Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex

vulsions whi some occasions occurred so soon as five to six A.P. AS x weeks after the operation. A few animals died during the first attack, but more usually the convulsions were not severe in the early stages and occurred at infrequent intervals. In the course of several months they recurred more frequently and increased in force, finally either proving fatal or else leading to a new and very profound disturbance of the cortical activity. Therapeutic measures in the form of repeated anaesthesia or extirpation of the scar were found to be unreliable, though sometimes they were unquestionably effective.

Besides the difficulties arising on account of the purely surgical interference itself, the experimenter has to take into serious account a further difficulty which is especially pronounced in the case of the cerebral hemispheres. In the living organism we constantly discover different mechanisms by means of which functional com- pensation of damaged and destroyed parts is effected. In the nervous system such vicariation and compensation of function occur in the most extreme degree. It is well known in the spinal cord—where it is facilitated by the complicated and varied course of the nerve fibres—and also in the peripheral nervous system. The effect of mechanical destruction of localized parts is thus neutralized to a considerable extent by compensation. In the highest parts of the central nervous system, which regulate the major part of the internal and external activity of the organism, the principle. of compensation and vicariation must be still mor unced.

Having at our disposal the method of MSittoned reflexes, related to different individual analysers, we Ch aA to determine and study the pathological disturbances ing the entire cortex following the extirpation of one or ano art, and also to use this study so far as possible in investi the problem of the general construction of the hemisphereg akdAhe significance of its separate parts. x The first change which oe the extirpation of some part of reflexes ; but in th ity of cases it is only the “ artificial ”’ conditioned reflexes W) disappear, i.e. those which were established in the laboratory Ke therefore relatively recent and little practised. If the “ ikari) conditioned reflexes have also disappeared they are always first to reappear ; but usually no disappearance of

the nat Noonditioned reflexes could be observed even though ow after the recovery from the anaesthetic ad- ministered during the operation. Examples of the greater resistance of conditioned reflexes to “ natural ” stimuli as compared with those established to “ artificial ” stimuli occur in every research upon partial extirpation of the cortex and there is therefore no need to give any special examples. As a rule the conditioned reflexes disappear after the operation, whether it is performed on one or both of the hemispheres and on whatever portion of them it is éarried out. The absence of “ artificial ”. reflexes persists for diffe- rent lengths. of time, varying from a single day to several months.

Fig. 8.—Dog’s brain showing the outer g e The nomenclature used is that of "T d Usually the greater the lesion the mofe prólonged is the absence of the reflexes ; but considering the w umber of our experimental animals we find in this respect notgpfew exceptions. Even in animals in which the operations were eet identical as to the place and extent of the lesion, ther at variations as to the length of time during which cond d reflexes are absent. It is highly probable that, apart(irqhy the skill and neatness with which the operation was perfor , the ultimate extent of the irritation and the destruction JD tissue depend upon the anatomical and func- tional peculia CO) of the operated animal. After the operation the RN xes never return all at once, but in sequence,

depending not only, as already mentioned, upon the stability of the reflex, but also upon the locality of the lesion. Generally speaking, reflexes belonging to those analysers which are most distant. from the place of the lesion recover quickest. For example, after the removal of the gyrus pyriformis [experiments of Dr. Zavadsky] the conditioned reflex from the surface of the mouth (the “ water reflex ” which will be discussed later) reappeared on the eleventh day, the reflex to the smell of camphor on the eighteenth day, the reflex to an increase in the general illumination of the room on the twenty-fifth day, while the reflexes to conditioned tactile stimuli failed to recover even by the thirty-fifth day. The experiments demonstrate a certain disturbing influence which has spread from the point of lesion over the mass of the hemispheres and has then receded to the point of origin. This disturbing influence is, of course, generally speaking, due to the irritation caused by the lesion. It has already been shown that the influence of very strong stimuli, and even a conflict between nervous processes of opposite sign, lead

