—_..__.__.

.— x-w-r'

 

 

 

 

 

TILE EFF:CT OF PERPHEI‘IAZ IT: ON FOCUS 0F AWE-ITION

IN SCIIIZOPHRL‘NIA

By
JOHN mm. 5131on

A.THESIS

Submitted to the School of Advanced Graduate Studies of
Michigan State University 0! Agriculture and Applied
Solemn in partial fulfillment of the mquiments
for the degreo of

DOCTOR OF PHILOSOPHY

Department of Psychology

1960

 

 

ABSTRACT

lhe present investigation was designed to explore a physiological
activity that is videly held to be involved in attentive behavior and to
test the hypothesis that experimental prowcaticn of this activity by the
drug perphcnazinc will be reflected in nemreble behavior. Since the
present desig: was not able to dcmnstrate drug eifects on this physiolo-
gical activity directly, interpretations are necessarily inferential.

Sixty schieophrenic female patients at Kalarnasoo State Hospital
eerved so So. All petimts vere medically cleared at physical cad sensory
involvumts. These were divided into three groups of twenty patimte
each. Medication vac edcinietered orally over a period of three con-
secutive days. lhe two experimental groups respectively received low-dose
perphenssine (12 mg. in divided doses t.i.d.) and high-does perphenesine
(A8 mg. in divided doses t.i.d.). vhereae the control group received a
inactive placebo. The double-blind tecimiqne was emioyed.

Stimlus materials consisted of two tasks designed to measure
tome of attention as considered in this investigation. One of these,
the W5 attention task, was a modification of procedures previously
used in tests of interference. The eecmd task, the broadened attention
task, presented So with opportunities to guess which of two possible events
will occir.

All materials were preamted on No. 76 (heavy weight) Iii-Art
hot-pressed, white illustratim board.

‘

 

v

v"

A-.. '1—

 

 

 

eriment t A t t 1'

Se ears required to respond to one of two simltneously pre-
lasted etinaali each of which was an inherent aspect of the one syflol,
e colored secaetric “stars. in the first instance. is ears recanted to
name shapes vhile imrins colors; in the second, nus colors vhile ig-
noring shapes. Difference scores betveen time (in seconds) taken to case

one stimulus was presented alone and time taken to case that sees stimlus
in the presence of the second interierins stimulus served as the basic data
{or this experiment.

Statistical analyses seploying the 3 test failed to differentiate
between the perform-Ice of the high-dose group and each of the other talc
creeps in the tvo separate parts oi this test. Melyses of the scabined
performance scores did diitemtiate bstvesn high drug and placebo in the
direction opposite to that hypothesised.

Accordingly. high-dose medication failed to affect performance e!
the hind called for in this experiment in the predicted direction. the
first of the major hypotheses of this investigation is this cassidered
not declined. This hypothesis was stated as tollovai Patients treated
with psrphanesine in dosage stunts presmed to stimlste the brain-ates
retiwler system will perform better on a task requiring "hsrroesd st-
tenticn" (modified Stroop test) that will patients treated with perphenacine
in dosage mounts presuned to inhibit. depress. or block brain-ates re-

ticular system activity.
the incidence of Partinscnian in the high-drug group is taken as

clinical evidence that 48 ms. of perphenatine a day exceeds that required
for optimal functimins.

iii

 

1'! t i B At! t! 1'

So were required to guess ehich of tee ovate (one less likely
than the other) would costar. The umber oi messes tor the "less likely“
event over the last eight trials at a ton trial series, served as the
basic data (or this experiment. Each trial consisted of ten events in
wish the ratio of less likely to more likely events was 2 to 8.

Analyses of variance over trials bet-eon the lee-dose drug group
and each of the other two groups significantly differentiated behavioral
effects of low-dose porphenasins. These effects were in the direction
of greater utilisation in the use of peripheral ones required for ace-
ccastul permanence.

Accordingly. low-dose drug medication may be considered as having
a significant effect on performance of the kind called for in this on-
periment. The second of the major hypotheses of this investigation is
time considered continued. This hypothesis was stated as follows!
Patients treated with perphenaaino in dosage manta presumed to inhibit.
depress. or block the brain-ates reticular system vill porters better
on a test requiring "broadened attenticn‘ (messing also) than will
patients treated with pet-phenaains in dosage anounts procured to stimloto

bralnpctcm reticular system activity.

iv

 

ACKNOHLEDGWENTS

The author would like to express his indebtedness to the now
who have in various ways contributed to this investigation.

For time and counsel generously given, and for cmvoying to no
at all times the need for and importance of Mean relationships in the
scientific setting, I as most deeply grateful to Dr. Donald H. Johnson,
Chairman.

I wish also to thank Drs. H. Ray Denny. Alfred G. Dietse and
Gerald F. King for their expressions of interest in the form of timely
and cogent criticism which contributed imeasurably to this study.

I can but inadequately express my indebtedness to willien H.
Kelly, M.D., for unselfiehly clarifying and sharing pertinent medical
insights and knowledge and for kindly encouragement throughout the
investigation.

In Charles B. Overbey, Jr., M.D., 1 cm much, not only for his
untiring efforts in integrating the conduct of this study but as well
for demonstrating that one's devotion to the welfare of his patients
need not be lessened by participation in scientific “search.

I wish to thank all those in the Department of Mental Health
and Kalenssoo State Hospital. especially V. A. Stchnan. M.D., C. M.
Schrier, 14.9.. and Miss Gwen Andrew, for providing the facilities and
setting necessary to the implementation of this investigation. For
invaluable help in the mechanical and detailed preparation of this
paper, I an indebted to Melisande McGrath.

V

 

To my constant motivators. Sib, aidy and Debbie, I offer my

thanks for the privilege of being indebted to them.

My greatest debt is to my wife, Helen. This thesis is dedicated
to her. to all those above, to the many umantioned who also helped, and
to the patients who taught me much of the meaning of dimity end hunility.

i'r-v‘lq' v-

 

 

 

worm

mos
m Bull-STEM ransom manor
mum AND THEORETICAL norm
ms DRUG INDEPENDENT VARIABLE
mmm 0? THE PROBLEM
Hypotheses
[HEW m
Subjects
Haterials
Merino“ l. Narrowed Ate-tin task
Experiment ll. Broadened Attention 'raek
Procedure
RESULTS
Experiment I
Ewes-inset ll
018603810!
SUNNY
REFERENCES

vii

’00.

 

LIST OF TABLES

table
l. honesty of muracteristios of 3s

2. Mossy and Analysis of Variance Between Means
of Grew Characteristics

3. Smoary of Perfomsnce Scores in Experiment I

A. Summary of Mean Performance Scores in Rapsriment l

S. Couperism of Psrfomsnce Between Three Groups of
subjects Required to Nam Gannetrio Figures in
’m of Interfering Colors! Ewerimmt l

6. Comparison of Perfumes Betssen lhree Groups of
Subjects Required to Hana Colors in Prams of
interfering Gsonetric Plains: Experiment 1

7. Cowarison of Combined Performance Changes on
Modification of Stroop Test Due to interference:
Marina“ 1

8. amsry of Performance Scores in Experiment ll

9. Sumnery of Mean Performance Scores in Experiment I!

10. latelyeis of Variance Between Lon-Drug and high-Drug
Groups at Eatperiment ll

11. Analysis of Variance Between LowDrug and Placebo
Groups on mcperimmt ll

viii

Page

22

23
35
36

39

‘2

 

LIST OF FIGURES

Pi sure

1.

2.

3.

A.

5.

6.

Structural Formula of Perphenazino
Photograph of Test Card 1

Photograph of Test Card I! (Uncolorcd)
Photograph of Test Card III (Uncolored)
Mean Performance Scores in Experiment ll

Schematic Paradigm Showing "flamenco-Activation
Relationships

in

Page

1!.

2!;

26

27

(.1

53

 

metros

Neurophysiological aspects and bases of behavior have been
given increasingly serious consideration during the past decade. A
umber of important works provide extensive and critical “cries of
past and recent developments in this area and prosnit a detailed state-
ment of the current status of this aspect of behavior as viewed from
«perinatal. anatonical. clinical. and psychelcaical approaches (32.

37. 65. 69. 55. $7. 63).

Recent experiments by Callouy and his associates (ll. l2. l3)
have been directed toward a search for insreasinsly nors neasurable
details of the relationship betwe. aurophysieloaieal activity ad
psychological behavior. By observing change in the focus of attenti.
following the «perinatal provocation of chance in mmhysieloaieal
activity. these investigators have provided further concrete evidence
of the importance of neurophysiologioal activity as a partial determinant.
at least. oi' behavior. the Callousy studies specifically lend support
to the theory that the focus of attmtion is related to the activity of
the brain-ates reticular formation. This brain sub-stratum. considered
essential in the control and maintenance of states of consciousness.

alertness. and wakefulness in the organics. is seen by Callovay and his
a group to produce narrowed attention when its activity is stimulated. and
broadened attention when inhibited. depressed. or blocked. The row. of
attention. narrow or bread. is considered in tonne of the extent to wish
peripheral factors influence or determine behavioral performance. reriphsral
l

 

factors are defined as “those relatively current enviromcntal events

Iiich are removed from the central focus of attention by space. by time.
or by difference of meaning" (ll). A decrease in the effects of peripheral
factors denotes a narrowing of attention: an increase. a broadening of
attention.

Adninistcring drugs Imam to have specific effects on the brain-
stem retioilar systen. these investigators vars able to observe clauses
in the toms of attention in apparmtly ml. healthy adult subjects.
Reticular system stimulants such as smyl nitrite. epinephrine. oath-photo-
nine. and various nerve asses produced narroeed attention (12. 13). while
atropine. a reticular system depressant. produced broednted attention (ll).

