur thn unufittitag a: Alcarsd Evita function induced a7 rnpcttnd canvulqtoan. tsunami of that. paracn~ alt$y truits. in th. pvncwuua a: aqu£V§lont duct... at Evita lunettun Illdl to 0th.: udtpsivn yu‘turna. attally an to m “mm-4'«ass-9W», a» am a. maman ’ hypluunic luau. the Inn. tha0r0£1oil natal a! tin acurnphyuialouic ¢ IdlpttVI znt¢ra¢tinnn1 hypcahc-is 1: nppliauqu ‘0 drug Gillan-at ig'n‘l ihcrnpy (2.11). "b woula sugguut at. yaynhupharnucnatsaally~1:0!!! tn tho extant that brain tuucslon In Il‘trfid ayataunttenklr. Yucca can bu nonsurud By tin olnatraanoaphulogrnn. althangh ant axalautvqu. Ulnar eh. eundttaouu at pcrnlntent n1£arn¢ hrgia run¢£1ou, ohtugua in aiuptntauu V111 ficaur, dcycnauut 0n prnutruutnwut tht pgrioanltty vurinhlus. 3!... «an h. apouttiaa, tad attitaa piogrunt law in ut lilllidt.‘0.vti¢1 av: nanotling thin nodal :0: variant ya:who$ropio Iz¢ntu. �1a iiuk; l. and tab». 3.3.2 rattcruu at iwhuvturtl nhnsun and Improvunous in auavu111Vt fhnrlpy. 5g; arch. 633: _!gzgg;gt. (in prnsu). a. tint, 5.: 1 Iaitsod fhnory at tho fiction 0! thytisdynnnta $303351... 2. la;§¢§da gang. g; 197*206, 1957. J. Unina£¢$a, 3.1. Ind Kuhn, 1.x.u 9593:; at ;;;ngtug 8M..; 4,“, ¢.c. rkants, 1955. laka, 3.5. and link, n.v' Ghatgct in » - ‘ s . l. A ; Satanic“, In. $nngungc During llocirauhuck Ihavtpy. r Ed. au¢n, 9. an: zubgn, a., Eran. s acrnttaa 1955, pp. 126-139. Ital, 3.1. tut rink. 3.: ruraouniity ructora 1a Behavinrtl laupnnio to Exactruahock Ikurayy. 3. xtnrgggzgh. 53 . &5«u9, 1959. tlnytar, a. raahtnh itchns nu. It! Ibrk, khrld Beak $6., lfiha. labs, B.L. and Fink, n.: Prsgnautit 731:: at Rartehnuh aritarAa in altuical lacyumau t0 cruvulsiwc thorapy. and £01101, 9.3. 2524“, 196a. $d§1fl1 an‘ Attattdo Pallusk, 2.: link, 3.1., u., Illa, {Bularornsu r sail.) ané euavultivv fhcrupy; gaggz_gggzg n¢n3, 23;, 329; xsr~191, late. 3.? una Social raatnra in lain, I.&., rilluck, x. rant, galactiua at Therapy in u Vtiuu‘nry lcnttl lbtpttll. a, :zzxsasg 5352, g; 21£~2¢a, 1957. 1, trauma”. 9» -ho 8 0 A: �13.. mm. 3.3... Mink, “put: 0: Psychiatric huugs and amt.» n. Mutton a: 91mm“. 565-515., 195’. In as an mu “on”. flak, 8.: Boominholuie tht banana“... it. and rank. is: a m alumina). Arch. “In-nun mm Mums. M: g mthat, y taut; a: antenna”. $3me Slum”, mum, mama, 1960. Mnualuz, «I. 11% . III-why, h, �153;! I Relatian Dotuvou Prttruatnnat Lfiuutnso Ambuhitnl Sodium and Withdrawal Io. ROIpOIuo clinical chant” atria: to an"? Truatuont then. or nor. aliniasl ltn- Hithdrawul rauc$103. ta that 2A». “A w.» Protrcstlcnt rnaponno to unotarbstll India: 39 EB 60 protrontncnt I.roapouoa to tits bnrbtt;1 nodttn )5 11 31 “x2 $12 . ' 13.26] ’ 6‘88, P < G91 < .05 . pct 00“ 21 10 12 3h .. m. per coat �153;; I! nun-n Mm. or Protruhmnt chann- Huh Sou“ to fight). 61131311 may; m: nut Input“ Hodn‘tolr ”mi Uni-pm“ «:2 - 10.30: 52: r «at. Q _ I with ”an“ m :8 19 68 22 8 3‘ 15 3 to .01 1 put out. «1m �mm lolattoa or again: rationality to eliuitnl g. tinctggghnak Rich thnrutclr gagrlrgd gggruvud Porlanggttz Swag. 11 to 25 0 $0 10 total icspmuac 33§EEI¢V0¢ rota! 15 9 1 2h -II ‘0 NI 23 11 13 0 h? �null-non mg If Maul res-nudity “on: to c1121”: Lluggagu Change. During treatment lumbar , a — 2 3 Or zutuong;gtz acgggu 11-25 (20) 0-19 (20) lutal B 12 11 3 25 15 not. �IA ‘ T Rolatton or Rorschach rusty»: ta clinical Icggoaau 1n cuuvuzuiva I Ind-rutaly Ilprcvvd tad lull taprovod Egagigggti novounat 39 11 (283) 28 (72!) laugh lwvununfi 58 28 (58$) 29 (hit) flu?;; I. rattan; :9 0 10: to ) For:tor: 001:: lo 3b 53 . 6.16. 7 32 p 21$ £601; :3 - 11.570 Both a and re re ” lotthor I nor ’6 num- a h 10 25 21: 25 38 xa awa‘h Xi‘an' ' 4.01 p 3.” {mi 661 “on, P uorrtuttuu {tr diocoatxnut‘r. 2? 21 <2 79% éhefi; .001 20 15 13 C4001 (83% $60!; 3h! �m1; Illntton at 8.31:1 rattorc to Discharge gg£iagl 1n convnlutvo lhurgzz I Iu‘n 1 833a 8 53.1 Itch turret-d 26 Inprcvod an! Uninptcvcd 23 Inc-vurod ,0 abnn that: 3 CV‘ I 1 retail! 3 9.h 10.6 so h1,8 51.6 h3.8 39;? 3!.) 11.3 17 35 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Prediction of individual patient response to convulsive therapy. VA Cooperative Chemotherapy Studies in Psychiatry, 6:317-24. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-58-024 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Photocopy of publication with Q & A and [preprint]. Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published http://exhibits.library.stonybrook.edu/mfp/files/original/884cdf6a7b2219d358f4de2dbe539c6c.pdf 9cffe53aff8acb515fe1485b11299ae1 PDF Text Text DEPARTMENT OF EXPERIMENTAL PSYCHIATRY July 31, 1962 Dr. Jean Gahn Chet De Laboratoire a La Faculte De nodeoine Directenr De Recherche A Le Pitie 18, Rue Jose-Maria De Heredia Paris 79, France Dear Jean: The meeting on EEG and Psychopharnaeology in not well organized, for a variety of reasons. are planning, therefore, to get together internally and discuss our cannon interests. Please enquire at the registration desk at the GIMP, or I will write as soon as I have the details of the meeting. we do not plan to preeentppepers, but to discuss: Munich was We (1) International EEG programs (2) A special meeting 1963 A special meeting with CINP 196k $3) k) Your Journal suggestion My best regards, and I look forward to seeing you on September 3. I am staying at the Hotel Regine Palace if you wish to reach no. Sincerely yours, Hrtgp flax n , . . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Cahn, Jean Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-022 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/14b14ea144611f9f0bcfa082d8785c3e.pdf ed54c1c45660a4f3995244d96a3b8de9 PDF Text Text DEPARTMENT OF EXPERIHENTAL PSYCHIATRY Dr. William Moeeinger North Shore Hoepital Menhaeeet, L.I. Beer 8111: that I submit the enclosed It ofis with some regret from North Shore Hospital stuff. the resignation letter New York am to develop a new peyoh~ summer I this leaving and research training facility in St. Louis. In iatric School of with the oonjunttion Washington University Medicine, the state is establishing an Institute of Psychiatry, and I have been naked to develop the programs. In addition, I have been appointed Research Professor of Psychiatry, and I look forward to e more intimate relationship with the academic world. I look Beck at my years of community practice with considerable fondness, for I enjoyed the hectic life very much. My associations at the North Shore Hospital were a most pleasant part of that experience, and I am most grateful for your support and interest in my efforts. My best personal regards. Sincerely yours, Hfsgp 911010 Mei"?ink, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Messinger, William Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-025 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/018bea4e577473193d2d461088130de5.pdf 7aa2698592a5188d51a083a646633da0 PDF Text Text BBF£RTKKHT John 0? EXFEalflxfiT‘L Pfixaflllrfir a. Daniuln, Jr. Dir¢otor forth Short Kanpital H&nhaaact. L.I. naar Hr. Buniels: Thank you for the lettar or renppointmwnt to tho Courtesy Start or the Diviuiau a: Kodiaina. Eftoctivu this sauna: I an usuuming n usv genition in at. Lenin, and I :3 thirntorc snbnitting this lettor at rusigna~ tion, arrestivn July 1, 1962. You will be plagued to know that my exporionee in thin connunifiy during uh» plat daaado has lad to my appaintnunt as Director at the newly eatubllahod research Qua tr&1aing facility at the St. Lauia fitnte 30:91:31. rag attacuri Institute of Paychiatry. My ‘ at the best wishes for the continued growth tad ancooaa Hoap1t&1. fiincaraly yuura, MFG” ' m« 313E, MOE! � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Daniels, John H. Jr Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-026 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/4effa77bb2590bb512d876a4b11958d2.pdf ed372fe1c0899019a90578df87ebff99 PDF Text Text ;. ”’4 ~33. / an 6. 1958. MW. at“ mm. W: lam mmmmmmmmnmwmmhy1m W,Whmmgmwmmyl9fi. Wt,mMuhmtmm1mm,wwmmm 461mm m:- $2» Man at W1.“ mm: gm, 11d ' m mmmnunzmmmmmaum um Mam. ”1-1:.me lawman-lamina“ in“whotindidmam» m.than banner and tits <3an nut? than who has this: activity m mm -&m,mmnwmqawmmmappemmedm WWW? » met - . I: m W95 1. twist)», I vault! madam ma mmmmnnwmmnmmMatwam. W you wry much for Mr mwmtim. 3W you". 93th of mm Maia-ism KFNB mm, Mia appartunity � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Diaz-Guerrero, Rogelio Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-030 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/e3fbb46852f441b88bc277c4033f3e35.pdf 17baf48a0b7109371b9cf912afef8c29 PDF Text Text January 25, 1962 Dr. Edwin A. Weinstein Dept. of Neuropsychiatry Walter Reed Army Hospital Washington, D.C. Dear Ed, Your suggestion of a conference on Violence is both timely and appropriate to the interests of the society. I have read the Scientific American article and its message is worthy of consideration. In that regard, some discussion of the negro passive-aggressivity as in the C.O.R.E. movement would be most relevant. For neurophysiologist, may I recommend Murray Glusman of N.Y.P.I.? His studies of brain stein lesions in cats gives an interesting basis for conjecture. In sociology, my confreres suggested Alfred McCluny Lee, Herbert Block of Brooklyn College, Joseph Bram and Dr. Bohanan. Of the old-time psychiatrists, Sheldon Glueck and David Abrahamson come to mind. Also, perhaps the Chesholm lectures of some years ago could be brought up to date. This suggestion is also consistent with the recent increased emphasis by the A.A.A.S. on community aspects of science, and additional suggestions may be forthcoming from their public policy committee. As for members of our society, I am handicapped in not having first-hand knowledge of students in the area who could discuss the issues. Nevertheless, the suggestion is appropriate and I would encourage its adoption. Sincerely yours, MF:dts Max “fink, M."D‘T � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Weinstein, Edwin Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-031 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/bd10187aa8669d0c91f1233f8d919e68.pdf 67e6424d21b4c9122a9d4493aba6267a PDF Text Text DEPLRTHENT OF EXPERIMENTAL PSYCHIATRY June 22, 1962 Dr. Eliezer Edelstein 5617 Oakmont Ave. Bethesda 1h, Maryland Deer Dr. Edeletein: Enclosed is a ticket ror the flight from Washington to St. Louie Thursday morning, June 28. When you arrive in St. Louis please go to the Eastern Air Lines ticket counter and there will be e message for you. If contact is not made, please call the secretary at Xieaion 5-6230. If there is a poseibility that you may not use this ticket please notethat you would have to cancel it by phone the day before. planning to show you around the hospital after arrive, and for your meeting with Dr. Kohler. There is a return flight at 5:30 which is approximately the time that I will be taking a flight to New York and we can go to the airport together. If you decide to stay over please feel free to do so. There are some other good flighta, especially a direct flight at 11:55. Looking forward to seeing you. you I am Sincerely yours, Haiwyink, M.D. Hrsgp cool. 0"" wt r’w / � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Edelstein, E.L. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-034 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/4872203974a7fbe8a08676b3961aa5be.pdf 0b80edb8bbf2256228843982d86c3ed1 PDF Text Text Juno 1h. 1952 Dr. Hilton Rooonbouu Albort Einstein College of Medicine Ensiohootor Road Bronx, flow Iork Door Dr. Roacnboum: I wont to take thin opportunity to thank you for As you unscented, rotorring Dr. Bliouor Edolutoin to up. nova and offered to try found 3 bin dolightrul person I have olroody we him Louis. in Fortunately, to place St. rocoivcd pornieoiou from tho state personnel authorities to appoint non-citisona to roooorch positions for limited period (up to 2 yours), and this will avoid the embarrass— uont ourtorofl by Dr. Edolotoin in Hookington. and Starting a now vouturo 1:, I8 you wall know. I on grateful for your consideration. Ky best personal regards. difficult, Sincerely youro, H1339 co: L.L. Robbin- ox n , . . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Rosenbaum, Milton Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-036 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/deea39b2602d26a50fea7d1812a420d5.pdf 49fe1270f01580aa91eadcf124479997 PDF Text Text DEPARTMENT OF EXPERIMENTAL PSYCHIATRY July 5. 1962 Dr. Leonide Goldstoin Bureau of Research of Neurology and Psychiatry Jersey Nauru-Psychiatric Institute Princeton, NH] 0 New Box 1000 Dear Loo, I have written to the aocretary of tho EEG Society regarding your membership and have not yet received an answer. As soon as I do, I will call you. Thank you for your kind invitation. My plans are very complex now, as I have just bought a home in St. Louis and must move my family before September. I do plan to be in flow York some of the time in October~xovegber, and shall try to arrange a viait early in that period. May I call you after the QINP and arrange more definitely? it Thank you. Sincerely yours, HFtdta Max Tank, 14.3. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Goldstein, Leonide Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-039 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/effefe674ddba1cd2b163cae0c973c99.pdf 6b2dfd443101d40701980dde8ba69cc5 PDF Text Text fixrlntlfili av xtysnznastnr ratnnxttnr July 3, 196! 8!. n. lifbfl‘t ”aflfi It narusiort Fragilant. lagrd ltllutdu .Ipitul 01” Mi; In!” ”any. Etc! 8?. luctinas new nucitaunnt tag! I tins I: a. with a rcaltnx t: it laulua-l It i vary it a aunts. Outta. in at. antic: {$35.3 luttar n! vauauuutsau trim lillnsau. In support in. nyprnaanttin my :‘r «In aflnqga‘cly unpvouo during than: start. ‘gtvuu In by the award at nirnatcvuthou ploucué. an 1 truut hurt vault aivunau k! beatnvc an. atauicc barn havn tun nunrd art. that hunter. 1‘4 to cash a proutaia¢ rut¢aroh apportuazty. 2 learn naxxuia. uatb'3uuu rust-t {or our agar it. it. it Rap. that tau any uninitillod utvirntiunn, and ulihandthcrcutarah;unnunuity prugauan citato tau thurupanttu visual far by :11 a! an. with my ymrannfil rtgtrfis, I rtuala. ' ‘ > $1naarcly yuuru, lrzmp anal. fifi?1flfifl§”fl§5:' � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Beskind, Hebert D. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-041 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/70e9167351c558708b3dd007cede2bc8.pdf 49bcea59e51712825e9a25a85b9024cd PDF Text Text fif’tkfflifl? 0' EIIRRIHIIIAL 151631123! 6111 31, 1911 at. 11111 1. 1111111, $111111 11111111 31111111 11131111 01kt, £111; '1’. 1111 1!. flbhhlntt I1 11 1111 11111111 £11 6111. I, 1111111111; 111 11111113 1 11111111 1111 1111 111111 at 11111111111 111111 11 11111 £111 111 1112! 