to a prolonged inhibitory after-effect. It is, therefore, only natural- to expect the same to result from a gorgias destruction of a portion of the cerebral cortex itself. When the conditioned reflexes finally get re-established they are found not only to regain their normal strength but often to exceed it, often also becoming considerably more stable eet before. The inhibitory process, on the other hand, grows wea any examples of this can be quoted from the experimen N disposal. Thus, after extirpation of a part of the ti gS of H. Munk in two dogs (see Fig. 13), the conditioned ali reflexes not only made a complete recovery but consider) creased in strength, and kept constant throughout every experiment, whereas before the operation they used to de&geas€ considerably towards the end of an experiment [experiment Dr. Eliason]. The increase in the strength of the conditionegPyeflexes was still more conspicuous in another dog, after emg the occipital lobes. The alimentary reflexes in this dog d before the operation 1-2 drops during the isolated sgt N e conditioned stimuli ; after the operation 13 drops [exp€rim@hts of Dr. Koudrin]. In many dogs there is

observed afte an operation a very definite prolongation of the salivary secretion ai follows the administration of an unconditioned ment of differentiations and conditioned inhibitions becomes more difficult and very often salivary secretion is observed in between the application of the stimuli—this never happening before. This last is most probably to be accounted for by dis-inhibition of the reflex to environment (see the seventh lecture). It is an open question whether this weakening of the inhibitory effect is the result of an increase in the intensity of the excitatory process or whether the excitatory process is revealed on account of weakening of inhibition itself.

Another peculiarity with respect to inhibition is observed after surgical interferences. The inhibitory process becomes inert ; and so to speak inflexible. As we saw before, in normal animals the inhibitory after-effect becomes with practice concentrated with regard to its duration as well as its extent. In the post-operative period this concentration proceeds extremely slowly and is imperfect. This inertia of the inhibitory process is observed not only in the reflexes belonging to the analyser which has been surgically damaged, but also in reflexes belonging to other analysers [experiments of Dr. Krasnogorsky].

In this manner the endeavour to demonstrate by means of experiments with extirpation the disappearance out of the normal cortical activity of the functions related to the extirpated part is complicated in the first period after operation by the geadral effect which the operation has upon the hemispheres as a whak lthough this unfortunate complication slowly and gradually, appears, it is followed, as already mentioned, by a second com ion which also affects the hemispheres as a whole, and whi pends on the de- velopment of scar tissue. The effect of ar varies widely in

different cases. After one and the sa he jo ration the injurious effect of the scar develops in some ca¥es quickly and is severe; in other cases it is slow and feeble. UnfQ@)inately the former was much the more common case in our e iments. The most usual effect of the scar consists in recurr: ttacks of convulsions, sometimes affecting the whole body, Ss etimes localized in one or another group of muscles. Suc plosive outbursts of excitation in the hemispheres have a véry pronounced after-effect upon their activity, In this respect ong- should distinguish changes which follow weak and rare attacks changes following violent attacks or frequently f moderate strength.

observing conditioned reflexes.from day to day it is very often possible to predict the approach of an attack of convulsions with accuracy. If, suddenly, without any obvious cause the conditioned reflexes diminish in strength and then disappear, it is an infallible sign of an approach of an attack of convulsions. Sometimes it is possible to notice a still earlier sign, consisting in the disappearance of differentiations, t.e. in a disturbance in the inhibitory process. After an attack has passed, the re-establishment of the conditioned reflexes occupies a variable length of time, requiring sometimes hours, and sometimes days. In some instances the re-establishment of conditioned reflexes assumes a complicated character. Immediately after the termination of the attack conditioned reflexes are present, but, some time after, they again disappear, now for a consider- able length of time. This may possibly be explained by an initial irradiation of the outburst of excitation, followed subsequently by concentration and negative induction. So far as the effect of very strong or frequent attacks is concerned their after-effect is very variable. In one dog they were apparently the cause of an absolute deafness ; another dog, which after the operation behaved quite normally towards men and towards other dogs and food, began after a severe attack of convulsions to dodge and run away from other dogs and from men. Finally a fresh attack killed her. A third dog, after numerous and frequent attacks, showed quite peculiar symptoms. The dog will be described in detail, but meanwhile I shall describe one of the symptom is dog, after the attack, all the reflexes returned ; they h wever, to be used with practically simultaneous reinforce Even small delays (up to 5 seconds) quickly led on repeti o disappearance of the conditioned effect, with refusal of nd development of sleep.

