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Neurophysiological and psychological changes induced by certain drugs

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NEUROPHYSIOLOGICAL AND P’SYCHOLQGJ.CAL .„GRANGES
INDUCED B Y CERTAIN DRUG.§, „
-
By
Oliver D. Fowler
dissertation submitted in partial fulfillment of the requirements
for the degree of Doctor of Philosophy, in the Department
bf Psychology, in the Graduate College of the
State University of Iowa
January, 1940
ProQuest Number: 10592859
All rights reserv ed
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a n d th e r e a re missing p a g e s , t h e s e will b e n o te d . Also, if m aterial h a d to b e r e m o v e d ,
a n o t e will in d ic a te t h e d e le tio n .
uest.
P roQ uest 10592859
P ublished b y ProQ uest LLC (2017). C opyright o f t h e D issertation is h eld by th e Author.
All rights reserv ed .
This work is p r o te c te d a g a in s t u n auth orized c o p y in g u n d er Title 17, U nited S ta tes C o d e
Microform Edition © P roQ uest LLC.
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11
Acknowledgment
To Dr* John Knott* Dr* Jacques
Gottlieb* end Dr* William Malamud* who di­
rected this work* with thanks to Dr* Walker
Thompson for his invaluable assistance*
ill
fable of Contents
Chapter
Page
1
1
IX
Introduction
The Effect of Adrenalin, Mecholyl,
Cocaine and Sodium Amytal Upon
Beaponaeis to Quantitative Eleetrlcal Stimulation (Chronaxia) *..»»,«
3
Apparatus and Procedure ••,«««*#•
6
Subjects »•«•*»***•*****••••••««»
12
Results
12
....
Discussion
XXX
The Effect of Adrenalin, Mecholyl,
Cocaine and Sodium Amytal Upon
the Electroencephalogram **••«*#•«*
25
Apparatus and Procedure ••«**•**•
27
Subjects
IV
19
....
29
Results ....
29
Discussion #**«***•««**«**«***•*•
38
Psychopatholog1cal Effects of
Adrenalin, Mecholyl, Cocaine and
Sodium Amytal *««.«.*»«»•».«*...»•»
50
Summary and Conclusions «*»•*•*«*•*
59
Bibliography
.................. 63
1
Chapter I
Introduction
the use of drugs as a means of experimental ap­
proach to psychological and p sychopa thological problems
affords direct access to certain physiological relation*
ships, and for this reason such methods have been widely
used (76) *
However, the nature of the observations made,
and the interpretations of the results have varied accord*
Ing to the particular viewpoints and objectives of the ex*
perimenters*
Kraepelin and His si, for example, carried out
their work with the hope of producing artificial psychotic
conditions which could be correlated with histological changes
produced by the drug, on the assumption that there la an or­
ganic basis for psychotic conditions*
Later workers in the
field of psychopathology have utilised more recent psychi­
atric viewpoints in the study of drug phenomena*
Such work
is examplified by that of Lindemann (65) and Lindemann and
Malaraud (67)*
A wide diversity of other attempts to gain
Insight Into the nature of psychological phenomena, both
normal and abnormal, through the use of pharmacological agents
might be quoted*
The purpose of the present work has been
the study of neurophysiological measures in relation to the
action of drugs affecting the nervous system and to the
psychological changes Involved*
2
In this study, the Influence of four drugs
ladrenalim,
&L
mecholyl,
will bo considered*
JtiAt
cocaine,
and sodium amytal
)
fhe study is divided into two parts,
according to the two types of neurophys1 ologlcal observations
made,
in both parts the psychological changes which occur­
red after the .administration of the -drug concerned were recorded,
These data consist of observations of and subjec­
tive reports given by the subject spontaneously or in re­
sponse to questioning.
In the first group of experiments,
measurements of rheobase, chronaxia and effects of repeated
stimuli upon Intensity and duration, respectively, with re­
ference to the chronaxia point, were made upon a peripheral
nerve and its muscle.
In the second group of experiments
electrocortical potentials were recorded and changes subse­
quent to drug injections were noted.
#
The adrenalin (epinephrine) used was the synthetic
preparation of the chloride in Is1000 dilution*
JUl
Ace tyl-B-methylcholine •
***** Cocaine hydrochloride,
Sodium Iso-amyl ethyl barbiturate*
3
Chapter XI
fh© Effect of Adrenalin* Mecholyl, Cocaine and Sodium
Amytal Upon Responses to Quantitative
Electrical Stimulation (Chronaxia)
She introduction of the time factor In studies
Of tissue excitability is generally accredited to Lapleque
(60)* who formulated the concept of chronaxia.
Hoorweg
and Weiss (83) had previously studied the relationship be­
tween intensity and current duration when comparatively
short durations were employed#
Prior to these studies,
the law of DuBois-Keymond, which emphasised only the Inten­
sity factor, was generally conceded to characterise ade­
quately the nature of excitability as determined by elec­
trical stimuli.
Lucas (68 ) in 1907 emphasised the importance
of the time factor, and Lapleque, In 1909 (49) proposed for
It the term chronaxia, which he defined as the duration of
current necessary to produce a threshold response when the
Intensity is twice the rheobaso, the rheobase being that
minimal intensity of current required to excite when the
duration of the current is greater than the critical value
below which the intensity become® dependent upon the time
of stimulation.
In the last two decades a variety of data
have been collected in which the time factor has been
measured (21, 29, 85) •
Determinations of excitability have
4
been carried out upon single nerve fiber preparations*
nerve-musel© complexes, sense organs* the spinal cord and
various areas of the brain* in relation to many factors
influencing the functional state of the nervous system* and
the concept of "chronaxic switching® (52) has been proposed
as a basis for the explanation of selective functioning of
the central nervous system*
L&plcqu© has differentiated
subordination and constitutional chronaxias (51), the for­
mer value being that obtained when the tissue in question
Is functioning under the influence of the nervous centers*
while the latter is that value ascribed to the tissue in its
own right after removal of this influence*
Modified technique® have been devised to permit
clinical studies upon man (38, 59, 82}«
While much work
has been done with drugs in the study of nerve and muscle
tissue* relatively little use has been made of available
clinical procedures in relation to the effects of drugs upon
man*
M&lamud, lindemann and Jasper (69), studying the ef­
fects of alcohol, found changes in the motor ehronaxie and
in the flexor-exteneor ratio under this drug*
lindemann
(64), using adrenalin, sodium araytal, cocaine, mescaline
and hasheesh, discusses similar changes with these drugs*
fhe results* though suggestive, were difficult of interpre­
tation, and the present study was undertaken with a view to
determining whether or not modifications in the apparatus
5
and technique used in such work would prove enlightening*
Oolle and Delvfll© (18) and others have suggest­
ed that excitability is not adequately character lead by the
two parameter® of Intensity and time alone, and the differ­
ence between subordination and constitutional ehronaxie®
Indicates that frequency of stimulation should also be taken
into consideration# especially in studies made upon the in­
tact organism# since in normal functioning of the nervous
system series of stimuli rather than discrete ones are the
rule# rather than the exception*
For these reasons a modi­
fication of the apparatus# permitting the use of repetitive
stimuli as well as single stimuli# was utilised# as in a
previous study by Weiss# Malamud and Fowler (84)*
A second modification# not used in any previous
study# concerns the type of electrode used*
Davis (20) has
commented upon the relationship of the ala© of the stimula­
ting electrode to the ehronaxie value of muscle# and Lapicqu©
(53) has criticized the work of Drundfest (36) and others
upon the basis of differences in the method of application
of the electric current*
The type of active electrode con­
ventionally used in clinical studies is that described by
Bourgulgnon (11) *
This consists essentially of a handle to
which la attached a chlorided disc of silver* covered with
canton flannel and bound with gauze.