1: 31111111 83111111 111111111 11 or 11111 11111111 31. 1962. 1 11 11:1 ’11 1111 11 9111111 11 1111 1111 111 91111111 1111 1111 111 11 111 1111111111 11 111111111 1 11111111 111 1111111: 9113111 11 1 111 111111 11. 11.11111 1I1111111d.;:z1111111 11 11. 1111., 11 u1xi 911:11111 11 911111111: 11 11 my 11991111111 11 1111 111 1111111111 611111111: 111111 1: 11111111. 11:11: 111 11111111; 111111 or 1111 711:, 1 11111 11191111 11 1111 1: n: 9111111 11 91111111 1111 111 £11 1111 111111 1111 11111 11 11111111 11 9113111 11111111 1! 1111111 11111 1.1.1.3.1. 11111 11~1715. 11 1111 11 11111 1111111 111111 1 11111 111111 I1 111 111111 11 11. 11111 11 1 $111 1111 11111. 1 1111 1111 11 11111 :1111 11 11111111 1111 91111111, :11 1 1111 1111111 1111.111 1111 £1111 111111111111 111 111111111 1111111111. 1 11 11111111 11 111 1111111111 119111111 11 my 1111111 19111111111 17 11. 111111 1111111, 11: 11 111 1199111 11mm11111 1: 111111111 11111; 11111 ”“Ia 11111111: 11111, 811:9 _ W � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Robbins, Lewis L. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-042 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/288d2962cef84e736cb8f3a74c1975e5.pdf f8ae3c7fc7739b3f61ad2c9b610ff85a PDF Text Text DEP‘RTHEHT OF EIPERIHENT‘L PSICHI‘TRY July 3. 1962 E 5 g Mr. Maurice Bachrach Adniniatrator Hillside Hospital Glen O‘ksg Lola, N.‘Y. Door Kauricez member or the to you for the Hillside family, have which given this Dopartmont you pationce and support during these last few years. For your help, kindness and patience, I am mott grateful. Enclosed is a copy of my formal letter of resignation, which I am submitting with the mixed foelfi.ngs of regret for our many unflllilled aspirations, and with excitement and enthusiasm for the future at Missouri. May I also take this Opportunity to invite you to us in St. Louis at your convenienco. I shall look visit forward toasuch an occasion an an opportunity to welcome You, probably more know a friand than any other the debt I owe and ocuworker. best personal rishes for your continued success at Hillside, I remain, With my Sincerely yours, MFlgp Max fink, H.5. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Bachrach, Maurice Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-043 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/af4c76bfe5e431d1fff69c3038e3c3dc.pdf 996d8ff4bd675aec376d0e175e4cf479 PDF Text Text {Y DEPARTMENT OF EXPERIMENTAL PSYCHIATRI June 20, 1962 Oscar Krisen Buros, Editor The Mental Measurements Yearbook Rutgers University New Brunswick, New Jersey Dear Dr. Euros: for your inquiry regarding the face hand Dining theuperiod l9h9-1952 a number of younger workers in the laboratory or Dr. Morris B. Bender at test. Thank you York University participated in studies of double simultaneous tactile stimulation. In the course of these investigations we developed a concept that the perception of two simultaneous stimuli was a learned procedure, achieved by most adults within 10 trials or the test. New In various populations failure to discriminate the two stimuli was common, especially in young children, severe mental defectives, aged, and most interestingly in adults with altered brain function regardless of cause. That is, adult patients with organic mental syndrom fail to diecrinw inate the stimuli within 10 trials. We have found this test so useful that we described such failure in adults as an index of the organic mental syndrome. In studying the responses of children and mental defectives we came to the conclusion that the ability to discriminate the two stimuli was to develop between the S and 7 year of life and was highly correlated on mental test examinations with a mental age of 6 years. We thus concluded that the face hand test as a satisfactory index of mental age above or below 6 or 7 years. �-2- I am enclosing a list of references which indicate the early publications of this date. The Director of the service, Dr. Morris B. Bender, summarized the studies of his laboratory in a monograph ”Disorders in Perception" published by Charles c. Thomas in 1952. for the test is extremely simple. the use of fingers or shemost two safety also enclosing a copy of a review report pins. recently published from this laboratory which may help you. The equipment It necessitates I an Sincerely yours, Mchp Gael. Hex"§ink, K75. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Buros, Krisen Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-045 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/04b7165b10e9ad1271963d332addd109.pdf 88c096b6ccb8aa8705b38695e1b7ac36 PDF Text Text June 11, 1962 Dr. Louis Kohler St. Louis State Hospital ShOO Arsenal street St. Louis, Missouri Dear Lou: letter to Dr. Edwalde, of letters including documents and the supporting and expertrained well Edwalds is reference. Dr. View of the qualifications of the in but ienced, and the interview that Dr. Ulett letters of reference and I had, I would be reluctant to make any definitive Enclosed is a copy of my senior appointment at this time. If his response is affirmative, I will call My you. regards. Sincerely yours, Hthp encl. Mewaink, Mffil � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Kohler, Louis Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-047 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/2abe54fcc21ff046a4219388a4cc31be.pdf 7494cacb74b8029025f805aa73c8cda8 PDF Text Text Jun. 11’ 1962 W. ROWQ HQ 36"!»4. Irving lvonan 766 m‘mfl flour Br. 10’ ‘0’. zdutldls tailoring our uo¢ting and talophono convaruatioaa, I ahnele like to take this opportaniiy ta bring you up ta data an cur program in Riuuouri and raqucat :tnr consideror a peanut: at tho heapiul as am: psychiatrist “ion on a auteur basis at $19,000. In addition, I would be 910.006 to rcaeauana appointnnnt to the Dana at tho 3t. Louis r 001 $0 Univcruitw at Hidiciuc {or cansid'rntion as Aasiatant Prorcaaor. 1: thin in o: intortat to yvn, I will rouonaond thin uppeintncnt in the lupcrintandcnt, Br. Loni: Kohlar. rh¢ Inatitnto will open thit tall, but as ywt, nkithcr tho 1.6. at: th. til-vi aehodulcs are npprotod. Patient 3.2. will begin, hou'vnr, about Soptalhor l ind the Stlff tar the units will bu drurn tram tn. hospital. Th. trsining prcgrulu ia.pnyahiatry will continue 80 ha nadir an. direction ct Br. Ibrim, who is th& pro-out Director at training, and it in a: intanticn in nsauao incrcasing r¢uponuibility for thin part a: sh. program. In rcviuwing yuur cruduntialn, both Dr. Ulctt and I Ive. plannoa with your inturnat tad your 0830.! nttitudn. rho touching crpuvionoounl linitod, hovuvar. and us agreed an: to «valuato this aspect at tho r0009: an. tinttthzuzgat S o ‘ I. ' secondly, in ruviowing yvur oduaatioaal tutors-tn I was inproauad taut thy bout toaohinz uppointnnnt would ho at St. Louis finivcrlity. l was countrninod, hou'vur, by th. roality that the at. Lani. Univurnity Department at Ptynhintry far prior appoiatnsnt VII artilablc. 0n rhuradny, I hnd the oppartunity to lost the Data as v.11 as tho «unaidata {or tn. chnirunnahip. w: had no chairutn and no Iaehnnia- diseutucd the rulatianahip or the stat. haapitcl and tho �was hc;rt¢ncd that tho Donn guru-d to consider upycintanatn at at. bout. stat. Koapltul rooono noudcd by an. superiutcndcut. Univ'raaty and I With tunic data. I diaounnad your rel. with Dr. Kahlcr and would rsoouliad that you Join the hospital start an a nutter (full tin.) bull. fur contestant by tho lupurtutuudont. at that 13131.1 rusponnlhilifiy would be that a: auction ddvotod we slashing. dtviulan allot with oonuldurnblc In bath dutiau, uh H111 hnvo in opportunity to d.tcruino not. udtquntuly'yvur tutorauta and rilctionahtp to tho training I would bu planned to have cu oppor‘nntty to work til. 92::vunl. “ M‘ It that. trranxcuautp are asroonblc, 1 wall like such rlocuuaudntioan to Dr. tablet and the appoint-Ont cgn b0 and. affectiv. My aaptoubur 1. bout rogurdo. flinonroly wants, ”‘3” m ’55. Hunt � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Edwalds, Robert M. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-048 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/66cea75854e6f5a7438950822e86b870.pdf 157c0b16db1cd15621640b7407efc7f8 PDF Text Text DEPARTMENT OF EXPERIMENTAL PSYCHIATRY Dr. G. Vsrdeaux; Laboratoire D'Eleotro-Encéfihalographie Centre Peychiatrique Saints—Anne 1, Rue Cabanie, Paris-XIV France Dear George, regarding Dr. Kugler is indeed a good difficulties in organization so far, is unlikely that any formal meeting can be arranged. I it would, however, be interested in an informal gathering of all workers interested in EEG. Such a meeting could be arranged late in the afternoon, or during a free evening. be possible to identify the workers in the field, It would know their interests, and determine if there is get to sufficient interest for a meeting on this subject either at the next CINP or at the International EEG in Vienna. Would you write to Dr. Kugler to suggest he discuss one. Your suggesting Because of the this with Dr. Bente and make the local arrangements. An announcement can then be printed in the GIMP program or a mimeographed invitation placed in the program at the time of registration. I am looking forward to our meeting in Munich, and extend to you and your wife, my best wishes. Sincerely yours, Mdets Max Fink, H.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Verdeaux, G. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-050 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/41551de0a37c382dd73e32d220b2c458.pdf 8690097b7ddad82ef80c197649674b43 PDF Text Text April 10, 1962 Verdesux, M.D. Centre Psychiatrique Saints-Anne 1 Rue Cabanis Paris 1h, France G. Dear Dr. Verdeaux: I am enclosing a c0py of the abstracts of the 1961 meeting, as submitted to the EEG Journal. In the event that the editors do not wish to publish these, I will ask you to send them on to Dr. Rothlin. Dr. Denber has returned without the opportunity to meet with you. Since we have no response from Dr. Cazzulo, I would suggest that we meet in Munich during the CINP. If this is agreeable to you, we can write to Dr. Bente to request a room; and we could send our invitations. If it is My to be done for 1962 it should be done soon. regards. Sincerely yours, MFzgp encl. Hex FInE, fi.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Verdeaux, G. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-052 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/425d89a5c88bec3bcf42737511553cd7.pdf 678c68b6b972848d7a1984b0904a69c9 PDF Text Text DEPARTMENT OF EXPEEEMENTAL PSYCHEATRY HILLSIDE HOSPITAL GLEN OAKS. N. Y. March 15, 1962 Dr. George Verdeaux Centre Poychiatrique Saints-Anne 1, Rue Cabanis Paria 1h, France _ Dear Dr. Vordoaux: Your suggestion regarding the publication of the manuscripts of the Montreal EEG symposium to Psvcho harmocolo ia was indood a good but I had already discussed wItE Dr. Henry your earlierdds, suggestion and, having prepared the abstracts, have asked his opinion. If the Editors will publish the abstracts, I believe the intorest of the meeting will be served. If they will not, I would be pleased to have your support for Paychcpharmacologia. Can we agree on a more definitive in Septembor? I have not heard from Professor Cozzulo;meeting and if we cannot stimulate his interest, would you ba willing to ask Dro. Flflgol and Brute whether they would wish to organize such a symposium after (or before) the GIMP in Munich? After all, this may be the best way of accomplishing our aim of another discussion. indicated ho will be in Paris March 26~27. Ifthis you could arrange to meetwith him to discuss this, it would be helpful. Dr. Rajotte at your hospital will havo Dr. Donbcr's schedulo and an Dr. Dunbar and I discussed and be appointment can be made with him. I am grateful for your kind thoughts and look forward to a successful convocation. My best personal regards. Sincerely yours, Hdets Max fihk, H.i. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Verdeaux, G. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-054 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/88d4351757b1f00ff9f9afd9dbde1fcf.pdf 1f462d76536144ca61b07f479938a259 PDF Text Text Hutch 15. 1962 Dr. Gnarge Verdaaux contra Payohiatriquo Eaiutcolnns 1, Rue Gabania Paris 1h, France Danr Hr; Verdenux: taut suggestion rcgurding the publication or the manuscripts of the Hontreal EEG qympoaium to P3 cho harma~ 0019 1 was indead a good hue, but I had already Eiacuased 9555 . Keary your aarlter suggeation and, having prc~ parqd thu tbttrtcta, hsvu aakad his opinion. It tho Editora will publiah the ubatructg, I beliave thw.1ntareat of tho touting will be sarvcd. It skoy will not, I vanld be pleaand to hava yuur support for Pagchcpharmacologfig. ca“ we agrea an a more definitive meeting in September? I hnva not heard from Protaauor Gnazulog and it we cannot atimulgte his intereat, would you ha willing to ark Bra. fltgol and Binta whothur thay'wnuld fliih to organisa such a sympocinm after (or before) the CIR? in Hunich? After all, this may be the hast way at accenplishiag ant aim of anothtr discussion. Pvt flfinhar and I discufised this and ha indicatad he will b0 in Paris Huron 26~27._ If you would nrrango to mutt with him ta discuae this. it would ha helpful. Dr. Rajetta at ynur heapitnl will have Br. Denbor'a achadula and un appointment can b. mad. with him. I am grateful far year kiné thaughts and lack farward to a suacoaarul convocatian. Kraut. Hy bust parsonul regards. Sinaarely yaura, Mix Fink, 3.3. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Verdeaux, G. