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

in drops per 10 Ti T T R aS D B seconds during ime . Conditioned stimulus tk G ' ea the isolated action A simia Gopitivo effect of stimulation of the usually ineffective places of in could be obtained also by some other devices— with aS p of positive induction, by means of dis-inhibition, and à by the use of caffeine. This animal obviously presents in respect of the affected cutaneous areas another instance of a maximal faiblesse irritable. In all our experiments, including those which are being conducted at the present time [Dr. Fedorov], the refractory areas of the skin regain as a general rule, sooner or later after the cerebral operation, their normal positive effect, as has previously been observed by other workers. The question naturally arises as to the mechanism of such recovery. The first explanation to be thought of was a possible existence of direct nerve tracts which had successfully replaced the crossed ones. For the purpose of testing this possibility we now in some dogs extirpated the cortex completely on one side and studied the conditioned tactile reflexes from the skin of the opposite side of the body for the whole time that the animals sur- vived (some of them living for over a year after the operation without attacks of convulsions). Up to the present such experiments have been completed on four dogs. Alimentary conditioned reflexes were employed in most cases; sometimes, however, a defence reflex to acid or to a stimulus of an electric current was also used, the electric stimulus being applied to the skin on that side of the body which was not affected by the cortical lesion [experiments of Drs. Foursikov and Bikov]. The results in all these experiments, in spite of many different modifications, were absolutely negative, and in,spite of increasing the cortical excitabliity by strychnine and, etn the cutaneous reflexes never returned [experiments of Dp ursikov]. Experiments were also conducted to determine wh¢ttef the tactile stimulation of the injured side of the body would pxayt any inhibitory influence upon other conditioned reflexes as if Nid after the partial sNnlents by Dr. Bikov].

In the cases of complete unilateral gxtixpation of the cortex no such inhibitory influence of the tact#e\timuli of the affected side upon the various positive conditjo reflexes (including tactile reflexes from the normal side e animal) could be observed, whether as an after-effect o the actual administration of the stimuli ; similarly also thé ctile stimuli did not induce sleep or drowsiness. These eo are the more important since the same places acquiredNgifong inhibitory properties in those cases where there had b Gp partial destruction of the cutaneous analyser. There was, of c SS no question of revealing any positive effect of the stimuli byary of the methods which were successful in the case

of partial extirpation. In the case of complete unilateral removal of the cortex, therefore, the tactile stimuli on the opposite side entirely lose their conditioned properties, both positive and negative. In other words, according to our experiments, there is no homolateral connec- tion of the skin with the cortex. Vicariation in the case of partial de- struction of the cutaneous analyser must therefore occur with the help of the outlying parts of the analyser in the hemisphere of the same side—a view which has already been advanced by other authors.

In order to study this question of vicariation more closely we resolved to produce an extirpation of as many of the frontal con- volutions of one hemisphere as possible, so as to narrow the area from which the compensatory effect might be derived. In dogs operated in this manner the conditioned reflexes to tactile cutaneous stimuli, although they disappeared for a very long time, did never- theless return. It was thought that the portions adjacent to the operated field might have taken over the function of the removed parts. However, additional destruction of these adjacent parts [experiments of Dr. Eurman] had practically no effect upon the re-established functions of the analyser. The vicariation of function, therefore, must be attributed to much more widely distributed cortical elements. This result.made it important to test whether the method which we used for tactile stimulation of the skin was not contaminated by an auditory component so that the reflexes which we observed could be explained by the latter. paratus was therefore constructed which, at any rate to our oN , was entirely without sound, and in order to make the c 1 doubly sure we placed between the apparatus and the skin a eWium which prevented the mechanical effect of the apparatus (he skin, without, how- ever, abolishing any possible auditgrwcymponent inaudible to us. Tactile conditioned reflexes could Qe HeVveloped without, but in no case with, the medium, in either n4rmal or operated animals, proving, of course, that under ordinary AMitions the reflexes were genuinely initiated purely by the tac @ptimulation and not by any accessory

We are inclined acoustic analyser OX parts of the cutaneous analyser remaining after the first operĝtion have only a limited function as compared with the Aon of the cortical elements situated in the extirpated nucleus of alyser. We hope to test this theory by experiments with co d tactile conditioned stimuli and by using a differentia- tion of the direction of brushing the skin and testing this differen- tiation upon those places which have recovered from their temporary loss of conditioned reflexes after the extirpation of the frontal lobes. These experiments are in progress at the present time. All the experiments with respect to recovery of tactile reflexes after extir- pation are, however, being vigorously repeated in view of their intrinsic importance and in view of the divergence of some results of recent experiments from one of our earlier observations (p. 362).

