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Rosenfeld Anne H.; Rosenfeld, Sam A.The Roots of individuality: Brain Waves andPerception.National Inst. of Mental Health (DREW), Rockvi le,Md. Div. of Scientific and Public Information.DREW-ADM-76-3527629p.Superintendent of Documents, U.S. Government PrintingOffice, Washington, D.C. 20402 (Stock No.017-024-00540-1, $0.45; There is a minimum charge of$1.00 for each mail order)

MP-$0.83 RC-$2.06 Plus Postage.Adults; *Electroencephalography; ElementaryEducation; Exceptional Child Research;*Hyperactivity; *Mental Illness; *Neurology;*Perception; Psychosis; Schizophrenia; *StimulusBehavior

ABSTRACTDescribed is research using computer techniques to

study the brain's perceptual systems in both normal and pathologicalgroups, including hyperactive children (6-12 years old). Reviewed arethe early studies of A. Petrie, M. Buchsbaum, and J. Silverman usingthe electroencephalograph to obtain AER (average evoked response)records of schizophrenics. The use of the AER to investigate how thebrain reacts to changes in stimulus intensity is explained.Summarized are major findings concerning AER abnormalities in_schizophrenics, manic-depressives, pure depressives, hyperactivechildren, and in normal behavior. It is proposed that stimulusintensity control serves as an adaptive protective role in the faceof potentially excessive stimulation; that schizophrenics might berepresenting this adaptive tendency to an exaggerated degree; andthat hyperactive children who improve with drug therapy are thosewho, prior to treatment, have the most abnormal AER patterns.(SBH)

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National Institute of Mental Health

The Roots ofIndividuality

Brain Wavesand

Perception$ DEPARTMENT OF HEALTH.

EDUCATiON A WELFARENATIONAL INSTITUTE OF

EDUCATION

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U.S. DEPARTMENT OF HEALTH, EDUCATION. AND WELFAREPublic Health ServiceAlcohpl, Drug Abuse, and Mental Health Administration

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Investigato1 Monte S. Buchsbaum, M.D.Adult Psychiatry BranchDivision of Clinical and Behavioral R e-rchIntramural Research ProgramNational Institute of Mental HealthBethesda, Maryland 20014

Authors: Anne H. and Sam A.

Date of Inte vie October 1975

enfeld

Mental Health Studies and Reports BranchDivision of Scientific and Public InformationNational Institute of Mental Health5600 Fishers LaneRockville, Maryland 20852

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FOREWORD

The brain has been an enigmaat times inscrutabk, attimes divulging minute Nts of information that act as'teasers," encouraging scientists to pursue elusive answersand experimental investigations. Now technological advanceshave enabled researchers to unearth information about thebrain that heretofore was imp ssible.

This monograph describes a research program, being con-ducted in the National InstitUte of Mental Health's intramuralresearch laboratories, that utilizes computer techniuues toextract responses of the brain's perceptual systems from sur-face electroencephalographic recordings. By presenting shortbursts of light and noise ranging in intensity from weak tostrong and by studying the brain's activity, the investigatorhas found marked differences between people's responsesbe-tween men and women, hyperactive and normal children, pain-tolerant and pain-intolerant persons, and between variousgroups of psychiatric patients.

The research has also identified abnormalities of perceptionand attention, suggested that treatment effectiveness for somemental illnesses can be predicted at a pretherapy stage, andconfirmed signs of clinical improvement in patients undergoingtherapeutic intervention.

This report exemplifies still another NIMH research en-deavor to sharpen our knowledge of the dynamics of humanbehaviorhow our environment can affect each of usandis important because it provides insight into some reasons forour actions.

Bertram S. Brown, M.D.DirectorNational Institute of Mental Health

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The Roots ofindividuality:

Brain Waves andPerception

At the core of medicine is an elaborate typology of humandifferences that forms the basis for diagnosis and therapy.As biomedical research progresses, these distinctions are re-fined, with increasing emphasis on particular characteristicsand functions underlying clinical differences among patients.

A physician-researcher at the National Institute of MentalHealth, Dr. Monte Buchsbaum, has tor many years been fasci-nated by the differences in the ways people react to senserYstimulation. As he put it:

Clinical practice in an emerp-er..y room quickly dramatizes individualdifferences in pain tolerance. I rsi.lember a Swedish carpenter who, de-clinMg analgesia, stoically allowed n.e to dig out a splinter from under hisfingernail with a scapel as he gaily discussed basebzdl. Holy men rest ontheir beds of nails; Lesch-Nyhan patients mutilate themselves; rockgroups blast listeners with sounds above normal auditory pain thresholdall of which raises the question: Hoy, do combinations of experiential andneurophysiological mechanisms work together to produce these variationsin tolerance of extreme intensities of serksory input?

During the past decade or so, Dr. Buchsbaum and many co-workers joining him in his unprepossessing but well-equippedlaboratory in Bethesda, Maryland have attempted to probethe brain's response to sensory input. Out of their researchhas come a better understanding of the differences between

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many groups of individuals: schizophrenics and normals,manic-depressives and pure depressives, men and women, chil-dren and adults, pain-intolerant and stoic individuals, bothnormal and pathological. These studies have also suggestednew diagnostic tools for several types of mental_ illness andhave given some clues to the aberrant brain mechanisms ac-companying these conditions.

Measuring the Brain's Responses: BackgroundThis research has focused on comparing differences in peo-

ple's reactions to the same stimuli and attempting to account:for them.

The approach combines techniques of several disciplines.Like an experimental psychologist, Dr. Buchsbaum studieshow people react to controlled little fragments of sensorystimulation, such as shoit bursts of light or sound. But insteadof scrutinizing people's observable behavioral resronses (al-though he will sometimes do that, too), with his colleagues,both humans and computers, he pores over brain responsesrecorded by the electroencephalogramor EEG. Were it notfor relatively recent advances in computer technology, the_sestudies _would be impossible because the tiny electrical mes-sages the brain emits in response to sensory stimulation("evoked responses" or "evoked potentials") could not bedetected amid the roar of the rest of the brain's ongoingactivity.