Obviously the dog suffered op ic state of faiblesse irritable such as was described in refere o another dog at the end of the preceding lecture. After each r’etrrence of the attack this peculiar symptom became more need. , It is natural to regard this change as due to a f 1 exhaustion of the cortical elements consequent on the c N ions ; the cortical elements now, under the action of ex O rapidly undergo a transition into an inhibitory TRY connection of which with sleep has been discussed p Gously. In this dog the functional exhaustion, like the excita aO producing it, affected the entire cortex. It is

often, We ver, restricted to the particular analyser which was this will be given later. In some cases the effect of the scar manifesta itself in a different manner, being limited to a hyper-excitability of analysers other than the motor one, and therefore not associated with convulsions. One dog after extirpation of the frontal lobes [experiments of Dr. Babkin] quickly recovered from the effects of the operation, but two months later it developed an extreme cutaneous hyperaesthesia which lasted for ten days : the animal would howl at the most gentle touch and-even at its own movements, and after this would shrink down into a heap on the floor. Evidently the scar in the cutaneous analyser served as a source of irritation to the cortical area of localization connected with the receptors of injury (subjectively pain), if indeed such analyser exists in an independent localized form. A still more interesting case was presented by another dog after a partial extirpation of the cortical part of the cutaneous analyser [experiments of Dr. Eroféeva]. One and a half months after the operation a vigorous attack of convulsions occurred. During this attack the animal was subjected to a further operation, the scar, which gave outgrowths considerably beyond the site of the original lesion, being carefully removed. The convulsions did not recur after

the operation, but another form of disturbance developed which lasted at each recurrence for several days. When either e imenter or food came into the field of vision of the left eye (thogh; l being operated on the right side) it quickly turned away, Ba if free ran away, showing signs of extreme excitation., The stimuli when applied from the right side of the animal RO ed no abnormal | reaction. Often, free and on its own, the do Ald suddenly glance | to the left, quickly jump up and run má aly ay. This can all be | interpreted if we assume that some aining portions of the scar

directly irritated the visual analyser @) one side, thereby producing a distortion of the effect of the e nal stimuli falling on the retina and altering the significance o visual object, which assumed in animal reacted as to a SS crete and definite stimulus—exactly in the same manner aren also with normal animals in response in the dog pre ly mentioned, which after an attack of convulsions most directly affected by the surgical interference. Examples of

exhibiting a violent general excitation. It is probable that the outburst of excitation resulting from the scar, after having freed the motor area of the cortex, was still retained for some time in the visual analyser. It is legitimate to regard these cases as the equiva- lent of epileptic disturbances of the motor analyser. The foregoing observations led to our planning a detailed investi- gation of the effects of direct stimulation of the different cortical

analysers. By permanently healing electrodes in different points of the hemispheres we are hoping to produce in our dogs by means of electrical stimulation definite changes in the reactions to our usual conditioned stimuli. The difficulties of technique have been overcome and the experiments are at present in progress. It is unfortunate that the majority of our experiments with extirpation were performed in the earlier period of our research, when we had not definitely realized the peculiarities of the different individual types of the nervous system and had not yet any knowledge of the pathological effects arising under the influence of functional, i.e. non-surgical, disturbances.