Psychologically. the findings of Callovay and his group have
i-portant and crucial implications. It a particular teal: is facilitated
by attention to peripheral factors. thni broadening attutiui viii inprove
behavior. However. performance on a task idiich calls for a filtering out
of distracting, pumpkin-ex factors will be impaired. Naming attention
rill of course have opposite effects. inprovina behavior at a teal: re-
quiring the filtering out of distracting peripheral factors. ehile ia-
pairing perfonname on a task calling for attention to ccntributive
peripheral factors. ‘

THE BRAIN-STEM RETICULAR FORI-lATION

Recent research into<nontal and psychosomatic disease has
pointed more and more clearly to the importance of a region deep vithin
the brain. This region. the rhinonccphalon. is the inner and older
brain; it lies hidden. most of it near the nidlins. covered over by
the outflow of the new brain. or neocortcx. whose culmination in non
marks his primary distinction.

Approximately three quarters of a century ago. Jackson (30)
theorized that the brain evolved in.phylotic layers of which the tapmost
layer is always highest in.comnand. Accordingly. it was felt that so
onch.ncu'top leyor developed. it modified for its con ends the mocha-
niche of the more primitive brain layers situated beneath it.

ln.l933. Herrick (25) appositionally reasoned that the rhinen.
cephalon served as a non-specific activator for the cortex. facilitating
or inhibiting looming. nonory. overt behavior and internal attitude.
At this time. it was generally accepted that the expression.of'emotion
was mediated by the hypothalamus . not only autonomic reactions that

result in pellor or blushing. quickcned heartbeat. heightened blood

pressure. mating. or peristalsis. but also responses involving striated

musclee. such so grimocoe and trembling of rage. it one also felt that

subjective morienco of emotion quite probably required cortical par-

ticipation. Obviously etimleted by Herrick'a proposal. Pwos (58)

searched for neural pathways meeting the hypothnlmnue with the cortex.

Based on an analysis of anatomical. experimental. and clinical data.

3

 

rapes ioend such connections by way of rhineooephaiic structures.

Dnenpected support for Pspaa' physiological enpiansticn at auction sac
inmediately available. than first annexincod. the tapes theory use highly
speculative and in need oi enpsrlmentsl continuation. the more initial
methods of «coloring brain hmtiai involve observation of l) the effects
of renewing or destroying a part oi the brain. 2) the reaponas to retinas
kinda of stimulation. and 3) correlations between behavior and spontane-
oua electrical discharges within the brain. never and Duty (35) un-
hnosinaly applied emerinntal mutilation o! rspes' theory a ten months
5.2... Papes' mar was pnbliehad. Intirpation o1 pcrtins oi the rhino
cephelon in a series of monkeys reaulted in striking streets cn notional
behavior. The Paper and never-lo” resorts inediately stiuleted vide-
sproed interest in the rhimephelon. it is beyond the cocoa of this
investigation to completely maria the studies that tailored. but the
importance of the rhinenoephelon in the nursed organisation oi motion
has beat well verified.

The ready acceptmcs oi the rhinsooephaion as an importer“:
physiological determinant of «notional behavior led to the investigation
of specific areas or regions a! this brain wbstretum. hen; the in-
portent and interesting of the current teaser-d: on the rhinsncephalon
is that being conflicted by Heath and his associates at Nlene (21). these

studies iollosed won lisath's observations as a participant in the
Colubieoareystone lebotay studies. in alt-lining the effects of lobste-
sies and related operations. heath noted that the nest consistent re-
mtiu in oneticnal overflow iron marries resulted iron rossvel of

that part at the prefrontal cortem thioh was comcted oith the septal

 

 

region of the rhinancephalon. By means of implated electrodes. the

death gimp showed that etimlating the asptal region resulted in en
alerting response and in behavior and. was considered to be more
generally favorable. Stimulation of other areas of the brain resulted

in the iaportant finding that the same emotional response sis-ye ac-
companied or folloued stimlsticn of a specific region. Such findings
lend moral support to ideas onmaesd by llarrid: (21.). rules (it).
Kiuver aid buoy (33). and others in opened up this line of investigation.
Isath's interest in the septal resin of the rhinansephelcn parallels
sonsiuat the investigations of nidbrsin ninetions by a somber of other
setters. Magma (38. 39) has fomsed his work on the activating system
of the brain stem. This amending retiwlar activating syatsn. as New
cells it. exerts an over-all effect on consciousness. than activated.

it facilitates both behavior aid the central alertness that chersoterises
the voicing state. morons Mom's system exerts its effect upon the
cortex in a generalised manner oittuut evidence of topographical local-
isation. denier (31) has outlined a corresponding system in the thsl-ois
topographically organised to snort an influence upon more restricted
areas of the certain In addition. Jasper use able to dononetrate that

a converse phumenen characterised the functional aspects of his thalnic
retinaler systcn. He found that stimulation of specific areas of the
cerebral cortex can modify the activity sithin the reticular system of
the brain stem. Tints. the latter is placed under the control of sensory
stimuli from without and cerebral cortical elaboration from within.
ninuich (27) and Rinaldi and iiimoioh (53. 54) have combined the reticular
systems of Magoun and Jasper as a unit and call it the masodiucephalic

activating system.

 

The importance of this system to contemporary speculation and

caporimentatlon and its overall contribution to an saplanntion of the
neurophysiology of behavior is reflected in the very recent publications
of two symposia, Brain Mechanisms and Consciousness (A) and Reticular
Formation of the Brain (50). These volumes represent a landmark in
nourOphysiological research with reSpect to behavior and provide on
important step toward the integration of the findings of physiologists,
psychologists and behaviOral scientists into a unified approach to the
understanding of behavior with reopcct to both its nourOphysiological

and psycholosical bases.

 

MERRIENTAL AND WWW astronauts

Room experiments by Callosny and his associates (ll. 12. 13)
suggut that changes in attentim reflect underlying naurophysiolcgical
dunno. The first of these (13) studied the effect of endogenous
smathetic activity on the perception of also. Stress can produced
in apparently normal healthy adults by the inhalation of snyl nitrite.
The provocation of sympathetic activity by this method led uhjects to
increase their estimate of a distant object relative to a near object
as mated to results obtaimd daring non-drug performance. Similar
findings were obtained with epinephrine and methamphetamine. 0n the
basis of these findings, Callcsuy and Thompson (13) hypothesised a
cannon nourophysiolcgical factor and called it "central smathcnimetic
activity.“ Since the three drugs used to promos physiological change
all mimic the cantnl component of sympathetic discharge. these outliers
concluded that an increase in central synpathcninetlc activity as
accompanied by a remotiat in the responsiveness of subjects to things
(stimli) outside the inmediate scene. This decreased mimtal
influence was called "narrowed attention."

To test the resulting hypothesised correlation between narrowed
attention and central eymathomimctic activity. Galloway and Dsmbo (12)
enacted a amber of experiments the results e: which confined or
lent support to the hypothesised relationship. In each osperiment,
neurophysiological promotion by various sympathemirsetic drugs produced
narrated attention reflected in a reduction of the behavioral influence

7

 

 

 

 

of peripheral factors. The findings reported by Callouey ad babe
include l) chases in sise catching produced by ayl nitrite. by
epinephrine. and by nethsnphctaniae. 2) shapes in nycgrephic activity

to a tone of no decibels following administration of nerve asses. ayl
nitrite. and anphotsniae. 3) chances in Game to various Iii-ill sith
aabetaine. and 45) changes in grossing behavior produced by nethaahetaine.
The behavioral cifects of incrcaacd emathcninetio activity
provoked by drugs. in terns of narrcued attention. are likened by the
athors to those produced by sudden ad strong action. untiety. end
paic. Studies by Kinsey (33). Shipncn (58). and Rohn (36). are cited
as illustrative of the dimiatia and reduction of attnuion to peripheral
ad enviroaatal factors during aetlaal states. Evidace for gaping
the drugs used above and actions together as eyaathainetic activating
provocstore is presented by Calleay (9) ad Bradley ad Elias (3). A
further. and very inortsnt oonscn daeaisetor of syasthoninetic activa-
ting dross ad aotias is that they both evoke an ”alert" EEG by stint.
latins the brain-eta retiailsr formation. In imcdiate suggestion.
important to the purpose of the preaat investigation. is that stimla-
tin: of the brain-stem reticular {creation will produce a chase in
attaticn such that the behavioral influence of peripheral ad environ-
mental factors eill be dininished or reduced. i.e. it viii narrev atta-
tion. Conversely. it follows that a blockade of the brain-eta reticular
cyeta rill result in behavior characterised by an increased influence
of peripheral and environmental rectors. he. the opposite of narrowed
attention. In addition. if drugs. sections ad procedures which produce
no srasel also produce narrowing of attention. then it simld follow.
according to Callomy and Bad (ll) that any drug thich produces the

 

opposite of EEG arousal (i.e. BIO drminess) should also produce the

opposite of 'hierrovad' attention (he. "amend" attention). in test
the broadened attention hypothesis. Calloay ad land (ll) selected
atropine as the independent variable. Atropine ideally satisfies the
requirasnts for the continued study of attatlon by Csllcay and his
associates since it evokes hidi-qlitudc aloe-ave activity in the BIG
(he. a drowsy record) ad raises the threshold icr EEG ”arousal" by
inhibiting or blocking rsticular-fctnetia activity. attributes which
are cppoeitiaal to the sympathcninetic stimulant agate used in studying
“narrowed” attention.