Ever since 1924, when the German psychiatrist HansBerger first put electrodes on the human scalp and tried to

ad the brain's electrical messages in the almost illegiblescrawl of the EEG, scientist; had been simultaneously chal-lenged and frustrated by this tantalizing clue to the humanbrain's responses to the outside world. Clearly, the brain'selectrical activity, as reflected in the EEG, must be affectedby events in the external environment. Even Berger knew thatloud noises would change ongoing electrical activity. But thechanges he saw were slow and inconsistent shifts of EEGrhythm, and not the clean, repeatable response patterns sci-entists love to work with. The EEG gradually became an in-valuable diagnostic tool for clinical neurologists, providingconsistent and identifiable patterns associated with epilepsy,brain masses, and other neurological disorders. But scientiststrying to identify evoked responses in the EEG were stymied;finding evoked responses was like picking out the ripplesstirred by a pebble thrown into an angry tossing sea.

Researchers interested in the basic question of how thebrain responds when the senses are stimulated could not get

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a satisfactory answer using the EEG technique until, in theearly 1960's, rapid progress in computer technology provideda simple way to detect evoked potentials: "signal averaging."By aggregating or averaging many EEG records odividual's evoked responses to a given sensory --.3timulus \vaspossible to make the relatively small ripples of evoked re-sponses stand out against the sea of background activitynow mathematically calmed b the averaging process. Theevoked response. now an uvera e evoked response" or AERas it is commonly calledwas tin Ily visible and availablefor study.

In the 19(10's, .as relative!y ine:pensive spot -e com-puters became more or less commonplace in neurophysiologi-cal and psychological laboratories :only to be replaced by ovenmore useful, 0.20nomical, and programable general-purposecomputers), many scientists became intrigued with the A ER,testing out and describing people's brain responses to all kindsof stimuli. Dr. Monte Buchsbaum was one of these. Afterhearing of some provocative behavioral findings by Dr.Asenath Petrie. an English psychologist, Dr. Buchsbaum torn-ed to an exploration of brain activity evoked by changes injust one dimension of sensory stimulitheir intensity.

Dr. Petrie had found consistent differences in the way cer-tain people performed on a standard perceptual task (Kines-thetic Figural Aftereffect, or KEA). Asked to judge the sizeof a standard bar after feeling other bars of different- dia-meters, some normal subjects repeatedly overestimated:others repeatedly underestimated. Dr. Petrie called the over-estimators "augmenters"; their opposites were dubbed "re-ducers." What made Dr. Potrie's experiments particularlyinteresting was her finding that these perceptual tendenciescarried over to another, somewhat unexpected, sensory di-mension. Dr. Petrie found that on a pain-tolerance test, thosewho had been "reducers" on the NFA test tended also to min-'mine pain stimulation: they were "Dv:in-tolerant." By con-trast, the KEA augmenters were prone to exaggerate painstimuli and were considered "pain-intolerant." That is, a shockto the arm that a reducer might stoically rate as "mildly un-pleasant" might be rated as "painful" by an augmenter. Dr.Petrie and others believed at the time that reducers' pain toler-ance reflected an overall tendencv to diminish the intensity ofall incomirw stimulation, regardless of the senses involved;some central nervous system mechanisms seomed to be regu-lating the level of sensory input.

About the same time that Dr. Pet ne was ,xploring thesensory reactions of normal subjects, Dr. Julian Silverman,another psychokwist, kk its using the KVA perceptual test with

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schizophrenics, trying to understand how distortions ofsensory perception in schizophrenia might affect and reflectschizophrenics grossly altered views of reality. He and othershad found that most schizophrenics were extreme reducers onthe KFA task. On the basis of this and other evidence, hesuggested that stimulus reduction by schizophrenics reflects"stimulus intensity control"the action by some internalneurophysiological mcc:hanism to regulate the degree ofsensory stimulation.

A collaborative effort by Drs. Buchsbaum and Silvermanprovided the opportunity to explore stimulus intensity controlii schizophrenicsbehaviorally, using the KFA test, andelectrophysiologically, using the AER combined with othertests of perception. One major finding by these investigatorswas that schizophrenics, who are generally extreme reducerson the KFA test, are also "reducers" neurophysiologically;that is, their brain responses (as measured by the AER) de-creased somewhat in size (amplitude) as stimuli became moreintense. This AER pattern differs from that seen in normalsubjects, who generally tend to show increased Ali Rs (greateramplitude) when stimulus intensity increases.

On the basis of this and other findings, these two investi-gators proposed what has been referred to as the "Buchsbaum-Silverman hypothesis": Stimulus reduction among schizo-phrenics probably reflects a self-protective mechanism to pre-vent excessive sensory stimulation. Schizophrenics may pro-tect themselves from high-intensity stimulation because theyare already loaded (or perhaps overloaded) with low-levelstimulation, to which they are particularly sensitive.

The Buchsbaum-Silverman hypothesis represented a de-parture from Dr. Petrie's earlier speculation. She thoughtthat stimulus reducers minimized stimuli at all levels of in-tensitv; the Buchsbaum-Silverman hypothesis suggested thatreducers only minimize relatively high-level stimuli. This issuewas examined experimentally through another study. If theBuchsbaum-Silverman hypothesis was right, schizophrenicsshould be extremely sensitive to low-intensity stimulation; infact, they should he able to perceive sensory stimuli othersmight miss (subthreshold stimuli). The prediction was con-firmed experimentally, but other studies have presented amixed picture of this sensory sensitivity. Supportive evidence,however, arose from a somewhat tangential direction. Studiesof people exposed to environments with minimal sensory stim-ulation (which can cause discomfort and hallucinations) hadshown that those who were pain-tolerant were better able toendure sensory deprivation than those who were pain-intoler-ant. Since p4On-tolerant individuals tend to be reducers and

9 5

reducers tend to be sensitive to low-level stimulation, thesepeople seemed to be able to -feed" their nervous. systems atleast some paltry stimulation from subtle little environmentalcues; the pain-intolerant augmenters, on the other hand, un-able to perceive the.se tiny scraps of stimulation, essentiallysuffered -sensory starvation" in the same impoverished en-vironment.

The early collaborative studies of Drs. Buchsbaum andSilverman convinced Dr. Buchsbaum that the AER was auseful approach to studying brain events evoked by sensorystimulation. For almost 10 years he has studied stimulus in-tensity control in normal and abnormal subjects, uF,ing theirAER records as evidence of underlying characteristics andconsistent perceputal styles. In some ways Dr. Buchsbaum islike a naturalist, hunting down and netting AERs as lepidop-terists lunge after rare butterflies, pinning them down, anddescribing their special identifying characteristics when com-pared with either run-of-the-mill butterflies or with certainexotic types that closely resemble them. But Dr. Buchsbaum'spursuit is more abst,-act. He is studying the shape of an ab-straction (average) of an abstraction (EEG) of unknownevents that occur in the brainusually when people are ex-posed to different sights and sounds.