After this preliminary review of the general effects of surgical interference with the cortex I shall describe in detail the results obtained by the fullest possible application of the method of con- ditioned reflexes to our operated animals with the object of determining the physiological significance of the eptie cortex and of larger or smaller parts thereof. In some of our animals a complete extirpati the whole cortex was carried out (one animal survived ae ation for 44 years). This operation had already first iene S i Kuced by Goltz, but it

mining by our method the relation rtex to the higher nervous activity of the dog [experimerky r. Zeliony]. The general behaviour of the animals after et extirpation of the cortex has been described in deton several occasions by Dr. Zeliony himself. I shall thertore OF l only upon the relation of conditioned reflexes to the cort Yi the usual conditioned reflexes were definitely absent i se Sna after the extirpation, and neither old nor new refléxeş “ould be obtained in spite of the most persistent reinforcing o cial stimuli or testing for natural conditioned reflexes, w Xenia our attention upon one peculiar conditioned reflex, according to our previous experiments, in contrast to all ee reflexes, was extremely stable. I refer to what

was undertaken in our experiments Gre special object of deter- ay D we term “the water reflex ”—a conditioned reflex in response to stimulation of the receptor surface of the mouth. If, by means of an apparatus which is placed in the dog’s mouth, water is injected after a few preliminary injections of acid, the water which under normal conditions evokes hardly any salivary secretion (at most 1-2 drops) now causes a copious secretion. Evidently the stimulation by liquid of some receptor nerve-endings of the mucous membrane of the mouth, coinciding with the effect of the acidity, acquires conditioned properties determining this large salivary secretion together with a corresponding motor reaction typical of the reflex to acid. The conditioned water-reflex, as will be shown later, possesses all the properties of a conditioned reflex. In the dog which survived the removal of the hemispheres the longest time (44 years), the water-reflex was established before the extirpation of the last

_portion of the hemispheres—the extirpation being performed in stages. The reflex measured 8-10 drops for injection of 5 c.c. of water. Beginning from the sixth day after complete extirpation of the hemispheres 5 c.c. of 0:25% solution of hydrochloric acid were repeatedly injected practically every day, over 500 injections being made in all. Only after seven months of this procedure did a salivary secretion to water appear, which gradually increased in strength until it measured 13 drops for injection of 5 c.cs. of water. Was this, however, a conditioned reflex ? Decidedly not. The reflex in this ease differed fundamentally from the ordinar = water-reflex, The most important difference was th be made to undergo extinction, which occurs wit the case of the real conditioned water-reflex inn water is injected several times in succession wji the acid. Inthe decorticated animal the effect of repeate ion of water became constant. By observing the dog aftexth4dministration of water the true nature of this reflex was rev . After injection of water the animal exhibited typical mggements, which otherwise were observed only when the animal hungry. It started walking to and fro with head bent low tching nostrils, as if reaching for something. On further i eration it became obvious that the

contact of water wit ucous membrane of the mouth evoked in this dog a stron onditioned alimentary reflex. This was corroborated: by the act that unconditioned reflexes, e.g. salivary reflexes, after Oval of the cerebral cortex, become at first I wonted strength and finally becoming very much increased above Hl normal. Hii To present the final conclusion of these experiments with the utmost reserve, the cerebral cortex should be regarded as the essential organ for the maintenance and establishment of conditioned reflexes, Hil possessing in this respect a function of nervous synthesis of a scope il and exactness which is not found in any other part of the central nervous system.

Of the individual analysers most attention was paid to the | acoustic, and I shall commence my description with this. An absolute | deafness following extirpation of a part of the cerebral cortex was | observed in three dogs. In two of these animals [experiments of IIN Dr. Koudrin] the cortical substance was rene posterior to a line starting from a point above and im ely behind the gyrus sigmoideus, stretching to the tip of rus sylviaticus and then [li passing along the fissura fossae sy ig. 9). The operation was I performed in two stages, first one and then on the other side. I Absolute deafness appeared im ately after the second operation. II One of the dogs lived for nig months after the operation, the other [ii for seven. In the third d xperiments of Dr. Makovski] a bilateral extirpation was perf the gyri sylviaticus posterior, ectosylvius II posterior and supra posterior. On one side there were included [fi also the middle dnd fife frontal portions of these convolutions (Fig. 10). | Absolute ones. occurred one and a half months after the operation. l On the day, ious to the deafness a weakening of the inhibitory observed : this was probably followed during the night by