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-055 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/cd1bbf11704e58f3272e6df1a4fb48fc.pdf 5ab42aba1800f81a6d70f20e400e2d41 PDF Text Text February 15, 1962 G. Verdeaux, M.D. Centre Psychiatrique Saints-Anne 1, Rue Cabanis Paris 1h, France Dear Dr. Verdeaux: During the past few months we have corresponded with the editors of Electroencephalography and Clinical Neurophysiology in the hope that we may use the papers of the June meeting for a supplement. The editors indicated considerable interest, but found the reports not documented enough. quote: expects a supplement, be reason— ably definitive and to have value as a source book of data. ...It has been a long time since we urged that papers be longer rather than shorter, but some such expansion would be necessary for documentation purposes; this means more To ”One especially to the Journal, to tables and more figures..." We have reviewed the recommendations and decided that the editors are correct. To create a better volume would require extensive additions to each report. We have, therefore, decided not to publish those reports together and are returning your manuscript, recommending you publish it separately. idea of such a volume is a good one, however, I would urge that you consider another convocation with the aim of a larger group, more inclusive presentations and more general discussion. It was recommended that our group meet again in Milan in September after CINP, and it was my impression that you, Dr. Gazzulo and I would plan such a and The meeting. �-2I am writing each participant of the Montreal symposium sharing the message of the two paragraphs. I would urge that a second meeting on first I'EBGr and Human Psychopharnacology’, be convened as planned; and if it for September 7-9 or August 31-September 2 (before or after Munich) the Western Hemisphere participants could attend at minimum could be arranged expense. In Montreal the subject of whether a consistent EEG change occurred was well discussed. I would suggest time be devoted to the following problems: 1. Techniques of 2. change and behavioral change. EEG changes in relation to classification (diagnosis of patients, with special emphasis on sedation threshold (Shagass), 3. EEG analysis. EEG pentothal threshold (Goldmann) and the pentothal non-responsivity in chronic schizophrenia (Cazzulo, Borenstein, Flagel & Bente) If the symposium extended over two-three days with 8-12.major reports and many shorter reports, the principal material wouid be gathered for a proper, data-oriented, evaluated supplement. We could again record the discussion, transcribe If and edit it for the monograph. the idea is agreeable to Professor Cszzulo and yourself, I will be glad to participate in developing the program, establishing financial support and cooperating in the supplement. I am most grateful for your participation in Montreal, and look forward to our meetings in Munich and Milan. My best regards to Mrs. Verdeaux. Sincerely yours, Hrugp encl. Max n , . . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Verdeaux, G. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-058 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/4c5694d14ad92e1e6b086623d9826bc3.pdf c7ca2063da12ee1dd8ea742118101ae5 PDF Text Text February 15, 1962 Prof. Carlo Cazznlc Dell Universits De Milena Via Besane Hilano, Italy Dear Dr. Cszzulos In our meetings in Montreal end Rome, it was the consensus that another meeting on "EEG and Human Psychopharuacology" be convened in 1962; and it is my recollection that Milan was proposed as the site. I on writing to Dr. Vsrdeaux and enclose a copy with this note. the host for the ”Second Meeting“? Would you be I have reviewed the GIN? prograu with the American find our subject is not represented, representative special meeting and and e would be welcome. ' As I indicated to Dr. Verdeanx, the material of the Montreal meeting was not detailed enough for e monograph. Perhnpm the 1962 meetings could be set up in such a wey as to make a good monograph as one product. I should be pleesed to participate in establishing such a meeting; and in participating it held before or after the sessions. I an grateful for your participation in Hontreal GIN? and look forward to our neettwgs in Europe. Sincerely yours, HFxgp encl. Hex Fink, ETD. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Cazzulo, Carl Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-059 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/4e86d898f876a2bda50b31a48e430b7d.pdf 862d7d33962caec90234d705063a34c1 PDF Text Text DEPARTMENT OF EXPERIMENTAL PSYCHIATRY May 8, 1962 Dr. Daniel Silverman 19th St. Philadelphia 3, Pa. 269 South Dear Dan: I would have been pleased to serve on the Eastern Audit Committee this year, but as my plans are rapidly changing, it is unlikely that I will be in New York on an extended basis by that time, and could not meet with the other members conveniently. I should be glad to serve the Society in another capacity, however, if you wish. EEG Sincerely yours, Hthp Mex Fink, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Silverman, Daniel Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-060 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/278c420a0a1a4b2a1ec5bc723d9a0d70.pdf 657807c7116ceb9f4f180e86f4e8da09 PDF Text Text April 23, 1962 James H. Ewing, M.D. Department of Psychiatry University of Pennsylvania Philadelphia h, Pa. Dear Jim: I have read your report ”Psychophermecology and Psychopathology" with considerable interest. Follow— ing the initial review, your comments on views of drug activity are cogent. While theoretical I am impressed by Rubin'e work, as I am by the studies of Weinstein (one of my teacher's) and Gottschalk, to whom you refer, each of these authors emphasize deriv~ of atives drug effects distant from their position (i.e., effects on brain function).theoretical Thus, Rubin implies central (brain) drug effects, but measures a peripheral effect. Similarly Weinstein and Gottschelk use speech patterns - also a peripheral brain effect. In each case, there is need for a more direct measure of brain function, in addition to this derivative. We have also been working on a "neurophysiologic-adaptive" model and I believe your conclusions to be true. Many thanks for the opportunity to read this review. Sincerely yours, MF:gp Max Fin}, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Ewing, James H. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-062 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/9a52ac6d4ee53133ddf290d78df0b888.pdf c493b780284d3f55359623c5be563f3d PDF Text Text April 13, 1962 Dr. James Ewing Mercy~Douglass Hospital 5000 Woodland Ave. Philadelphia h3, Pa. Dear Jim: for your courtesieo during my yesterday. I read the enclosed reports with visit able interest on my return Journey. I am alsoconsiderenclosing Dr. Morris' report which I would ask you to return to him aid indicate I shall send him a copy of our triThank you hospital studies separately. Good luck in your studies. Sincerely yours, MF:gp encl. Max Fink, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Ewing, James H. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-064 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/0ef415f042dd69fc9ead2e3b614b5b89.pdf 0f73eb44537a23393b57aeaa435f1528 PDF Text Text h/18/62 Biographical Sketch arriving late at a Joint meeting of the departments of psychiatry and neurology at a leading New York hospital, 0n Fink tells of being Jokingly asked by the chairman on what side of the "professional" aisle he would take his Max seat that night. The two aspects of his interest and training in neurology and psychiatry are reflected in his professional career which has been devoted to research studies into the neurophysiological and psychological aspects of psychiatric treatments at Hillside Hospital. While develop— ing the programs of the Department of Experimental Psychiatry, Dr. Fink was a practitioner in the North Shore area, and it was during this period that he took an active part in the activities of the N.P. Society. In 1959-60, he was president of the Society -- thgryear the Society saw the founding of the Newsletter and a re—organization of the committee system. Eaziaggiperience answering the tdsphone and as an observer of the excitements of his father's busy medical practice aroused his interest in medicine at an early age. pro-medical student on the Heights campus of New York University, he undertook his first research study as part of the biology honors program -- an analysis of the "periodicity in mitotic behavior of the neural tube of the embryonic As a chick". While he achieved many scholastic honors as an undergraduate, none are so prized as his election to the honorary political science society, Alpha Pi - as the single �-2pro-medical candidate in a class of pre~1aw candidates! Medical education at Bellevue during the war years and a rotating internship set the stage for military service. "interest" in neurology sent to the School of Military Neuropsychiatry and‘a career in psychiatry. With separation from the service, and feeling that there was more to the world than his stateside experiences allowed, he shipped out as surgeon, first with the Grace Line to the west coast of South America and then with the American Export Lines to the Mediterranean. Coming ashore in New York from a cruise, he was introduced to the young daughter of passenger friends and soon after, began the courtship with Martha which led to marriage in 19h9. After the cruising sojourn, training continued in Montefiore, Bellenue and Hillside Hospitals. Concurrent training at William Alanson White Institute led to his receiving their Certificate for Physicians in 1953. It was at Bellevue, while a student with Morris B. Bender, that he launched his research career. Stimulated by Dr. Bender's pioneering perceptual studies, his first interest was in simultaneous tactile stimulation tests as reflections of brain dysfunction. Studies of carotid angrcgraphy, psycholinguistics, electroencephalography and psychological tests followed rapidly as aspects of behavior under conditions of altered brain function. These interests became the foci of Because of an he was wL~.nAufiA-m~ �-3the programs in convulsive and drug therapies at Hillside which have occupied his full time interest since 1958. This work has been honored by awards of the Electro- shock Research Association and the Society of Biological Psychiatry, and recently, by appointment to the National Institute of Mental Health Connittee on Clinical Drug is also consultant to the Director of the Division of Mental Diseases of Missouri, and is participating Evaluation. He in developing the programs of the new Missouri Institute of Psychiatry. Tennis and skiing are the principal recreational interests of the Fink family. Last August the family Joined Jonathan in camp where Max was the camp physician ~spending most of his time on the courts and water skiing. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: none Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-065 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/1afcab86ca0f8cc242c066faeecfd660.pdf edcea8413d3958398b9b307d0ffa4210 PDF Text Text April 9, 1962 Dr. Leo Hollister V.A. Hospital Palo Alto, Calif. Dear Leo: No, the outline form is not better! Thanks for your If we had more such, we might read them. the way, how can one treat “about four patients” chatty report. By (nialamide)? I agree with your views of "long acting" preparations. We had tested the spansule chlorpromazine and compazine against their respective tablets, and found better drug dosage control and fewer "side effects" with the plain tablet (and cheaper as well!). I vote for a newsletter! Sincerely yours, MFzgp flax FInE, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Hollister, Leo Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-066 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/891155d2715c9e620ae9402506252320.pdf 20770caf96446e3f38a6c2cb6d80d1ae PDF Text Text March 22, 1962 Aaron Stein, M.D. 11ho Fifth Avenue New York, N.Y. Dear Aaron: It is with pleasure that I recommend the article by Drs. Abraham Kaplan and Henry J. Lefkowits, "Influence of Staff Attitudes and Environmental Factors on Treatment Selection" for the 1961 Radie Gnekow Award. The work is original; is a study of Hillside Hespital patients and illuminates a hospital problem; and was accomplished by the cooperation of a resident psychiatrist and an attending physician. The problem of staff attitudes aféecting treatment is an important issue to which Kaplan and Lefkowits have made a substantial contribution. to a In addition to rewarding a hospital resident will fine study, the award to stimulate staff interest in the Journal, thus accomplishing the aim of the Award! do much Sincerely yours, MF:gp Max"§ink, H.57 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Stein, Aaron Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-067 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/ba2e554403292ad1e4c97c6757ff4ab1.pdf 308f7a71f5e12695563ed648b2bd616c PDF Text Text March 19, 1962 Dr. Seymour Perlin Department of Psychiatry Montefiore Hospital & Bainbridge Ave. E. Gun Hill Rd. Bronx, N.Y. Deer 8y: pleased to write this letter on behalf of I have known during the past three During this time I have Hillside Hospital. at years been his supervisor in research dufi.ng his residency; and a co—worker in the somatic therapy program of the I am Dr. Lefkowits, whom hospital. Dr. Lefkowits is s sincere, thorough, and responsible As a resident he stood above his class in his worker. research interests and his willingness to accept respona sibility. As a consequence of his excellent record, he was promoted to the position of junior psychiatrist and assigned new residents for supervision as soon as his resident period was ended. During that period he also undertook a study of the milieu influences on selection of treatment at our hospital. He showed considerable ingenuity in this study, and the published in the JOnrnal of the Hillside report was recently He was an active participant in the research also Hospital. seminars of the hospital. Lest fall, this Department instituted e psychophernecologic after-care clinic. Dr. Lefkowits was put in charge, and his excellent fiudgnent in the management of the shawn the unit units ‘~ wa:nit was a deficit tperstion/ e.