Before launching into a description of Dr. Buchsbaum'swork, let us pause for a moment to describe how scientistscatch and label AER "specimens.-

Netting and Naming AERs: The Waveca ,her's Cra tThe AER record is the basic raw material for Dr. Buchs-

baum's studies. One can stretch it, or squeeze it, run it througha computer grinder or a gauntlet of critical researchers. Butwhatever one makes of it, all the information is secreted in therecord itself and the events that seem to elicit it The recorditself is deceptively simple. By the time the computer hasfinished its initial averaging handiwork, the almost un-decipherable scribble of the EEG record has been translatedinto a relatively clear monogram : a voltage wave, with a fewcrests and troughs, and scattered Hokusai-like wavelets rid-ing on top.

By itself, the wave has only limited meaning: one person'saveraged brain responses when a stimulus of a given intensity(say a quick, medium-bright light flash) is presented repeat-edly. But when this record is compared with a person's aver-age evoked responses to other light flashes of different intensi-ties, and when the response patterns of many different individ-uals are compared, important differences begin to emerge. In

6

1 0

OnSti mu lus

Of f

A TYPICAL AVERAGE EVOKED RESPONSE to a stimulus (for example,a light flash). This picture of an AER is "snapped after the ongoing brainactivity is averaged out.

a typical AER the first dip is followed by a rapid rise to ahigher peak, followed by another dip and peak before therecord levels off. "Crests," troughs,7 and -dips" are descrip-tions too vague for the scientist; more precise labels are need-ed, preferably ones that permit exact measurements, such aslatency and amplitude of the AER. Although a scientist canmeasure other features of the wave, Dr. Buchsbaum's experi-ence and that of others have suggested that these featurescarry important aspects of the brain's message when we per-ceive, for example, a light flash. The ambiguity of even thesefew features, coupled with inherent variability in humanAERs, presents more than enough challenges to a scientist'sinterpretive powers. Whatever untold riches are locked inother unmeasured aspects of the wave will have to await theattention of futire research.

The P, N, amplitude has some interesting properties. Forany person, when the stimulus intensity changes (in this case,the light), the P, N, amplitude changes. Thus, for the sci-entist interested in how the brain reacts to changes in stim-ulus intensity, there is an objective way to measure thesechanges: One can compare the heights of P, N, under differ-ent conditions of known stimulus intensity.

The neurophysiological origin of this P, N, peak is onlypartially understood, but it reflects the collective action ofprobably millions of neurons in the brain somehow inducedto fire (or not fire) by messages coming in from light re-ceptors in the eyes that say effectively, "Wow, something ex-citing just happened." In many ways Dr. Buchsbaum, reading

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ILatencil

ITTT

'1

1

1

1

1

P1

-N1 Amplitude I

I

StimulusOff

Ni-P2

Amplitude

FEATURES OF THE AER, P, is the first reliable peak and is often used tomeasure how long it takes the nervous system to respond to the stimulus--a time called the -latency.- The amplitude, P,--N is the voltage difference(in microvolts) between the crest at P, and the trough at N. The amplitude,is the following trough to crest.

AERs averaged from EEGs picked up from the brain by elec .trodes on the skull, is like the football fan described by RobertBenchley in "How to Watch Football":As almost everyone is late in arriving at a football game, there is aperiod of perhaps twenty-five minutes after the kick-off when you aremilling around outside the gate in the crowd, looking for your properentrance. This is perhaps the most trying period for the spectator. He hearsoccasional barkings from the quarterback, followed by terrible silence,and then a roar from ono side or the other, he can't tell which. Almost any-thing may have happened. The visiting half-back may be racing down thefield for a touchdown, or good old Grimsey of the home-team may havecaught a forward pass on the enemy's three-yard line. Alternate waves ofapprehension and elation sweep up and down the fur-clad back of thetardy partisan. What to do? What to ao?

In Dr. Buchsbaum's case, it might be more accurate to sayhe is trying to hear the reactions of one part of the crowd toone or several footballs hurled into the stadium while the gameis going on. At any rate, it is clear that he is not sitting in a$50 seat on the 50-yard line. (Other researchers are investi-gating what is going on inside the brain, but they are watch-ing quite different teams. Electrodes can be placed in thebrain, but usually box seats for brain activity are only per-mitted in animal research. In humans, scientists usually h.aveto be satisfied with a shadow of tl nhenomenon, a kind ofPlatonic peek inside the brain.)Dr. Buchsbaum has relied on the changes in the latency and

amplitude as they respond to different stimulus intensities.8

1 2

All the helter-skelter P, N,'s can be represented by just twopropertiesthe average amplitude of P, N, and the slope ofthe P, N, responses wheu plotted against stimuli of increas-ing intensity. Surprisingly enough, the slopea simplestraight line at various angles for different peoplecan pro-vide clues to their personalities, their emotional stability, andeven to their thoughts. At the heart of Dr. Buchsbaum's re-search might be found the maxim : "Different slopes for differ-ent folks.'

For Dr. Buchsbaum, the P, N, (and sometimes N,is a wedge to divide and compare people man or woman, in-somniac or not, schizophrenic or normalall on the basis ofthe relative steepness of a line that is an idealization of anindividual's evoked responses to four stimuli of different in-tensitier, such as light flashes. (Actually, each of the fourpoints that determine the line is the result of averaging 64 ormore of an individual's responses to repeated presentations ofeach of the four stimulus intensities.)

Although there is wide variation in the response slopes ofdifferent people as they respond to stimuli of increasing in-tensity, a given individual will tend to show the same generalslope whenever he or she is tested. Furthermore, people withthe same type of slope often share other enduring character-istics in commonboth behavioral, and, sometimes, in otheraspects of their AERs.