good health, for another month. During this period new conditioned reflexes were developed to stimuli belonging to the tactile, olfactory and visual analysers. The animal died during an attack of con- vulsions. Other animals, which were operated on in exactly the same manner as the last, continued to react to sound, though in some cases they survived the operation even longer. How can we explain the absolute loss of all auditory reactions ? Since it must be regarded as definitely proved that after complete removal of the whole cortex dogs still continue to react to sound, it must be admitted that in the three cases of absolute deafness described above there must have been some damage of sub-cortical structures or a development of inhibition which spread into the sub-cortical areas. The latter possibility ought not to be excluded,

since on histological examination (unfortunately athe Onis no damage of sub-cortical structures could be observ urther, in the first two dogs a general reaction to light; whic first entirely disappeared, returned two months after the onion, and a con- ditioned reflex to light even reached its p Nerative intensity ; finally, it is well known how extremely Ow different impulses originating within the hemispheres inhikjt reflexes of lower centres. : If such an inhibitory effect is acceptes the cause of deafness in

involving any other analys As a rule the general ory motor reactions (pricking up the ears and lifting the head) after removal of the temporal lobes or of the whole posteri half of both hemispheres, return within a few hours, or a day or t most ; in some cases they do not disappear reaction to sound is an unconditioned investi- onging to sub-cortical regions, since it remains present in dogs even after removal of the entire cerebral cortex. The rest of the auditory reactions must be attributed to the cortex, and these functions of the acoustic analyser at first entirely disappear after the limited operations described above, then return, never, however, recovering completely.

When, after bilateral removal of the temporal lobes, the investi- gatory reflex to sound has already returned, as well as conditioned reflexes to stimuli belonging to other analysers, all auditory condi- tioned reflexes are found still to be absent. Such a state may last for many days or even for several months, depending upon the extent of the operation.. Moreover, it is of importance that both temporal lobes should be removed at one time, or in two operations shortly following one another, first on one side and then on the other. If the two operations are performed with a long interval between them the phase of complete disappearance of auditory conditioned reflexes may be absent. What does the temporary absence of auditory conditioned reflexes mean? Several possible interpretations can be advanced. First, it is possible that the cells of the acoustic analyser still remaining after the operation are rendered incapable of developing a state of excitation, and under the influence of external stimuli pass directly into an inhibitory state, it may be on account of being weakened by the operation, or on account of being decreased in number, or on account of being previously ke reserve and not involved as a general rule in the activity of tR stic analyser before the operation. Second, it is possible t Cifter the operation the analysing function of the cortical part e acoustic analyser is so diminished that all the sounds now ing the dog, both inside and outside the laboratory, acquire id Q al qualities and therefore, more frequently than not, fail to boi} che with the unconditioned stimulus, with the result that the conditioned significance of the definite acoustic stimulus didgjpears on account of extinction.

Finally, it is possible that er the influence of the operation the synthetic activity of the stic analyser, involved in the mainten- ance or establishm conditioned reflexes, itself weakens or temporarily disa . Special experiments were performed in order to test thse guppositions [Dr. Krijanovsky]. se was made of an auditory stimulus as a conditioned conditioned inhibitors of the same alimentary reflex ere established in a dog; one was a tactile stimulus,

Three days after bilateral removal of the temporal lobes (Fig. 11) the positive conditioned reflex to camphor had already reappeared. The conditioned inhibitors remained practically without any effect for several more days, but from the twelfth day on gave a full inhibition. It was noticed now that any other sounds had exactly the same inhibitory effect as the original conditioned in- hibitor. All positive acoustic conditioned reflexes were absent at this stage ; neither the sound of splashing of acid nor the sound of cracking of biscuits, to both of which under normal conditions reflexes developed with extreme ease, could be made to evoke a conditioned response. The fact that any sound acted in the capacity of a real conditioned inhibitor and not as an agent of external