’l‘hrceproeeduresuereossdbytallesayendladtcteet the
behavioral effects of atropine a normal healthy auhults. he of the
procaures. the Strap end Gottsciusldt teats. core selected because
aocesshul perfornace a each required subjects to concentrate and
attend only to those stiaii uduich acre sithia the central focus of
attatien ad to ignore or filter set all intrusive or interfering
stinuli peripheral to the iaediate focus of attatia. i'hese tasks
call for operations diich are core easily acoaallshcd ad patterned
by serenely attadins subjects shcrcea the third protease. the luchins
test. according to this interpretation. is performed more succesehully
by broadly attending subjects. lhc results unfirnu the above inlicd
hypothesis relative to the effects of s reticular subatace inhibitor.
atropine. in that performance on the luchins teat sea inuproved shile
that on both the Stroop ad Gottsohaldt tests was impaired.

These studies by Callouey and his group. conducted over the past
few years at the reyduiatric institute of the University of Maryland.
provide not only an important contribution to our understanding of the

 

lO

neurophysiological basis c! behavior. but perhaps sore importantly. sake
sore couprehonsible and understandable the results oi other investigators
by applying the concepts of narrowed and broadened attention to these
results. As an mic. Callouay and band (ll) cite the sort of Miles
(M) who dound that atropine decreased discriminating reaction-tine
udiile increasing aiapie reaction-tine. Atropine. by neurophysiologically
broadening attention. improved the subjects. capacity to discriminate

by enlarging the subjects' field of attention. in a sinple reaction-ties
situation. requiring the iiltcriag out at intrusive and interiering
stimuli. subjects did poorly because atropine-provoked broadening of
attention sound to direct subjects' attention to peripheral stimuli
ehich served as detractors and thus iapsired periosouuee.

Similarly node eore understandable in tense of the Calicoay
concepts o! attention are studies of the effects of psychological
provocation oi the reticular tor-nation. Pally (‘7) using threat to
create strong suction and thus stimulating the reticular systen cith
manying Etc arousal and increased swaths-lactic activity. pro-
voked narreuued attention in his subjects and obtained impaired performance
on the Luchins test. he iqlied earlier. test success on the luuchins
test requires brcsdnsd attenti- - attention to changing details of
the earlier problems peroitting siqler acre oeosoaical solution at
the last tun probl-s.

As a final sample e! the application oi the Csllcvey concepts
of attention to the understanding and explanation oi behavior so utilise
the results oi one oi Klein'- (3‘) nest provocative experiments. Very
thirsty subjects sore divided into what Klein called high interference

 

ll

lid loo intertercnce groupe (booed en Stroop teet paler-menu.) o- the
heeie of uhet hoe been eeid here, theee eroupe ney he cheruterieed ee
broedly end narrowly ettending groupe reepeetively. ‘i'heee thirety eut-
Jecte were ehoun e eeriee oi picturee (elected teehietoeeepiceily {or e
very short period of time) in the center oi ehieh one . object deeiened
to appeal to e thirety pereon. Peripherel to thie nuclei control object
were e number of neutral objecte. Recognition of peripherei objecte .0
noet difficult for the low interference group of euhjecte (the nerrouly
ettending group) mo were continuity drew: to the highly ettrective
central object. a: the other hend. the high interim group of enh-
jecte (the broadly attending group) vere ehle to iaore the highly ep-
peeling central object end explore more fruitfully the periphery of eech
picture.

the application of the nerrev lid brood mte e! ettention
to on understanding and exploration of the verioue heheviore eheerved
in come! heelthy euhjeete juet ceneidered my be mnded to eoeunt
tor much of the behevior mtly erpleined in ouch diveree ten-e ee
thoee invoked by oleeeieel lumen theory or the dynenic bulletin-e
o! peychoenolytic peychology. in e ei-ple eyelid conditioning eituetion
(60) high anxiety (increeeed nerroving of ettention) leede te nore repid
conditioning since the rether uncomplicated etimuiue condition requiree
little or no perticipetion of peripheral lecture for ecquieition. On
the other hand. if the conditioning eituetion is incroeeed in conplexity,
high enniety moon inferior perfomence. the would hypotheeite thet
decreeeing anxiety. end thue broadening the attention required to cope
with the complexity of the eituetion. would improve performance. Psycho-

enelytio and other psychodynemic iomletione, based on e theory of

._ — «VJ-i

 

12

threat and fear may be explained and described in part as the consequence
of the behavioral response associated udth the focus of attention (obvi-
ously narrowed in the case of severe emotional states) to environmental
stimuli. Characteristically maladaptive. neurotic end psychotic behavior
both represent a failure to utilize all relevant environmental cues which
would modify the perception of the stimuli considered threatening and
thus produce e corresponding change in reaction to such stimuli. within
the laboratory. both narrowed and broadened attention may be required,
depending on the situation, for successful performance in specific tasks.
Some of these have already been discussed; many more can.be suggested.
However. realistic adaptation to the requirements of social living demands
behavioral responsivity based on e broadened focus of attention. In
general, schizophrenic patients suffer from a catastrOphic restriction

of adaptability, no matter whether this consists of an inability to

react to the environment because of their pathological internal stimuli
(hallucinations),or because of their inability to realistically integrate
external events (delusions). or because of their inability to react at
all (withdrawal, stupor) (57). The ellouable interpretations of the
results of this proposed study might contribute to e further under-
standing ol this disorder in terms of neurophysiological correlates of

behavior.

 

 

'
l
e
l
- e
u
I

   

THE DRUGvINDEPENDENT VARIABLE

The drug, perphenasine (Trilafon). is en amino-derivative of
chlorphenothiazine. Chemically it is lO-(3-(l-(2-hydroxyethyl)oh-
piperazinyl)-pr0pyl)-2-chlorphcnothiaeine. The structural formula
is shown in Figure l. -

The core of the molecular structure of perphcnazine, as with F“
all the phenothiazins compounds. is the phenothiazinc nucleus (Figure i!
i). It consists of two benzene rings connected by s sulfur atom and
e nitrogen atom. Chlorpromssine. the prototype of the phenothissine
compounds by virtue of its early introduction and extensive investiu
gation, has s chlorine stem attached to the nucleus in the 2-position.
and s three-carbon "side chain” attached to the nitrogen atom of the
nucleus. The third carbon atom in the side chain is followed by another
nitrogen atom and the remaining vaiences of the nitrogen atom are filled
by two methyl groups (Figure 1).

Changes in the structure of chlorpromazine, at the end of the
carbon chain and to a lesser extent at the 2-positicn of the nucleus,
have been made in search of compounds possessing increased clinical
and therapeutic efficacy concomitant with reduced toxic risks and
untoward side effects (18, 26, 23).

Perphenazine, in common.udth chlorpromazine (Thorazine).
premarins (Sparine) and triflupromazine (vesprin) has a chemical
structure which includes three carbons in a straight chain. Freyhen
(18) considers this chain to be a characteristic of drugs included in

l3

N

CH2

CH2

I
CH2
I

N

/\

CH3 CH3

(Thorazine)
Chlorpromazine

 

14

Figure l

N

Phenothiazine Nucleus

 

"Cl e

N

CH2

CH2

0H

(Trilnfon)
Perphenazine

 

15

that he cells the ”chlorpromssine model.” The significance of this chain
in blocking mid-brain retimlsr systus sctivity, use pointed out by Iiiundch
(26). In addition to the three carbon straight chain. the structure of
psrphenasine includes s piperasins radical and. with prochlorpererine
(Comparins) and trifluopsrasine (Stelarine). is included in the group of
drugs Frsyhen has called the 'proclorperasins aodel.' interesting. end
important for the present study, is the observation that drugs possessing
the pipernsine radical are said to produce.alsrting. arousal and stimu-
lsting effects (23). An equally interesting and.provocative observation
is the structural similarity of the phenothissines to the entiodepreesivu
drug imipramine (Tofranil). Hinwich (26) regards this drug as s stimlent.

Finally, adding to its intriguing possibilities. perphenasine.
when first introduced early in.l937 use heralded as s full-range tran-
quiliser recommended in various dosages for treating the entire spectrum
of nationally disturbed pstisnts (11).

Preliminary clinical investigations summarized by Schsring
Corporation established perphenesine es s potent tranquilising esent
uith important behavioral effects. Anxiety. tension, apprehension. esp
greasion, psychomotor hypsruactivity and fear have been found to be re-
lieved following moderate dosage chemotherapy with this drug. The broad
sternctic action claimed for'perphenasine is such as to quiet and relax
patlgnt.*u1thout dampening or reducing awareness. Patients are said to
exhibit renewed interest in their work and surroundings. The emotional
stabilisation produced by this chemical compound is reported to increase

the pstisnt's capacity to respond to psychotherapy and other therapeutic

MMNIe

 

 

16

.Also, at moderate dosage levels, the*more serious side and
toxic effects have been observed infrequently or not at ell. Photo-
sensltivity, despite deliberate attempts to elicit this experimentally,
has not been produced. Repeated studies of liver function, blood.
urine, and visual fields have not revealed perphenasina-induced abnor-
malities. Although jaundice. bone-narrow depression and narrouing of
visual fields have been associated uith the use of various other tran-
quilising drugs, they have been notably absent in studies with path
phmzinc.

The only serious side reactions reported are extrapyramidal
symptoms, at times simulating those at the Parkinson syndrome, uhich
occasionally occur following high doses (20 mg. daily) of the drug. A
decrease or withdrawal of the drug quickly abolishes this reaction or
it medication must be continued. control oi these symptoms can be
achieved by the concomitant administratien.of en anti-Parkinson drug
such as benztropine nethenesulfonste.