In use, the electrode
6
is dipped in physiological saline solution and then held
in place by hand upon the subject1® skin over the motor
point of the nerve , which Is first found by exploration.
Such an arrangement for stimulation is open to several ob­
jections, as was determined by a preliminary study made with
the obj set of eliminating as many uncontrolled factors as
possible,
The values obtained with this type of electrode
were fouad to- be influenced by slight movements of the eon**
tact surface on the skin, by alterations in the pressure of
the electrode upon the surface of the skin, and by spreading
and evaporation of the saline solution on the surface of the
akin*
Accordingly, an electrode (to be described shortly)
was devised to eliminate these factors,
sM Ssaaa^gi
The chrcuiaximeter used in this study consisted of
the condenser-discharge type of apparatus described by
Bourgutgnon (11), with, however, a variable resistor of
20,000 ohms in the shxmt-circult for the subject Instead of
the constant resistor of 11,000 ohms employed in the Bour*
guignen circuit.
By means of this modification, the reels*
t&nce in the shunt-clrouit for the subject could be adjusted
so that the total resistance was always held at 10,600 ohms,
This value was selected, since its substitution In the for*
mula for the time of a condenser discharge, T a *375 K C
7
(where T Is in seconds, H in ohms, and C in microfarads),
simplifies the formula to jfc £ 4 0 (where | is In milli­
seconds and C is in microfarads) , and the chronaxie is ob­
tained directly by multiplying by 4 the capacity value
found*
A 280 volt B-eliminator, supplied by 110 volt
alternating current, was used a® a charging source for the
condensers*
The condensers were thermostabile and accurate­
ly adjusted*
The unit used for repetitive stimulation consist­
ed of a motor-driven revolving drum having projecting
teeth which as they passed a pair of contacts served as a
switching device, alternately closing the charging circuit
to the condensers, then opening this and simultaneously
closing the discharge circuit to the patient; the number
of times that this charging and discharging process occurred
per second equalled the number of teeth which passed the
pair of contacts per second.
These contacts were movable
and could be set at any given position along the drum so
as to encounter any desired number of teeth up to 50 per
revolution of the drum.
A doubling gear ratio arrangement
allowed either on© or two revolutions per second of the
drum; thus frequencies up to 60 per second could be ob­
tained.
An Indifferent electrode, consisting of a 6 x 10
a
cm* silver plate, chlorided, covered with canton flannel
and soaked in physiological saline solution, was fastened
to the subject*s chest*
The subject was placed in a re*
dining position, with the arm and fingers relaxed*
With
a small electrode of the Bourgulgnon type, 5 mm* in dia­
meter, as the active electrode, the skin surface of the
forearm was explored, using stimuli of varying intensity,
in order to locate the optimal motor point, which was then
carefully marked*
All determinations were mad© upon the
radial nerve and the muscles supplied by it*
An electrode,
consisting of a small rubber nipple with a hole in the top,
an inner coil of chlorided silver wire sealed through the
side, and having a bottom diameter of 5 mm*, was then at­
tached to the dried surface of the skin over the marked
motor point by means of collodion*
After the collodion
had dried the electrode was filled with physiological
saline solution by introducing the needle of a syringe
through the small hole in the top*
Thus a non-polarizable
electrode having liquid contact with the skin over a con­
stant surface area and at a constant pressure was formed*
In previous work the customary procedure had
been to depend upon sight for the determination of the
threshold response, watching the surface of the skin for
indication of contraction of a muscle or movement of a
tendon, and attempting to duplicate the least perceptible
response by variation of the intensity or time factor,
• i*
thus obtaining the threshold for the variable In question.
This method is, however, open to several objections.
The
results are dependent upon lighting conditions, with re­
ference to the position of the subject*© arm, and a slight
shift in position may alter the visibility markedly,
lore-
over, the success of the method varies with individual
differences in anatomical makeup*
In some cases the move­
ment is easily perceptible, the muscle or tendon being
thrown into bold relief when the current is applied and
becoming imperceptible at a rather distinct threshold
value.
In other cases the amount of subcutaneous fat and
the structure and disposition of the subcutaneous struc­
tures make the movement difficult to perceive and the end­
point a matter of some conjecture.
Because of these dif­
ficulties the use of some other method was decided upon.
The use of various mechanical devices seemed limited either
because of lack of sensitivity or impracticability in ap­
plication under the experimental conditions.
It was found,
however, that the sense of touch could be used to decided
advantage over the visual method.
Following this procedure,
the observer placed his fingers on the skin surface at the
point at which h© found th© response to be most easily de­
tected, and the stimulus was then varied above and below
10
the threshold in accordance with the usual method for deter­
mining the threshold*
By this means the results obtained
were much more consistent and the ©nd-point markedly more
distinct than was the case when the visual method was used#
A variation of one or two volts often sufficed to abolish
or re-establish the response*
Furthermore* the great in**
dividual differences encountered in the previous procedure
mere eliminated to a considerable extent* because of th©
greater sensitivity of the touch determinations#
For these
reasons determination of the threshold by the touch method
was used throughout the present series of experiments*
After adjusting the resistor of the ehronaximeter
to compensate for individual variations in skin resistance
in order to obtain a total resistance of 10,600 ohms* the
determinations were begun*
Ihe rheobas© was first deter*
mined* then the chronaxia#
Ifext * with the duration of the
stimulus kept constant at the chronaxia value, Intensity
values necessary to produce the threshold response at fre­
quencies Of 4* 8 * 12, 18, 24, 50, 40, 50 and SO stimuli per
second were determined* the repeated stimuli being applied
for one second Intervals*
Following this, th© intensity
value was kept constant at twice the rheobasic value, and
durations of stimuli for threshold response at the fre­
quencies mentioned were determined*
11
Two control experiments, using no drugs, wore
run m
week subject on separate days*
The first control
eaqperlment consisted of three series of determinations of
rheobas#, chronaxie, and Intensity and time variations with
repetitive stimulation, these determination series being
separated by 30 minute Intervals*
Throughout the experi*
mental period the subject was reclining, and had received
instructions to relax and lie quietly*
The second control experiment was made following
at least a day*® interval after the first experiment*
In
this period a complete set of control determinations was
made, followed by a hypodermic injection of saline solution*
Two subsequent set® of determinations followed, one 15
minutes after the Injection and one 45 minutes after the
injection.
In the drug series of experiments the same pro*
eedure was followed as in the saline control experiments*
A set of control readings was made, followed by Injection
of the drug*
Immediate and later determinations, 15 and
45 minutes* respectively, after administration of th© drug,
were then recorded*
Observations of the subject*® behavior, span*
t&neous remarks, and information in response to questioning
were recorded.