‘ the”H§HT€ET“Biructvr decided to discontinue the clinic. ‘ ;é 15%...ng ”$3M , . �It is my impression that his idontificstion with psycho- pharmacology : : ;ww, I decision to leave Hillside. Dr. Lefkowits is ‘ ; ._: M; in the To WW” capable young descriptive training and a good grasp of somatic therapies. He gets along well with patients and with his peers. He is methodical, occasionally cver~ meticulous, serious, and friendly. I have no hesitation in recommending him to you for a within his abilities ~ for he will serve the position institution well. psychiatrist. He a has good Sincerely yours, upsgp Max Fink, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Perlin, Seymour Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-069 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/b6f6f4ee667b489b3d0e128c82391b08.pdf ef4eac08b7e954cba968f13c3a704cf1 PDF Text Text '51 March 19, 1962 Dr. Sheldon Gaylen Director » Community Mental Health Board 618 County Office Building Plains, White N.Y. Dear Dr. Gaylon: I letter on bohslf of I have known during the past three years at Hillside Hospital. During this time I have been his supervisor in research during his residency; and a co-workor in the somatic therapy program of the am pleased to write this Dr. Lefkowits, whom hospital. chkowits is a sincere, thorough, and responsible resident he stood above his class in his research interests and his willingness to accept respon~ sibility. is a consequence of his excellent record, he was promoted to the position of junior psychiatrist and assigned new residents for supervision as soon as his resident was ended. Dr. worker. As a period During that period he also undertook a study of the milieu influences on selection of treatment at our He showed considerable ingenuity in this study, and hospital. the report was recently published in the Journal of the Hillside He also was an active participant in the research Hosgital. can nars of the hospital. Last fall, this Department instituted a psychopharnacologic after-care clinic. Dr. Lefkowits was put in charge, and has shown excellent Judgment in the of the unit. Because the unit did not suit themanagement changing present lungs of the institution, and as it was a deficit operation the Medical Director decided to discontinue the clinic. �It is impression that hiaidontification with psychodisinterest in the vision of residents in psychotherapy wore factorssuperiniho my pharmacology and his seeming decision to leave Hillside. is a capablo young descriptive has good training and a good grasp of somatic therapies. He gets along well with patients and with his peers. He is methodical, occasionally overmeticulous, serious, and friendly. I have no hesitation in recommending him to you for a position within his abilities - for he will serve the institution well. Dr. Lofkowits psychiatrist. He Sincerely yours, MF:gp Max Fink, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Gaylen, Sheldon Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-071 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/7945149c392e31c38842ee7678a799d5.pdf 56153a1139b429d6dce264a507c0b294 PDF Text Text {5 January 23, 1962 Dr. Leon Banker! Department of Psychiatry Downetete Medical Center of State University or N.Y. hSO Clerkean Avenue Brooklyn, H.Y. Deer Leon: Some months ago you enquired about in psychopharmecolegy. I am taking the EEG studies liberty of sending you this draft copy of a summary of our studies, with my View of the present relevance for the field. The figures are still at the photographer, and I will send them to you when available. My regards. Sincerely yours, Mthp finale .ex ea ,‘fi.5. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Hankoff, Leon Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-1-072 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/ea67059b06d2778f4825496f6d12e6a1.pdf eb586394985e0e211ce0596a4e830b00 PDF Text Text December 28, 1962 Boleslaw Skowronoki 130 West Mch York 19, New Street New York Skowronski: Dear I thank for your recent vary I have withheld from roplying until letter. knew whether I would be in New York in the yOu much I near writing to future. As thio seems unlikely, I am indicate that there are, indeed, a number of‘ opportunities for peroonnol in the laboratories in St. Louis. However. the principle experianoo reflected in your ourriculum vitae is in microbiology. Suoh a laboratory is not being established at the present time. I would be grateful to know the kinds of experinnoe you have had, with specific reference to such questions: What biostatistioal Operations have you carried out? . » to In what laboratory procedures pharmacology are you proficient? do in a psychiatric hospital setting? What related kinds of work would you like to Again, my thanks for your inquiry. Sincerely yours. MISSOURI INSTITUTE OF PSYSHIATRY Max Fink, Director M.D. MF:bk Please address all oorrospondence to: suoo Arsenal Street, St. Louis 39, Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Skowronski, Boleslaw Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-073 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/6ec0ab683ea1370a8fb76aa704514f27.pdf 493d0eec84bda6714039ce7c5e7bd093 PDF Text Text December 28, 1962 Dr. w. P. Wilson Department of Psychiatry Duke University Medical Center Durham, Morth Dear Carclina Bill: In checking the galley proofs of an article on EEG soon to appear in Gil Glaser’s book, I have dacided to make reference to the article which I have submitted to you for the voluma reporting the Duke symposium. So that I might report the reference accurately, can you tell me if you already have a publisher and who the dditors arc? My best wishes for a happy Naw Year. Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY Max Fink, M.D. MP2bk Please address all correspondence to: snoo Arsenal Street, St. Louis 39, M6. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Wilson, W.P. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-075 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/d80cd8112757dd7cba73af652e8d0c22.pdf f42ac12053098709b1d19d9d75c9d9b0 PDF Text Text Dec-nabs: 18. 1962 Dr. '1‘. 2mm mm Ros catch mutants Untmntty of California Los Angola. California Dear 121*. Ram: 11mm read your roam attain ta EEG Journal “carding tho catamaran» systom far nmoolectm: data with mtorut. M I am now «plowing a similar ”atom. lwould apprwtatc m. ”Mammal-'3 name and nodal numbcr of tho digital transport used in your systm. Thank ran. minutely. MISSOURI INSTITUTE OF PSYCHIATRY Max Fink, M .D. Duwtor Mszk Please amt-cu an correspondunm to: 5400 Annual Strut. St. Louis 39. Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Estrin, T. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-077 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/dd945b8e51ceab1d03f418cffc932545.pdf 430e267e4bc4cc28ac75b70de80fa3e5 PDF Text Text WW) gum §K§x Mammy“ *3:ng gagfi EEE ‘ Vin? 9% MN R? \3. RE? XE Pi m\fi rtx Er. \viiwggsrx ,8 \Ar {Ai‘ “wk? 3 {kart} g F \§\ \«QK. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Estrin, T. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-078 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/77e00fd48b2ae10d054a64d0e6d48b62.pdf 8c747e1d4bce4e28d2d823decdd1c06b PDF Text Text Bacamhar W. 70 Lani-la l7 . 1.952 Linn East 83rd Street 28. Haw York mm a. '1’. m: my findings in your meant 1m. u was WelnevarDr.gottaknnwhimmll. Immafthemny weekdahis emtasy. milligram If AW W: 12m and mm ragard fur patients. Ha provided a mildew {If a Malena 1n the an Marian. m1 tn share this loss, which 18 felt by all students ofWt I an writing ‘th WhB Hy beat regards far the flaw 23w. Sincerely Max We. Pink. '14. Directer m Way. D. 51* Elm-e mam; emea to: was Arum smut. 8%. Lama 39. No. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Linn, Louis Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-079 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/3ae8b5457d4fa06a5f3d126a9a0a50b1.pdf 90307413a92089e7ccaf86fa84e130b1 PDF Text Text flaeenhar 13, 1962 Mr. Gilbert 8. Emu, Managing Editor Aréhivea af General ruyehiatry 535 Narth Danrhorn Street Chicago 10, Illinnis ANA Dear Hr. Casper: The nmxt isaua nf thy Aréhivea of Gennral Fwychiatry includaa an articlc writtin by Dr. Dunald F. Klein and myself entitled "Behaviaral Rnnctian Pttterna with Phenothiazinex". I will be grateful if yau can water an eras» for 109 additinnal reprints with anvers far my paraanal use. If this can ha done. glanse sand 1 regular raqunat farm and the churgaa, and I will pay diruetly. Thank yum very muéh. Singerely yours, HISSGURI IHSTITHTE 0P PSYEHIATRY Max ‘I 16!: w Fifik, Diruetur H. D. Airmail Platte «adreas correnpandenea to: sane Aracnnl street. 8t. Lnuia 39, Mo. 1 1 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Cooper, Gilbert Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-083 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/cdda28add0dcfe8aeb1c01b171652f41.pdf b3d7df0eb7c38724ff886ba743a5dd4f PDF Text Text December 6, 196a_ Dr. Nat Siegel Hillside Hospital P. O. Box 38 Elan oaks, Haw Ybrk Dear Nat: I wanld be glad to split the cast of 200 capies of the article an muaial eaaawurk. fibula yam please put the arder in? If yuu daeide yau do not want copies. let me know and I will send the order in from here. Sincerelj'yaurs, MISSOURI INSTITUTE GP PSYCHIATRY Max Pink, Direetor M. D. Please address carraspnndence to: sane Arsenal St.. St. Louis 39. Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Siegel, Nat Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-085 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/c1a178c8de3748a136b8786e6345eb22.pdf c5598cf0399314e85013a4a19a140485 PDF Text Text November 29, 1962 Mr. James W. Montgomery Librarian, Hillside Hospital P. O. Box 38 Glen Oaks. New York Dear James: Congratulations on your new appointment and I am delighted that you have the opportunity to develop the kind of library that you have wished for such a long time. Mrs. Matheson has worked very hard in developing our library and we are now in the process of expanding our stack epece to accommodate journals of many year‘s duration. In addition to the usual library functions, I have already begun a collaborative study with the scientists at Washington University in information retrieval. Next spring. when we have our Computer Center established. I trust that we will be able to undertake such studies and provide such information services as may be of interest to our scientists. Like all new ventures. this one has had its difficulties and developing staff has been a slow and tedious job. However, some very fine scientists are coming to join us this winter, and I am delighted because I anticipate an exciting future. Good luck on your new appointment. My best regards . Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY Max Fink. M. D. Mfzaw Director Please address conspondenoe to: 5400 Arsenal St. , St. Louis 39. Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Montgomery, James W. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-086 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/9e40025f9650ad1c0338a95dd6d10c9d.pdf 9fb7ae979aa2020635c3a770dcf0392a PDF Text Text Novomba' 26, 1962 Training Material: & Information Services Division MoGraw Hill Book Company 330 W. 42nd street New York 36. N. Y. Gentlemen: appreciate copies of the two reports recently prepared by your Dtvtuon for the United Status Public Hoalth Sundae conference held at the Audio House. The reports included, an outline of a biomodloal munch information :yntom and uoondly, a genus! donoription of a computerobuod information retrieval system. I would ' If 01mm of then reports are in the public domain. appromato mounting copies. It prior to tabulation. I would thou are any oharqoa, pica so indicate I Thank you for your cooperation. Sincerely yours. 'lwwo—pw MISSOURI INSTITUTE OF PSYCHIATRY Max Pink. M. D. Mrzaw Director � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: McGraw Hill Book Company Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-088 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/6d50d0c437c47f2a6e66d0e442e7cd5f.pdf a9ff4c3a78db90c1f253fc8cecf9a50c PDF Text Text � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Kelsey, Ellis Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-090 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/933cd0a053b051ec19f62cf4182989ff.pdf 37e3a7af7f24ecc0960257d0d248474c PDF Text Text DEPARTMENTAL CORRESPONDENCE DATpecczml r37; SUBJECT Consultation Fee To Mrs. Howell . ~ Martin A. Green, 13, 1962 M. D. DEPT Hospital Bus. Mgr. Assistant Dr. Green actecl as an ad hoc coz'lsultant for me in the employment of Dr. Mawgerison. He interviewed Dr. Margerison on November 30th and then discussed his recomendatiom with regard to the employment of Dr. Margerison as a neurophysiologist at the Institute, with me on December 7, 1962. is a part of the Missouri Institute of Psychiatry's recruitment expenses. This � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Howell, ? Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-092 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/cc7bbd43cf119b9ab9fd93128c21e3d6.pdf 1313e556161d5efadbe0490d787cb30d PDF Text Text Novombcr 29, 1962 Dr. M. Ralph Kaufman Director. Department of Psychiatry Mt. Sinai Hospital Madison Ave. and 100th Street , New York. New York Dear Dr. Kaufman: indeed. grateful for your kind wishos. as I am for the fine model that Mt. Sinai has set for me during those many years . It was largely through my experiences at Bollovuo and the Mt. sinai Hospital with Dr. Bender that I was launched on this research career. For this oxperienoe. and the support of my many friends. I shall always be thankful. By best wishes for the success of your new Institute. I am. Sincerely yours. MISSOURI INSTITUTE OF PSYCHIATRY ....._ . ,1..._rw»_,,. ,. r—nw-w‘vwv Max Fink, M. D. Director MFunv "MW-runaways:- m‘v'—— m n. n.- Please address correspondence to: 5400 Arsenal Street. St. Louis 39, Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Kaufman, Ralph Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-096 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/c3e227637df7f41167a0589dbfb7e0ed.pdf 71e7d1637defb62ee0e4f51af73bed18 PDF Text Text November 28. 1962 Dr. Paul Hooh Department of Mental Hygiene Albany, New York Dear Paul: During your recent visit to St. Louis. the local newspapers carried a summary of your remarks which. in their brevity, were tantalizing. The essence was supporting of the present programs of Dr. Ulett to such a degree, that I am writing to ask whether we can obtain a copy of yom' report as well as permission to quote from it in preparation for his presentations before the legislature of the State of Missouri. As you know, we are embarked on developing programs in Missouri that in many ways follow the leadership of New York. We are modeling om' Institute along the lines of the New York State Psychiatric institute. and your remarks may be helpfultin presenting some of the statewide programs. Thank you vm much for your cooperation. My beet regards . Sincerely yours. MISSOURI INSTITUTE OF PSYCHIATRY Max Ftnkg M. B" MFtaw Director Please address oorrespondenoe to: 5400 Arsenal Street, St. Louis 39. Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Hoch, Paul Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-097 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/7109f79663df4364a300e5f1e76962ce.pdf 84d215f4ae018f26bd24e0c2546ead68 PDF Text Text :33, w .. 3 . - 3;“? ' 0 ' ' . "I ‘y 43w:gigDUH 1;ny , -. . V V '. _ 3' 3%. .3 ":- ’3 V 6333333 36.333 "5-H“? A III IIII 53‘ 31““ "1"3‘43‘i “‘1' I3333" 1ntIrII4a1I . V , V _ ,6,“ v.‘ , _' ., f," 1V _ ‘ 5&1” {. ”III I IIVI manta! an IIIIIIIEEG Slov1ag* an. 333m:- I11: ‘ 'ucuzopuygholcgical ehIanI I1th TIIrI III 6: lItIbIIn IIvIrIl ::ud1II 61I1I1ng VIpIc1£1¢ PQIflhglfigtctfiKplttl «,Igo wa1th BEG Ilpuing. '1 (VIII IEII 3 613 63‘ “‘6, 63% V V ., I“ r ‘3 AK , . 