Following the terminology of Dr. Petrie, Dr. Buchsbaumcalled the steeper lines (reflecting a rise in AER amplitude toincreasing stimulus intensity) "augmenting" slopes, and theshallower lines (reflecting, in some instances, an actualdiminution of AER amplitude to increasing stimulus inten-sity) "reducing" slopes. So, for any sample of the population,whether randomly chosen as "normals" or deliberately chosento reflect some behavioral or genetic characteristic, the differ-ences among individuals can be characterized as those withrelatively steep AER amplitude slopes ("augmenters")- andthose with relatively shallow slopes ("reducers"). Not onlYcan the slopes of different individuals be compared withingroups, they can also be compared across different groups.For example, if the AER amplitude slopes of several womenare compared, there is quite a bit of variation; but on theaverage, when women are compared to men, women tend tohave more augmenting slopes (a finding which, as we shallsee later, Dr. Buchsbaum has studied in considerable detail).

One exciting result of this research has been the demonstra-tion that groups of people with certain forms of mental illness(such as schizophrenics, manic-depressives, pure depressives,and hyperactive children) have, on the average, AER slopes

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Latency(time)

Amplitude

Amplitude

Low

Augmen ting-High Amplitude

Augmenting-Low Amplitude

Reducing

Stimulus Intensity High

IDEALIZATION OF AER LATENCIES AND SLOPES. The latency (top)typically decreases as the stimulus intensity increases, whereas the ampn.tude (middle) typically increases with greater stimulus Intensity. The lineconnecting the four idealized Pv-N, responses can, depending on the in-dividual and the conditions, appear dramatically different from the oneshown, For example, those shown in bottom diagram show other possibleP,N, responses to the same stimuli

that differ from one another and from groups of normal in-dividuals. In addition, the AER amplitude slopes of individ-uals with the same illness can be used with some success topredict who will and will not respond to treatment. It is toosoon to know whether the AER technique can ever be devel-oped to the point that it can he used for iliagnosis and treat-ment-outcome prediction, but at least the promise is there.The problem, of course, is that use of the technique requiresthat patients show a distinctive AER pattern that will prac-tically shout out: "I am a schizophrenic" or "I am a manic-depressive patient who is likely to respond to lithium treat-ment." Currently, while there are typical differences in AERslopes (and other AER characteristics) when groups of men-tal patients are compared with one another or with normalsubjects, these differences are not always sufficiently consist,ent or large enough to permit accurate diagnosis.

For example, as mentioned earlier, Drs. Buchsbaum andSilverman found that schizophrenics, in addition to being re-ducers on the KFA test, are AER reducers as well. That is,their AER amplitudes generally slope downward as the stim-10 14

ulus intensity increases. However, not all groups of schizo-phrenics will show the same slope. In fact, in some of Dr.Buchsbaum's latest studies, using somewhat different visualstimuli, other groups of schizophrenics barely have a reducingslope; rather, they show more of a level straight line. Still,groups of schizophrenics never seem to show a strongly aug-menting slope (although, of course, individual schizophrenicsmight). Since normal subjects tend to have augmenting slopes(though not very dramatically), schizophrenics, as a group,can be distinguished from normal subjects.

Among the sources of problems in trying to find stable cor-relations between various AER slopes and various forms ofmental illness are, of course, the patients themselves, whosebehavior, even on a simple perceptual test, can be quite varied,and whose thought processes (which can affect the AER) areeven more skittish. (What might schizophrenics think of sit-ting in a room, with eletcrodes attached to their scalps, whilelights continually flash at various intensities?) In addition,there is the problem of psychiatric labels. Psychiatric diag-nosis is still in a crude state of development. A given patientmay receive somewhat different labels from different psy-chiatrists, with the result that groups of patients diagnosedas schizophrenics may differ widely in their behaviorandeven in their neurophysiological functions.

AERs and Psychopathology

Dr. Buchsbaum and his fellow researchers have been moreinterested in studying human perceptual stylesboth normaland abnormal (as indicated by the AER)tban in investi-gating the causes of mental illness per se. Nonetheless, theirresearch has yielded some potentially significant approachesto more accurate diagnosis and treatment of several types of.psychopathology. Their findings have also suggested that, asmany scientists ligve shown behaviorally, abnormalities .ofperception and attention often accompany many forms ofmental illness. By showing that perceptual abnormalities occurat the level of brain function (whatever the AER represents,it is surely brain activity), these studies lend support to theview that abnormal neurological processing of sensory infor-mation may have a significant role in mental illness. Whethersuch abnormalities are root causes in and of themselves or areflection of Yet other biological problems and tendencies re-mains to be seen. And of course, the existence of AER ab-normalities in mental illness does not suggest which specificanatomical and neurophysiological aspects of the nervous sys-tem are implicated.

b 11

We will now summarize some of the major findings of Dr.Buchsbaum and his colleagues concerning AER abnormalitiesin schizophrenia, manic-depression, and depression, conclud-ing with a related study of hyperactivity in children. Thesestudies have been addressed to several major questions:

How do the AERs of groups of individuals with these typesof mental illness differ from the AERs of groups of normals?

Between patient groups that present similar clinical pic-tures (e.g., manic-depressives in the manic phase vs puredepressives) are the AER.s different?

What happens to the AER before, during, and after treat-ment in patients given various disease-specific treatments?

To what extent can the AER predict treatment response?What might AER characteristics seen in various patient

groups suggest about their neurophysiological functions?Dr. Buchsbaum and his associates have found a number of

provocative, though preliminary, answers to these questions.First, before treatment there are relatively distinctive AERpatterns for each type of illness that permit one to distinguishpatients from normals. Second, in some cases relatively cleardistinctions can be made among patient groups with differentdiseases, based upon AER patterns. Third, pretreatmentAERs can often indicate who will and will not respond totreatment. Fourth, during effective treatment, AERs can con-firm signs of clinical improvement, as AERs return to morenormal patterns.

Schizophrenia

Compared to normals, whose slopes usually rise, schizo-phrenics have reducing slopes. Although the result was notstriking, Dr. Buchsbaum found that those schizophrenics whohad been the most extreme reducers at the beginning of hos-pitalization showed a slight tendency to respond more favor-ably to treatment later in their hospital stay. This pattern ofbetter treatthent response among those initially most ab-normal has been found in subsequent studiesoften more ob-viously than in the case of schizophrenics. At present thereis no explanation of this finding (one might expect thosemildly abnormal to return more readily to normal). It shouldbe borne in mind, however, that if the Buchsbaum-Silvermanhypothesis is right, and stimulus intensity control enablesschizophrenics to protect themselves by reducing their re-sponse tr high-intensity stimuli, then extreme reducers arebetter protected. In that sense, although their extreme reduc-tion is abnormal, it may be adaptive; and from the point ofview of self-protection, these schizophrenics may be "health-ier". than those with more normal AERs. Obviously, there is

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16

Amplitude

Low

Schizophrenic Slope (Reducing)

Stimulus Intensity

SCHIZOPHRENIC AND NORMAL AER AMPLITUDE SLOPES

H igh

much room for speculation, but for the moment the mysteryremains.