Fig. 15.—O and Roman figures :—Numbers of the places stimulated. Aragos :—Con- ditioned reflex in drops of saliva (1 drop =0'01 c.c.). The figures to the d left of the Roman figures were obtained by stimulation of the right and left sides of the añimal respectively. The tactile reflex was established on the left side at place O. The fig G oWs the spontaneous bilateral formation of accessory reflexes. Note that the strength mrefiexes at correspond- ing points is identical on both sides of the animal. The ich was established. at

Besides studying, in the manner dexcribed, the relations of the tactile analyser in a single hemisph&e) we have also investigated the interrelations of the analysers @Pfhe two sides. An observation has already been mentioned th ctile conditioned reflexes which were developed for differe (as n one side of the body reproduce themselves a TO surprising accuracy on the sym- metrical places of the dtheg Side of the body. This phenomenon has been especially carefully examined by Dr. Anrep, and its occurrence was demonstrate for positive and negative reflexes to tactile stimuli (see Fi It was naturally expected that the development

of a differentiation of symmetrical places of the skin on opposite sides of the body would turn out to be a matter of considerable difficulty, and this actually was found to be the case [experiments of Drs. Bikov and Grigorovich]. What is the mechanism of this curious phenomenon? It was only natural to consider first the commissural connections, and in actual fact section of the corpus callosum completely abolished the whole phenomenon. After the section conditioned reflexes to tactile stimulation of the two sides became entirely independent of one another [Dr. Bikov]. The positive and negative tactile reflexes developed on one side now completely failed to reproduce themselves spontaneously on the other side; in order to develop conditioned reflexes on the other side the tactile stimuli had to be independently reinforced. Tactile conditioned stimuli were established with the use of food, the use of the unconditioned defence reflex to acid, or the use of the defence reflex to electrical stimulation of the skin. The electric current in these experiments was of such strength as to produce only a withdrawal of the leg and an investigatory reflex, but no violent defence reaction. The experiments were varied in many different ways, but the result was always the same. The reflexes were confined to the side on which they were developed ; reflexes on the other side had always to be developed independently. There was also no longer any difficulty in establishing reflexes of opposite sign for symmetrical places on oppositegsides of the body. This is illustrated by the following experiment

After section of the corpus callosum a t stimulation of the right thigh was given excitatory propa an of the left thigh- inhibitory properties ; and a tactile sti tion of the right shoulder was given inhibitory properties a e left shoulder excitatory properties. The four eee f course, to be developed rand ose ts SOR ERM =. ee tactile EEA von O eea | gam 30 seconds 4. Righi thigh 4 4. }, | | Right shoulder 0 ma t: Left shoulder ; +4 AOs , Left thigh 0 Orr z Right thigh 3

In conformity with the above results’ all extraneous stimulations of the skin applied on one side of the animal, e.g. a thermal stimulus of 50° C., and a weak electric current, by evoking an investigatory reflex produced an inhibition only of the tactile reflexes on the same side of the body. These experiments were conducted on three animals. l i Along with the experiments which were primarily designed for investigation of the tactile analyser, mention must be made of ex- periments with complete removal of the frontal lobes [experiments of Dr. Babkin]. The frontal lobes were removed upon both sides in front of sulcus praecruciatus and sulcus praesylvius down to the lower margin of the hemispheres, involving destruction of the olfactory

lobes (Fig. 16). Sometimes the knife during the ope S, and in almost every case the subsequent pathological p (as shown by post-mortem examinations), involved part of rea behind the line indicated. The experiments were condu n four dogs. In all cases the old visual and auditory coneitīeged reflexes returned and new ones could be established sogn r the operation. Dis- turbances—and considerable onesie’ only in the tactile 1-6 months after the operation, d ecurring in all cases on account of severe attacks of convulsi ring this time no positive tactile reflexes could be re-establis or places on the body, but reflexes could be established i De cases for places on the extremities. Good negative Ai aer, in which the tactile stimulus was used as a conditi G@jnhibitor, could be produced for any place of the skin. The imals suffered from a persistent cutaneous

