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Dear Dr.

Please find enclosed for your review and transmission 7 lan unsolicited proposal entitled, "Psychophysiologic ond Verbal Correlates of Altered Consciousness during Amytal Interview."

The proposed research will correlate electrophysiological, psychologicol ond verbal meosures of both patients awaiting trial ot the male psychiatric prison word of and nomal control subjects

in the amytal interview situation. It is believed that the approach described in the proposal will further elucidote the effects of omytal with regard to behavioral aspects of emotion, deception, ond memory.

A starting date of October 1, 1966 (olternate November 1, 1966) with the project to extend for one year is reguested; two additional years ore recommended. Direct cost support in the amount of \$. is requested for the first yeor, estimaled budgetary requirements are \$ for the two succeeding years. The principal investigotor is and the co-principal investigotor is

I may be contacted ati

August 18th,\_1966. Dr. recording of

Il will be out of the United States from July 28th through is currently studying techniques of eye movement

His temporary residence address is.

Your consideration in this matter is appreciated and I lock forward to a favoroble reply.

Sincerely yours,

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jJune 15, 1966

EASEDSEP 1083

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PSYCHOPHYSIÔLOGIC AND VERBAL CORRELATES OF ALTERED CONSCIOUSNESSOUPY A

and

ABSTRACT

The proposed research is on'experimental exploration of altered consciousness during on omobarbiiol interview in order to more accurately define and evaluate clinicolly observed chonges in verb behavior. Hypotheses bosic to this research and derived from several years of clinical experience with amytal interview on the lare: (l) The primary and predom nant effect of intravenous amytal is on "anxiety-tension" and the usually associoted constriction of aff (2) While imminent and focol issues of the patient's ottention (e.g., the crime for which he awaits trio malingered hemiplegia, etc.) remain particularly impervious to the effects of omyial, more peripherol material is dealt with in greoter detoil, elaboration and indescretion as though the patient were confrc ing the material without constriction or coution due to oppropriote opprehension pre-programmed under stress prior to the amytal interview, i.e. the subiect consciously or unconsciously decides how to deal with cerfain questions before the interview. (3) Amnesio for the contents of the interview may be due to an impairment of "consolidation" processes of memory ossocioted with disconjugate eye movements. Experimental and cont ol subjects will be selecled from patients ot the male psychiatric prison word of

Additional control subjects will be recruited from the student pop

lation at} Psychiatric interviews ond psychological tests will be employed to evaluate personality structure, anxiety levels, intelligence, and suggestibility of the subjects. Verbal responses will be recorded to equated word association, biogrophical dota, and test questions before, during, and after amytal interview odministered in a double-blind control proc: Electroculagruph, EEG, and GSR will be monitored and correlated with the interview ond verbal test material. Verbal responses will be evaluated against independently verifiable control materiol, psych physiologic and psychslogical variables in a double-blind fashion.

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1. RESEARCH PLAN

A Introduction

(1) Current status of work in this area

Intravenous sodiumamytal hos long been observed to exert a significant influence on an individual's mental state. The mnost dromotic effect wos the tempcrary resolution of catatonic stupor in schiz ophrenia and reoctive depression (Blockween, 1930; Lorenz, 1932). As "amytal interview" introveno amytal has fomed the basis of special diagnostic and therapeutic techniques, "Narcoanalysis" (Horsley 1943), "Narcosynthesis" (Grinker & Spiegel, 1945). Underlying principles ond theoreticol basis in regord to clinical application remain obscure. At the same time its established clinicol use over the past thres decades enables one to avoid unexplored phomacologic pitfalls.