Manic-Depression

Continuing their studies of mental patients, Dr. Buchsbaumand other colleagues turned to manic-depressive& Severalstudies by these investigators revesied that such patients,many of whom seesaw between euphoria and melancholy(although some seem to stay more often in one phase), gen-erally show augmented AER slopes steeper than those ofnormal& These rather augmented AER slopes are seen re-rardless of the manic or depressive phase in which the patientis tested.

For some time, lithium carbonate has been used to treatmanic-depressives. As often happens with medication, patientswith the same disease labels respond differently ; some getbetter, some are unchanged, and a few may even get worse.And, as also happens, lithium treatment has some undesirableside effects; physicians would like to assure 'that those whomust undergo the risk of side effects are likely to benefit fromthe medication. Some of Dr. Bucbsbaum's findings suggestthat in the future it may be possible to use the AER to predicta patient's response. In studying manic-depressive patientsbefore, during, and after lithium therapy, Dr. Buchsbaum andhis colleagues have found that those patients with rather ex-treme AER augmenting slopes prior to lithium therapy aremore likely to improve than those with more "normal" slopes.Again, the principle of the most abnormal being the mostimproved seems to follow here. In addition, in patients respon-sive to lithium treatment, changes in AER amplitude slopeare correlated with clinical improvement; as patients return

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17

A ptitude

Low Stimulus Intensity High

MANIC-DEPRESSIVE AND NORMAL AER AMPLITUDE SLOPES

to more normr,1 behavior, their AERs also become !torenormal.

Depression

Another group of mental hospital patients has also capturedDr. Buchsbaum's research attention : pure depressives. Thesepeople, who sometimes clinically resemble manic-depressivepatients during their depressive phase, are not simply manic-depressives minus the mania. Recent biological evidence pointsto the fact that different biochemical factors underlie the twoillnesses. And clinical experience has shown that they respondto different medications. Because of the clinical similaritiesbetween the two diseases, it would be helpful to have as manyobjective-ways as possible to distinguish between them. Again,the AER technique shows prorrAse, although results are onlypreliminary. Distinguishing manic-depressive from pure de-pressive patients is easier with men than with women.

Manic-depressiveswhether male or femaletend to haveaugmenting slopes. Male manic-depressivbe are thus easilydifferentiated from male depressives because the former haveaugmenting slopes while the latter have reducing slopes. Fe-male manic-depressives present more of a problem, since they,like female depressives, have augmenting slopes; however,their high-amplitude AERs are usually a &agnostic giveaway.Thus, the AERs of the depressives are different from manic-depressives, and AERs might offer the clinician yet anotherway of distinguishing among the faces of gloom.

1.4

1 Q

Male

Manic-Depressive

Amplitude Depressive

Low High

FemaleManic-Depressive

Low High

Stimulus Intensity

MALE AND FEMALE RESPONSES BY DEPRESSIVES AND MANIC-DE-PRESSIVES. Note the mate depressive response pattern, which does notwern to be a linear s:ope. More patients will need to be tested to determinewhether this Mverted "tr is indeed charactariatic of all depressives. Maledepressives appear to be distinguishable from manic-depressives by theirpattern of response white females are distinguished by the difference inmagnitude.

"Hyperactive" Childnahn

Among the most challenging children for parents, teachers,and researchers alike are those restless "hyperactive" young-sters medically diagnosed as having "minima brain dysfunc-tion" or MBD. As Dr. Buchsbaum has observed : "Minimalbrain dysfunction (MBb) is apparently the single most corn,mon cause of behavioral and educational problems in child-hood." As, yet there is no cure for hyperactivity, but manysuch children, seemingly boundless in energy and typicallyflitting from task to task (or trouble to trouble) like nervoushummingbirds, can be brought calmly to earth through care-fully regulated doses of amphetamine. (Paradoxically, whileamphetamine =LI as a stimulant in most adults, it has a calm-ing effect i9...ehildrenat least in hyperactive ones.)

Compving the AERs of hyperactive and normal children ofthe sam ages (6-12 years), Dr. Buchsbaum found that thehyperactive children tend to have AERs characteristic ofyounger normal children. Hyperactive children also have con-siderably more variability in their AERs than normal chil-dren, with latencies and amplitudes that change from stimulus

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to stimulus more than they do in normal children. In addition,compared to normal children, hyperactive children tend toshow shorter latencies; that is, their AER response-times tendto be faster.

Since hyperactivity may be, as some have supposed, a dis-order of attention, and differences in attention have beenshown to affect the later parts of the AER record (that is, theN, P2 peak), Dr. Buchsbaum speculated that the later por-tions of the AER record would show dis tinct differences be-tween hyperactive and normal children. Indeed they did. Hefound that the amplitude of a later AER peak was higher inhyperactive children than in normal children.

By studying the AERs of hyperactive children before, dur-ing, and after treatment with amphetamine, Dr. Buchsbaumhas been able to identify some response patterns that seem tocorrelate with therapeutic success. Treatment-responsive hy-peractive children are those who, before treatment, have themost abnormal that is, immatureAER latency patterns;conversely, those whose AERs seem relatively mature beforetreatment are unlikely to respond. According to Dr. Buchs-baum, 64 percent of hyperactive children who will respond toamphetamine treatment can be identified by their AER latencypatterns before treatment. Once treatment has started, po-tential treatment-responders can be distinguished from non-responders by changes in their AER amplitudes: Comparedto their pretreatment AERs, those who will benefit fromamphetamine show a more reduced AER amplitude slope,while in those who will not benefit, the slope augments some-what. (Clinical impros,-ement is also related to significantlyreduced AER variability during successful treatment-) As inthe findings above, hyperactive children who improve withamphetamine are those who, prior to treatment, are most un-like normals.