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The rigu 6 or thI convulc yo group 1I 50$. low, 1o th6‘61curo for the e fggp 101 IIIIIIItt r3IhI 3é(:>&,V 51. 3 f'iorproIII1nI 10% E plIggPo3V 0666 1 , ' ~ ' = III6I 66"; 3 - Ir ' II Ii II ~w3’6336666}§~ ¢‘~»«1 72w. » mM ”“5. II pehli 1”33 6‘3.;3I3 5t»§fififi?"lyz,~;x 3.;; f¢fi§_ .Vg M " 9' .6 , .,“_ ~ “3‘13““. “’3. 3‘3. _m ‘333063 * �,, "7 NW rvmw. ..__w. WW“ V" , M M%Jl Wmm, 744 “'44." 3-3ng afmégflfiij MW} flMW/f7yaw2kmifwwasla07 644%, at 792/»«5 .4 _... % W 7/“ Myc x41 2//<A~&/ 1:? W «4 £4 )MMMW’Q/MKM /~/MIi Q £?J{/’w/'/‘°‘“Wud «04. MW”! {M (f/MM aflfiiwufisr/ AM ' '- ._ , a [MWf aux (3/ .-.. 61,7, (’m c it mt? C 9‘ W WW z jay? WWW,“ “(M/éw f ..--—v- @W} * Mae/WM WM; z 3/ 5/7“»! 5/6/74: . 54/” /r-— 74 1? {44:1 “46"." LCM/Mada. g! 4’»; h I W! -:/a‘( z/tlaa’... lo. 4‘44“)” r{l/L4:‘ $1.44 {(0/ §?/ A¢(£ul W51.— ,0 Joe IA, I W1 WM/ [27%- ‘ 5,4,7“ � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: none Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-100 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/e4ea42734b18b3ecb49ebc34d2b96568.pdf 0be59b6bb1b1d238f4ba6ad5978a1b2f PDF Text Text November 8, 1962 Dr. Ira Belmont Albert Elenstein College of Medicine Beet Chester Road konx, New York Dear Ira: Enclosed is a letta' from Dr. Robinson regarding the Rorschach report. pleased that it has received the acceptance of the editors. but find that they have some questions which require an answer. I am Their firet question is one that we have discussed at length and while we had agreed to report only these findings which were significant, I believe this should be made clear in the text. I know of no theoretical reason why ”psychic enwizere“ should have the effects measured by these scores. and specifically with schizophrenics . Do you? The second question has never come up before and I would be interested in your comment. Is there some way of analyzing the data anew following their suggestion? I have sent a copy of the letter to Max. If there is some merit in getting together to discuss this. I plan to be in New York at the meetings between December 5th and December 8th. If this is not necessary, Iwould be pleased to hear from you by mail . Sincerely yours. MISSOURI INSTITUTE OF PSYCHIATRY Max Fink, M. D. MF:aw Director one. Please address correspondence to: 5400 Arsenal Street. St. Louis 39, Missouri � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Belmont, Ira Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-101 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/ea844e53a4fdc073832e256d86283eb3.pdf e55c9998edc8bea624378e4ef37140c6 PDF Text Text ' nyne-wwjiw’wr'”?flfl p. We 1, 1962 Dr. Arnold Blmberg Hillside Hospital 0. B“ 38 Po ' Glen Oaks, New York Deer Arnold: It has been sonar weeks about opportunity to talk emetimos it seems research problems. years .. since The work here is have bed en going very well, we for tin last few weeks I have had w first opportunity to work with pstients in the new setting. I me writing because I believe we here as metal opportunity to oerry out a study which may be of interest to you. As I review the oherte or sub of my patients, I find that they have been on psychotropic medication for months, and in some instances, for years. Today I saw a men who hes been receiving 3 vesioty of phenothissines since 1956 without a significant period without medication. As I recollect, you were quite oonosmod some years ago about the longutorm effects of such mdioation. I do have the opportunity to take those patients off medication, and this will be data. None or the patients have had an adequate work-up before hand so that it would be impossible to nuke any statement regarding s "shame" in any medical measures. However, if we simply survey 9. large umber of subjects we shmld be able to make s aux-mine. tion of mother or not certain blood constituents or functions are "abnormal" for the ego. end Home my questions. is Gould first ask for a white count, differential hemoglobin and other of the blood elements. Also, s. "liver profile". These ere the routine studies which oould be dorm. However; I an sonoemed thet fie were to take snob measures only, then we would probably gain very little information. Are were some laboratory studies, albeit not routine, that you or Hemnight suggest tomb such a study worthwhile? it As you sen it is e lot of work. I move patients to the wards gun, we bed our dedisetion on the 22nd. That went very well in lid-Ootober, end end I believe that us have s. pest deal of support, not only fronthe Governor end the politioiens, but the wblio es all. W staff is growing end if ell the candidates who hen agreed to ems, some betmen new end next Jen, I should heme e very 1well qualified experimental group. I new Just let it be known thet I en interested in the essistenoe or s full-tine plosioien for our resemh wows. The hospital bee a large audios}. start and tor relationship to thee ms hes been quite good. I hope, on one of your visits to the �mow-It, that you will have tho oooasion to visit with no and by then I should be able to show you laboratories that my be a. happy outgrowth of our Hillside experiences. The children are quite! happy in whool and have made Manda very very satisfactory and I an plowed with mob that. I have found in St. Louis. As one can expect, the most difficult part of no): a move is the loss or Moms. quickly. Our home is m 013 last. note. I have had opportuniw to go over the Hillsido data on a few occasions. I 1mm: that Mu ham written to tho computing cantor of. Washington University roqmoting sons in the analyses, andIbope that thesawillbo 1301 . 1% best. regards to Barbara and “31m yourself. Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY Max MFsaw Plane address oomopondomo to: Fink, Director , 51.00 M. n. Arsenal Sol, St. Louis 39, Missouri � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Blumberg, Arnold Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-104 Date A point or period of time associated with an event in the lifecycle of the resource 1963 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/7f55063f3605fba2188e6b0adecb61d7.pdf c0906b0f8611a346f6af111d0693324b PDF Text Text October 29. 1962 Dr. Sidney minotoin Depot-hunt of Rommution Medicine Alba-b Einstein College of Modioim Road and Morris Pox-k Ammo mmmmr Now York 61, New York Door Sid: bill from the APA and the note 3m mooivod myfor division authorship. It is they WM out I apply obvious to u that the Division of Physiological and Oman .tholog is probably the ow clan-at to w mo of imam”. I would be mum, thomfom, if you would include one I have m1: 1: W quolii’iontiono are satisfactory. Louia. Ian www.mkmmatImdetoSt. of our laboratories a of description enclosing the taking liberty in your 1, thus may be of intomst to you. Please lot. on take this oppwtuniw to invite you to visit us on your noxt trip to tho mount. as I 1mm My best regards, Sinooroly yours, MISSOURI INSTITUTE OF PSYCHIATRY MI! Way W, Dirootor M! D. out. Plow odor-ea: oomapondonoo to:- Shoo Arsenal Stroot, St. Louis 39, Mo. �AMERICAN PSYCHOLOGICAL ASSOCIATION Division Secretaries for 1962—63 1. DIVISION OF GENERAL 14. DIVISION OF INDUSTRIAL PSYCHOLOGY PSYCHOLOGY Dr. Gregory Razran Psychology Department Dr. Brent N. Baxter Prudential Insurance Company 763 Broad Street Newark, New Jersey Queens College Flushing 67, New York 2. DIVISION ON THE TEACHING OF PSYCHOLOGY Dr. T. L. Engle 15. DIVISION OF EDUCATIONAL PSYCHOLOGY Dr. Julian C. Stanley, Jr. 2021 Kendall Avenue Indiana University Fort Wayne Center 1120 South Barr Street Fort Wayne 2, Indiana 5. DIVISION OF EXPERIMENTAL Madison 5, Wisconsin 16. DIVISION OF SCHOOL PSYCHOLOGISTS Dr. William Itkin Chicago Teachers College North 5500 North St. Louis Avenue Chicago 25, Illinois PSYCHOLOGY Dr. Frederick A. Mote Department of Psychology University of Wisconsin Madison 6, Wisconsin 17. DIVISION OF COUNSELING PSYCHOLOGY Dr. Dorothy M. Clendenen The Psychological Corporation 304 East 45th Street New York 17, New York 5. DIVISION OF EVALUATION AND MEASUREMENT Dr. Roger T. Lennon Harcourt, Brace & World, Inc. Tarrytown, New York VISION OF PHYSIOLOGICAL AND PSYCHOLOGY --~M.. COMPARATIVE\ (Approved in September 1962) For Information: Dr. Sidney Weinstein Dept. of Rehabilitation Medicine Albert Einstein College of Medicine EastchesterRoad and Morris Park Avenue New York 61, New York i/wwux \ '_- ” .- ' __/ ‘7.DIVISIONOF DEVELOPMENTAL PSYCHOLOGY Dr. Frances K. Graham 2927 Harvard Drive Madison 5, Wisconsin . DIVISION OF PERSONALITY AND SOCIAL PSYCHOLOGY Dr. Rosalind D. Cartwright University of Illinois College Of Medicine 912 South Wood Street Chicago 12, Illinois . THE SOCIETY FOR THE PSYCHOLOGICAL STUDY OF SOCIAL ISSUES—A DIVISION OF THE APA Dr. Margaret Barron Luszki 1509 Golden Ann Arbor, Michigan 10. DIVISION ON ESTHETICS Dr. Henry Gleitman Department of Psychology Swarthmore College Swarthmore, Pennsylvania 12. DIVISION OF CLINICAL PSYCHOLOGY Dr. Sol L. Garfield Nebraska Psychiatric Institute 602 South 44th Avenue Omaha 5, Nebraska 13. DIVISION OF CONSULTING PSYCHOLOGY Dr. Ruth Bishop Heiser 10 East Sharon Avenue Glendale Cincinnati 46, Ohio 18. DIVISION OF PSYCHOLOGISTS IN PUBLIC SERVICE Mr. Luigi Petrullo 2431 North Edgewood Street Arlington 7, Virginia 19. DIVISION OF MILITARY PSYCHOLOGY Dr. Philip I. Sperling 6108 Augusta Drive Springfield, Virginia 20. DIVISION ON MATURITY AND OLD AGE Dr. Walter D. Obrist Department of Psychiatry Duke University Durham, North Carolina 21. SOCIETY OF ENGINEERING PSYCHOLOGISTS— A DIVISION OF THE APA Dr. Harry J. Older The Matrix Corporation 507 18th Street, South Arlington 2, Virginia 22. NATIONAL COUNCIL ON PSYCHOLOGICAL ASPECTS OF DISABILITY—A DIVISION OF THE APA Dr. Leonard Pearson Rest Haven Rehabilitation Hospital 1401-17 South California Boulevard Chicago 8, Illinois 23. DIVISION OF CONSUMER PSYCHOLOGY Dr. Gove P. Laybourn, Jr. Marketing Research Department General Mills, Inc. 9200 Wayzata Boulevard Minneapolis 26, Minnesota 24. DIVISION OF PHILOSOPHICAL PSYCHOLOGY (Approved in September 1962) For Information: Dr. Edward Joseph Shoben, Jr. Teachers College Columbia University New York 27, New York �DIVISION AND STATE ASSOCIATION MEMBERSHIP In its Annual Report for 1962, the Policy and Planning Board has again emphasized the importance of division membership and, in addition, has asked the Central Office to provide information about joining State associations as well. Division Membership. Listed on the reverse side of this sheet are the names and addresses of the current Division Secretaries. Two new divisions, Philosophical, and Physiological and Comparative, were approved by the Council of Representatives in September 1962. These new divisions do not have officers yet, but a name is given of a person from whom information may be obtained. It i: necesmry to write directly to flee divirion for application blanks and for information on specific requirement:. Deadlines and requirements vary among the divisions. Each division has the right to establish its own requirements for membership, so long as those requirements are not lower than those set for APA as a whole. Divisions may also restrict their classes of membership. Information about the requirements and classes may be summarized as follows: APA requirements only Divisions Member 1, 5, Associate 1, 8, 9, 10, 18, 20, 22, 8, 9, 10, 18, 20, 22, 24 24 Special requirements Fellow All divisions Member 2, 3, 6, 7, Associate 2, 7, 14, 15, 16, 17, 19, 21 No class of Associate 3, 5, 6, 12, 13, 23 12,13,14, 15, 16, 17, 19, 21, 23 (The expression “APA requirements only” means that election as an Associate or Member is based on meeting general APA requirements, and applying to the division. Most of the divisions have additional requirements. Where there are additional requirements, it is to be assumed that the APA requirements must also be met.) State Anociation Membership. In its 1961 Annual Report, and again in 1962, the Policy and Planning Board has emphasized the importance of membership in state psychological associations. The minutes of the 1961 meeting of the Council of Representatives show the following action: "Council endorsed the Policy and Planning Board statement that all psychologists be encouraged to join their State associations. These associations are becoming increasingly important in local and national alfairs, and it is important, therefore, that they be representative of psychology and psychologists.” There is an affiliated association in every state except Alaska, plus associations in the District of Columbia, Puerto Rico, and the Province of Ontario. In the typical case, joining the association is a simple process for any member of the APA. Information may be‘ obtained easily, by writing the secretary of your affiliated association. A list of the names and addresses of the secretaries is enclosed. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Weinstein, Sidney Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-105 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/44c2206592b7bc1992250fb4eb77cdaf.pdf 7c617c920710d244570bf4c7263d2ed3 PDF Text Text x; 'Oetdber 29, 1962 Dr. Hewett: Kosi University of Michigan Medical Center Ann Arbor, 1416131833 Dear Ken: last few who have Men quite hectic, ee I have waved q latex-em free New York to St. Louie. I did, in feet, receive the kind letter from Dr. ween appointing m u Winter of exhibit: These for 1962-63. I wrote to him at that time indicating that I would rather not serve in this capacity at this time, since I would be preoccupied by w present change of losetion. Also, the most important time for the coordinator to function in during the weeks imdietsly preceding the nesting during May. This rent, the matings of the Aux-ism Payebietrie Association era hem held in St. Louie, and mush of w the has been pee-seamed in entieipntian or that nesting. Dr. Ulett and I will partieipete in may at the best responsibilitisl during that time and it would be diffisult for me to em out both functions satisfactorily. It is, wearers, with regret, that I rsqmet relief from this assigment for 1962-63. Al I indicated to Dr. Harlan, I would be played to participate more ”timely in tbs pregrm of the EEG Society after this year. My beet regards, Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY Max 14me Planes address correspondeme m, Director to: Shoo Arlene]. M. D. Street, St. Louis 39, Miuom-i � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Kooi, Kenneth Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-107 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/9bcdf86d3e50416d0730934aba0ec6ad.pdf 21f2f70753d4686935b29c64b8de5dcb PDF Text Text my Dr. Omen 26’ 1962 Wale: Sate Heepitel Museum-its Metropolitan Walther: Sh, D.” D?