Blood pressure and pulse readings were taken
just prior to each set of electrical measurements*
12
At the conclusion of* the experiment* if the
subject was to he used again with another drug, the motor
point used, was carefully marked with methyl violet to in­
sure its use in subsequent determinations#
In all of the
experiments of this group, each subject was used six times,
at dates two or more days apart, and at approximately the
same time of day#
The series for each subject consisted
of a control determination with no injection, a control
with saline injection, subcutaneous injection of 1 cc*
adrenalin hydrochloride in 1 1 1000 dilution, subcutaneous
injection of 10 mg* meeholyl, subcutaneous injection of 50
mg* cocaine hydrochloride, and intravenous injection of
3-3/4 gr* sodium amytal*
Th® subjects were eight patients of the Univer­
sity of Iowa Psychopathic Hospital and one University
student*
Two of the patients were diagnosed as hebephre­
nic schizophrenia, one as catatonic schizophrenia, one
as simple schizophrenia, two as manic-depressive depress­
ed, one as psychopathic personality, and one as psychoneurotic*
Tables 1, 2 , 3 and 4 present the individual data
obtained during six separate experimental periods utiliz-
13
ing the nine subjects*
These tables egress the maximum
oli^ng© obtained for th© measure in question after the
injection of the drug# the figures being expressed as
positive or negative# according to whether the maximum
Change was an increase or decrease over the control mea­
surement taken at the beginning of the experimental period*
87 maximum change is meant the greatest difference be­
tween this first control determination# prior to the In­
jection of the -drug, and either of the later determina­
tions j that is, if the difference between the control
reading and the reading Immediately following injection of
the drug was greater than th© difference between th© con­
trol reading and the reading at the later period, this
difference was recorded* If not, th© other difference
was recorded*
Thus any tendency to consistent change
Should appear in th© table*
Table 2 shows the maximum change in volts and
milliseconds of rheobas© and ©hronaxl©*
Table 2 express­
es these changes In percent of rheobas© and chronaxie*
Table 3 shows the maximum change in volts and milliseconds
as a result of summation effects with repeated stimuli*
Table 4 expresses th© latter changes In percent of inten­
sity and time*
If the controls are compared with th© results
for each drug, it can be seen that there Is no tendency
14
for any drug to produce a consistent change In any of
the me&awree taken*
There are fluctuations both in sign
and in magnitude, as In the control values, hut in light
of th© control values there ar© neither any marked changes
In magnitude nor consistent deviations In sign which are
obviously ascribable to the effect of the drug*
likewise, ,
no conclusions can be drawn as to th© possible influence
of psychopathological states*
!fwo possible conclusions thus present themselves*
(!) the psychological effects produced by the drugs used
are not accompanied by any detectable peripheral manifest
tations of alteration in excitability, or (2 ) such manl~
f©stations may occur but are not detectable by the methods
used*
15
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19
In order to emphasize the nature of the re**
suits obtained in this study* mention will be mad© of per­
tinent researches in which changes in rheobas© and chronaxie
have been studied in relation to the action of various
drugs upon physiological preparations.
M* Lapicque and
Vahl (58) found that in the cerebrate or decerebrate frog
large doses of caffeine reduced th© motor chronaxie of
the sciatic nerve to half the value of the sensory chronaxia,
when the thalamus was intact*
They report that th© effect
of caffeine on the motor chronaxia is more distinct when the
cord is free from the thalamic influence*
M* Lapicque and
Hattan-Larrler (57), using 1 mgm* doses of adrenalin, found
a reduction of the chronaxie of the gastrocnemius muscle
of the frog to one third its original value within thirty
minutes*
Adrenalin is also reported to diminish an in**
creased muscular chronaxie due to fatigue.
M« Lapicque has
stated (50) that stryohnlne increases the excitability of
the motor nerve without affecting that of the correspond­
ing muscle, and that a dose of this drug fifteen times as
great Is needed to produce the same effect on peripheral
nerve when the higher centers are destroyed.
Chloroform
and ether may completely alter the chronaxie and rheobase,
according to Buchanan and Garven (16), and 1. Lapicqu© and
so
legendra (55) have contended that changes in excitability
of Myelinated nerve produced by chloroform, other, cocaine
and novocain® are paralleled by the morphological changes
In the nerve, the chronaxie diminishing and the, rheobase
Increasing with progressive swelling of the myelin sheath,
Hie action of scopolamine, according to Rudeanu and Bon-*
vallet (73), is to equalize the chronaxias of antagonistic
muscles *
Other work in addition to these resear ches might
he quoted, which indicate that similar results might be
inferred to be observable in studies upon man.
It la evident, however, that no such results
have been obtained in the present experiments.
Several
possible differences In experimental technique at once sug­
gest themselves#
One Is that many of the drug effects
which have been reported have been obtained with pharma­
cological agents applied directly to the nerve or muscle
in question, a procedure which would give a much greater
concentration for local action of the drug, but which pro­
vides no information as to the central changes which are
the primary Interest of the present study.
The type of
stimulation employed in the clinical procedure Is, because
Of its nature, more complex*
Possible sensory stimulation
and proprioceptive Impulses due to the muscular response
may complicate the picture,
stimulation through the skin
is necessarily more diffuse and indefinite than that ob­
tained by diroot application of electrodes to a nerve
trunk or muscle, even when electrodes of the type des­
cribed in this study are used#
Another serious problem
Is that introduced by the multiplicity of nerve fibers in
the nerve trunk*
Since, in a spinal nerve supplying stri­
ated muscle, a wide range of fiber diameters and corres­
ponding variations in excitability of the individual nerve
fibers may be found (24, 54), the meaning of a difference
in threshold for the nerve trunk is not clear*
Moreover,
the relation of trunk fibers to motor units of the muscle,
and the alternating behavior of motor units in muscular
response only add further to the confusion when any attempt
is made to reach a physiological interpretation of measure­
ments made through the skin upon intact human nerve or
muscle*
Even if it were granted that by the methods used
it is possible to measure accurately the chronaxie of a
peripheral nerve and its muscle without reference to the
above mentioned factors, there is still contention as to
the theoretical significance of chronaxie*
These contro­
versial points have been well summed up by Davis and Forbes
in their review (21)*
The interpretation of subordination
and constitutional chronaxles is intimately tied up with
these controversial points*
Even the supposed Influence
of the nervous centers in“;detei^ning-:st^^dinatilda
83
chronaxia values ha© been contested, Lambert, Skinner and
Forbes (47) having found In on© series of experiments that
©hang©© In rheobaae and chronaxle found after section of
a peripheral nerve# and supposedly due to release of the
peripheral nerve from central control, are correlated only
with proximity of the section In the nerve to the elec­
trodes*
Davis and Forbes have cited such evidence bearing
upon subordination, pointing out that subordination now
appear© to be due to an alteration in the intensity factor
rather than in the time factor of excitability, and that
If subordination is, a© It appears to be, a polarisation
effect which alter© the rheobase of the nerve but leave©
the time factor unchanged, the role originally assumed for
chronaxle in the co-ordination of the nervous system can
no longer be upheld*
Further, the concepts of isochronism
and the dependent theory of chronaxle switching, which were
advanced to explain activity and co-ordination in the cen­
tral nervous system, have been shown to b© unwarranted a©
strictly applicable laws, both by experimental evidence
and by theoretical analysis.