-AERs and Normal Behavior

Dr. Buchsbaum has explored AERs in a variety of humans,some of whom are ostensibly "normal," and others who, for avariety of reasons (often largely behavioral), are labeled as"abnormal." His AER studies have revealed a rather widespectrum a brain responses when these different individualsview the same stimuli, such as four lights of four differentintensities. For the most part, as we have seen, groups of be-haviorally abnormal people show a band of AER patterns thatcluster differently from normal peopleusually tending to-ward the extremes of normal response tendencies (for ex-ample, appreciably steeper slopes of augmentation or reduc-

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tion, or shorter response latencies, or greater than normalaverage amplitudes). In some instances, normal AER char-acteristics for one sex or the other are changed (as in thecase of manic-depressive women). Clearly, the concept ofabnormality would be meaningless without some notion ofwhat is normal. But as Dr. Buchsbaum has discovered, theres considerable variation in AER patterns even among people

who have served as his "normal" subject& (It is even possibleto find, scattered among these subjects, individuals whoseAERs might suggest to a careless observer that they shouldimmediately volunteer to enter a mental hospital rather thanan experimental laboratorybut as far as anyone knows, they,too, are "normal.") One continuing focus of Dr. Buchsbaum'swork has been to identify the relatively stable differences inAERs among groups of normal individuals, and try to under-stand why they exist. In normal individuals, their responsedifferences may reflect inbuilt and enduring differences in theways humans process sensory information. If normal humandifferences can be understood, they may provide some clues tounderstanding the exaggerated responses we see in mentalillnesses.

As we have seen, the AER amplitudes of normal personsmay have augmenting or reducing slopes (although usuallythese patterns can be distinguished from the steeper augment-ing and reducing slopes characteristic, say, of a hyperactivechild or a schizophrenic). What is the biological basis for suchAER differences among normal individuals? To what extentare they genetically determined, and to what extent does priorexperience play a part in these relatively stable characteristicsof individuals? To answer questions such as these, scientistsoften turn to twins, comparing the degree of similarity be-tween pairs of identical twins (who, coming from the samefertilized egg, share an identical genetic makeup) and thedegree of similarity-between fraternal twins (who come fromtwo different fertili2ed Zggs and are no more alike geneticallythan any two siblings). If genetic factors are at play in theAER, then the AER patterns of identical-twin pairs shouldbe more alike than those of fraternal-twin pairs. (Ideally, thesearch for pure genetic effects should be conducted with iden-tical twins who have been raised apart, to offset the effects oftheir common upbringing; however, such subjects are ararity.)

In a study of 60 twin pairs-30 identical and 30 fraternalDr. Buchsbaum found support for the thesis that AER pat-terns reflect genetic endowment : The AERs of pairs of iden-tical twins were far more alike than those of pairs of fraternaltwins. Both identical twins of a pair tended either to have

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augmenting or reducing slopes, while fraternal-twin pairssometimes showed conflicting AER patterns. Such findingsmust be qualified by the recognition that, since identical twinsfrequently are raised more uniformly than fraternal twins,their prior experiences, rather than their greater geneticsimilarity, may account for these results. Nonetheless, it seemsunlikely that such differences in upbringing would affectAERs significantly. One may reasonably assume that stableAER patterns may reflect, at least in part, one's genetic make-up.

Many lines of biological and psychological research, includ-ing Dr. Buchsbaum's, suggest that the minds of women arephysically and functionally different from those of men.Whether the differences are the result of genetic factors and/or cultural conditioning is not yet known. The preceding twinstudy, like many conducted by Dr. Buchsbaum and others, re-vealed that normal women tend to show a greater degree ofAER augmentation than do men. Also, on the critical P, N,first AER peak, women's responses are about 25 percentgreater than those of men.

However, emotional states can modifyand even reversethese sex-typical response patterns. For example, anxious andneurotic men tend to have augmenting slopes while equallydistressed women tend to have reducing slopes. In short, mal-adjusted individuals tend to respond like normals of the oppo-site sex.

Why do men and women have different AER patterns? Theanswer has been elusive and still is only fragmentary. Sex-linked hormones seem an unlikely cause, since, as we haveseen, sex-linked response patterns can be reversed by anxietyand neurosis (unless we assume these emotional problems re-flect or affect the level of sex hormone present). Furthermore,AER differences between boys and girls can be demonstratedas young as 6 years of agelong before the gonadal hormonesappear. In addition, sex-linked AER differences exist in the40-to-60-year-old group when women's estrogen levels aredimin ished.

Could the cause be differences in brain weight or in skullsize? Women do have slightly lighter brains than men, sug-gesting that for purely physical reasons we would find differ-ences in AERs between men and women. However, otherstudies have shown no relationship between brain weight orsize and the AER. In summary, the answer does not seem tolie in the anatomy or physiology of the sexes, but rather insome underlying neural style.

Pursuing one more biological possibilitythe geneticchromosomal differences between men and womenDr. Buchs-

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Imam and his coworkers found some encouraging clues. Theyexamined the AERs of patients with abnormal sex chromo-somes. This study suggested that there is some relationshipbetween sex chromosomes and AERs. Normally, males haveone X and one Y chromosome (XY), while females have twoX chromosomes (XX). Looking at patients with X0 chromo-some patterns, where the sex-determining chromosome is ab-sent, these researchers found the AERs of XO males to be verymuch like those of women. One possible hypothesis is that theY chromosome exerts some genetic effect that attenuates AERamplitude.

Dr. Buchsbaum's interest in individual differences, fueledby Dr. Petrie's earlier discovery that variations in individ-uals' pain tolerance were correlated with other perceptualtendencies, has led him to see how AER patterns are relatedto pain and noise tolerance. In one study, subjects were givenrelatively mild electrical shocks of various intensities on theforearm, and asked to rate each shock as "just noticeable,""distinct," "unpleasant," or "painful." AER reducers weremore pain tolerant than augmenters, making little of stimulithat augmenters found painful.

Exploring another dimension of pain tolerance, Dr. Buchs-baum looked at the effect of suggestion on pain. The AERs ofthree groups of subjetts were compared. One group simplyexperienced shocks of various intensities; a second groupheard music during the shock-test,period; a third group, toldin advance that music would reduce pain, also heard musicduring the test period. Subjects in the third group, who hadreceived a form of suggestion, tended more toward a reducingslopeand to be more pain tolerantthan those in the othergroups. This appears to be what Dr. Buchsbaum calls a"neural placebo reaction"; that is, suggestion actually seemedto fool the nervous system into "believing" that the painfulstimulus was less intense than it was. A belief in the analgesicpowers of Beethoven-may hot enable yoU to sleep on a bed ofnails, but it may help on the next trip to the dentistif he,before drilling, turns on the stereo and says, "You won't feela thing."