Side reactions of a less serious nature from the medical point
of vieu'heve been.observed. These include blurred vision. nasal conges-
tion, and constipation. mly eild hypotensive effects have occurred
Uhich in my instances are believed to be associated with relief of
anxiety and tension. Mild insomie and motor restlessness, easily con-
trolled by othaeraans, have been reported in some patients. Hypnotic
effects are minimal (18).

Published studies reporting on pcrphenazine in addition to

strictly clinical triels have not yet appeared in large embers. Ayd

(I). treating tumty-iive elderly psychiatric patients (age range 60-80

   

17

years) uhose predominant symptoms were extrema anxiety, agitation and
excitement found perphenazino clinically effective in those disorders
in which anxiety is paramount.

Cahn and Lehman (3) administered perphenazine to eighty-four
female patients and report perphenazine to be a useful and safe agent
in the treatment of acute and chronic disorders. As with the Ayd study,
lack 0! controls weaken the interpretative aspects of the study. In
both studies, aide reactions were mild and when they did occur were
quickly abolished by appropriate counterumeasures.

In a preliminary report. Mason-Browne (42) presents some tenta-
tive findings with perphenasine. A more detailed account of this same
study is presented by Masoanroune and Borthuich (43). They treated
seventy-five chronic patients (36 males and 39 females) with a mean
age of 41.8 years. All the patients displayed anxiety and over-activity,
or were problems in management. The double-blind technique use used
udth patients divided into three groups of tnenty-five. The three
groups were each subjected to a different treatment schedule; Group I
was given perphenazins 16 mg. t.i.d.; Group II. chlorpromazine 25 mg.
t.i.d.: and Group III, an inactive placebo 25 mg. t.i.d. All medication
was taken orally in tablets of the some shape. size and color. Duo
ration of the study was thirty days. Urinary, blood, and liver function
tests were made before and after the trial. Blood pressure, pulse,
respiration, nausea, restlessness, anxiety. alertness, confusion. and
insomnia were charted daily. A quantitative evaluation of behavior
(acute anxiety cluster of the wittenborn Rating Scale) was obtained
pre- and post-test. Patients were also measured on a battery of tests

consisting of tapping, dotting. digit symbol, digits forwards and

 

 

 

18

backwards, and Porteus Mazes. Perphenazine was significantly effective
in alleviating acute anxiety. In addition, teyping and dotting perv
formonco was significantly superior than that with either chlorpromazinc
or placebo. No differences were obtained on other performance tests.
All tents, udth the exception of the Portous Mazes, showed the greatest
change towards improvcmmt in the group treated with perphenaeine. The
placebo group showed the least change. In this study, the authors conclude
that the drug acts principally on the alerting system of the brain stem.
Its potency is placed at Siva to ten times that of chlorpromezine. and
its therapeutic ratio is improved. Side effects were minimal. The term
sciatic is substituted for trenquilizer which 10 considered a misnomer
since. in the Opinion of these investigators. these drugs affect crude

or basic consciousness.

 

STATBdEN‘l' 0? m PROM-m

rho roe-it cocoon-Into o! phomoooiogicol Ind wrophyoiolosicol
odvmooo, oopooiolly with roopoot to tho odvont of tho truquiiioins
drugs aid tho furthor cioriticotim at tho tunotim of tho mid-brain
rotiouior oyoton. roopootivoly. hoo oponod up now orooo of investigation
into montol illnooo. i'ho litorotnro on tho tronouilioing drop oill not
to rovioood ot thio tioo oimo with o! it io not portinut to our probioo.
Hitler (63) hoo providod o room at! pointokina roviov oi tho invooti-
utiono routing pharmacological Mo to tho dio'ooio. mutation
and trootmont o! poychopotholoaiool ototoo. hortoot tor tho promt
invootigotion io tho: thoy oli pronto oidahroin roticulor (collation
octivity (2. 25. M). in vioo of tho otudioo by Colloooy om! hio oo-
oociotoo which roioto W in tho toouo oi ottutioo to Mo in
oid-broin rotiailor activity. tho otoorvotiono of. Rio-id: (27). Rinoldi
(Si) and Rinaldi no Hiuoioh ($2) oro both intorootins and provocativo.
Thou invootigatoro ouggoot thot tho ottoct on mid-brain rotimlor
activity of low-don phonothiaoino dorivotivo drugo io inhibitory: high-
dooo. otimloting.

Tho proqu to ho invootigotod in tho promt otudy my thuo bo
ototod oo follow: it difforont doooo of o phomthiooino dorivotivo
drug hovo diiforout otfooto‘ at tho ootivity of. tho mid-brain roticular
mton, and thou in turn oro rotlootod in diiforancoo in patient bo-
hovior, thou pationto trootod with ditioront mnto of tho drug ohouid
porfom differently on tooko calling for oithor nomd or bmdonod

i9

 

ottontion ond thooo ditforencoo ohould bo opplioohlo to oxporimontol

otudy.

'iho to major hypothoooo to ho tootod my to ototod opooilioolly

oo follows:

I.

II.

Pationto treatod with porphmoino in dooogo mu
proouuod to otinuloto tho hroin-oton rotioulor
oyotom will porter- bottor on o tool: wiring
”narrowed” ottontion (mdiliod snoop toot) thou
will. potimts trutod with Who in doom
mt: proomod to inhibit. doprooo, or block
broin-otom rotiwior oyoton activity;

Pationto treatod with porphmoino in doooao motto
presume to inhibit, doprooo. or block tho broin-
oton roticuior oyoton will potion bottor on o took
roouiring 'hroodonod" ottontion (guoooing mo)

than will potionto trootod with porphonooino in
dooogo omounto proounod to otinuloto hroin-otol

reticular oyoton ootivity.

 

METHOD

Sub jocts

Sixty female echimphrenic patients at Kalamazoo State Hospital
served as subjects in both emeriments of this investigation. All were
medically cleared of physical and sensory involvements. Each patient
was clinically considered capable of comprehending the experimental re-
quirmonto end of participating cooperatimly. A emery of the charac-

teristics of the patients may be found in Table l and 2.

Material:

   

Task I (lhrroxnd Attention Task)

me materials are modifications of those esploycd by StroOp (59)
to study interference. Described by llmrstone (61) and more recently
«played by Klein (34), Collomy and Bond (11) and Brovcmsn and Lemma
(6), the procedure involves the simltoncous presentation of two etimlus
attributes, color and shape. which are inherent aspects of the same syn-3501.
In the present inwstigetion. the superimposition of one of the four
primary colors on one of the four simple geometric figures selected met
the criteria of ixflxerency mid simltancity of presentation. The eatperi-
mentsl materials for this task consisted of three 15" x 20" test cords
and three 3” at 4" conceponding practice cards.

Test Card I (Figure 2) contained ninety-six geometric figures
each black-outlined on white and one inch square in also. An equal

timber (twenty-four) of squares, circles, crosses and triangles were

 

 

 

 

 

 

 

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and . om em mad p om ems oH um
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mma Ha mm mod N mm mea «H w:
saa ma Hm Hod m: mm Hod ma mm
med ea mm mom :H mm mos ea om
and ma NH mma ma om ems ma em
Fwd ma pm mud we mm maa NH mm
flea NH m: ::H pa mm mea ma he
Hod om m: Asa m: m: _ maa ma Fm
oma we a: med :: a: mad mm . Pm
mad. mm a: ooa am m: 01H mm mm
mad em m: med . mm mm mos gm Hm
.Hma so we com um m: mma . we a:
a. med mm mm mad .sm pm mam Hm mm
2
ema Hm mm mad om mm mom Hm 4m
mma Hm mm was am pm Oma. mm om
mod mm m: Hma mm m: mza mm :m
mea pm em mom mm m: :ma mm . am
oaa H: om ooa mm m: ems o: . m:
mfigom mfipfloz GH 9“”me monfiom 39.202 GH mhwmfi wdfisbnw BPQQS a.“ mHmle
as nofiomNHaepfiemom no mw<. ea nofipeefiaepaemom no «me me aoapeafiaepsmmom a“ uw<
cameos. co apogee pawfioz mo apogee pnmflm: mo name»;
Aom u zv moose opmoeam .Aom u zv moose muse swam flow n zv macaw more see

 

ZOHBEEOAH momdflmmm .mo mOHBmHmHEoiqmdmo ho 533m
E

 

 

n 35.3..

 

 

table 2

mama»: or mmmcmntsncs or um ems use) In me ran-3m mm

 

 

 

W
_ Mean ngth of

Matmmt ll Mean Age Hospitalization Mean Heiglt

to”. . f t 9“. my”. .inA Months ; , in Pounds

Law Drug . 20 38.35 23.55 : 148.25

Higx Drug ‘J 20 : 39.53 . 26.1.5 153.25

 

 

Value of P from an . ‘1
analysis of variance , .39 .33 . 1.66
batman means ' ‘

 

 

 

'-' 'III '4‘;

2 tor 2 and 57 4.1. . 8.3.

 

.
l ' I C 0 v * I
W t *
W w

 

a

.UO#AOD¢ADO¢A

.OfiADAéUOAéOU

ADO¢DOA#OAD¢
u. sAvAUOAvAODAvn—AO

 

 

, .MLAerouoaoaeD.
.¢ADOA¢DOD¢OA
_oeaueaoneuao.
“Doeauoaeaoue:
r111: , :1z:4 I, ,‘, :;‘ -:+:‘:s':riar.+i _‘ 1zt

 

 

25

arranged in eight columns and twelve rows such that each figure appeared

twice in each row and three times in each colmm. No figure succeeded
itself in any new or colum. All figures were separated on all sides
by onedhalf inch.