It is also pointed out that
mathematical formulations of excitability either obtained
empirically of derived theoretically have failed to yield
any single Index of tissue excitability which may serve
as an adequate representation, and that chronaxle must
■Its merits as an approximate empiri­
cal index*
Inasmuch as measurements of rheobase, chronaxle,
and effects of repeated stimulation as described herein
have failed to reveal any significant facts about the ac­
tions of drugs, It Is suggested that a different criterion
of excitability, possibly the determination of the strengthduration curve, might prove more enlightening In further
work*
That the failure of the results reported here to
indicate any consistent changes ascrlbable to the effects
of drugs might not be due entirely to difficulties In
making clinical measurements as compared to measurements
mad© upon physiological preparations, Is suggested by the
work of Ihoefel (45) who Investigated the effect® of co­
caine, chloral hydrate and urethane upon chronaxle and up­
on entire strength- dura 11on curves, using frog *s nerve
and muscle*
Enoefel found that the curve® shift, that the
chronaxle does not vary directly with the excitability as
determined In this manner, and that these affects are in­
dependent of the nature of the stimulating electrodes,
are not due to the "alpha" effect, (a slow excitability
found In muscle when fluid electrodes are used), and cannot
be attributed to pseudochronaxies $ the further statement
1© made that it I® questionable whether any single point
can adequately represent the entire curve.
S4
Whether or not utilisation of the entire
str©ng th-durat1on curve as a measure of excitability would
have any theoretical significance in further clinical
studies is not pertinent here! the fact that chronaxle
measurements alone m y not he valid Indexes of shifts in
the curve is important *
In the light of suoh evidence it
would appear that inconsistency of chronaxle changes ob­
tained under the effects of drugs does not necessarily im­
ply inconsistency of changes in excitability#
However, in
view of the many factors Involved* It would seem wise at
the present time to forego any attempts at theoretical In­
terpretation of results obtained In clinical studies, and
to has© such measurements upon the possibility of finding
empirical data which might prove useful in differentiation*
2B
Chapter'III
fhe Effect of Adrenalin, Meoholyl, Cocaine and Sodium
Amytal Upon the Electroencephalogram
EXectrocortlcaX potentials ■seem to- offer the
possibility of more direct access to the neurophysiological
processes underlying behavioral changes#
Since drugs may
be used to produce modifications both in physiological
processes and in psychological ones, and since much pro-*
vlous research has been aimed at correlating electroeneephalographi c changes with changes in these two areas,
studies of the electrooortical record in relation to the
effects of drugs would seem to afford opportunity for gain*
tog information as to the nature of psychophyslological
processes#
Previous Investigations concerning the relation^
ship of drug action and eXeetroeortical variability have
indicated that this Is a valid field of research#
Berger
(9) reported that caffeine, cocaine, atropine and morphine
produced a change in the electroencephalograpliic record
characterised by the displacement of the 10/sec# alpha
rhythm by a faster beta rhythm*
Berger believed that the
beta waves corresponded to the psychophysiological pro­
cesses and he called them the material symptoms of the
psychic processes*
26
Gibbs* Gibbs and Lennox (36) have studied the
action of twenty drugs upon th© electrocortlcal poten­
tials*
the only drugs Which produced any marked change
In the ©leoirocortical record were scopolamine, morphine,
ether, alcohol, and a number of the barbiturates*
Those
drugs which produced muscular symptoms, notably scopolamine,
were characterised by high amplitude bursts which corre­
lated with muscular twitches*
Drugs such as ether, alcohol,
and the barbiturates, when used in anaesthetic doses suf­
ficient to produce stuporous or sleepllke states, gave re­
cords showing large amplitude, slow frequency waves, similar
to th® type encountered in normal sleep*
These studies have not attempted to correlate
changes in psychological processes with changes in the
electrocortical record*
Since the electroencephalogram may
serve as a measure of the physiological limits of behavior,
it is important to know whether or not increase or decrease
in its predominant rhythms is related to increase or decrease
in the complexity of psychological processes*
Utilizing wide
empirical limits of frequency, Gibbs (33) has suggested that
certain types of abnormality are characterized by either a
release of great energy at extremely slow frequencies, or
a release of great energy at extremely fast frequencies*
These limits clearly exist in the case of the epilepsies,
87
and there Is some reason to believe that a lesser degree
of relationship holds In the range of normal behavior,
that is* that more rapid frequencies are related to more
complex stimulation, as studies such as those of Knott
(46) and fravis and Egan (80) indicate*
Upon such evi­
dence, it was decided to attempt to systematically fit
the data obtained Into the concept of frequency limits
of behavior,
Apparatus and procedure
fhe same drugs were used as in th© experiments
upon electrical stimulation, the only difference In the
experimental situation being that instead of the elec­
trical measurements, a continuous record of electro cortical
potentials was taken*
Contact electrodes of the flat metallic type
were placed upon the subject, the indifferent electrode
upon th© ear lobe and the recording electrode upon the
scalp over th© left occiput| both were secured with col­
lodion*
fhe apparatus consisted of a four-stage capaci­
tance coupled amplifier (time constant s *67 sec*) coupled
to a Boehm© ink-writing oscillograph by means of a special
four-tube matching amplifier*
With the subject in a reclining position, having
been Instructed to relax and to keep his eyes closed, a
as
control record of several minutes was made#
Throughout
the recording# obvious movements which might produce
muscular artifact a were indicated upon th© record* and
these portions were disregarded in analyzing th© data.
