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. 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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. Spontaneous Seizures and Related Electroencephalographic Findings Following Shock Therapy, J. Nerv. 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. ABS-#87. Cohn, R. (l9h5): & EEG Psychiat. Study of Prefrontal Lobotomy, Arch. Neurol. 5;: 351—357. Denber, H.C.B. (1957): Discussion, Symposium on the Psychopharmacologic Approach to Schizophrenia, Second Int'l Congress of Psychiatry, Zurich. Fabisch, Effect of Chlorpromazine on the Electroencephalogram of Epileptic Patients, J. Neurol. Neurosurg;_& Psychiat. 29: W. (1957): 185—190. 10. Fink, M. Fink, M. Quantitative Studies of Slow Wave Activity Following Electroshock, EEG Clin. Neurophysiol. §: 158 (abst). and Kahn, R.L. (1956): Delta Activity to Quantitative Serial Psychiat. (in press). and Kahn, R.L. (1957): Relation of Behavioral Response in Electroshock: Studies, ll. . A.M.A. Arch. 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. (l9h6): Changes in Electroencephalogram and in Excretion of 17 Ketosteroids Accompanying Electro-shock Therapy of Agitated — Depression, Psychom. Med. Q: 2h6~251. 17. Jacobson, E. (1955): Suavitil, et Nyt Stof Med Specifik Virkning pa Centralnervesystemet, Ugeskrift for Laeger, 117: 1147—1151. 18. Khhn, R.L. and 19. Kahn, R.L., Graubert, D. and Fink, 20. Kahn, R.L., Fink, Fink, M.: 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. (1956): Relation of Amobarbital Clinical Improvement in Electroshock, A.M.A. Arch. Neurol. M. Test to Psychiat. & 21. M. 1g: 23-29. (1957): Changes in Languages During Electroshock Therapy, in Psychopathology of Communication, Grune & Stratton, Kahn, R.L. and Fink, M. (in press). (1957): Perception of Embedded Figures After Induced Altered Brain Function, Am. Psychol. 12: 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, M. Stratton. W. (1956): J. Hillside Epileptic States Following Electroshock Therapy, HOSp. 2: 258—263. �- 16 REFERENCES 25. Klotz, Incidence of Seizures, with (1955): M. Prefrontal Findings, in Psychiat. 1E: EEG Lobotomy, A.M.A. Arch. Neurol & Ink—1&8. 26. and Kwalwasser, S. (1956): Relation of Changes in Memory and Learning to Improvement in Electroshock, Korin, H., Fink, M. Conf. Neurol. 16: 88-96. 27. Kwalwasser, S. and Caplan, M. (1952): A Case of Prolonged Insulin Coma: Treatment, J. Hillside Hosp. 1: Ins-155. 28. Liberson, W. EEG T. (1956): Effect of "Tranquillizing" Clin. Neurophysiol. Drugs on EEG, 8: 523. (1957): The Occurrence of Epileptic Fits in Leucotomized Patients Receiving Chlorpromazine Therapy, J. Neurol., Neurosurg., & Psychiat. 29: 105-107. 29. Liddell, 30. 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. 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