Test Card 11 (Figure 3) contained a total of ninety-nix.oneoinch
circles. An equal number (twenty-tow) were tinted in each of the four
primary colorSI red, yellow; blue, green. Each color appeared twice in
each of twelve rows and three times in each of eight columns. No color
succeeded itself in any row or colum. All colored circles were sepa-
rated on all sides by one-half inch.

Test Card Ill (Figure 4) contained a total of ninety-six one-inch
colored geometric figures. The figures and colorc'worc identical to
these used on Test Cards 1'. and II, respectively. Arranged in eight
columns and twelve rows, each color and each figure appeared exactly
twenty-four times, twice in each row and three times in each calm.

No color or figure succeeded itself in any new or column. All colored
figures were separated on all sides by coo-hall inch.

' The corresponding practice cards contained we each of the four
geometric figures used in Test Card 1: four circles each tinted in one
of the primary colors used in Test Card ll: and one each of the four
geometric figures each tinted in one of the four primary colors as in
Test Card 111.

The stimlus materials oere dram and enter-colored by a graduate
art student on No. 74 (heavy weight) fli-Art hot-pressed, white illustra-
tion board.

Subjects were presented with the Test Cards in.tho following

order - I. II, III, III. Each one preceded by its corr89pondin3 practice

 

 

26

Figure 3

 

.‘CQQCFCC
c.

OOCCOO'Q £7
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27

Figure A

 

 

 

 

 

card. Practice cards were placed flat on the table, face-up, directly
before each subject. Test Cards were placed upright at slightly‘more

than e 90 degree angle on a stand fifteen.inchc3 from the edge of the

table and directly in front of each subject. Each Test Card was con-

cealed by a blank card which was removed for the test proper.

Each subject one asked to name the four shapes on the practice
card for Test Card 1. She was then told. "Underneath this empty card
there is another one with lots of shapes on it just like the four on
this little card. You are to name these shapes as fast as you can as
soon as I take this blank card my. Do the top row first and than.
without stopping, do the next row and keep going until you've done the
whole card. Are you ready? Go ahead!” The blank card was removed
immediately after the directive, go ahead! with the simultaneous
activation of e hand-controlled stop watch. Upon completion, Test Card
I one removed from the stand and replaced by Test Card 11 nhich was
covered by a blank card. The practice card for Test Card 11 was pre-
sented to the subject udth instructions to name the four colors in.which
one each of the four circles was tinted. Testing with Test Card ll
proceeded es‘uith Test Card I. In the instructions to the subject, the
word "colors” one substituted for the word "shapes." Upon completion,
Test Card I! was removed from the stand and replaced by Test Card III
which one concealed by a blank card. The practice card for Test Cord
ll! was presented to the subject‘with the following instructions: "On
this little card there are four, colored shapes. The colors and the shapes
are the same as the ones you named before. I want you to name the four
shapes only and pay no attention to the colors. Just tell me the names

of the four shapes on this card just like you did before and pay no

 

 

 

 

29

ottmtion to the colors.” Following the subject's comprehension of the
task, she was given the following instructions: "Now I'm going to unc-
oover another his care on which there are many colored shapes. 1 want
you to none only the shapes on this card. Remember, only the shapes and
pay no attention to the colors. Just so you did before. do the top row
first end then go right on to the next row vithout stopping. relate all
the shapes on the cord as fast as you can without stopping. And. member,
pay no attention to the colors." The processors at this point was similar
to that anployed with Test Cards 1 end 1!. Upon omplction, ‘reet Card
III was retained on the stand and immediately covered by the blank card.
The subject was again presented with the practice card for Test Card Ill
and was told! "This time, I want you to none the colors on this little
card and pay no attention to the shapes. Reamber. just give me the
mes of the colors.” tolloving the subject's emprehension of the task.
she was given the following instructions! "l'm going to show you the
sum card you saw a little uhilo ago, the one with all the colored slmpes
on it; This time I want you to me only the colors and pay no attention
to the shapes.” The remaining instructions and procedure mm similar

to those used previously with this card with the appmprinte interchange

of the words "colors" and ”shapes."

Task II (Br-cadence Attention Task)
The materials and procedures for this experiment were suggested
by techniques originally used by Humphreys (29) and later by Grant (20),
Bruner at al (7). and Cellmmy and Dmbo (12). Subjects are required to
guess which of two equally likely events will occur and then observe

whether or not the guess was correct by observing the event. After each

30

event observation, 3 new guess is made. followed by another obser-
vation, etc... throughout I series of trials. The frequency of the
two mt. is then changed such that one of the two want: become:
nor. likely and the other. less likely.

The materials used in this investigation were designed for
individual administration and consisted simply of 3 x 1. inch cords
wt frat No. 74 (heavy weight) iii-Art hot-proceed, white illustration
board. In the center of the face ride of each of these cards in o
one-inch red or blue circle. Set l consisted of ten cards. Five of
these cards contained a red circle; and live, a blue circle. Set it
also consisted of ten cords. On eight of these cards, the circle was
red; on too, blue.

The subjects were first presented with Set I and given the
following information and instructions. "Hero is a stack of cards.
0n cone of these cards, there is a red circle (subject is about a card
with red circle on it) just like thin one. and on some of the card:
there in a blue circle (subject in them a card with a blue circle on
it) just like this one. Romanber non. some cards are red; and coon are
blue. the going to mix then up just like this (cards are shuffled) so
that we don't know which cards are red and which are blue." Cards are

then placed in a stock, face com, before the subject. "I would like

you to 9.198! which color is on the top card. Recenter, it has to be

one of two colors. After you guess, I'll tum it over so you can see

mat the color really is. Now make your guess.” As soon so the subject

makes her guess, the card is turned over and the cminer says, ”it is

a (none of color) one" and pieces it aside, face dam. The subject is

 

 

 

 

   

31

asked to make a new guess for each card in the stack after uhich the
card is turned over, named by the examiner, and placed in the discard
stack,face down. After completing the series of ten cards, 8 shuffles
them for approximately fifteen seconds during which the subject is in-
formed that the procedure is to be repeated. Three series of guesses
are obtained for Set 1. After the third series. Set it is substituted
for Set I and placed before the subject udthout comment. Ten series of

guesses are obtained with Set 11.

Procedure

The sixty female schizOphrenic patients who participated in
this study were randomly assigned to one of three groups of twenty
patients each. Each of the groups use than assigned to one of three
treatment schedules by a blind randomization procedure. The medication
schedule for each of the three groups was determined on medical advice
and approval. Group “D (high-dosage perphcnazine) received 48 mg. of
perphenasine daily; group LD (low-dosage perphenazine), 12 mg. of
perphenasine daily: and group r (perphenacine plecebo),en inert saline
compound. All tablets administered were identical in size. color and
shape. Each medicated teblet contained bwmg. of perphcnszinc. Each
patient received s total of 12 tablets e day. Group RD received four
ewmg. tablets of perphenazine. t.i.d.: Group LD, one 5 mg. tablet of
perphenazine end three A mg. perphcnazine placebo tablets, t.i.d.: and
Group P. {cur hung. perphenazine placebo tablets, t.i.d.

All patients included in the study were withdrawn from all
Previous medication for e period of at least three full days. taperi-

mental medication, following one of the three schedules adapted for

 

'w

n

n. w
“4.5-

 

 

32

this investigation. contimsd for three caeseutivs days. teats oars
conducted on the day following conpletion of the nedieaticn schedule.
The subjects were mined in a randomised order pith the assumes of
the two tasks reversed with moccasin subjects. the conduct of the
investigation, relative to all the randomisation aspects. no controlled
and supervised by a colleague.

‘i‘he double-blind condition as present throughout the study.
i.e.. neither this investigator nor the patient us aware of the map
to with she use assigned nor the nedicatim she had received. i'hs
meaning of the tasks to the subject use not investigated in the present
instance to the extent of obtaining quantitative and objective data. All
evidence however. including apontmccus seanents cf the patinte III vard
lid medical personnsi,indicated that the patients viewed the tasks as tests
of speed, mental alertness and of intelligence of some kind. As such. it
is considered highly likely that each patiut was set to participate and
respond optimally. Each patient one told that she was being asked to
perform a umber of tasks wish vouid provide the medical staff with infor-
mation useful in its efforts to help her. All observation were node
individually in the suns room under relatively constant conditions of
illumination and room tonpcreturc. Punishing: and equipment in the room
care not novod or changed airing the period of study. lhis included the
e0 n M n 30" table shieh provided the surface on «rich the test materials
vars placed. The subject and minor sat at adjacent sides of the table
oith the subject seated to the left of the miner eluys in the ease
pcsitim in the soon. A 200 utt bulb uspcndcd directly abcvo the table

he used to illuminate the test materials. No shadows were cast in any

 

 

 

 

   

33

instance. The physical conditions are thus considered to have been

relatively identical for all patients.