All observable physiological and psychological changes
were recorded* any marked Changes being noted also upon
the ©1©ctroen©ephal©graph!c record*
An analysis of the records thus obtained was
made in terms of the mean number of waves per second#
fwo thirty-second strips of the control portion of th©
record were read#
fwo similar strips of the record after
the administration of the drug were read# one strip im­
mediately following the injection of the drug# allowing
sufficient time for physiological changes to occur * and
the other strip several minutes later#
Iheee times were
approximately 2 to 5 minutes and 25 to 30 minutes after
the injection*
fh© mean frequency of the control strips
was then compared with the mean frequencies after the
injection of th© drug#
Critical ratios were calculated
for differences in mean wav© frequency between the con­
trol portion of th© record and the strips immediately
following th© Injection and later#
Records were mad© with control Injections of
physiological saline solution and with the same dosages
of drugs a# ucod in the study upon electrical stimula­
tion, with the exception that administration of sodium
amyt&l was discontinued before th© full dose was given
in eases In which the subject showed signs of drowsiness
during the injection*
Subjects
the subjects used were patients of the Pay-*
chopathic Hospital of the University of Iowa and students
of the University*
Hine were normal subjects, six patients
were diagnosed as schisophrenic, four as manic-depressive
manic, one as manic-depressive depressed, on© as psychoneurotic and two as undiagnosed psychosis*
Be suits
fable 1 show© the mean frequencies obtained be­
fore and after saline Injections administered to five sub­
jects of the types Indicated*
Ho psychological changes
were indicated except the report of the depressed patient,
who said that she felt a little more excited after the in­
jection*
Th© oritleal ratios Indicate that no significant
changes in mean wave frequency war© obtained in any of
these oases*
Table 2 presents th© mean frequencies obtained
before and after adrenalin Injection© given to 7 subjects*
The only significant change In frequency occurred in the
m m
Of th© psychoneurotic, who had bean suffering from
anxiety ■symptoms* and who reported a return of these
sys$»toagu
In this case there was a statistically sig-
nlfleant decrease in mean wave frequency as an Immediate
effect, the drop being from 11*6 to 10*4 waves per second*
Table 3 shows the effects of meoholyl Injec­
tions*
In three of the seven subjects, significant in­
creases in mean frequency were obtained shortly following
the injection*
Since the drug produces marked physiological
changes which in most instances cause some discomfort, it
Is difficult to evaluate psychological changes*
The state­
ments of the subjects were all referable to the physiological
changes*
Table 4 Indicates the effects of cocaine injec­
tions*
Of the eight subjects, three showed significant
Increases In mean wave frequency and one showed a signifi­
cant decrease*
These changes all occurred as later effects
of the drug, in contrast to the immediate effect® obtained
with meoholyl#
The most marked psychological reaction ac­
companied the decrease of frequency In the manic patient,
who showed an even greater amount of activity, with, however,
little attention to environmental stimuli*
Another manic
patient In this group showed a significant increase in mean
wave frequency; psychologically the change was not as marked#
31
He talked mere loudly, was somewhat more restless than
before the Injections and reported a sensation of light­
ness,
She other subjects with whom significant increases
in frequency were found were normal Individuals, one of
whom showed a marked psychological reaction, characterised
by extreme anxiety*
fh© other normal subject reported
vivid mental images and a return of his faculty of eidetic
imagery which he had seen failing for some time*
fable 5 presents the values obtained in the
experiments with sodium amytal*
In all of these cases ex­
cept on© a significant increase in wave frequency was
found*
Of the ten cases showing this effect, eight showed
an immediate significant change, while in the other two the
change was slgnlfleant only in the later reading; however,
oven in these two cases the immediate mean wave frequency
is higher than that of th® control*
In all of these eases
th© psychological effect of the drug was quite noticeable,
in contrast to th© inconsistency of reaction to the other
drugs*
Six of th© ten subjects showed increase in speech
activity, while a heightened affective state, tending
towards euphoria, was observed in all but two*
The reaction
of the depressed patient who showed an increase in mean wave
frequency which is not statistically significant was not
essentially different from th© others.
32
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1*
The effects of adrenalin*
The results of the experiments with adrenalin
are essentially th© same as those reported in the electro*
eneephalographic study by Gibbs, Gibbs and Lennox (35),
who obtained no appreciable effect upon the electrocortical
record in six experiments in which doses of 0.5-0*8 mg* of
epinephrine hydrochloride were given*
In th© one case in
the present study in which a significant change was found,
i.e., that of the psychoneurotie who reported a return of
his anxiety symptoms, the drop in mean frequency is pos­
sibly related to th© changes noted by Lemere (60) and
others with respect to the ©motional state of the subject*
Kubln, Hoagland and Cameron found an increase in the delta
index (also frequency phenomena) accompanying states of
©motion*
Lemer© reports a decrease in th© amount of alpha
rhythm present under conditions of ©motional tension.
Berger (6) and Adrian (7) have also commented upon the
necessity of having th© subject under optimum conditions
of relaxation In order to obtain th© maximum amount of
alpha activity, other factors being equali and It may be
noted parenthetically that muscular tension may appear as
a specific component of what is referred to as "emotional
tension*1, since, according to Cannon’s viewpoint, an emo­
tional state act® to prepare the organism for immediate
39
action#
Therefore* if it is borne in mind that the mea-
sure taken is the mean number of waves per second* it Is
not surprising that a lower value was obtained after the
Injection of the drug* with its concomitant psychological
and physiological changes#
8*
The effects of meoholyl*
As previously noted* the physiological changes
produced by this drug tend to render difficult any evalua­
tion of psychological changes per £©* and for this reason
no attempt to correlate behavioral changes with changes
in th© electroencephalogram is made#
However* a signifi­
cant increase in mean wav© frequency was found in a portion
of these oases* and a tentative eaeplanation for the changes
thus produced may be advanced*
Mecholyl is aoetyl-beta-methylcholine, a choline
derivative which differs from certain other choline de­
rivatives* according to Simonart (77)* in that It has a
powerful stimulating effect upon the terminations of the
post-ganglionic fibers of the parasympathetic nerves,
while the nicotine-like effect of choline* acetylcholine
and other derivatives upon the autonomic ganglia is feeble
or absent#
It is said to be more stable than acetylcholine
and less easily hydrolyzable by the tissues*
40
In th© mecholyl series of experiments, the
typical effects of parasympathetic stimulation were eli­
cited, to a greater or lesser degree, depending upon the
individual subject*
Of these effects, the ones to b© con­
sidered here are vasodilatation, as evidenced peripherally
by flushing of the skin, constriction of the bronchioles,
as indicated by labored respiration and reported difficulty
in breathing, and a tendency to lowered systemic arterial
blood pressure*
fhere was also tendency toward increase in
pulse rate with the dosages given*
Various workers have Investigated th© changes in
th© ©leetroeneephalographic record In response to cerebral
circulatory changes and to variation in the alveolar ten­
sions of carbon dioxide and oxygen*
Bremer (15) has re­
ported that the presence of 20$ 000 in respired air caused
th© disappearance of slow rhythms with remaining low ampli­
tude, higher frequency potentials, as recorded from the
fllsolatedn cortex of the cat*
Bennox, Gibbs and Gibbs (65)
have shown that the rate of cortical potentials in man is
Influenced by changes in th© COg content of alveolar air*
Gerard ($0,52) has shown similar effects in man, reporting
increased rhythms as the effect of COg lack, and increased
rat© and amplitude, followed by abolition of the rhythm,
with 002 in great excess*
With mild 002 excess, as in volun­
tary apnea, he reports that th© 10/sec* waves ©re broken
41
up into more rapid wavelets, while the rapid 40/see*
rhythm Is probably enhanced,
Sugar and Gerard (78) re­
port that daring advancing anoxia, brain potentiate pass
through a phase of increased frequency and often Increased
amplitude. Indicating a transient stimulation, en route to
depression*
Gibbs, Davis and Lennox (54) obtained slower
waves of cortical potentials when an acute fall in blood
pressure was produced by pressure stimulation in the case
of a subject possessing a hyperactive carotid sinus re­
flex*
Similar dependence of the characteristics of the
electro cortical record upon oxygen tension has been shown
by Davis, Davis and Thompson (22) .
Hetnbecker (37) , Thompson and Kimball (79) and
others
have shown changes of a comparable nature in nerve
fibers, indicating an increase in the irritability of
nerve at the onset of asphyxia.
Thus there appears to be
considerable evidence that interference with the vital gas
exchange processes, whether through anoxemia, hyper eapnia,
or reduction in cerebral blood supply, may result in a
period
of hyper-irritability of the nerve tissue involved*
Possible cerebral circulatory changes need also
to be considered in connection with the mecholyl experi­
ments, since, according to McNaughton (71), the innerva­
tion of the intra-cranial vessels does not differ essen­
tially from the innervation of blood vessels elsewhere in
42
th© body,
Schmidt and Hendrix (74) found evidence of
Ihbraeranlal vasodilation upon injection of acetylcholine
end of meohalyi in oats end rabbits*
It is also known
that many drugs> such as nitrites and alcohol, dilate th©
cerebral blood vessels (27), and Increased 002 tension Is
also said to produce such an effect by direct action upon
the walls of the blood vessels (70).