Many early theories exploin Jhe effect of omytal bosed on Hughling Jockson's concept of the release of lower centers resulting in "releose of unconscious materialos in dreans" Hemon (1938); Delay (1949). attempted to give this a structural basis by claiming that omytol narcosis "led to a tempc ory depression of activities of corticol cells". Lindemann (l932) stated thot the drug in turn pemittec an "increase in neurophysiological activities in older parts of the broin". Freed (1946) felt thot the release of strong affects occurred frequently enough to justify the localizotion of the site of action to the diencephalon. Grinker (1945) also suggested that the action was on the diencepholon, and was depressive in nature, so thot anxiety producing impulses "no longer bombord the cortex". Kubie & Morgolin (1945) agreed Mat the drug by its "psychologically analgesic" oction lessening the potient': need to defend protective symptomatic structures permitted exploration of poinful areos of experience which had been repressed. Masserman (1958) stressed the commonality of the action of amytal and ot drugs, ond concluded, "there is no doubt ihot alcohol, morphine, barbiturates and bromides and most so called ataractics, and similar drugs used in 'psychophammocologic doses' oct as corticol depressant cousing impoiment of finer perceptions and discriminations, constrictions of the interpretive field an progressive disorganization of adaptive responses". Weinstein (1954) sow the shift in behavior as "ch in symbolic expression" representing an adoptive and more effective defense in a situatien of greater stress. Brickner (1954) felt that verbal moterial elicited under amytal wos os systematized os ony oth. mentation and demonstrated underlying mental mechanisms of froctionalization, reuniting and compa words. These underlying verbal structures were not generally evident in the waking state.

Gottschalk (196:) summarized the effect of barbiturates on human behovior as characterized "(a) decreased attention to stimuli; (b) warmer, more appropriate mood; (c) decreased anxiety; (d) increased contact and communication; (e) reduction of psychotic manifestation". Despite the work of Meuhlberger (1951) and Lorenz (1932), Gerson and Victorafi (1948) demonstrated the fallibi of amytal as o truth serum.

Recent experimental investigotion has revealed that the affective changes due to amytal ore readily meosurable with a stondardized roting scale technique (Trent, 1962). Likewise, no evidence been found for specific dr general effects of differing pentobarbital dosages on six different meosure (pausing time, tolking time, total elopsed time, fluency, total power, and mean pitch) of vocal bel (Starkweather and Hargreaves, 1964). Moreover, although Chlorpromazine affected pausing time ar related verbal content, Amytal had no selective effect on these constituents of spontoneous speech (Goldman-Eisler, 1965). Nonetheless, it is imporont that Amytal was found to increase the subjec certainty of recall in the perception of geometric figures (Brengieman, 1958). Kelley, et al, (194 using Amytal as an aid to the Rorschoch methad found an increase in the number of responses ond le constriction and sterotypy. Sato (I962) examined students under Amytaland found increased produc

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in affective responses on the Rorschach while the GSR revealed diminished levels of cutonomic excitement. Miller (i964) studied:. escope ond avoidance in rots and altributed the behavioral effect of Amytal to a "differential effect on the fear mechanism". The findingi of the obove studies as well as our own clinical impressions suggest that Amytol influences behavior by a reduction of "anxietytension."

(2) Rationale of approach to problem

It is well known that the evaluotion of drug effects is difficult due to individual differences in 'psychological, biological, physical and social status. Thus, the dosage administration of drugs usuall. is regulattd by the physician according to the potient's response. In general, the omobarbital intervic has been conducted on the bosis of the clinician's skill in monitoring and detecting the potient's state - consciousness. It is proposed here that psychophysiological responses during amobarbital interview ma: index the patient's offective-cognitive status.

The general hypothesis of this proposal is that intravenous amytal offects behavior through the mitigation of anxiety and an alleviation of tension. An independent meosure of the drug effect on the level of consciousness is required. Shogass (1954) introduced measures of EEG ond behaviorol response os indicators of sedative tolerance. However, other investigators have reported difficulty in detemin the sedation threshold occording to Shogoss' criterio (Ackner & Fampiglione, 1959). More recently, t inhibition of the galvanic skin reflex by sodium thiopental has been demonstrated to indicate both sed and sleep thresholds and differences in these measures between psycirotic ond psychoneurotic depressec subjects (Perez-Reyes, Shands, ond Johnson, 1962). It would seem pertinent to employ the GSR in ad tion to the EEG os a monitoring response during the amytai interview.