 

   

 

RESULTS

m t I d A t t '1'

Table 3 marines the performance scores (to the nearest whole
second) for each subject according to the experimental conditions. The
anaeriment provided each subject with too opportunities to respond to
one of too simltanecuely presented atinuli each of which use an in-
herent aspect of the same symbol. a colored geometric figure. In the
first instance. the subject was to time shapes while igioring colors; in
the second. name colors uhi ls ignoring shapes. Difference scores betvesn
times taken to name one stimulus alone and time to ones that ems stimulus
in the presence of the second interfering stimulus served as the basic
data for this snpeflnent. 'l‘he algebraic addition of s ocnstnt eliminated
minus values and rendered the data more manageable without violating any
aspect of the statistical analyses and allowable interpretations. me
too sets of difference soorse vans plotted separately. Since sash distri-
bution of source was approximately bell-shaped. no transformation use neces-
sary. A rearson product-moment coefficient of correlation. r I .1“.
between the too sate of difference scores for all sixty patients indicated
that separate analyoco should he made. Table A sunnarisee the moan perb»
formance scores. in seconds. ofvthe three groups of subjects according
to the experimental conditions. Separate t tests were made between the
mean performance scores of the high-drug group and the low-drug and placebo
amps in naming geometric figures in the presence of interfering colors.
(Table 5.) The resulting ; ratios of 1.57 and 1.35 for 38 degrees of

3b

   

 

   

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mm mm aaa ama ama mma mm mm 0p mm am moa om we mm pma .maa amm
mm moa mm ooa om mm aoa maa moa mmm moa pom am om pa am mm ap
aoa am mm mp am am ooa oaa mm pm mm pp . ap pm aoa mma mma mpa
an m: om mm mp maa pm woa om moa mm ooa aoa om ow ap mm am
aoa mm op aw mm mm mm mm am mp mm mp mm mm mm moa :p aoa
maa maa mam mam apm aom aoa waa mm ama am oma maa mm am 0ma mp mma
mm mm mm mam mp omm aoa ow ap am pm aoa maa moa am ooa am mm
om mp op aoa om mma am paa am maa ooa oma mm mm mp mm mp poa
woa mm mm mma om pma ooa am mm mm on am pm maa pm om om pm
aoa mm aoa moa ooa pma oaa moa mm maa mm paa moa ooa mm mp am mp
u“ moa me am oma mm mpa maa maa mm moa mp om moa ooa mm mp mm mp
woa mm 0p ap am mm mm aoa mm mp an ap mma pm mma mm mm moa
ooa mm m: om ma mm moa maa amp ama mp mma am pm mm pm am ooa
ooa aoa mp mm mp am aoa aoa mm mp mm pp aoa am am mma om ama
moa ama mma mma maa mma moa maa mp mm mm pm aoa mm mm moa pm ama
mm aoa mm op om mp aaa mm mma mma maa oaa oaa moa mm moa mp ooa
mm am an mp mm mp mma mm omm aam amm mam maa mp ama oaa aaa mma
mm ooa ooa pma moa ama maa mm am mm on moa oaa oma pma mpa pma mma
mm mm ap am mp moa mma aoa ama ama mm mma mm mm mp mm pm poa
ooa mm mm pm mm mm mm mp mp moa om mma aoa mm pa mm ma pm
ooa + ooa + E HHH H a ooa + 8a + E Ha Ha a ooa + 02 + B Ha H H
HH->H H-HHH HH->H H-Haa HH->H H-HHH
Emma , . $39 $39
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table i

 

PERFUME SOORES ON A MDIFICATXM 0! m "SM” TEST 0! man: ms
OF PATIENTS TESTED UNDER Dim mm mm

 

 

 

 

 

 

Changes in ferfcrnence
M a o
1 11 III IV 9 100 9 100

new Drug 20 115.50 81.60 106.55 83.1w 92.05 101.00
High Drug 20 119.55 86.30 119.60 92.55 100.05 100.25
flaoebo 20 128.85 90.“) 120.20 89.15 91.35 98.75
* 1 - Netting Geonetric Figures vixen presmted alone.

11 . liming Colors than presmted alone.

111 :- Naming Geanatirc Figures in presence of interfering Colors.

IV - Naming Colors in presence of interfering Gonnatric figures.

 

 

-".~"~~""*‘W?M a, . ——-— ‘j‘ ' ‘

 

 

 

57

Table 5

 

 

MARISON Ol' PEWE CHANGES ON MDIHCATIONH

0F armor TEST DUE TO INTERFERENCE
(Naming Gmtric figures in presence of interfering Colors)

 

 

Treatmnt .
0 g It Mean Score Differntce t
Lou Drug 20 92.05
8.00 1.57
High Drug 20 100.05
8.10 1.35
Placebo 20 91.35

 

 

 

 

 

* Time in seconds for naming Gee-atria flames in presence of
interfering Colors - ties in seconds tor nsning Geometric

figures alone 0 100.

 

 

38

freedom were found not significant. High-drug dosage may therefore be
considered statistically indistinguishable in its effects as compared
separately udth low-drug and placebo medication and the null hypothesis
of no effect is tenable.

Similarly, a comparison chmeen.performance scores of the high-
drug group and the loubdrug and placebo groups in naming colors in the
presence of interfering geometric figures resulted in‘g,retioe of .88
and 1.69 (Table 65. For 38 degrees of freedom neithsr'of these is sigp
nificant and the null hypothesis of no effect udth regard to highodrug
medication is tenable. 1n emery. high-drug medication may be con-
sidered as having,no significant effect on performance of the hind
called for in this superiment when the two performances are considered
separately. Since the differences shown in the last tun columns of
Table A are parallel. on analysis of the combination of the tuo‘might
prove fruitful (Table 7). A comparison.of the mean combined performance
scores of the high-drug group and the low~drug group resulted in e‘s,
ratio of 1.77. For 38 degrees of freedom, this is not significant and
is in agreement with the results of the separate analyses. A comparison
of the high-drug group and the placebo group resulted in n §.ratio of
2.15 which for 38 degrees of freedom is significant at better than the
.05 level of confidence. it may be concluded that combining the two per»
fomancs scores results in a more sensitive measure which barely reaches
the conventional level of confidence. The direction of this effect is
apposite to that predicted. The first of the major hypotheses of this
investigation is thus considered not confirmed according to the experi-

mental conditions and statistical analyses employed.

 

Table 6

CMARISOII Ol‘ renounce CHANGES OI EDIYICATIOII

”WMWETOWWB

(ll-in; Colors in presume of interfering Geoaetrie Fimm)

 

 

"“h‘“ l M s D its e t
can Score i rene
lee Drug 20 "11.80
It.” .88
High Drug to 106.25
7.50 1.69
Placebo 20 98.15

 

 

 

 

 

* Time in seconds for nosing Colors in presence of interfering
Cemetrie Figures . time in seomds for seeing Colors alone

0 IOOe

 

 

 

 

table 7

CGiPARISON OF CMBINED fERlDRMANCE CHANGES 0N MDIHCA‘HG‘
OF arm TEST we 1'0 WWMCE

 

 

Treatment
Group I Mean Score Differ-ice . t
low Drug 20 m.“
11.90 1.71
High Drug 20 206.30

15.80 2.14
'1...“ 20 190.00

 

 

 

 

 

   

51

gépcrinent If (hrogdonchAttcntion_Tosh)

The performance scores for all sixty subjects are summarized in
Table 8 according to the echrimcntal conditions. Mean performance scores
for each group for each trial are presented in Table 9.

Figure 5 is a graphic representation of the group data in Table
9. The number of guesses for the "less likely” event over the last eight
trials served as the basic data for this experiment. This decision was
based on an inspection of the performance curves in Figure 5 which illus- '-
tratcs graphically the systematic tendency of the low-drug group to ma}: r
loss guesses for the less likely event than the other two groups over E
trials. .Accordingly the data were subjected to an analysis of variance
involving repeated.measuremonts of subjects in independent groups (16).
In the analysis between the loundrug and high-drug groups, Table 10, the
main effect of treatment method is significant (F - 0.4li d.f. - l and 33;
p (.05): the main effect of trials is also significant (F a 3.70: d.f. - 7
and 2663 p.001). The significant interaction variance, treatments x trials.
(F u 6.54; d.f. - 7 and 206; p (.001) is interpreted as meaning that the
obtained difference in trend among the two groups cannot be reasonably
attributed to chance. As a product of the joint effect of method and.
trial, the interaction variance tollsnusthat one of the treatment schedules
(low drug in this instance) is more effective over trials.

The analysis between the low-drug and placebo groups (Table 11)
further strengthens the suggestion that low-drug patients are provided
vdth an advantage in performing the task presented over trials. The main
effects of treatment (P - 10.33, d.f. - l and 38: p (.01) and trial (F a

$.05: d.f. a 7 and 266; p .001) are both significant. The interaction

 

variance, treatments 3 trials. is also significant (F - 3.23; d.f. - 7 and

266; p (.01).

 

Table 8

 

S

ON EACH OF THIRTEEN TR A

UENCIES FOR UNLIIGILY COLOR (BLUE) OF PATIEh.