analyser and in the movements of É nimal. The dogs lived for their legs during the experiments, and kept quiet only when the loops were discarded. Temporary disturbances in maintenance of posture and locomotion were observed. . The animal would often assume an unnatural pose—drooping head and arched back, paresis of the extremities with twitchings. The motor disturbances were most pronounced in the movement of the mouth, the dog immediately after the operation being able to take food only with difficulty, and having to be fed by hand, especially in the case of solid food. The above were the only peculiarities of note.

In respect of the thermal cutaneous analyser only a small number of experiments have been performed. From these it appears that the thermal, does not entirely coincide with the tactile, analyser in cortical localization. In the case of extirpation of the gyrus praecruciatus [experiments of Dr. Shishlo] tactile conditioned reflexes for the hind limbs were re-established a few days after the operation, while the thermal reflexes (to cold and to a temperature of 474° C.) conspicuously lagged behind, taking four weeks longer before they returned.

The method of conditioned reflexes was applied also for the verification of the statement made by some authors as to a definite relation of the gyrus pyriformis to the olfactory analyser. The ex- periments were performed on six dogs which had different “ artificial ” and “ natural” secretory and motor reflexes [experiments of Dr. Zavadsky]. Different unconditioned reflexes < lso. carefully observed. The first of these reflexes to rea LAS after complete bilateral removal of the gyri pyriformi and jacent part of the hippocampus were the olfactory ones. ements of the nostrils in response to olfactory stimuli were t so soon as the second or third day after the operation. third or fourth day the dogs could select accurately out of man per bags those that contained meat or breakfast-sausage. Sa sixth day the conditioned reflex peared, while on the fourteenth day

an artificial alimentary c Rioned reflex to the odour of camphor be- came quite definite. sipped conditioned olfactory reflexes had a positive effect in thokN t trial, evidence of a spontaneous recovery. Finally oe ee aa A the question as to the nature of the so-called motoNggea of the cortex. Is it in all its complexity and delicacy of gorn a receptive field and analyser of stimuli initiated within t \S eleto-motor apparatus of the organism? In other

wore comparable to other regions of the cortex which serve as receptive fields and analysers of stimuli falling upon the animal from the outside ? Or is it a region physiologically distinct from the remaining parts of the cortex ? Is it physiologically comparable to the posterior or to the anterior columns of the spinal cord ? This question is nearly as old as the discovery of the motor area - itself, but at the present time there are only a few observers who regard the motor area of the cortex as corresponding functionally to the posterior columns in the spinal cord. In the hope of procuring some fresh evidence we approached the study of this question from the point of view of conditioned reflexes, using some definite motor activity as a conditioned stimulus, and then experimentally deter- mining the localization of this reflex in the cortex. The experiments performed bearing on the motor analyser of the cortex are rather more complicated than other experiments with conditioned reflexes in respect to technique. I have, therefore, no hesitation in giving these experiments in considerable detail, and illustrating my description by a large number of examples [experiments of Dr. Krasnogorski].

Passive flexion of the tibio-tarsal and the metatarso-phalangeal joints were used as conditioned stimuli. The flexion was performed in the following manner. For the passive flexion of the tibio-tarsal joint the thigh and the leg of the hind limb were fixed in a plaster cast attached to a metal frame which was screwed down to the table. In order to employ the metatarso-phalangeal joint the tarsus and metatarsus had also to be rigidly fixed in a special cast, € ion of the joints was performed in the preliminary a by hand

and later by a special mechanical device. When th x to flexion of the tibio-tarsal joint of the left leg became xe) hed the effect was tried of flexion of the same joint of the o e leg. The reflex was found to be spontaneously present j n the case of tactile conditioned reflexes. We now started,t elop a differentiation of the flexion of the Hig oy joint (toes) of the left leg from flexion of its tibio-tarsal jointNénkle). The differentiation became established after 42 reinf ents of the flexion of the toes contrasted with 74 flexions of kle. This differentiation spon- taneously reproduced itself e respective joints of the right side also. Since flexion of Cysint invariably involves a mechanical stimulation of the skin(qyfich by itself might have been responsible both for the condi ed reflexes and the differentiation, further experiments had performed in order to dissociate the cutaneous component fro e actual flexion itself. For this purpose all sorts