Current research on dreaming has produced definitive data linking eye movements to dream material (Kleitman, 19ć3). Likewise, the subject's lock ofattention to the environment associated with reverie has been related to the oppeorance of wandering eye movements during conditions normally eliciting a vestibular nystagmus (Wendt, 1941; Collins, 1963). Ront ond Mozzia (1965) found thr disconjugate eye moverr ents occurred during anesthesia and were correlated with o loss of memory for pictorial material. Westheimer and Rashboss (196l) provide evidence thot borbituates interfere with eye vergence movements. The value of using eye movements to ascertain the patient's altered state o consciousness in the amytal interview must be explored. Aport from the possible relation to the verba qualitotive spects of the potient's altered state of consciousness, eye movement monitoring may also provide an effective index of both sedation and sleep thresholds. In summary, the psychophysiologica variables in the proposed reseorch on the amobarbital interview are the galvanic skin response (GSR), electroencephalogram (EEG), and electroçulogram (EOG).

Another aspect and the primary focus of this problem will be in the delimiting and characterization of altered consciousness. Artusio, (1955) has shown that there is o slage during ether onesthe: at which patients ore unable to fomm new memories although their mental function is intact os measue by responses to spoken words, prablem solving, old memory, etc. This area has been traditionally handled through clinica! interpretation of the patient's verbalizotions vis-à-vis the interviewer's quer Gottschalk (1961) emphosized that different methods of sampling the verbal behovior of a subiect und drugs may give somewhat different information about the psychopharmacologic effect of the drug. In order to obtain additional evidence of both affective and cognitive changes, it would be appropriate employ a standardized verbal test, in equated forms, previous to, during, and following the omytal interview. The earliest used and most fruitful verbal test has been that of word association (Woodwor 1938). Responses in word association tests are regulated by both affective and cognitive processes. T

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proposed study will e:nploy a stondard free association test ond a special voriant. In the fii:t, stimuli word lists will be prepored from esloblished noms (Palemo & Jenkins, 1964) into sets motched for associative "preference" (Moran, et al., 1964). In the second, both stimuli and responses are availc in a forced-choice item. A more complete description of these tests is presented below in the proced section.

An important aspect of our project is the "non-loboratory" subject. In essence, the ortificiali of experimental work with contrived and difficult to manage laboralory stress is absent. The experime subjects are to be selected from anong those indifed foç serious charges under observation at the psycl Pric prison ward of These subjects are living under realistic stress of overwhelming personal significance. The immense annual admission rate of 1500 pemits selection. the "higher-caliber", cunning criminal without gross personality deteriorotion or psychosis.

The approach to the evoluation of the subject's state of consciousness during amytol interview consists of: (a) subjects under real-life stress, (b) psychophysiologicol indices of EEG, GSR, and e movements, (c) psychological tests of personality, anxiety, intelligence and suggestibility, (d) ps) tric-clinical interpretation of the subject's state of consciousness, and (e) interview and word associc tests to index affect and content of thought processes.

(3) Specific Aims

a.To explore cognitive and affective verbal patterns in individuols under stress during altered states of consciousness resulting from intravenous amobarbital.

b. To corre'ate-and monitor alterations in consciousness os indicated in verbal responsiven under intravenous amytal by πieans of EOG, EEG, and GSR.

B. Methods of Procedure

(1) Subiects

The experimental subjects for this project will be the patients of the male psychiatrie prison of These subjects will be selected ot random to include 20 crimir 16 years or older, ot averoge of beffer intelligence and without overt psychosis. The first control gro will consist of 10 criminals, opproximately matched to the experimental group as to oge, alcohol or drug oddiction, and piychiatric diagnoses. Concomitantly, a second control group consisting of 10 paid, nommal volunteer subjects will be recruited fram the student population at

personnel office. Fifteen subjects, the first control group and five of the second control grcup, will receive, independent of the experimenter's knowledge, only soline du the suppcsedly amytal interview. It is planned that the study should continue for three years to comp! a totol sample of 120, i.e. 60 experimentol and 60 control subjects.