Bronk (15), Lennox,
Gibbs and Gibbs (00) and others have emphasised the fact
that cerebral blood flow Is normally controlled by the
amount of cerebral activity*
However, in th© case of a drug
which acts directly upon the circulatory system, such as
the one under consideration, we might expect to find changes
in the electroencephalogram in which vasodilator effects
play a part*
fhe importance of oxygen lack, and, particularly,
of carbon dioxide excess, in local vasomotor control of the
brain, has been pointed out by Gerard (31) *
fhe factors
Involved, then, In considering vasodilation as a possible
mechanism in the present problem are the action of mecholyl
and th© action of excess C02 or of oxygen lack.
In view of the evidence quoted, it seems plausible
that the following chain of events Is responsible for th©
increase in mean wav© frequency of th© electroencephalograph!©
record found In a certain proportion of th© cases In which
mecholyl was used;
(1) Peripheral vasodilation tends to
43
lower the systemic arterial blood pressure, although an
increased heart rate may keep the pressure at approximately
the same level in some oases*
(2) Constriction of the
bronchioles, due to the action of mecholyl, occurs*
TTnder
such conditions respiration is more difficult and the
alveolar COg is increased*
occur*
Simultaneously oxygen lack may
(3) ¥n«odiXatlon of the cerebral blood vessels,
due to the action of mecholyl, occurs.
(4) The vasodilation
of the cerebral blood vessel© is augmented by th© direct
effects upon the vessel© of 0Og excess and possibly oxygen
lack*
(5) Under these conditions, the OOg balance between
the cerebral tissues and the blood stream is no longer
normal, and removal of this metabolite is not as efficient*
(6) The typical alterations In the eleotroencephalographlc
record due to QOg excess, and possibly oxygen lack, are
found*
An alternative explanation might be made, of
course, upon the basis that the augmented cortical activity
is due, not to the stimulating action of excess 00g , but
to the action of mecholyl upon the synapses, in accordance
with the neuro-humoral view that acetylcholine acts as a
mediating substance in synaptic transmission in th© central
nervous system*
While this is a possibility, th© present
uncertainty as to th© nature of synaptic transmission in
the .central nervous system is well known*
Cannon and
Eosenblueth (17) have indicated the overwhelming evidence
for chemical mediation in th© autonomic nervous system,
while pointing out that such evidence Is of necessity in­
ferential; and the greater difficulty of obtaining even
inferential evidence of an unquestioned nature about synap­
tic transmission in the central nervous system is obvious
because of the characteristics of this system*
In support
of a chemical interpretation of the results, however, is
th® work of Bonnet and Bremer (10), who report a clear
stimulating effect upon the ^isolated*1 cerebral cortex of
the cat, as manifested by its electrical activity, after
the injection of small dosages of acetylcholine into the
carotid artery*
Among the effects reported are an augmen­
tation in frequency of the spontaneous waves*
Further re­
search should clarify the nature of this effect*
3*
The effects of cocaine*
As noted before, there is apparently a corre­
lation between psychological changes and eleetrocortical
changes under the effects of this drug*
One case in this
group is divergent from the others, that of the manic
patient who showed an augmentation of his excited state,
accompanied by a significant decrease in mean wave fre­
quency of the electroencephalographic record, in contrast
45
to th© other eases in which the psychological changes were
accompanied by a significant increase in mean wave fre­
quency,
Fischer and howenbach (£5, £5) report large elec­
trical disturbances of the cortex with stimulating drugs*
of which cocaine is included*
Berger (9) referred to the
faster beta rhythm which displaced the alpha rhythm in his
experiments with this drug as indicative of change in the
psychic processes*
While it Is somewhat difficult to
order descriptions of behavior given in such terms as
restlessness* garrulousness* agressiveness, impulsiveness*
and alertness (19* 67) to a neurophysiological concept such
as that of cortical excitatory state as set forth by
Jasper (35* 40)* there appears to be little doubt that co­
caine* in effective doses* has a stimulating effect upon
the central nervous system* and that this effect spreads
from the higher centers to the lower ones as the sis© of
th© dosage is increased (19)«
The results of the present
series of cocaine ©aperiments* then* seem to be in accord
with the general view that increased frequency of waves
in the electrocortical record is indicative of augmented
cortical activity (41)*
4*
Th© effects of sodium amvtal*
The most consistent electrocortical changes were
obtained in th© series of experiments with this drug* and
46
psychological changes were obtained In each ease.
Batter
control over the effects of the drug 1© to be attributed
in this ease to the method of administration# which was
by intravenous injection, thus allowing an observance of
immediate effects while the drug was being given*
The
psychological change® vary individually# and are dependent
upon the dosage and rate of administration, but in general
there is a tendency toward euphoria# loosening up of
speech# loss of some psychological “inhibitions*, and
general bodily relaxation, followed by drowsiness or sleep
if the subject 1® not stimulated or If the dosage is
carried further*
An attempt was mad® In this series of
experiments to avoid sleeps inducing concentrations of the
dru&*
Previous research has shown that amytal may in­
crease the amount of alpha rhythm present In the elec­
trocortical record, presumably because of its relaxing
effect, just a® conditions of relaxation In general tend
to favor the production of the alpha rhythm (1,6)*
Gibbs,
Gibbs and Lennox (35), using phenobarbital sodium and
pentobarbital sodium given intravenously, report changes
In th© records comparable to those obtained during normal
sleep when dosages sufficient to impair consciousness
were given.