- “my: Iueneleeingeeepyofthe Wofmmpoeiuheldetthemld or peyehietry omen in the discussion. Ian may also - , Eunice}. en 1n The reference “eh interested interested in an article written by kdieimue edditiam re ”we be in 1961. ‘ e 5: you is marked H. Helmhen and H. «that: 361;, 1961. These also presented CINP eomreeaaaet Munich, September at this authors who have dam some work an this abject ere; F. Flugel of klengeng P. Berene'bein cf Villejuif, Paris; end 0. Gazelle of Milen. Parenthetioally, both Dre. Cezanne and Flugel will be at the Sahel Conference on October 3131'. in New York. The An by Dr. additional report concerning the Itil. and He has done a metal EEG is W included in the abetreete and exhenetive etndy of the pentbthal hie mung-apt: ie new in the heads of the University Osmium response tea- their emeiwretien for his doctorate. I anticipate having Dr. R11 cone to this leboretm-y at the end of this year. It is w hope that. we will be able teeerryoutthe studies efegreupofeehieepbreniepetientewbohem failed to respond to therepiee by e embimd EEG-memeneephelmephie drug eveluetion etudy. I mid be pinned to dieenee thin with you, car - ad ether eepeete of the therapy resistant problem, at your convenience. Let me take thin epportuniw to extend an invitation to visit theee laboretoriee ~ w duringyournextvieittotheflidweet. Sincerely rem-e, MISSOURI INSTITUTE OF PSYCHIATRY Fm, Dinette! Mex 14an M. D. one. Plane eddreee correspondence to: 51300 Areenel Street, St. Louie 39, Missouri �_, 1 -. Parnate } brand of tranylcypromine F01” g more rapid onset Of action leaders in psychopharmaceutica] research � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lindsley, Ogden Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-110 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/0123f436acabef677c2f59897725ef50.pdf 5d5f604bfbefb2c7db634aba3dcb58ab PDF Text Text / Wfiw Min Dr. A. Green 10 Brinrclifr Brita Pm Wuhington, Nam 10!! Bur mm. Institute of Paulina-y is an mm training ventral: center. In View of your mom aquarium in uni-clog, us would be plemd ta hm you Micipate in a seminar during the month of Janina. If you can specify the date thntyouwbe available in St. Innis. w mambo planned to hm you not with our amt. Except. for January 13th and 16th, and January 211.26, I should bu annual: on any other day that. month. and The Missouri. My but personal roam-dc, Simorely yours, MISSOURI INSTITUTE OF PSYCHIATRY m Fink, H. D. Wu“: Plates address: Director mopendtm to: Shea Arcana Street, St. Lani: 39, Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Green, Martin A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-111 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/82ceebcfc3562e9af38f69b4975ed9b3.pdf cbfbd6cdd5515515e3ade59fbc70c3ee PDF Text Text _;,y u 3&1 ' . '1“:‘. in =. , f‘ s October 23 Dr. Robert. B. Cahan The Langley Porter Newepmhiatria hm Parnassus Avenue San Francisco 22, , 1962 Institute California Dear Dr. Cnhan: Please excuse my daisy in answering your letter, but in the interim I have changed my location to the new Missouri Institute of Psychiatry. In w atudica at. the Hillside Hospital m did not have any system of coding mar EEG records for IBM. Most of our work was in frequency malyfia and all the data for tinny-four frequencies were transcribed tram tha spacial write-u outs of the mutt-mm to data sheets. Analyses have been done on the individual frequencies and we have nude no effort to sunny our basic mam-d: in any other my. I an 31101031133 a reprint of one of our latest reports, as this my give you an idea chant our method of handling our data. If you desire any new infomtion, I should be glad to angular any specific qmstions. Sincerely yours, MISSOURI INSTITUTE OF PSYCHIAIRY Ha: Fink, Director Hme M. D. 0”. Planes address correspondence to: Shoo Arsenal Street, St. Louis 39, Mo.» � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Cahan, Robert B. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-113 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/506a8fdb00729a96eea19a7fa9e39f62.pdf 9df0c139ea7761516e996a90b689a76e PDF Text Text October 19, 1962 Mrs. Gloria Podrid Hillside Hospital Po 0‘ Ba 38 Glen 0&0, New York Dear Gloria: I have an opportunity to discuss the tub-hospital study early next If you have the gamma of the paper "Sociopeyahologieal Aapacta of Psychiatric Treatmnt in Three Voluntary Hospitals", you be able to run of: 50 3091039! ate}: of the tablet, luvs, and and than to month. m by mid “war 5th? . far we have not heard whether this piper has been accepted in publication and I have may om copy. Dix! m mks a “email a: a draft appreciably 1713/62? If we did, would you and In about. 15 copies? It not, no if you hue my othor lanai). of this paper and it it it: So not too early 3 draft, could you run of! 15 «pica? Swarm-1y I have» aunt. Don min the paper for Psychophamealogia uhieh has hen accepted for utilisation. here are some mowed oditarial dbeniae toauadtotha oditm-sanw nopy with amateur «summations he ukau. You light can by getting his approval tau.- nking a Mail, and naming the two 803316! the «liter wiphos from the stemmed version. If no, aauld you plum and m 10 capiaa? Wtwit mum ' » manna, If there in am rowan not to Mb 11 stencil perhaps yen could do this in your lawn time over tho next few week». Thank you very ml: for pending the :dditional eopioa at the book to Dr. Bogthilet. Did you have any luck with a. tuner on the first package? Simrély yours, MISSOURI INSTITUTE OF PSYCHIATRY Mu Fm, Director Address correspondence to: Shoo Arsenal M. D. Street, St. Louis 39, Hiawuri � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Podrid, Gloria Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-115 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/94fc50a945ec4dcc71c580fff4b8005b.pdf f887e81321d0c5a939dbf1cdde97a488 PDF Text Text ”u“. October 22, 1962 Mrs. Gloria Podrid Hill-idly Hospital P. 0. Box 38 6101: Mo, Now York Dear Gloria: list of the people to whom we sent the bibliography? you did, then either send the list to me, or, if you have some the, would you send the following note to each om? If Did you keep a "I are the plotted to tell monogram of 1963. that Elsevior has owed to publish thOphamoology early in that I brim it up to date for 1962. you EEG Tiny have gained and Human If there are related references which we have omitted, would you please send than to shortly? Plans 111ch any refer-anon which may now be in press and which you expect. u very to appear 1m in 1962. or early in 1953. Thank you for your cooperation.“ I would upptooiato 1: you could do this for nah. me. Thank you Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY M, Director MD: mun: Addreoe oomopondenoo M! D. to: MAI-canal Street, St. Louis 39, Missouri � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Podrid, Gloria Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-116 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/c65079c1c3e0831b691c728e7dd3d623.pdf b1b39d658afe491171160a410ae7d210 PDF Text Text W—v-w . v—v ~/-v memgr October 18, 1962 wmrww.M~—vwrqu,m<vn~,-,mwm-m—lu-mm.~vgwm-WW min—w m""m Min Bomis Pun Bachrach Photograpl'ara ha Eat. 50th Street New York 22, N. I.» Dear Miss Poe: Immrrythntlhavetmldfimee upsolong,but1nlv manganywen atmmmutwotwmru Ihm hpt. ’62:: numbers of that: picture: that are of greatest interest and m1 tron him to time wits to you regarding additional prints. Thmk you for your cooperation. Shear-«13‘ you“, MISSOURI INSTITUTE OF PSICBIATRY Mm... MIX m’ H. D. ww-W—Iv-s- Adda” correspondence to: '1'“ shoe Arum Street, St. 77/2?- A2,, 7 7/57 m M? 77/? - / </ (mwgémy J . Louis 39, mama � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Poe, Bonnie Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-117 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/a3ba5437cea047b39e473af2247b4140.pdf 823c9d6e24779dfd3f8836f9117a927b PDF Text Text 7 a.” W... -v , 4 -_ ”WV “Winn“ _Wv.o.w.,._____r‘._w'w ,. ind, wowow...“ V _. .mwwnvrmow., «cw. anurwa—or-..‘ October 17, 1962 Dr. Joseph A. Epstein I-hmpstoad Medical Cantor 230 Hilton Ammo Hamp‘tfla-d' Li Ia, N. Y. new Joo: Thank you very mob for your letter regarding Mr. Jones Barnes. I have tho feeling that our Mow or w alter ego is operating in Nassau Coonty, for I have left to take on my new role as Director of the Manolo-i Institute of Payohiutry. Life has been quite hectic them last few months, and it in only now that Mirth: and I find the time to relax and look back. There are, as you know, many problems in relocating, but wo are vary planned with our new homo and the opportunities presented no. The children are quits vol]. adjuotod at this point in their new schools, and we am beginning to portioipato in oomunity offairs one main. to On om of your have you around m trips to the visit on to now city. West Coast I would be pleased give no the opportmity to show you Sinooroly yours, MISSOURI INSTITUTE OF PSYCHIATRY Fink, Director Max M. D. MFaaw Address correspondence to: Shoo Arsenal Street, St. Louis 39, Missouri who. “WT � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Epstein, Joseph A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-119 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/9f2ca073a8b2e328522f38600159383b.pdf 4405162a2c5c8d2950de3e4dc5c4fcc0 PDF Text Text October 17 , 1962 M. Ma: Pollack Hillside Hoapital P. 0. Box 38 Elan Oaks, New York Dear Max: It no 11199 chatting with you yesterday ottoman. I shall, few days, make the within not” regarding tho program here and and it. on to you. m wt Enclosed is a atatomn‘b tron tho Senator Gluten This should be charged to M'! 2715 except, that you my approprintoly charge ans-halt of tho $h00 to MY 2:798. wt Ishouldlihtotaknthisoyportunflytofmllythwk yonforyom-girt. Itmoxtmmlythooghtm ortho and I have dooidod to use it. in w office. Tait}: group the calendar xiv-n m by tho Homo Neuropsyohiatrio Society, I pom very fine desk pieces. now have Simonly you", HISSCXJRI INSTITUTE OF PSYCHIATRY Mu Fink, Director 24an em. M. D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Pollack, Max Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-121 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/3ae9ce704af5d7a114a7fa72530a1799.pdf c30d03772ba2e3a6bf86ddb399a61e85 PDF Text Text October 17. 1962 Dr. Lewis L. Robbins Hilllide Hospital P. O. Box 16 Glen Oaks, New York Dear Low: I was very grateful and planned with the gift which you so thoughtfully mloeted for no. Our the you-s I haw remind a variety of mounts, but this volm is along the most appropriate and moat useful. I an grateful to you and tho staff of Hillside for your kind thoughts. During these past four weeks as I have booms increasingly involved with the ram details of my new position, the emotional rulings of the past new months ham a loosened significance, and, I bellow, their not-o appropriate lovala. I find that my experiences at Hilloich have gimn a background to mom this role. On one ooouion after another, when mounted with nowl qmationa, I have thought back to the mlutiena and momndatim which would have boon appropriam at Hillsido, and with minor modifications, have adwtad than here. n umd . W best regards, Sinnersly yours, MISSOURI INSTITUTE OF PSYCHIATRY y” Mlew Address correspondence m’ Director to: 51.00 M. D. Arsenal Street, St. Louis 39, Missouri � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Robbins, Lewis L. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-122 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/b1db7bbb22eff63247669abccdb3a152.pdf 4ff9e4ad655e7ab735164fedd4b27254 PDF Text Text r“..- , WWW—.mm. mx—m . 3«7 1"!“an WW.»- .7 vi t. T. October 18 , 1962 r—w .- ~r..-u.,—-v“w,..,.uvv.- r—ruwv-v n-u—v ”Wuwupm-qu YTW. I: ~ ~wnwm~vwwr~ 4,. . ,w. "w. .,...v..r Staff Departmnt of Marinate]. Paychiatry Hillside Hospital P. O. Box 61911 38- Oaks, New York Dear Friends: Three days ago I received a package from Hillside and was both surprised 3nd pleased with the selection Hospital of gifts. I have put both the desk sat and the to uoc and believe that both are most approprictcdictionary to my present needs. I regret that in the hectic days of Mich-September I was unable to be with you for the formal presentation. I would have enamel being there, and hope that m can get together sum time anon. Accepting your good thoughts, I am taking the liberty copy of the announcemnt or the new Institute, knowing that in this you will see the potential fulfillmnt of com of our and upirationc. of enclosing a mm My best regards, Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY HF HI: Fink, Director nu M. D. 0m- Addrcsa correspondence to : Shoo Arsenal Street, St. Louis 39, Mo. , / � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Hillside Hospital Staff Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-123 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/2c052c9ab31c5ce72e749d9173ebafd7.pdf c87285acf627750fa92715c504ab8108 PDF Text Text '7’- my ,V—.,.- October 25' 1962 Dr. Max Pollack Hilllido Hospital Pa 0. BOX Glen Oaks, 38 New York Imeorrytohnve cmeedyouwonbarmatinuyphone can yesterday, but I was calling on H! 2715 budm.8§ and believe it proper to eel: the hospital to woept the ohm-gee. Hemmer, if this is a problem to the program, I shell not ask this again. we I haw been dieeueeing have acme some of the date with James Vanderplns and toaeonoineionwhiehlehouldlihetoehmwithm. the have we been this to obtain a correlation tin during poet year matrix some: :11 the principal item in the study. This should be done for the total population. Depending on whether we home a news of tanning missing "rubles, end the reenlte of the first analysis probably should be reputed for the aciaophrenic sub-group; however, in going over the original covariance analysis of the behavioral ratings and the soul" derived for drug sensitivity, it is clear that neither not of mama-u m the nut representative of our mph. Dr. Vamierplae hwmeeomwed, and I believe that we should undertake, a factor analysis of the'threo primipal rating melee (Lorr, Lorr Ward, and Johns Hopkins) At no forourtotelpopnntion. Input, thisvaeelao nakedbyone orthe rotereea in the paper matted by Hitler. hhile I was mutant about doing this Int Mk: I have hed occasion to review the whole problem and I believe that we should do it here. I hope you amour, and girls to lay out . it uillbe helpful tho following information. We if you would ask the are pertaining-1y interested in three than, mduonld “k thet the em sheets as used in setting the covariance detu be used again. have the first two oolunne blank up to idontii'y the task; next, 160:3in patient umber, mutant type, and mow-pout more. Thentm mamboleidoutestodigitmnbere for 10 minus, continuously for etch subject. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Pollack, Max Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-125 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/7cab6d288888dcf259847df4258eb16c.pdf 32bee8dc39dd7ed3b5d426bf370e0c5c PDF Text Text The Johns Hepkina' seals 53.530“. we . each item score pro and post- by . scale a each item pm and post. Len Ward Lox-r interview scale. the dictm scores, by Don and veal! following will be helpful if should make as few me as possible, were to punch the forty items for each examiner separately pro and that Here you have two it we post for eech subject. I think these three scales are more than enough to give us a picture the factorial dimensions for this population. I have the facilities of have these scores punched here and shall send you both the cards and to our analyses It when was nice they are done. chatting with you again. Sincerely yours, MISSOURI IKSTITUTE 0F PLYCIHATRY Mu Fink, M. ”Mme. -.., wvm. specific tasks are: MFsaw Director 13. w. WW I. , r .,,,.-,. ,, ”r .. ,7, ”t. ,... WWW~.Ww—._-‘.vfl cr Please address correspondeme to: Shoo Arsenal St... St. Louis 39, Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Pollack, Max Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-126 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/f664b98ece443f7aef3d2579142535a8.pdf 89986112da3ac894d55ef81628d63dd5 PDF Text Text '1 «WP-"f ‘v-I C. October 8, 1962 Mr. Hauriee Baohruah Adniniatratur Hillsido Hoapital P. 0. BOX Glen Oaks, 38 New Ybrk Boar Maury: interested in knaping tha Hillside Hospittl'a AI tho Isak: roll on, and I anxtuo-d daily with Inny daciaiona thtt are required to establish this eontor,.I find my experianno in Haw Yark most invaluable espooially, sons of tha adm&niatrat1vu education which I You nmy be scrapbook up to dike. - recoivud in yuur office. Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY max Fink, H. n. Director Mrzaw encls. 2 Addroaa correspondence to: Shoo Arsenal Street, St. Loni: 39,Misuour1 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Bachrach, Maurice Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-128 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/5aa968a008514cbe5afb775252131278.pdf 8241e9564e469a0f68d98c0ecbc2ff17 PDF Text Text HISfiOURI INSTITUTE OF PSYCHIATRY Shoo St. kennel Street Louis 39, Ho. October ‘2, 1962 Dr. Willisn Hoe. Antler-eon Roswell Hospital Wiokford, Essex, England Dear Bill: I to have the opportunity to ohet with you during w hasty visit to London. I was stimleted to find that you had looked upon language natures es an ignorant tool in beheviorsl research. I have felt for s meter of years that this has been neglected, although I not admit, that many scientists in Annie: have noon miles of tape with the ostensible sin or ”anelysing" the» at some later date. As early as two days ago I hue visited a. netionelly known Amer-loan soientiot end was intrigued to find that he had been room-ding initiel and weekly interviews for his first two harmed depressive patients (over a four-year was pleased period) and use now looking about for methods of analyzing these upon a formidable teak: Enoloeed you 1will find reprints of a number of studies done at Hillside during the past few years. These are prinative and I believe their primipsl Justification lies in the support gives no for continued study. It you are interested in some further intonation, I would mggoet that you write directly to my fox-nor esmiste, Dr. Joseph Jeffe, 285 Central Park West, _ it ‘ New York, N. L, who has continual them Thank you studies. for your hospitality. Sinoereh yours, MISSOURI INSTITUTE OF PSYCHIATRY Ml! Mme 6300 M, H. D. Dimetar � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Anderson, William Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-129 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/dec39f2892a2460b53161c8f13689d1a.pdf 57e5f8ec599f313f6dd8ae06b6ece2d3 PDF Text Text MISSOURI INSTITUTE OF PSYCHIATRY Shoo St. imam Street 15111! 39. ”0o Mr. James W. Montgmry Medical Librarion Army lot-and Neural Library Hillside Hospital P. O. Box 38 Elan Oaks, New York Dear Mr. Montgomry: I have now unpacked all my books 1nd hau._,oought the two have requested. I brought wither one with no and on you only recall that I road these earlier this you and ontioipato having rota-nod than to you. ‘ will be planed to know that I found some other that belong to you, homwr, and I am asking w librarian to paoktheaa and anuithamontoyouintho You books next. few days. are growing rapidly and I an very exalted about. library's future. Mrs. Mathem'n in worm very tall, we have already obtained an assistant for her. I look to having the library novad to the new building within next two moka. We have the and forward the mymxrnsxt trlptotm want, I shallbepleaoedto mviait as. m best regards, Sincerely yours, MISWD‘RI INSTITUTE OF Max 1*?me Fink, Director M. D. PmHIATRY � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Montgomery, James W. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-131 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/addbbbce7ff72da7bde1e233c1a78761.pdf 4dcdf74a8f8346620282325ed6a0635f PDF Text Text October 16, 1962 Mrs. Podrid Glam-1a Hillside Hospital P. 0. BOX 38 Glen Oaks, New York Dear Gloria: Hy reprints are still in boxes and we have not had an apportunifiy to upon than. Wauld yum please send the reprints reqnostad to Dr. throa? Sincerely'ynmrs, MISSOURI INSTITUTE OF PSYCHIATRY Max Directar Manw o Fink, 2c, L mug 0;: Addrala correspondence \M. to: . v M. D. 4%,) Shoo Arsenal Street, St. Louis 39, Missouri � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Podrid, Gloria Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-133 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/62221f7548af52db5ed261572c13f304.pdf bd0baf6bdc5f58d408569b3bda48eca4 PDF Text Text , __.. NW...” inn-«r, culmwwn-mwm w; September 26, 1962 "u"— , WW r w...“ .m‘.W.,..: Drs. Donald chin and Ms: Pollack Hillside Hospital P. O. Box 38 Glen Oaks, New Door Don flux: & York Thank you for your recent note. I shall try to answor your questions striatimt E l. ghgggggtx A good idcs, and I have taken the liborty of making sons sditorisl comments. Tho conclusion promises individual profiles. Row do you plan to do this? Sinus I will_bo unshlc to participate-meaningfully in there analyses, I would suggest you submit this from Hillside Hospital only, under your Joint authorship. I would be pleased to road the draft report as urittsn. 2. All covarianco analyses are in the master books or the “duplicate” book. Tho covariance of the Rorschach (Problon 15) was given to Ira and a copy of the write-out is in the big book. Covariance of "new” ratings are in the large book and should have your notes with them. 2-7... " One copy was given as well. to It is you marked Problcm llull, dated April 6. work and should be in your desk for your ' ‘ ‘ Tanisha." separate cover I am sending you (with orrors corrected after sz machine processing); the operative prooodurc for IBM program; tho program dock for the 7072; tho uritcoout or the program; and tho test problem writs-out using this program. This is a completed program for book tests, and can be run on a 7072. It cannot be run on a smaller machine since it needs a large momory. Program zoos to stop of ”table look~up” which is very timo consuming and bust dons by secretaries. Roforsnos is Siogol's Non—parametric 3. nggpflggggggiggg; the original U-tost and Under test sheets Statistics. (r ,ngw . in.‘ H, “5.5.3; w»: (5) Cost: We will be billed $400 for this job. This will b. added to tho Scptsmbsr ststomsnt from the washington University Bulgatur“fisitcr. Sines it is applicable to 2715 and 4798, I will cuggost that uncuhalf tho cost be charged to each grant. �.u.“ ,_ ... ‘1. or». 3 “' Dra. Donald Klein & Max Pollack Septembor 26, 1962 ~2~ (b) Runs: The Washington University center program fbr us at the fpllowing charges: For punching data €2.72/hr. For 7072 tima $5/min.(user‘s will run this rat.) subjects x 3 drugs) will take about $20 for both de and K-H takns about 1 minute on 7072. sun of punahing. data, have the girls If you wish any runs on the presently availablesheets (covariance will do nicely) transcribe the raw data to shoots on and send than to us barn. to punch 100 problems (50 Each , Good lmk with thc » APA. Sincerely yours, MISSCXJRI MaxFink, eraw INSTITUTE OF PSYCHIATRY M. D. �Summary: Self—descriptive questionnaires have been advocated as a preliminary device in psychiatric case study. In this investigation various patient-rated instruments were analyzed, and the selfuratings were compared with measures N of ward and interview behavior and with psychiatric diagnosis. symptom, mood, Selfbratings in the areas of attitude and social attitudes using the: 1) Frank (John Hopkins) check Attitude Scale one hundred and 4) list; _2) Clyde California F Mood personal Symptom Scale; 3) Whitman Scale were obtained in forty-four voluntary psychiatric in—patients referred for psychotropic medication. In addition, each patient was rated by observers l) Jenkins Psychotic Reaction Profile using the 2) Clyde Mood Behavior); Scale; 3) Hillside Hospital Somatic Treatment Referral Scale A (Ward and 4) the Interview section of the Lorr MSRPP. factor analysis of the self-descriptive scores resulted in the following factors: 1) Clear Thinking; 2) Somatic Complaints; 3) Dysphoric Complaint; Mood, Dependent Action; 5) Aggressive Mood A) Friendly and Action; 6) F Score, Friendly Action and 7) Angry-Dependent—Withdrawn Feeling. A factor analysis of the description by observer scores resulted in the following factors: 1) Angry; 2) Withdrawn; 3) Tension-Apprehension; 4) Communicative Disorganisation; 5) Somatic and Neurotic Complaint; 6) Sleepy Depression; 7) Guilty Intropunitiveness and 8) Rate and Reactivity. �E .2Those each patient, factor scores were analyzod as and led to groupings according l) Self-descriptive profile; The profiles for to: 2) Description by other relationship between those groupings psychiatric diagnosis will be discussed. and profiles, , �NcnoPerametric Statistical Tests Operating Procedure Date should be punched in the following format: 1. The first card should be blank (or at The other will 79 columns particular problem. be printed as the least numeric) in column 1. first line heading for that 2. The second card is a control card punched in format (1!; containing the following information: minimum 2 e. of 3. > 11 12 b. for ebeolute scores. the number e 1 or a 2. of columns for this problem 1 means the signed scores Il, 1013) - maximum of 10, will be analyzed; 1013 - up to 10 numbers giving the number of elements in of 150 for any one column. cards follow, punched in format (SH , 15F5. 0); and be 5 i.e., the first colunno may contain identification will ignored. There should be a set of date cards for each column, one set right after the other. However, each column must start on a new card. Alec, the number of elemente for each column must correspond to the number punched in the control c. each column, maximum 3. The date card. The preceding gives the format for one problem. Any number of problems may be run at one time, with no pause in between. The complete data sets should follow one right after the other. The date should be put on tape They will be read from tape 3. Output can go on any unit. in card will be image form on tape 2. (Fortran card—to~tape). tape The systems , fl tape mark in written on the output tape by the system at the conclusion of a net of problems. If the Batch Compiler is on unit Q, units 1 and 4 are ready, and alteration switch 1 is on, a tape merkjwi11 be No . added. Otherwise, it must be done manually. . ��1 ff!) QE’ [(9); TE i“. WA V ' Vt C61,”); 5/: /4 (0/ 0 )7 0”“: ." £IW€ -f .:. if mb 5 If" ; {1” f ‘1- ‘13 MO .1... I... “1;,;‘/: .51, ' ,,~ ESE’FE , CLUKQ. . "W? . I V“ M"? V a... 531.21..» .1... jig-74 .. quE~ 2.25:); 5.1...2...‘ m . - . ' ‘ 3’ gr. ' :1 y} TLZQ. ""57“ c... 41.. .~+ w 31'3"..." bL$W¢fiM, (Lt/’1 emu/.9 ii)! 9; .13 £3." '. . f E "( . “g .5...” E m .3... (A ‘ ‘1'" ‘ J ., 2.1? XHIE"3 \. a... .71.... :.;}:.~{.. 5d. _"‘E“h< 2.3.3? ,g ”I.“ , Wl+l4 J 13.3 ‘ V f. E." 4 . 39km. (Effigy. .: imave EC/‘om Tna/ w: H haml' Em cw. 1...... 2, 1M]. 3, 0..u+fa+ w. Th‘ 5y; +33% 71.274; Cam 7... an 9515+, , )9... f j... S CLM’;,#' . a... ”0 'bttyt stw‘i au+f0+ fysfimLara; ..+ of 09...)... If (E... 3...... COMM... L. )..an+5, "1.1.16.sz Hem mom/IQ E7)! JCE'QL'- UvnE‘ _0EA 0 ql+wa+tomf VA filial? 0? 3. SW)/‘Ualq_ £M~H ‘i .9 (<2. . I 96:. . ‘V «E-fim cm. EEW _ L a 34 U - 4: CE 4.44%”W01?) W 3.. (amoEQ-CE'A an; “ES"EME are ‘1’“ If?“ <2, v ’ 1}». 5 WE (Em/E.” VE/ZUJ'U‘ In c: *9 E a. gym/E :3 wflqVEC :4...“ affine. Witt/(«70.119 . m;‘13,“!wa ((3 ,fl.’<{:2wm<<~.wm%w M‘M. .5 Ea)... E99 E , . E J Fflmc‘lv .1 a; 0915 £4” ((2,; cE‘w'Em. C234 V69} ‘ 1L5. 3]. O+¥l<leWWE§§ . <24 ”£14.... a v E m. M... ”mg. ' . mm, (91rd; ft (E: y (.6 E5251” ”EH/1.1“. E < 73 .5 “I “5.55%.: 3}” (1;. “w... .. J .1 3;? , ' } :3. .. ..,..... 1 , 35? 3/1": 3; . Efiji E: E97: ,«a [‘3‘ 3 (4.3.2.... � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Pollack, Max Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-134 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/6cf679260f53419b5f665b6061a01c05.pdf a812de79742fae519781b1e7f37bfcb9 PDF Text Text .H n—ysmmvw; Awr("w' . September 24, 1962 Dr. Maurice Bachroch Administrator Hillside Hospital 75-59 263rd fitreot Glen Oaks, Wow York Dear Mourice: it while will be impossible for you to forgive me, I want you to know that I was torn between two pressures that I was unable to be at Hillside last Friday. Before going to Europe I moved my family, and loft Martha with painters, plumber, electrician, as well as three reluctant children who had to start in new schools. I called home from Munich and again from London, and on both occasions, was disturbed to find that I not needed at homo. I ohortcned my trip, theraforc, to arrive two days earlier. When I got home there was much to do, and was only this weekend that we were able to look about us and feel it that we could relax. In the excitement and in the mesa, both at home and office, I put the Hillaido Hospital air travel card aside to send back to you. I cannot find it. As you know, in my this is very unlike me. I called Mrs. PDdrid on Friday and I would appreciate asknd her to notify United Air Lines. your cancelling this card, and notifying the credit agoncy regarding the cancellation. My best personal regards, Sincerely yours, .IIEBOURI INSTITUTE OF PSYCHIATRY Max MPzau Fink, M. D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Bachrach, Maurice Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-136 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/98ddcd7dd01da45a6098291db060a444.pdf 65bcf671402b1c21f98011d84fe31c71 PDF Text Text k, 8.13th 18, Mr. 1962 Nathaniel 319301 Hillsidc Hospital P. 0. 