of mechanical stimulations of the skin were applied, touching, pressing, gripping, and rhythmic stretching of the skin on one side of the joint and folding on the opposite side in imitation of the natural stretching and folding in the case of flexion of the joint. The latter kind of stimulation produced the strongest effect. On repetition of these cutaneous stimuli, of course without any rein- forcement, they finally became entirely ineffective while flexion itself, which was always reinforced, continued to act. It was realized, however, that all these precautions did not afford absolutely definite proof that flexion by itself acted in these experiments as the sole conditioned stimulus. It seemed quite possible that all our variations of mechanical stimulation of the skin did not entirely reproduce those accompanying flexion of the joint. It was essential to find a more conclusive proof that flexion itself became a conditioned stimu- lus. We expected to find such proof by completely excluding the cutaneous Component by extirpating those cortical parts of the tactile analyser which were known to stand in relation to tactile stimuli from the areas involved, namely, the gyri coronarius and ectosylvius (see Fig. 14, p. 347). Previously to the operation additional alimentary conditioned reflexes were established to tactile stimulation of the hind limbs at five distinct places and to a tone of 500 vibrations. The operation was performed on the left side of the cortex. The tone was the first conditioned reflex to reappear, and this occurred on the seventh day. The first trial of the flexion on t, Q aged. (right) side—on the eighth day after the operation—g negative result. The second trial—performed on the same d ave a secretion of 2 drops during 30 seconds. The trial on th day gave a secretion of 3 drops : on this day a simultaneous ghi}rtlation of the five tactile .

places on the same extremity rema ntirely without effect. On the twelfth day the reflex to oe hed 5 drops, while the stimu- lation of the five tactile places ‘olding and stretching of the skin still remained without effect the thirteenth day the folding and stretching of the skin ov a joint exerted an inhibitory influence upon the effect of t egpd applicà simultaneously. Again, when on the fifteenth EN eenth days the left (undamaged) hind ex- tremity recover the inhibitory effect of the operation and the tactile stimulation of this limb gave already a considerable secretory AG the same tactile stimulation applied simultaneously with foldi€g) nd stretching of the skin over the right joint became

right joint had now become, as an after-effect of the operation, inhibitory instead of excitatory. Nevertheless, flexion of the joint continued invariably to produce a salivary secretion. The following are the results of some of the individual experiments : Tactile stimulation of left planta Flexion of toes (right leg) nom Flexion of toes (right leg) 2 6 Tactile stimulation of 5 places on leg 0 8 Tone 7 7 Flexion of toes (right leg) 5 6 Stretching and folding of the 0

Experiment on the fifteenth day after the operation Flexion of toes (right leg) @ 6 Stretching and folding of the skin over right paw 0 20 Flexion of toes (right leg) xO 1 6 Tactile stimulation ot Na 4 6 Tactile stimulation a Pinte 0 6 Tactile oe 3 f and left plantae 0 Tactile = left planta | Experiment on the EO} h day after the operation. — Flexio (right leg 43} T Ti ulation of left planta 5 Ttilx.stimulation of left planta ther with stretching and Ofolding of the skin over the N right paw 0 6 actile stimulation of left planta 4

The above experiments justify the two following conclusions. First, that a passive flexion of the joint by itself, i.e. independently of the involved cutaneous component, can serve as a conditioned stimulus. Second, that the stimuli arising from such movement and the associated cutaneous stimuli have different areas of repre- sentation in the cortex. The problem remains therefore to determine the localization of the cortical area of muscular proprioception. The problem was solved by the following experiment performed on a dog in which the gyrus sigmoideus dexter had been completely

Fig. 17. removed two months previously, since when us motor disorders had prevailed in both extremities of the lef . During the opera- tion the gyrus sigmoideus sinister had als n very slightly damaged, but not sufficiently to produce a turbing influence on the extremities of the right side. Thejatefle conditioned reflexes in this animal were normal over the wep surface of the skin. We began with the establishment of a cpgditioned reflex to flexion of the right (i.e. homolateral) netatarnendlangea joint. This reflex developed very quickly. We no the differentiation of the flexion from its cutaneous compo using all the above-mentioned variations of mechanical stif~nufetion of the skin and the joint, and never, of course, reinforcjn®the cutaneous stimuli. Within a month the differentiation Os fairly well established (although it was not always absolute), (Wing that the right side was normal. The following is an SO taken at random :