(2) Apparatus and lests

a. Psycholpgical Variobles. All subjects will be initially screened ani evoluated olong th following dimensions: (1) Personality chorocteristics interpreted from the Minnesota Multiph Personality Inventory (MMPT) on the clinical scales (Hathoway & McKinley, 1951), (2) Anxi level estimated From the Taylor scale of manifest anxiety (Toylor, 1963) and the IPAT-8-pora fom anxiety battery (Scheier & Cattell, 1960), (3) Intellectual functioning as mcosured by

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Wechsler Adult Intelligence Scole (WAIS), ond (4)Suggestibility tendencies os indicated by the Borber Suggestibility Scole (BSS) with both objeclive ond subjective scores (Barber, 1965).

b. Psychiatric interview-- This procedure involves a relotively exploratory, dynamicolly oriented, and open-end interview designed to elicit matcriol on the person's basic personolity paftern os well os materiol related to recent events leoding to his crime and hospitalizotion on the prison word. Interviews with control subjects will be aimed at the evoluation of their basic personality orgarization and their response to stress as altered by 1.V. amytal. All inter .views will be toped, transcribed, and then evaluated in light of corroborative materiol from eye witness accounts, arresting officer's report, parole and trial records. Control subiect materiol will be assessed along similor personality dimensions by three independent raters.

c. Word association tests-- Two different types of word associaticn tests will be used, namely free association and binary forced-choice. In the free associotion lest, critical words relating to the subject's recent crime ord/or oreas of personality conflict will be interspersed with standard "neutral" stimuli. Measurements will be made for response latencies, thematic content, ossociative "set" or preference, and commonality.

The binary forced-choice association test is designed to measure individual differences in semontic hobits os different from syntoctic or relotional ossociation hobits (Nunnolly, Flougher, and Hcdges, 1963). Four types of choices, evaluative-good (pleosant words), 'evoluotive-bod (negative words, eg. ugly, sour), denotative (ottributes, eg. long, sharp), and categorization (classificatory, eg. reptile, coed) are combined into subscoles. For example, contrasting the evaluative-good and the denototive tendencies, Orange: sweet round In this manner individual differences in the use of different modes of semantic response to objects in the human and moterial environment are measured. The test instrument subscoles os now constructed have Kuder-Richordson formula 20 reliability coefficients ronging from .62 to .79. Measurements will consist of scores obtained on the combined evaluative and the cafegorizationdenolative balance scoles.

d.Examination rooms - Amobarbital interviews will be conducted in the seclusicn room on the male prison ward at 1

e. Psychophysiologizal Variables - These voriables will be recorded on a six-channel polygraph. Four channels will be used for EOG in the detemination of eye movements by use of periorbitally placed surface electrodes. Electrodes will be located on eoch eye at the outer and inner conthus for horizontal movement and directly obove the supraorbital margin and below the infroarbital ridge for vertical movement. The electrodes wili be of the nonpolarizable silver chloride type. One channel will be used to record the galvanic skin response. Silver silver chloride electrodes with a starch pasle of 0.05 N sodium chloride solution will be used in measuring the GSR (O'Connell, et al., 1960; Edelberg & Burch, 1962). The opparent electrical resistance to an applied current of 8 microamps/cim?: between the palm ond the forearm reference site will be continuously recorded. The EEG will be monitored with a monopolar occipital electrode orrangement. These variobles will be synchronized with the verbal material through the use of voice operated relays and event markers.

(3) Procedure

The experimerita! subjects will be allowed five days to adant to the ward tanimn in-- l-

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psycho!ogical tests, psychiotric interview, ond word ossociation fests. Within Ihe following week the amytal interview will be conducted. with preselected material, equo'ed for particulor relevonce, that earlier was or wos not directly probed for by the interviewer.

The subject will recline in bed and be prepored for EOG, EEG, and GSR recordings thot will be taken throughout the test period. After on initial rest period of five minutes, a continuous drip of nomal soline solution will start. A second five minute period will elopse to allow the subject to accommodate to the needle in his arm. During this interval, an eye Fixation test ond on abbrevioted form of the binory forced-choice word ossociotion test will be administered. The eye fixation test will requi e the subject to fixate successively illuminated targets at voried but preset degrees of seporotion in horizontal, verticol and intemmediate loci from a centrol reference point of fixotion. The word ossociation test will corsist of a randomized somple of items from the subscales of the binary forcedchoice test. At the end of this interval, a 2-1/2% sodium amytal solution will be injected ot the rate of l.ócc/minute. Or, in the case of certoin control subjects, the normol soline will continue and no amytal will be introduced.