The AER is a particularly useful research tool in part becauseAER patterns are relatively stable for different individualsover time. Response patterns of individuals may vary slightlyfrom trial to trial with the same stimulus, but these variationsare relatively small compared to AER differences between andamong subjects. Generally, a person with a reducing or aug-menting slope will show the same pattern rather consistently(unless, as we have seen, abnormal subjects are given medica-tions that change their AER patterns). Indeed, Dr. Buchs-baum's twin study suggests that the tendency to respond with

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an augmenting or reducing slope in adulthood may be genetic-ally predetermined. Howeverand there are always "how-evers"many short-term situational factors can modify aperson's evoked-response patterns. As the experiment withshock and music has shown, expectations can color one's re-sponse patterns. Several studies have demonstrated that theAER is closely related to a person's short-term psychologicalstate; in fact, what he or she thinks, feels, or expects maydetermine the shape and size of the AER more than the actualintensity of the stimulus. Dr. Buchsbaum, like many scientists,has found that, by understanding the conditions that makeAERs unstable, he can learn to control them better in subse-quent experiments. Thus, while basically interested in rela-tively stable AER patterns, he has explored how subjects'expectations can change their AERs over very short timeperiods.

Let us imagine, for a moment, that you are the subject inan experiment, which is a carefully contrived variation of thestandard light-flash study. After EEG electrodes are attachelto your scalp, you are invited merely to s.vatch the cominglight show. You see a long, uninterrupted series of brief lightflashes of various intensities that seem to fall into some pat-tern. Perhaps you will note that they seem to run in sequencesof four, in ascending order of intensity ; at other times thepattern may be less apparent. In fact what you are seeing isa complex series of light flashes made up of two subpatternswhich alternate irregularly. In light pattern A, four lightflashes are presented in order of increasing intensity, let ussay 1, 2, 3, 4, from weakest to brightest. In light pattern B,the order is changed to 1, 3, 2, 4. The weakest light is stillfirst and the brightest is last, but the middle intensities areswitched. You, the subject, actually are presented with a stringof flashes in the sequence AAABAB, so that the regular,ascending light pattern appears three times, followed-by al-ternations of the irregular and regular light patterns.

If you are like most of Dr. Buchsbaum's subjects, yourAER will show an interesting expectation effect, even if youwere not consciously trying to figure out the sequence. For theregular, ascending A pattern, your AERs will reflect the actualintensities of the stimuli. But for the B pattern, your AERwill be somewhat strange; you will give an excessive responseto stimulus intensity 2, responding as if it were the more in-tense stimulus 3. In Dr. Buchsbaum's view, this inconsistent'response reflects the incorrect expectation that pattern B willbe exactly like pattern A; in essence, your AER response re-flects what you think should be there, and not the actual stim-ulus. (Believing is seeing!)

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If you enjoy being an Imaginary subject, there is anotherexperiment in which to participate. In this study, which usesthe same light sequence (AAABAB), you will be taught thetotal sequence in advance, so you know exactly what to expect.You will know, therefore, that the second stimulus in eachgroup of four indicates whether it is a regular, ascending se-quence (the A pattern) or an irregular sequence (the B pat-tern). This time, your AERs probably will be even morepeculiar than in the preceding experiment, reflecting moreabout your internal state and less about the actual intensitiesof the light flashes. For both the A and B patterns, your A ERsprobably will be elevated (that is, will have greater ampli-tude) for the second stimulus in each group of four. To Dr.Buchsbaum, this elevated AER reflects the significance ofthis stimulus to the viewer. Seen another way, each time thesecond stimulus appears, it confirms what you were led toexpect; your elevated AER is like a confirmatory "uh-huh."The important point, for Dr. Buchsbaum, is to recognize that,although people appear to have relatively stable AER tenden-cies, a person's AER at a given instant may reflect what mat-ters most to him at that moment, rather than his overall AERpattern or the particular stimulus characteristics. In short,even in the humdrum task of perceiving light flashes, we donot simply process perceptual information mechanically and"objectively"; the very act of perception is infused with ourown subjective meaning.

Beyond the implications of such findings for those who seekto find some "objective" reality, there are some practicalcaveats for scientists engaged in AER research. Iden tifyingstable AER patterns for individuals and groups requires greatcare in the design, conduct, and analysis of studies, lest a mo-ment's meaning be mistaken for an enduring mind-set.

ToWard a Theory of Sensory Qiierload

From birth to death, biological organisms continually strug-gle to maintain their identity, equilibrium, and integrity inthe face of environmental flux. At every level of biologicalexistencefrom individual cells to the total organismthereseems to be a defined band of environmental conditions foroptimal performance; too much or too little of even a goodthing can be lethal. Living organisms are in a constant tizzy,trying to maintain stability despite the vagaries of the en-vironment. In his book The Wisdom of the Body, the eminentearly 20th-century American physiologist Walter Cannon calledthis process "homeostasis." He and others have identified in-numerable mechanisms by which the body keeps itself in dy-

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name equilibrium. To take one example, all animals mustkeep their body temperature within relatively narrow limitsto survive. Warm-blooded aniinals such as mammals have theequivalent of a thermostat (the hypothalamus) at the base ofthe brain that senses and controls body temperatureturningon flushing and sweating when hot and turning on shiveringNvhen cold. Some scientists believe that the ancient capacityfor homeostatic regulation of body temperAture once gavemammals an adaptive edge over the gigantic cold-bloodedreptiles; when the great Ice Age came, we mammals shiveredour way to survival, while dinosaurs froze to death and ex-tinction.

Does our homeostatic equipment include some generalmechanism that attempts to maintain a continuous optimalstate of overall nervous system activation ? This view is at-tractive but as yet not well supported. However, the researchis suggestive. F'or example, studies have shown that temporaryor permanent mental impairments can arise from eithersensory overload or underload, and, since the 19th century,it has been repeatedly demonstrated that humans do not re-spond behaviorally in direct linear proportion to increasingintensities of sensory stimulation. At the AER level, at veryhigh levels of stimulation (extremely loud noises or brilliantlights) our brain responses normally level off or reduce, as ifsomething says, "That's more than I can take." For those withreducing slopes, this point seems to come at fairly low stimu-lus intensities; for those with augmenting slopes, at muchhigher intensities.