CI

SUMMARY OF GUESS FRE

42

 

 

 

 

 

my Hmmmm :tmmd: mmlnmm \OMONN
a H:NHO wmmmm mmmdo :NNHH
4:. OWNHO \OWHO: LnLRLnLth lanmO
S mwwmo msoom wmm:m :momm
g (n NMNNH :amm: mamwm wmdmm
"Em :mHMH mmomm mzmzm MNHMN
53F (“£1“de ”\NNNLA \ozmmln mmmmm
gigs-'0 mmmmr— CONNNm naming :mdmm
E in m-zi‘dd'i‘ MOOWLA U\.;i-U\b-U\ U\IA\D—:YN
m : mmamm swamp W#WPM W#MN©
m mmxoxoxo \Ompmm mammtnm .:i*U\Lr\U\\O
m mmspm mpwmm :mmmm woman
r-i mmzmoo .zrooxo-nxo mpmwm memm
m madam mommo WOJHH Ndmmm
fl asmwm moaoo sormm NHHmm
fl Odmmm momHO mosom mommm
8 g onm: mooma'mammfl moamm
: m Hmmw: moomo m#mNH momgm
5*u) H:me mNHdO WNMHN momo:
mg» mswgm mmomo mmmom :HWJ“
gfim :swgm mmsmw wmmHH MHHmm
in U\ Ind-(132:1- \Otnmr-Im NNWW‘ND mem—zr
m : mmhg: mmmpm :mwsw mmzmm
m :mwwm mmmg: mwmpm mswsm
(\i ll\l1'\\Ob-.;f U\\O\Omlf\ \ouvou'x: \D\0u'\U\.:i'
r-i dwmxom Ind-NJ“) \Ommmm Lf\.d'l!\|!\ll\
Q moamm HONOO mmmo: HHNON
fl maam: mwwma ONHON NNNNO
fl NJONH mmomm HHHo: zoama
A S Ndoam NHNHH oomom NNNNH
8 m mmHNN HJMHO NHHHM HO:NN
:Ew :HHMM mmaHH :Nmo: :mmoo
‘33» MOOMH HNmNN HmNHm :JMHH
gam maowm Hmzmm HomH: :Nmmo
g in \o.—n~\om Ni‘\O\D\D 0‘30me :rmmmm
: mmsmm FNNNW :mmm: mammm
m LAUNLA\0\D "\\OU\\DU‘\ (“maid-KO :0?)me
N \omsmm Inuuntnm ggmuun \D—d-dt—‘tm
H smmmw mwawm #Pmm: mmsmm

Actual ratio of colors for first 3 trials, 2_§}EEJ for last 10 trials, 2

 

 

Bhg
Rd

SRfi

*

 

‘3

ones axoaum N gene—nu a!» Hula Man ”you axoaun n oenumuu oouau «chum you aheaou no Dane: C

 

 

 

2 .n nhé 8.." co.“ On.n on...“ 005 an; 8.0 an}. «06 nn.n mm .m. on enough
83 no." «fin no." 36 no.“ as; 2.6 nn..~ 86 anon 86 83 on man an:
on." o.—.« mm.“ on; 8..“ ON.“ an." nn.N on; 3.n ca; on; 8.... ON web 33
mu 2 S S o m p h o n a m N a
33.5. 95.5
z assuage

0335 houou 393.25 be someone no .3952 E3:

monHHn—zou Egg Hzmmmhmuo cues magma mguuuka ho mgg ugh. he was“. toznmwmag < 20 mmzoum ”Drama—Emma

o 0.3:

 

Table 10

 

ANALYSIS 0? VARWCI 0' "mm '60!!! or M mm 0' PATIO“!
TESTED MR mm mm Mina“ (LOU-DOS! AID HIGH-NI!
DRUG) urn um TRIALS 10! EACH cm

 

 

”I!“ 0! he
Variation n- o! W d.!. 5100!! r
let‘s-i Treat-ate 95.1! l 93.71 t.“
let-In patients in
use m m a 21.69
total between
patina 920.00 39
lets-a Trials 38.08 7 S.“ 3.70
lnterectiau '
Trials I treat-ante 67.32 7 9.62 6.55
htmctius peeled
petinte I trials m,“ a 1.57
mm vithin ‘ ‘
pun-u 92.2.9.2 .232
total 11.17.00 319

 

 

 

 

 

 

 

ANALYSIS OF VARIANCE 0! PERYORMMCE SCORES OF A cm OF PATIENTS

table ii

 

TESTED UNDER DIFFERENT TREADIKN‘I’ MIRRORS (Low-DOSE DRUG AND
IDFNTICAL PLACEBO) mm mm TRIALS FOR m cm

Source of

 

 

 

 

 

 

Mn. *
mum frames 123.00 Y 1 125.00 10.33
let‘s. patina in
0- m M a 1 12.2:
Total between
patients 587.20 3’
m MIll 50.10 7 ’01“ ‘0‘,
Interaction: ' l ,
ma. 3 trectuntc 36.50 7 5.20 3.23
Interstitial: peeled
patients 3 trials M 163 1.61
Total within 1
p-mnc- mm as
Total 110‘.” 1 31!
M A ‘ ‘

 

 

 

 

     

O
I
O
I
. c
u
o

 

Reference to Tables 10 and ll will reveal that one error term as

used for the test of similiconco tor trunncnts and o second error tons
for the tests of significance for trials and interaction. it is to be
noted that the test of significance for trutnonts is booed on indopondat.
randomly assisted groups of patients. idioms the tests o! significance
ior trials and interaction between trials and trout-nits is based upon

the cans pscinitc involving possibly the presence end street of corro-
lotion. loose-o of these considerations, too diiioront error tons on
cdvissble; one (or the possibly consisted dots obtained iron the some
patients ad one for the dots obtained tron independent groups of rmdonly
assisted patients.

In armory. low-drug nodioctim my be considered so having s
significant effect on portonnsnco oi the hind called for in this savori-
mt. The second of the major hypotheses of this investigation is thus
considered confirmed according to the onerinntcl conditions and stop
tistiocl analyses enploycd.

 

DISCUSSION

The results of the two marinate of this investigation may be
viewed as failing to support the hypothesis that “patients treated vith
perphenasine in dosage nsounta presumed to stinulate the brain-star
reticular syste- will perform better on a task requiring narrow attention
than will patients treated nith perphnasins in dosage counts procured
to inhibit. depress. or block train-st. reticular systea activity" and
supporting the hypothesis that “patients treated aith perphesssina in
dosage unonnts praaued to inhibit. depress. or block the train-stem
reticular system nill parforn better on a test remirins broad attention
than will petiuts treated with pesphsnasins in dssass mounts presumed
to stimulate brain-stem reticular oyster activity." in View of the above.
a re-enminatian of the walnut“ osnditicns see-s urranted.

A raven-insticn of the natarials used in both the mt.
of this investigation serves to reaffir- the original sans-ption that
the three essential eaperinsntal require-ants tor the observation of the
locus of attention as caneeptealised in this study are tulfillsd. lines
introspective reports of the outset to Inich a person ignores or utilised
peripheral factors are unreliable, inter-stint about the focus of attuti.
met some ties inferences based an observed behavior (10). if factors
lying outside the central locus of attention easily influence behavior.
we nay infer that the process of withdrawing from or ignoring peripheral
factors is minimal and the toms of attention is broad. lf peripheral
factors are effectively ignored such that the process of withdrawing

b7

m:£"¥71‘~_' eat; 1'; 2::

 

 

from than is urinal lowing to little or no effect on behavior. than

it can be assumed that the tone of attention is norm. these obser-
vations. translated into ennerinental lore relative to behavior.havc
three regiments which are prenaed inherent in the sunniosntal
netsrials c! this investigation! _

l. Both tasks present situations in ohich the subject's

attentiu is directed towards one aspect of the current

environmental situation.

2. lath techs precut stint“ with are tuned iron the

central tonne of the subject's attention.

3. Both teats provide a season of the subject's behavior

with reflects responsiveness to peripheral stiuli.

The adoption cl daily docaeu of l! and it no. at pctphanasine
es medication levels ehich would press-ably depress and activate. rs-
spcctively. the mid-brain reticular oyster. though hosed on the corroborative
advice and approval of a teacher of. physician-psychiatrists. not be con-
aidered a conduct arbitrary decision based on clinical experience and
information ehich at the time one cdcittedly meager. Evidence for pro-
coming. by none other than tech periornsnca. that M as” in enact,
does stimulate the aid-brain reticular systen is provided by hinaldi and
flinvich (52) and Ham (no) in show that the mractivity of this system
is reqonsible for the production of Parkinsonisn. In the present study
nine of the toanty hidn-drug patients shoved. vhsn tested, the charac-
teristic troncr and behavioral restlessness of Partinsonisn as W
to none in the low-drug or placebo groups. In addition. of the patients
dropped from the study tor various reasons. Partinaoniao vac given as the
cause only in those patients rho had been started an high-drug osdicaticn

 

 

 

69

but had to be withdrawn because of entrance reactions Inching continued
participation in the study clinically contraindicated.

dancing. than. on the basis of the production of Partinscnins
in high-drug patients that the brain-ates reticular cyst. is. in effect,
ctiunlatad and activated by to no. of pcrphenasine daily in divided doses
(or three connective days. the apparently negative rennitc are indeed
surprising and perplexing.

Drugs and procedures which sons to narrov attention include neyl
nitrite, a vasodiiatori ncthnqnhetnnine. a synpcthnsinctic; an anti-
chclinecterase nerve gas. vhich is permathcnimstic: and the
vasoconstricting cold proaccr proccntare. This rather heterogeneous
group of agents have at least one thing in canon; they all seen to
have a ctinanlating effect on the mid-brain reticular cystns as chain
by an alert EEG. in cm with the above group of agate. high-docs
perphenasine also stimulates the rid-brain reticular cysten but unlike
than. at least within the pres-it national frooewcrt. it does not
narroo attention. in tact. as previously indicated. reference to Table t
suggests that the high-drug group one the coat pennalisad of the three
groups in pardon-inc the narrcesd attentiu tact. this greater diffi-
culty in ignoring or filtering out intrusive stirnnli is oppositional to
annotations in the precannm of n annarinentaiiy alerted aid-brain
reticular cyctenn. A possible oaqnianation ehich might be put fonnrd is
suggested by the incidence of Partinsonism within this amp tinich mascots
that the level of stimulation was too high. Broadbent (5) invokes on
activation theory of attention. among others. tdnioh appears to be useml
in the present instance. his concern is with the effect on behavioral

efficiency as a dunction of ievcl of stimulation and activation of the

 

so

nervous system. Since Parkinsonism is indicative of a disruption of
the integrity of the nervous system which renders it less efficient in
its functions. the activation theory seems to be in harmony vdth.theso
results. Further support can.bc obtained from Robb (22) who suggests
that too high a level of activation is detrimental to efficiency because
of its disruptive and disorganising effects.