30138 Glen Oaks, New York Dear Rat: failing me, but the title "The Disposition of OutcPatiint.Applicanta“ brings no specific report to my mind. I presume you are referring to tho outnpatiamt study which hue been rattling around fbr some.monthe. If so, congratulations. If not, would you send mo 8 copy of this papor no that I will My bacomo Inory 15 acquainted with it? Thank you very much for your kind wishes. I should be pleased to have you visit us in St. Louis on your naxt trip West. My best rogards, Sincuraly yours, Max ”Pita Fink, M. D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Siegel, Nathaniel Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-139 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/faf87998fe3d8ac4de8d92ffaec8bedf.pdf aab90d245823b0b1e3ff04540ae2a7b1 PDF Text Text August 31, 1962 Mrs. Glorla Padrld mm of Expulmml Psychlcmy Hlllnldo Hospital 75:59 263ml Strut G-lm Gala; Ncw Yul: Dad! Glorla 2 Plans. sand to: Dr. Walter Knapp, Celumbu Psychlcmlc Unlvmlly, Columbus 30, Okla, the follawlng refs-mu: lmlMo, Stat. 60, 57, 53, 37cm! 34. m Also, Wmmhed coplas cf the papers by Don and myself; pattern; wlth chlarpromzlne and pafierm wll-h lmlpramlna. Also a mlmeoaraphod copy of the lamt EEG in human myahophamoology, 3, by myself and Andaman. Include aka a blblloorapby ( EEG and Human Plychophwmacology, ”514961 ). ~. ‘ , ' a mess. See you Smemlm Nth. I , can't get than out of my own fllu, slnco they can . Slnceroly yam, Max Flak, M.- D., Director Mluwrl lmlMc of Psyehlatry � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Podrid, Gloria Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-142 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/c69ecb5695dfbccfd65849adf8f3143c.pdf 5f0867c26782abc18d494e0d423cbb48 PDF Text Text fl August 1h, 1962 New York Host hS New York, 2 Bout State Education Department Street New York Sir: Would you mid-August from kindly changa my address of rocord as of Hillside Hospital to: Max link, H.D., Director Missouri Institute of Psychiatry St. St. Louis 39, Hiaaouri Shoo Arsenal thank you. Sincerely yours, Hrlgp ax n , . . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: New York State Education Department Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-143 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/9f0cdc08e69e6c2705bc6e41c60dd5ca.pdf 60a265cab4f6d8a2b9cd90803436afa4 PDF Text Text August 10, 1962 Clyde J. Lindley Executive Secretefiy, VA Cooperative Chemotherapy Studies in Psychiatry Peyohiatry, Neurology & Psychology Service Veterans Administration Us hington 25, n.c. Deer Clyde: Would you kindly change ny address of record as or uidoiuguet from Hillside Hospital to: flex Fink, H.D., Director Missouri Inotituteoof Psychiatry Shoo Areenal street St. Louie 39, Hieeouri Thenk you. Sincerely yours, Hfagp ax o , . . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lindley, Clyde J. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-144 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/68e616328d10b22af1448529bd2c2573.pdf 27ff0f057ef7a98284a25435463aaec0 PDF Text Text a”) ¢/// February 16, 1962 01r : Clyde J. Lindlaywaa ““Exncuntvamsaéretary, VA Cooperative Chhmotherapy Studies in Psychiatry Psychiatry, Neurology & Psychology Service Veterans Administration Washington 25, D.C. Dear Clyde: enclosing an abstract and title of our presentation in Cincinnati. Thank you for the second invitation. I will try to make the sessions, but am not sure at this point. have asked my associate, Dr. John Kramer, to audit the meetings and would be grateful for your I am K approval. Good luck! Sincerely yours, MFxgp encl. Max n , . . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lindley, Clyde J. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-145 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/dc503c207ea1f0d05a1defefb9ad4f84.pdf c062cbef7c135114b07b5f121137bd92 PDF Text Text August 3. 1962 Hr. John A. Hailey The state Board of Rogiatration for the Hauling Arts of Missouri Jefferson City, Missouri Door Hr. Hoiloy: Enclosed is the completed cpplication for licencuro to practice nodioino in Hiooouri by endorsement of tho National Board; and the too or $25. My naturalization numbor is A~1h3186, dated 7 February, 1930, Philadelphia, Ponnoylvania court. Thank you for your cooperation. Sincerely yours, Hrtgp cool. finx FInE, M.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Hailey, John A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-148 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/837094ec4d2cdef0559eb4b52876a51a.pdf 6134dc48fce5614519c60db8ce415ea3 PDF Text Text DEPARTMENT OF EXPERIMENTtL PSYCHIATRY July 19, 1962 Dr. John Hubbard, Exec. Seo'y. National Board of Medical Examiners 133 S. 36th Street Philadelphia h, Pa. Dear Dr. Bubbard: I am requesting liconauro in the atato of Missouri the basis of oortificition by the National Board of Medical Examiners. A photocopy of my certificate, 1&562 is appended to the application. Pleaoc complote section 21 and return to mo for on filing. Thank you I for your cooperation. ‘Sinooraly yours, MFagp encl. Max fiInE, H.D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Hubbard, John Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-149 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/a142cbf1894dc92bb119c864adbe24d0.pdf dc58e3ecb5be3ac2f8b7b8603955d943 PDF Text Text July 13, 1962 Executive Secretary of the State Board ofhnegietration for the Healing Arts Box Jefferson City, Mo. Sir: Dear I am pleased to submit the enclosed application Certificate from the State Board of Registration for the Healing Arts of Missouri on the basic of a certificate from the Niticnal Board of Medical Examiners. Photoctatic copies of the diploma from New York University College of Medicine and the certificate of the National Board are enclosed. The addreeo on record in Missouri Institute of Psychiatry - Shoo Arsenal Street, St. Louis 39, Ho. Thank you for your consideration. Sincerely yours, for a HFtdts One a Max Fihk, H75. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Registration for the Healing Arts Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-151 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/120f559cfb7276558b0f62a9c7f1f3ad.pdf d78b17fcb83c89ea9ab544c3b13acfc4 PDF Text Text DEPARTHEIT 0! EXPERIHENTAL PSYCHIATRY August 3, 1962 A. Rueeell Lee, H.D. The Tavietook Clinic 2 Beaumont London, street v.1, England Dear knee, in London from September 9th through the 12th and am staying at the Carlton Towers. I: you are in London during that tine please drop no a note there. I would love to get together with you and learn aora or the I plan to be goeeip or England. that I an leaving New York In conjunction West. and following Greeley'e advice to go with Waehington Univoreity, I an establishing a research By new you may have heard center similar to P.I. in St. Louis. Hy beat regards. Sincerely yours, Hrsdte ax n , .‘. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lee, Russell A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-152 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/a50aa9bd884b8adb227943b13d0689e9.pdf 4e7343d3bdcaa3e1656e77b45b7c9cf5 PDF Text Text May 18, 1960. A. Russell L00, H.D., 1h Holmdalo Rosa. Landon, N.w. 6, England. Dear Russ: VI should like very much to June 30, and shall call urtor wa visit with you on arrive in Londen. I ctn very well.imagin¢ the problems of Macy’s far your efforts. I had met Sir Aubrey Lewis in Atlantic City and discussed the iosuib111ty a! visiting hi: heapital with him. I shall writ. to him dircctly. and Gimbel's, but thanks my boat rogurdl. Sinatraly youra, eraa � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lee, Russell A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-154 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/b998dc0924034797bc6ef224220255cc.pdf 861318106954978ad7de484823d99797 PDF Text Text April Dr. A. 68 25 5 196° . Russell Lee, Greencroft Hampstead, Gardana, London, H.W, 6, England. Dear Russ: I wrote regarding the possibility My present plans my being in Europe this summer and I to ha in London during pravide tcr my u;33. Martha, 28 from Juno to July 2 I abould tha five day period much be to able to spend an even: mg with you like very and would be pleased if you would set asida some time during these days. While I have a strong aversian to mixing business and pleasure, I beliovc I would liku to visit tho Mandalay. I knav or no on. thore diroctly, ind bcfore asking some of my friends from Englund who are new hora, I wandur it you arc su££iciently acqutintcd with tbs staff to bu able ta help an arrange a short visit? of \ Some months ago last littor. china; in tho hoapiul I huntud at hav. continued at a rupid rat. I think whan yau roturn to tho Stntos, 8 visit to Hillside should muko you proud to be tn tlumnua My best rugnrdu. which Since my the: Sincoroly yearn, Eu fink, uraan 21.15. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lee, Russell A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-155 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/6d8f05ad7a65dddf76662ee095b92e5e.pdf c7fd21934abe6025f3d89990977fede9 PDF Text Text December 23, 1959. Dr. A. Rueaell Lee, 68 Greeneroft Gardens, Hampetead, London, England. HAY. ' g 6, Dear Ruse: I was very grateful for your kind letter and invitation ea well as reprinte. Hex and Bob thank you for your consideration. We were pleaeed to read of your opportunity. We know if no finer institution for psychoanalytic etudiee than Tavietook Institute and congratulate you on taking advantage of what pronieee to be a fine educational experience. Back here, there have been many changes. Dr. Robbins has taken over and hie positive approach ie apparent to Do you recall the aany probleae in moving patients all. from the ward to the cottages and occasionally back again? In June Hort Waehepreee and my staff convinced Lew to create‘ a noonovenent ward in Lee I. Patients have been adaitted unit and have remained there for their directly to this This has worked out well and effective hoapital etay. December first the hoepital ie divided in eectione, each of which is a living space for patiente during their total hoepital stay. Alec, the hectic matter of adminsione and waiting liete is being modified, an that at preeent there in no waiting liet. In our own program, we have completed our convulsive therapy etudiee. We are now involved in a doubleublind fixed dosage schedule multiple drug evaluation program. This program has had a significant impact on everybody etatfl and patienta alike. So far, a few patiente have completed the initial study period and we are very enthuen iaetio. With luck, we should be able to say eouething intelligent about pharaacotherapy in 1962. �Dr. A. Russell Lee (Gentd) #2 is leaving to work pattern is about the eeme although, with the third your training program appravel in site I envieege some changes in attitude including a greater interest in fellowships. with By You may know that Bob Kehn Perlin in Hontetiore. Otherwise our stuffing I plan to be in Beale in July and, tine permitting, I should like very much to visit Tavieteck Clinic and also the Mandalay. I shell write to yet beforehand it I can make arrangemente. Hy beet wishes for the Rev tear. Sincerely yours, HFIJB � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Lee, Russell A. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-156 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/9f6bc317d665735cc49cb44f40d885d3.pdf 031ba58e63c2864e12bdad5247d091a3 PDF Text Text August 1, 1962 HERO To: From: Hrs. Groghen Dr. Fink Please continue to withhold salary amounts for annuity purposes until $1000 in available (Sept. 1). Thereafter issue full amounts due on basis of $25,000 per ennum. I shall notify you in late September regarding this annuity payment. Thank you. Sincerely yours, Hrtgp ex n , .D. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Croghan, ? Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-2-158 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/1a6e81f58866596a65b39d74c82882eb.pdf e5d2fa93fb4bb105ab27e4736d256bfd PDF Text Text January 3, 1963 Dr. Zdenek Bohdanecky c/o Research Institute for Pharmacy and Biochemistry Kourimska l7 Pfiaha 3 ” Vinohrady' Czechoslovakia Dear Dr. Bohdanecky: which you . Remember any I am enclosing the reprints requested in your letter of 1, 1962. present, we do not have available cepies of J. Hillside Hospital 1956 5:67, At and 6:197, 1957. Sincerely yours, MISSOURI INSTITUTE OF PSYCHIATRY Max Fink, Director M.D. MP:bk Encl. Please address all correspondence to: 5400 Arsenal Street, St. Louis 39, Mo. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Bohdanecky, Zdenek Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-4-159 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence http://exhibits.library.stonybrook.edu/mfp/files/original/1a301341ee893af342432ac1b6427be9.pdf 8711d72b75d66a0aae6b5188b91864b9 PDF Text Text meow-no: 5400 Arsenal Street St. Louis 39. Mo. January 7 , 1963 Dr. Nathaniel Sioqol Hillside Hospital P. 0. am: 38 Glanoaks, New York _ Dust Nat: What a nice way to begin the new your! First. Received a fem copies of Social Casework and was able to show the“ to tho swinl warn" that increasing my penitlvu rohtiomhip with them. Then. today Received the reprints on tho 30618101888 paper. haw mitt» to Bob, I nannies this on: of thu more vainable reports that we haw writtou in the put tom yous. Ivan quite A: i unhappy that the larger «pandas not been «calmed by a major psychiao trlc journal. Whoa 2- am Bob in New York he indicated that he had remind an “auction" . I haw mitten ta him asking for a copy (if that letter and {a his suggestions about thc next stop. I haw not rweivad a reply. I would b. grateful if you would call him and no if somathlng can be done to have that tarpon publish“. ’ the minutiae. I believe you should and a {no maples of this reprint from Social Problems ta Milt Guonblatt and Gardner Murphy. I! have some additional com” I would be qratdul fer a few more. In ‘ My best m with” to: the New Your. Sincaroly you", MISSOURI INSTITUTE OF PSYCHIATRY Max Pink. M. 1). Director Ml'ur � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Siegel, Nathaniel Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-017-4-162 Date A point or period of time associated with an event in the lifecycle of the resource 1962 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Correspondence