The omytal solution will be started without the subject's knowledge. Concurrently, the subjec will be interviewed as to standard clossificatory information, eg. oge, residence, occupotion, etc. The interview will continue until clinicol signs of altered consciousness, eg. slurred speech, affective appear and the non-specific or spontaneous GSR octivity has chonged. This lotter event is regarded a indicotive of the drug effect threshold. The administrotion of the drug will now:be, slowed to maintair wokefulness in the subject. The subject vill now receive taped word association tests (free and binary forced-choice) for a 15 minute period, and eye fixation tests before, between, and after the word associotion tests, Material for roall following the is r:view will be presented to the subjectrcorefull " timed intervals with reference t the presence of d.onjugate eye movements. A concluding.interview of about 10 minutes will attempt to elicit material of particular relevonce to the ir dividual's psychiatric-legal status, The entire session will be completed between from 45 to 60 minutes. All ve responses and interview materiol will be tope recorded for subsequent onalysis.

The control subjects will receive identicol tests. However, in the cose of,the nomal volunte group, no ward odoptation time will be scheduled although the same testing intervals will be maintai: These subjects will be interviewed with respect to specially prepared factual material ond items of pe sonal informotion to be withheld unknown to the experimenter. Motivation of the subjects will be re lated by combinations of aversive consequences, eg. electric shock to the leg, decrements in moneta compensation. Standordized instructions and procedures will be used to control for ony bias due to su ject-experimenter relations and other social voriobles.

Test data will be treated by the following methods: Interview data will be summorized and t lated according to topics and stenotyped for independent rating of categories and affective content t qualified stoff psychiatrists. Topic categories will be divided between spontaneous ond nonspontonec moterial relevont to central or focal issues ond peripheral matters. Further subdivision will be made based upon detailed scrutiny of the obtained dato, fitting such topics os illegal actions, sexual beha social relationships, elc. into standord units of subject matter, orientotion (pro, con, and neutral), standards and values (premises of moterial), traits and subjective states (feelings). Each topical recc will be checked for completeness, comprehensibility, consistency, uniformity of coding units, and inappropriate responses. All stotements will also be classified as to factuol, preference, and identif nature. Numerical ratings will be made of the coded stalements as to the intensity of offect and the degree of closeness to focal issues. Amenoble data will be transformed to mutually exhaustive classc coded, ond key punched for computer handling. Response profiles of psychological test scores, wor associations, GSR octivity, (nonspecific and stimulus-elicited), EEG measuresand eye movement

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parameters for individual subjects and distributions of these variobles for greups and total somple studied will be prepored. Correlational procedures ond where indicaled multivariate analysis of varionce and covariance will be corried out to establish the significance of findings. Comparisons will be made between the nondrug and amytol dala wilhin individuals and within and between the experimental and control groups.

Particular attention will be given to the onalysis of eye movements during oltered stotes of consciousness. This measure wili be exomined for chonges in the rate and sequence of spontaneous and smooth tracking movements, the incidence and frequency of fixotion change ond blinking, the coincidence of "type" of eye motion with specific emotionally toned interview material, the quolity of directed eye vergence motions during target fixation tesls, -and the variolions in binocular coordination (conjugale and disconjugate movement). Since preliminary tests have revealed that, visually observed, disconjugate and divergent eye movements are associated with amnesia, it is planned to incorporate real-time data reduction of this variable by an analog signal correlotor after further confimatory testing. The experimental design as described obove is schematically giver in Figures I and 2.

Significance

The results of these studies will odd to bosic knowledge on the mode of interoction between anxiety and thought as expressed through verbal productions. This has for reoching implicotions for the theoretical con cepts of psychotherapy. An opportunity will be aforded to fest' clinically derived postulates formulated on the change of behavior under intravenous omytal and related drugs. In por ticular, a significant evaluation of the use of amytal in eliciting informalion during interrogation will be obtained. Standardizotion of these techniques will permit their application ond comporison with the effects other phammacologic agents havè on verbal responses. Particular phenomena such as the dramat resolution of catatonia and stress inducted stupors will be further elucidated. Predictive methods to assess potential for explosive assaultive and homicidal behavior of hcbitual drug and olcohoł users will be explored. This is of limely importance in view of the fact that fuily half of the currently recorded homicides are associated with drug or alcohol use.