Bremer (14) has presented ©lectroencephalo-
graphle evidence to show that the effects of the volatile
47
anaesthetic®, such m
ether, differ in their mode of ac­
tion from that of the nonvolatile anaesthetics* such as
the barbiturates*
this difference*
Berger (7*8) has also commented upon
Beecher* McDonough and Forbes (39,40)
and Forbes and Merisan (28) have raised this question in
connection with their experiment® on sensory stimulation
under barbiturate anaesthesia#
Bremer* a view was that
ether acts equally on all elements of the sensory response,
while the barbiturate© act selectively on the after-discharge,
which he relates to intercalated cortical neurones#
Of In­
terest in regard to the possibility of thalamic block pro­
posed by Berger (7) is the work of Keeser and ICeeser (42,
43), who studied the distribution of barbiturates in the
central nervous system and found the greatest concentra­
tions in the dlencephalon, especially in the thalamus, while
Koppanyi, Dill© and Krop (44), using larger dosages, found
the distribution equal throughout the various parts of the
central nervous system*
Bremer (18) and Derbyshire, Kerapel, Forbes and
hambert (23) report the appearance of low amplitude, higher
frequency potentials as the immediate effect of ether upon
the cat, and Berger (5) obtained an increase in the higher
frequency potentials of the human electroencephalogram
during the excitation phase of chloroform narcosis*
Gibbs,
43
Olbb® and I*©nnox (35) observed higher frequency waves
under alcoholic intoxication*
Beecher and McDonough (S),
smking a statistical study of mean wave frequency, report
higher mean frequencies with the volatile anaesthetics
than with non-volatile anaesthetics*
however, are not given*
Control frequencies,
There is thus a variety of evi­
dence which would point to differences between the volatile
and non-volatile anaesthetics when given in large dosagesi
however, as Walter (81) points out, the barbiturates when
used in smaller dosages do not necessarily have the effect®
on the electroencephalogram described*
Moreover, if the psychological changes are con­
sidered, the tendency to euphoria under sodium amytal in
the present experiments and the similar tendency under al­
cohol, high or low oxygen tension, chloroform and ether is
suggestive of a common stimulating effect upon the cortex,
either by removal of inhibitory influences, thereby allow­
ing an augmented activity, or to direct effects upon the
metabolism of the cortical neurones, such as those postu­
lated by Rubin and Freeman (78) in their study of the in­
fluence of cyanide on human brain potentials*
Perhaps the
only study directly comparable to the present one on sodium
amytal is that of Lemer© (61), who guv© slow intravenous
Injections of sodium amytal to schizophrenic patients and
49
noted on accentuation of the alpha rhythm during the pronarcotic stage of its action# which h© indicates parallels
the clinical Improvement with Increased accos ©ability and
rapport*
With continued administration of the drug# he
reports that the alpha waves break up into faster# more lr«*
regular waves# interspersed with delta waves*
He suggests#
from his work# and that of Shapiro (75) on oxygen consump­
tion rate under sodium amytal# that this drug probably acts
by depressing cellular oxidation# with resulting anoxia#
and an increase in excitation followed by depression of the
cortical neurones*
m
Chapter IT
Psychopathologleal Effects of Adrenalin#
Meoholyl# Cocaine and Sodium Amytal
In the entire series of experiments including
both groups# namely# those In which electrical stimulation
was used and those In which eiectrocortlcal potentials
were recorded# there were 1© cases which received adrena­
lin# 16 which received mecholyl# 17 which received cocaine#
and 20 which received sodium amytal.
While the relation­
ships of some of the psychological effects obtained to the
neurophyslological measures taken have been pointed out
and certain theoretical Implications discussed# a survey
of the pay chops tho logical changes themselves seems appro­
priate*
1.
%he effects of adrenalin.
One case of this group Is of exceptional inter­
est.
She subject was a manic-depressive patient in the
depressed state# who experienced recovery as a result.
Be­
fore the Injection he had been depressed noticeably and
had voiced feelings of worthlessness.
Shortly following
the Injection he said that he did not feel so hopeless# and
that the world looked somewhat brighter than usual.
He
remarked that he felt almost as If he could laugh at his
51
own troubles $ smiled, and
suddenly
burst Into laughter
and tears ©f happiness, saying, "What a damn fool I was
t© worry about those things I**
While his affective state
was markedly ©hanged, he retained symptoms of retardation*
Upon returning to the ward, he did not revert to his depressed state, and was later discharged from the hospi­
tal*
toother ease in which the psychological change
under adrenalin was marked was that of a psychoneurotic
patient who previously had been suffering from anxiety
symptoms but who recently had not experienced this state*
After the administration of the drug there was a recur­
rence of the anxiety state*
This result Is similar to
that reported by Lindemann and Fines Inger (66), who found
that anxiety states occurring in psychoneurotic patients
could be reactivated by administration of adrenalin or
mecholyl*
The two eases mentioned represent the only re­
actions obtained with adrenalin which may be interpreted
as "true" emotional reactions*
One schisophrenic and on©
manic patient reported that they felt somewhat afraid, but
the emotion was not marked*
One depressed psychoneurotic
patient reported that she felt a little excited and had
more "pep".
One normal and one psychoneurotic patient
said that they felt more relaxed than prior to the in­
jection*' M x . O f the oases reported feelings of discom­
fort or restlessness, while three schizophrenic patients
mad# no response and evinced no signs of emotional dis­
turbance.
Eight of the sixteen cases commented upon
physical sensations referrabl© to the cardiovascular
Changes produced by the drug.
Landis and Hunt (48) have pointed out the diver­
gence in psychological effects obtained with this drug
under certain conditions*
While no data which do not per­
tain strictly to the experimental situation have been in­
cluded in the present work, it is of interest that one
patient, the psychoneurotic who said that she felt a
little more excited after the injection, was reported to
have become emotionally upset and to have experienced a
crying spell after returning to the ward, although prior
to the experiment she had been less depressed than usual,
and was considered on the road to recovery from her
diseased condition*
The two normal subjects used in this
series of experiments also reported later changes after
leaving the laboratory, which they express as bordering
upon emotional excitement, though they did not report
such changes while In the experimental situation*
Linde-
raann*® suggestion (65,67) that the environmental conditions
53
are of particular Importance in such drug studies seems
significant In view of these reports*
2*
The effects of mecholyl.
In all of the cases in which this drug was used#
the physiological changes were quit© obvious*
Thirteen
of the 10 cases commented upon the presence of physical
sensations arising because of these changes*
Aside from
these sensations# there were other reactions of some In­
terest*
One catatonic schisophrenic patient burst into
spells of violent laughter# but did not speak or reply
to questions*
One depressed patient and one schisophrenic
patient reported feelings which they described as ”silly*
or
funny11* while one depressed patient and one schisophrenic
patient became somewhat more communicative when questioned*
Nine of the cases experienced feelings of discomfort or
restlessness* while two made no comments aside from re­
ferral to physical sensations*
3*
The effects of cocaine*
Of the six schisophrenic patients, two remained
uncommunicative under this drug in the dosages given* while
in the other four# schizophrenic thought processes and re­
productions became more evident*
oases the result was quite marked*
In one of these latter
The patient, a catatonic
§4
who had been mute prior to the injection, began to talk
freely* accused those In the room of misconstruing her
remarks# and spoke to hallucinatory characters and to
herself in the third person# largely ignoring environ*
mental changes hut occasionally weaving these into her
thought processes*
Of the three manic patients* two showed an In­
crease in rate of speech productions and flight of ideas*
the most exaggerated reactions being accompanied by rela­
tive Inattention to environmental stimuli.
Two of the depressed patients found it easier
to talk* one becoming rather euphoric, and their remarks
had a self-centered trend* while a third depressed
patient said that he felt more at ease* though no other
change was reported or observed*
One depressed psycho­
neurotic became very loquacious and tearful* speaking of
his difficulties in a self-pi tying manner.