Time interval Conditioned stimuli applied ected (a between during 30 seconds drops duri stimuli 5 ps during - Flexion of the right joint 6 6 Stretching and folding of the skin over the right joint 1 6 Flexion of the right joint 5 8 Stretching and folding of the We began now to test the reflexes on the left (i.e. heterolateral) side of the body. Stretching and folding the skin over the left hind paw was entirely ineffective right from the very start, in accordance ~

with the symmetrical spontaneity of development of reflexes discussed before. In contrast with the right side, however, the reflex to the flexion itself was also absent. When the flexion on the left side was now reinforced, the corresponding mechanical tactile stimulation, when tested separately, was found also to have acquired secretory properties. On contmuing these experiments, in spite of most persistent attempts at development of differentiation, it was found impossible to develop a conditioned reflex to flexion sepgadtely from the tactile cutaneous component. As soon as the effect chanical | stimulation of the skin was extinguished the re Qio flexion in- variably disappeared also. On reinforcing the nage the cutaneous reflex also invariably returned. The resul ese experiments must be interpreted as follows : pure flexiog A the left side was by itself ineffective, but the reinforcement of the flexion of the joint produced a positive effect through the agency of the tactile component unavoidably accompanying flexio n contrast. with this, the differentiation between the fle and the tactile stimulation on the right leg was constant a, ite definite. The table shown on page 360 is an example. NO The experiments © jat the gyrus sigmoideus is the area of cortical representatięn stimuli initiated in the skeleto-motor apparatus during passive flexion. A Unfortunat have not pursued this study further and have not employ variations of the experiments other than those

described. Before arriving at any final conclusion the experiments need to be repeated and more fully substantiated. If one bases conclusions on the experiments as they stand, the motor area of the cortex must be thought of as an analyser of the impulses from muscles and joints (proprioceptive), exactly as other areas are analysers of impulses from stimuli acting on the organism from the outside (exteroceptive). From this point of view the entire cortex represents

Number of minutes Conditioned stimuli applied Salivary Secretion during between during 30 seconds 30 seconds stimuli = Flexion ; right joint 8 Reinforced zi Cutaneous; right joint 2 ; 1 Cutaneous ; right joint 1 } Not reinforced 14 Flexion ; right joint 8 Reinforced 14 Cutaneous ; left joint 7 14 Cutaneous ; left joint 6 14 Cutaneous ; left- joint 4 Not reinforced 14 Cutaneous ; left joint 3 14 Cutaneous; left joint 14 l l4 Flexion ; left joint 4 Reinforced 6 Cutaneous ; left joint 4 l l4 Cutaneous ; left joint 1 > Not reinforced 14 Cutaneous ; left joint 1 f l4 Flexion ; left joint 0. Reinforced

external environment of the organism. Obvin@ty, if one accepts this hypothesis in relation to the motor agtiyity, there is good reason to extend it to the activity of m QJ ot all, other tissues of the organism. The important rôle ed by auto-suggestion with all its extraordinary aspects, a xample, imaginary preg- nancy, and all sorts of imaginary(disé%ses, can be understood from the physiological point of view ~ if we admit the existence of Pathological disturbances of the cortex, result of surgical interference (continued) : attempt to correlate the general post-operative behaviour of the animals with the disturbances in the activity of individual analysers.

Ir may be considered as firmly established that removal of the entire cerebral cortex converts the dog into a comparatively simple reflex machine. The animal retains the relatively limited number .of unconditioned reflexes, but is completely deprived of the more complex and delicate co-ordination of its activities with the external world, since these adjustments are solely based upon innumerable conditioned reflexes established through the intermediation of the cerebral cortex. We possess also some knowledge as to the signifi- cance of different areas of the cortex—the cortical analysers, the united function of which determines the complete adjustment of the organism with its surroundings, or, in other words, determines the behaviour of the animal. A great deal can be learned of the physio- logical activity of the cortex as a whole by careful obserygtyyn of the general state of the animal after extirpation of dengi orioa areas, whether such extirpations are free from & “operative