As yet, there is no way to demonstrate conclusively thatthe nervous system is designed to maintain some optimal levelof activation, nor does anyone know exactly how such a pro-cess might occur anatomically and neurophysiologically. Thecentral nervous system has been shown to exert some controlover the peripheral sensory receptors, but how this happensis unknown. There appears to be some control across the differ-ent sensory modalities, so that, for example, we do not usuallygive equal attention simultaneously to information from allthe senses; when we are attending visually, our receptivity tosounds diminishes, and vice versa. The whole field of attentionand its neurophysiological basis is fascinating, but fraughtwith contradiction and controversy. The search to understandstimulus intensity control may well be bound up with investi-gations of attention and expectancy. (It should be rememberedthat both schizophrenia and hyperactivity have been character-ized by some scientists as disorders of attention.)

Drs. Buchsbaum and Silverman have not gone so far as tosuggest a homeostatic model to explain augmentation and re-

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duction. But they have proposed that 5timu1us intensity con-trol serves an adaptive, protecC.ve role in the face of potential-ly excessive stimulation. Those with strong reducing slopes,hypersensitive to low-level stimulation, seem to close out theworld's clangs, pains, and glare in a bid for neurophysiologicalsurvival. Schizophrenics might be seen as representing thisadaptive tendency to an exaggerated degree Those with strongaugmenting slopes on the other hand, prone to be understimu-lated because of tileir insensitivity to low-level stimuli, seemto turn up the amplification of the world, allowing themselvesto flooded with sensations at higher levels. In some ways,

peractive children may represent exaggerated versions ofthis potentially adaptive response.

At present, the studies of Dr. Buchsbaum and his coworkerspresent us with many unresolved chicken-and-egg problems. Doschizol5hrenics respond to high levels of stimulation becausethey are hypersensitive to low-level stimulation ? Do they havereducing slopes because they are schizophrenic? Does schizo-phrenia represent a failure of protective stimulation-reductionmechanisms? Do schizophrenics suffer from sensory depriva-tion effects caused by closing out high-intensity stimulation?Do all of these effects reflect yet another mechanism at workfor example, a shift of responsiveness from perception ofthe outside world to internal perception? Might the brain's"background noise," deliberately excluded by the AER tech-nique, encompass other essential components of the totaldynamic equation? As yet we have no way to know. We havebarely found a way to document electrophysiological responsesto external stimulation ; a new frontier awaits us concerninginternal stimulation, perhaps requiring, as did AER research,another technological breakthrough.

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Supplementary ReadingsBuchsbaum, Monte S. Average evoked re,ponse and stimulus intensity in

identical and fraternal twins. Physiological Psychology, 2(3A) :365-370,1974.

Buchsbaum, Monte S. Avsrage evoked response augmenting/reducing inschizophrenia and affective disorders. In: Freedman, Daniel X., ed TheBiology of the Major Psychoses: A Comparative Analysis. Long Island,N.Y.: Raven Press. (In press)

Buchsbaum, Monte, and Silverman, Julian. Stimulus intensity control andthe cortical evoked response. Psychosomatic Medicine, 30(1) :12-22, 1968.

Buchsbaum, Monte, and Wender, Paul. Average evoked responses in normaland minimally bruin dysfunctioned children treated with amphetamine:A prelim nary report. Archives of General Psychiatry, 29(6) :764-770,1973.

Buchsbaum, Monte; Goodwin, Frederick; Murphy, Dennis; and Borge,George. AER in affective disorders. American Journal of Psychiatry,128(1) :19-26, 1971.

Buchsbaum, Monte; King, Cathy; and Henkin, Robert I. Averagz evokedrewonses and psychophysical performance in patients with pseudohypo-parathyroidism. Journal af Neurology, Neurosurgery, and Psychiatry,35(2) :270-276, 1972.

Buchsbaum, Monte; Landau, Stephen; Murphy, Dennis; and Gooduin,crick. Average evoked response in bipolar and unipolar affective

: Relationship to sex, age of onset, and monoamine oxidase.Riologicii Psychiatry, 7(3) :199-212, 1973.

Buchsbaum, Monte S.; Henkin, Robert I.; and Christiansen, Richard L.Age and sex differences in averaged evoked responses in a norTnal popu-lation, with observations on patients with gonadal dysgenesis. Electra-encephalography and Clinical Neurophysiology, 37(2) :137-144, 1974.

Buchsbaum, fd. S.; Mollino, .1. A.; Pons, L. B.; Coppola, R.; and Murphy,D. L. Individual differences in noise tolerance and the auditory andIdsual evoked response. (Unpublished)

Donchin, Emanuel, and Lindsley, Donald B., eds. Average Evoked Poten-tials: Methods, Results, and Evaluations. Washington, D.C.: U.S. Gov-ernment Printing Office, 1969. 400 pp.

Landau, Stephen G.; Buchsbatim, Monte S.; Carpenter, William; Strauss,John; and Seeks, Michael. Schizophrenia and stimulus intensity control.Archives of General Psychiatry, 32(10) :1239-1245, 1976.

MacKay, Donald M., chair. Evoked brain potentials as indicators of sen-sory information processing: A report based on an NRP work session.Neuroseiences Researr,k P lgram Bulletin, 7(3), 1969. (pp. 24268)

Schechter, Gail, and _wri, Monte. The effects of attention, stimulusintensity, and imiividual differences on the average evoked response.Psychophysiology, '0(4', :392-400, 1973.

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Silverman, Julian; Buchsbaum, Monte; and Henkin, Robert. Stimulussensitivity and stimulus intensity control. Perceptual and Motor Skills,28 (1) :71-78, 1969.

Sileeman, Julian; Buchsbaum, Monte; and Stierlin, Helm. Sex differencesin perceptual different!ation and stimulus intensity control. Journal ofPersonality and Social Psychology, 2543) :3A-318, 1973.

Stevens, S. S. The psychophysics of sensory function. In: Rosenblith,Walter A., ed. Sunsory C. 117imunicaion_ New York: M.I.T. Press andJohn Wiley & Sons, Inc., 1961. pp.

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U.S. G PSINTW4O Orn 1971 271-835

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