On intuitive grounds, the above explanation seems reasonable.

But it is not the only or even the best explanation that can be offered.
There is evidence that increased activity in the‘nid-brain reticular
system may result in a decrease in sensory input (36). This squares

with Hebh (23) rho looks upon attention as the process that produces the
selectivity of a response to a stimulus and describes it as ”a central
facilitation of a perceptual activity." This process, ue infer. can‘bo
rendered inefficient by too intense stimulation. he refers to BBC findings
indicating that all parts of tho brain are continually active so that any
incoming excitation.must be superimposed upon an already existing exci-
tation (23). This sapect of the problem is also discussed by Broadbcnt (5)
who invokes a filter theory of attention uhich is concerned uith.tha ss-
loction oi! a stimlus which may be delayed or blocked due to a high level
of activity thus leading to behavioral inefficiency.

A third possible effect of excassivc neurophysiolOgical arousal
is an influence on central integrativewnschanisms (18). No clear expla-
nation is as yet available, as is true uith most if not all neurophysi-
ological theories of behavior, but it has been shown that stimulating
the mid-brain reticular system can somehou interfere with the central

processes necessary for the assimilation of an experience (18).

 

 

 

51

The above neunphysiolegiosl evidence is pres-ted to captain
the possibility that over-setivatien oi the aid-brain reticular systea
on lead to a relational disruption of the central aervscs systole finish
nay citen nabs interonoes about behavior tailoring werinantsl appli-
oetion er pres-station a! stimulating agents ecositat hbioua. la vier
at this. the captive r'esults obtained in Mari-ant l (Ibrrevsd Attention
Task) oust be considered as. at least. emivocal in tones of the stated
hypothesis. The first part of this hypothesis states that "stints
treated with porphaasina in doasn matte prone-ed to stinulate the
brain-star reticular system sill....." laced on the opinions o! the
psychiatrist-physicians idle served as medical advisers and omeultnts
throughout the study. it is proud that the aperinntal provocation
oi the mid-brain reticular syst- Iith high-dosa-perphenasine did. in
afloat. MG. maephysiolegicel arousal. That a behavioral counter-
part. parrot-d attentiu. use not concouitantly produced is aplainsble
on the basis at possible mrophysiologioal attests oi overstimlatioa
at this aural sub-”ates.

The results at this study are econ to agree vith those a! Callovay
(l0) and Galloway and land (ll) with aspect to drug attests on broadened
attention. lnportmt diiierncas in the experimental conditions used
in these studies and those used in the presnt investigation warrant a
cautions approach. hovever. in seaming the operation of identical
processes. Atropine. smytal. alcohol. and loo-does perphenssine. are
all scooupmied by behavior characteristic oi broadened attention pra-
nsnably due to s nourophyeiologioal dampening oi the mid-brain retinalar
system (10, ll). But here the major siailarity ends. A drowsy atropine
EEG is not accomsniod by behavioral drowsiness. Imytal and alcohol. at

 

 

 

52

the other hand, produce drowsy behavior as well as a drowsy EEC. Low-
dose perphcnasine also produces both a drowsy £33 and drowsy behavior

but unlike the other three agents. the drowsy reactions are imediately
reversed by internal or menial stimulation. As Canomy (10) suggests
smething underlying acute-physiological arousal mid be the most parsi-
monious generalization about the drugs studied. and the most parsimonious
explcmation for the behavior observed would be in toms of focus of at.
tention. But parsimony alone. as is well agreed upon. does not necessarily
establish laws. In addition to the drugs. differences in research subjects
contribute to difficulty in accounting for apparently expected results.
Although no physiological or psychological measures of anxiety were in-
cluded in the pmsent study. a population of. hospitalized female schizo-
phrenic patients is prcsmed to bring to an experinmtal situation effective
response tendencies unlike those of volunteer Johns Hopkins undergraduate
and first- and second-year medical students motivated by the offer of four
dollars for approximately two hours' time.

Differences in task procedures are indeed marked. important in
this respect. are the possible semen and uncommon factors in the procedure
used by Callomy and his associates and that used in the present investi-
gation. Many of these factors may have important implications of behavior
other than toms of attention.

In general. the results of this investigation appear to be in
harmony with a growing body of literature which is intent on detailing
and specifying much that is implicated in this study. Helm (M). White
(62). Samuels (56). Easterbrook (15) and others have separately directed

themselves to a consideration of the relationship between activation and

 

   

53

performance. mough attacking the problem from mouhat different view-
points md theoretical positions. each gives convincing support for a
lawful relationship between level of activation and perfonnsnce de-
scribed by an inverted 0 curve.

The inverted U shaped curve has been show to hold in numerous
learning and perfommcc situations when responses are plotted against
activation level (is. 51).

On the basis of these recent Ittomptl to integrate the facts oi
the relationship betvom performance and activation. Helm (41) presents
an experimental paradign (Flame 6) which schmaticslly (emulates

permanence-activation relationships.

Figure 6

PERFUIEWfiCS ACTIVATION RELATIONSHIPS
CORRESPONDING TO INVERTED U SHAPED CURVE

Activation Level Expected Performance Level
Lou Low
raioderate Optimal
High Low

The paradign is intended to show that from low activation up to a point
that is Optimal for a sim task. level of performance rises monotonically
with increasing activation level. Beyond this optimal point the relation
because nomonotonic. Further increases in activation produces a tell in
performance.

The paradigm appears to provide a neat description of what occurred
in the first experiment of this investigation. Apparently 12 mg. of

perphenazine was not enough to improve behavior and 43 mg. was too much.

 

5h

Crucial to the present discussion is the problem. unanswered
here, of the extent to which the two tasks used in this investigation
differ in complexity and the precise level of activation which is optimal
for each.

An extension of the present design might well incorporate ap-
proaches that would handle the problem of weightin3.£or task complexity.
It could also include an increased number’s! drug-treated groups each of
which would be administered the drug in graduated fixed amounts. This
would permit the observation of performances with drug dosage extending
in fixed amounts over e wide range.

Phrther efforts'might tell consider drugs other than.porpheneeine.
Since the effect of activation on psychological functioning is much in
need of explanation and understanding. efforts need not be limited to

studies on attention.

 

 

 

 

SURNARY

The present investigation was designed to explore a physi0103ical
activity that is widely held to be involved in attentive behavior and to
test the hypothesis that emerimentel provocation of this activity by the
drug per-phenezine will be reflected in measurable behavior.

Three groups of patiente were medicated orally over a period of
three consecutive days. The two experimental groups respectively received
low-dose perphcnazine (12 mg. in divided doses t.i.d.) and high-dose
perphenezine (48 mg. in divided doses t.i.d.). whereas the control group
received an inactive placebo. The double-blind technique was employed.

33 were presented with two tasks designed to measure focus of
attention.

In the first task, 33 were required to respond to one of two
eimltaneouely presented etimli each of which was an inherent aspect of
the cone symbol, e colored geanetrie flame. Difference ecores between
time (in seconds) taken to name one etimlus when presented alone and
time taken to nme that some stimluc in the presence of the second
interfering stimulus served as the basic data for this experiment.

Statistical analyses failed to differentiate between grmpe on
the two separate parts of this task. Amiyece of- tho combined performance
ecoree differentiated between high-drug and placebo groups in the di-
rection apposite to that cXpectod.

High-dose medication is considered as having failed. to affect per-
formance of the kind called for in this experiment in the predicted

55

 

direction. The first of the major hypotheses ie not outlined. Thie

hypothesis was etatod as follow“ Patinte troeted with perphoneeine

in douge emanate proumed to etinmlete the brainy-eta retimler eyetem
will perform better on a tank requiring "nemd attention" (mdilied
snoop test) then rill petiuite treeted eith pertheIine in m
mute presumed to inhibit, depreee. or block hrein-eten miouier eyeten
activity.

The incidence of Perkineonin in the high an; grow it telten
ee clinical evidence of eetivetioa end etinletioe mating the behevionl
dete end ellomble intent-outline ell-Met equi‘ul.

in the second tut, Se were required to men which of two events
(one less likely than the other) would ocwr. me umber 0! menu (or
the "less likely" event ”fwd u the belie date hr this ”trim. Each
trial consisted o! tee mt. in uhioh the ratio of leee likely to more
likely «ante was 2 to 8.

Statistical enelyeee eimilitently diliemtieted beheviorel effects
of low-don perpheueioe. the” eiteete were in the dinetioe oi greeter
utilization in the nee oi peripheral ouee required to: euooeeetul ”flamenco.

m eeemd o! the ne‘er hypothuee ie continued. Thie hypotheeie
was eteted as follow" Petiute treeted with perphneeine in douse mute
presumed to inhibit, depreee. or block the mien-eta utiouler eyeten vill
pertain better on e teei: requiring W ettentin“ (peeeins gene)
than will petieute treated with perphmeine in deuge “to ptemed

to etimleto brain-stun reticular eyeten nativity.

 

1.

2.

3.

A.

5.

6.

7.

9.

10.

11.

12.

13.

 

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Ayd, F. J. Jr. The physiologic and neurologic action of chlorpromarino.
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Bradley. 3. s. and Elkoe. J. Eftocts of some drugs on the electrical
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Broadbent, D. E. Egrcggtion and communicagigg. Neu'torki Pergamon

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