One patient
diagnosed as psychopathic personality became more talka­
tive and felt impelled to reveal his unrequited love for
a nurse on the ward*
Of the three normal subjects, one showed no re­
action* one reported a return of his former capacity for
eidetic imagery# and one experienced a state of extreme
anxiety*
55
The changes obtained with this drug are to a
large degree corroborative of previous studies upon nor­
mal subjects and mental patients (67)*
Such work has
shown that the subject may become excited or aggressive,
exhibiting impulsive outbursts, often showing anxiety#
It has been noted that there Is an Increase In communica­
tiveness for psychotic manifestations, with a tendency
in schizophrenia to vivify faXciflcations and to elaborate
compensations*
Self-assertiveness with relative Indif­
ference to environmental factors Is common, the mental
patient often foregoing his own critical viewpoint of his
abnormal experience© and defending them to the outsider*
The nature of the reaction obtained Is of course colored
by the subject1© past experiences and the nature of the
environmental setting*
4*
The effects of sodium amytal*
Because of the directness of administration and
ease with which the dosage may be controlled, the results
obtained with sodium amytal were more consistent in com­
parison to those obtained with other drugs*
Improvement In contact, characterized by more
responsiveness to environmental changes, was most marked
In the eight schizophrenic patients who received this
drug*
Unresponsiveness and mutism In these cases were
temporarily replaced by an appreciation of environmental
stimuli approaching that found in normal persons*
Those
catatonic patients who prior to the injection had remained
entirely mute became conversant and answered questions
about their personal lives, the change appearing quickly as
a rather dramatic effect*
Sixteen of the twenty case© showed an increase in
communicativeness, speech flowing more freely and having
acre spontaneity, while four of the cases were less coimmmicative, doubtless due to surpassing of the optimal dosage
to obtain this effect*
If the concentration of the drug in
the blood stream becomes too great, the sedative effect
characteristic of the barbiturates is obvious, the subject
becoming relaxed and drowsy, and his speech being slurred*
This reaction also occurred as a later effect In six of the
other cases during the experimental period, and Its occur­
rence in the remainder of the cases Is probably limited by
the time of experimental observation.
Care was taken
throughout the injection of this drug to administer the
solution slowly, thus preventing the too sudden onset of
lethargy and drowsiness which would mask the other effects
desired.
An increase in emotional warmth was typical, this
effect being apparent in seventeen of the twenty case©#
57
One normal subject, one schizophrenic and one manic patient
did not shew any appreciable change in this respect*
This
change was seem in various degrees, some of the subjects
becoming rather euphoric*
The apathy characteristic of
schisophrenic patient® was alleviated in these patients.
While the schisophrenic patients under the influ­
ence of this drug seemed temporarily to approach normalcy
to a greater or less degree, there were, nevertheless,
definite indications of the psychotic conditions, such as
associations! defects or reproduction of hallucinatory
material*
Such evidence was apparent in six of the eight
schisophrenic oases,
These changes substantiate previous work with
this drug (67), much of which has been done with schiso­
phrenic patients because of the increased access afforded
to the patient’s thoughts and experiences*
The subject
characteristically shows a decrease in his powers of criti­
cal judgment, which he is accustomed to exercise in regard
to social and moral standards, and any difficulties which
have arisen because of his attitudes in this respect seem
less pressing*
Because of this, he is able to communicate
material which h© would otherwise withhold due to the fear
of criticism of others*
He feels emotionally more com­
patible with those who are in M s presences consequently
58
he talks more freely and can often be guided in his con­
versation by the Interviewer*
Apprehension and antagonism
are lost to a great extent# being supplanted by a state of
pleasantness# tending toward euphoria*
59
Summary mad Conclusions
Keurophyaiological measures and psychological
changes have been studied in relation to the action of
f e w drugs * adrenalin * macho lyl« cocaine and sodium amytal,
upon normal subjects and mental patients*
Control ©xperi*
meats with saline injections were also made,
the experiments have been divided into two
groups*
In the first group measurements of rheobase,
©hronaxi©* and effects of repeated stimulation upon intent
sity and duration of the stimulating current with reference
to the chronaxie point were made before and during the
course of action of the drug*
In the second group electro*
cortical potentials were recorded throughout the experi­
ment*
In both groups a record of psychological changes
directly observed or reported by the subject was kept*
*2h© electrical measurements mad© In the first
group of experiments did not show any tendency to marked
or consistent changes after the administration of any of
the drugs*
Marked psychological changes were obtained in
several of the experiments#
Difficulties encountered in
clinical measurements of this type of physiological re­
sponse and controversial theoretical points which might
have a bearing upon the results are discussed*
It appears
probable that a single point on the strength-dur&tion
60
curve cannot adequately characterise excitability*
Sum**
raation effects in the intensity and time parameters
obtained with repeated stimuli do not appear to give
further aid in such characterization when the measure**
ments are made with respect to a single point on the
curve.
In the second group of experiments, In which
©lectroenceplialographlc records were secured, a statis­
tical treatment of the data In terms of the mean number
of waves per second was made*
Ho statistically signifi­
cant changes in mean wave frequency were found in the
experiments with saline injections*
Mo psychological
changes were obtained in this group except a subjective
report
of slight excitement by one patient*
In the adrenalin experiments, one significant
decrease in the mean number of waves was found, this being
in the case of a psychoneurotic who reported a return of
his anxiety symptoms*
Mo other significant changes were
found, nor were there any marked psychological changes in
the other experiments with adrenalin in this series*
The aeries of mecholyl experiments showed signi­
ficant
increases in the mean number of waves per second
In three of the seven cases*
Evaluation of psychological
changes was difficult because of the marked basic physio­
logical reactions which the drug Induces*
A tentative
61
explanation for the changes obtained in mean wave fra*
quency of the electroencephalogram la advanced*
Of the eight cocaine experiments, three showed
significant increases in mean frequency and one a signifi­
cant decrease in mean wave frequency of the electrocortioal
record*
fhss® changes appear to he related to psychological
changes; marked psychological changes did not occur in the
experiments in which no significant change in mean number
of waves per second was obtained*
In all except one of the experiments with sodium
amytal, significant increases in mean frequency were found*
The psychological effect of the drug was quite noticeable
in all of the oases*
From the evidence reported, It is difficult to
state whether or not the psychological and physiological
changes accompanying the action of the drugs used are at­
tended by changes In the peripheral nervous system, since
failure to obtain indications of such changes by the mea­
surements described (chronaxia) might be due either to the
absence of such changes or to the difficulty in detecting
them by the methods employed*
Sphere appears to be a fairly consistent relation­
ship between psychological changes and significant changes
in the mean number of waves per second of the electroen­
cephalogram, when such changes occur as the effects of the
62
drugs used*
fhcrmaed ttmenfcaX activity" is associated
with Increased frequency#
Ho data pertaining to a down­
ward direction of change were available in this research.
Experiments of this nature would seem to offer a fruitful
field for further research concerning physiological corre­
lates of behavior.
©3
Bibliography
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Adrian* E#D* The electrical activity of the cortex*
Froo* roy* Sac. Med*,, 1935* 29, 197-200*
2.
Beecher, H#K.* & McDonough* F.K# Cortical action
potentials during anaesthesia* J* Neurophysiol#
1939* 2, 289-307*
'~
3*
Beecher* H*K«* McDonough* F.K#* & Forbes* A* Effects
of blood pressure changes on cortical potentials
during anaesthesia* I. ieurCDtoslol* * 1938* 1*
324-331*
.
4*
Beecher* H*K* * McDonough* F«K«# & Forbes* A* Simi­
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81-03*
3*
Berger* H* TJber das Blectrenkephalogrsm dec Mensehen#
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©*
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7*
Berger* H* Ibid#* ?III Mltteilung#
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8*
Berger* H* jpyyj** IX Mltteilung#
Nervenkr ** i W i * 102* 338-537#
9#
Berger* H* Ibid** XIII Mltteilung.
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Arch. Fayehlat.
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