Facilities

The general ward facilities of the

lis in charge are ovailoble for these studies, Included are personnel familiar with handling patients under stress as well as ossisting in patient care during amytal interviews. Appropriate neuroradiologicol and electroencephalogrophic studies of selected patients are performed os part of hospital care. In addition to the usual equipment and medicotion necessary for patient care there is available two Norelco tope recorders with special booms and microphones for recording the patients' production: during an amytol interview and foot pedal for transcribing afterward, There is also a Gray Audograph and Dictaphone to assist in handling the detailed biogrophical material.: Office and loboratory space are provided by the 1

sultation and use of their equipment and personnel. Dr.
of Anesthesiology. has also offered the use of his focilities.

is avoiloble for con-Chairman of the Departme

General facilities at are available for control ospects of these studie Office and laboratory spoce are provided by the Deportment of Psychiatry. Reody access to consultati with experts in electroencephalogrophy in the Deparlment of Neurology ond liason octivities with the Department of Physiolagy and Phamocology exist. The Department of Biomedical Engineering is avai

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IST.UMENT

Psychological

Profile and Standard score

ler Scale and IPAT Lattery

Standard Scores

∴IS

IQ;verbal;performance

Barber S. Scale

Objective and Subjective Scores

Verbal Behavior

nesota and Navy Tests

Commonality,Probability, Content,Latency

lunnally's Scales

Evaluative,Categorizing, and Denotative Scores

Psychiatric Interview

Categorized .Topics, Content Anabysis,Intensity and Relevancy Ratings

Psychophysiological

Polygraph

Wave pattern, alpha

Recoráings

conjugate-aisconjugate, fixations and blinks,quali of vergence,sequence and rate of tracking movements etc.

conductance units,latency, amplitude changes,frequenc of nonspecific responses

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FigUre 2. EXPERIMENTAL SEQUENCE AND DATA ANALYSIS

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for consultation and limited use of voried equipment, e.g. anatog computer. A Tandberg tape recorder, microphones, Edison Voice Writer, and office equipment are avoiloble for use through the Sub-Department of Behaviorol Sciences. A compuler unit and services are present for data reduction and analysis. A six-channel Grasspolygraph:with oppropriate preomplifiers is\_availotle, on a loen bosis from the Department of Neurology, for use with the control subjects ot i

1lSupporting Data

A Previous work

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References

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Horsey,J.S.,Narcoanalysis,lS43,London,Oxford Nedical Publicatior

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Page 14 Shagass,C., A sedation threshold:A method for estimating, tension in psychiatric patients, EEG and Clin. Neurophysiol.,l954,6, 221.

Starkweather, J.A. and Hargreaves,W.A., The influence of sodium pentobarbitai on vocal behavior. J.Abn.Soc.Psychol.,1964,69 (1), 123-126.

Taylor,J., A personality scale of manifest anxiety, J.Abnorm.
Soc.,Psycho1.,1953,48,285-290.

Trent,C.,Changes in the Clyde Mood Scale produced by a sleep threshold dose of amobarb1tal. Psychopharm.,1962,3,468-472. Weinstss- ,1,5,408-472.

Weinstein,F.A. and Malitz,S.,Changes in symbolic expression with amytal sodium, Am.J.Psychiat.,1954,III,198-206. LA-LL

Westheimer,G.,Rashbass,C.,Barbiturates and eye vergence, Nature,1961,191,833-834.

Woodworth,R.,Experimental psychology. 1938,New York:Holt.

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BIOGRAPHICAL SKETCHES

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BIOGRAPHICAL SKETCHES -

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BUDGET ESTIMATE FROM OCTOBER 1, 1966 (ALTERNATE NOVEMBER 1, 1966) THROUGH SEPTEMBER 30, 1967 (ALTERNATE ÓCTOBER 31, 1967)

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DIRECT COST BUDGET ESTIMATE FOR FIRST YEAR AND CONTINUATION OF PROJECT

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ADDENDUM TO

PSYCHOPHYSIOLOGIC AND VERBAL CORRELATES OF ALTERED CONSCIOUSNESS

All reseorch carried out in this project shall include signed stotements of.

informed cunsent by the subjects and also provide for confidentiality of doto. These

procedures will be carried out according to the standard policies of both

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