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

was discontinued. Soone AA this, the delay was extended again, but only to 15 secon gO d of to 20 seconds as previously. Salivary Time Conditioned stimulus Gosia in Motor reaction and during 15 seconds drops during general behaviour 15 seconds 10.44 a.m. Bubbling 64 Alimentary 10.54 Weak tone 54 a ae age Metronome, 120 per 6 Investigatory reflex minute followed by ali- mentary reflex E BY (erage Electric lamp 4h Alimentary PEISEN, Buzzer 44 - F L245, Bubbling 34 A rai; Weak tone 54 Lively alimentary

It was seen that the administration of the metronome led to an immediate disturbance of all the succeeding conditioned reflexes, which entered into a phase of equalization passing into the paradoxical phase. The disturbance, however, went much deeper than this. On the following day and for a long time afterwards the cortex was unable to withstand any kind of strong stimulus without undergoing complete inhibition. The fact that the maximum disturbance in the central nervous activity does not appear immediately on ad- ministration of the causative stimulus, but atto eA e or more days has been observed in many animals. The onde an experiment which was performed on the day EB t t administration of the metronome :

To all appearance the dog was at this time perfectly healthy. The cortical disturbance continued for 11 days without showing signs of any improvement, and we therefore determined to avoid any further use of the strong tone and to damp down the sounds of buzzer and bubbling. The following is the first experiment : Conditioned stimulus Salivary a Time applied Secretion in Motor reaction and during 15 seconds drops during general behaviour 15 seconds 10.20 a.m. Electric lamp 64 10:27 ig, Weak tone 5 10:327, Weak sound of 34 bubbling 10.40 ,, Weak buzzer 64 Alimentary reaction 10.48 ,, Weak tone 44 in every case 10:56; Weak sound of 44 bubbling PA a Weak buzzer 5 UES E oe Electric lamp 4

The experiments gave similar results on nine successive days. After this the strong stimuli were again applied, with the following result : A Experiment of 27th March, 1926. oe Cond’tioned stimulus Salivary X . Time applied Qvior reaction and during 15 seconds general behaviour 4.2 p.m. Strong buzzer 4 Alimentary ce Rae Electric lamp 1 4 4.16 ,, Strong sound of Q Turns head away, bubbling and declines the food 4.23 _,, Weak tone Q) Takes the food re- luctantly 4.30 ,, Strong bugz@®) 0 Signs of general ex-

When free upon the floor the animal behaved quite normally and took the food with avidity. After an interval of one day an experiment was performed again with the use of only weak stimuli, and all the reflexes were found to be present. Conditioned stimulus Salivary. i Time applied Secretion in Motor reaction and during 15 seconds drops during general behaviour 45° Weak bubbling Gite 4.10 ,, Electric lamp 4} 4.19 > Weak buzzer 6 Alimentary reaction 4.26 _,, Weak bubbling 64 in every case ASL hs Electric lamp 3

To sum up, these experiments show that the transformation of an inhibitory point of the acoustic analyser into an excitatory one occurred only gradually and imperfectly. Moreover, and this is more important, it rendered this point abnormal so that its stimula- tion by the conditioned stimulus of the metronome immediately led to a profound disturbance in the activity of the entire cortex, leading finally to an inability to withstand an g conditioned. stimuli without passing into different phases o bition, including the phase of complete inhibition. At first normal activity of the cortex was comparatively quickly re on discontinuing all ter period, with further stimulation of this point, the dist Ko took on a more permanent character. Since other a i continued at this time to

e must be regarded as a result of terference in the acoustic analyser, me circumscribed part, the stimulation diate effect upon the function of the eads to a protracted pathological state. These obser, Ds to my mind reveal once more in an almost tangible form Kc Jnosaic character of the cortical activities which has been di aa already. i The dý ance in the activity of the entire cortex which has just escribed can be regarded as being produced in either of

a strictly localized functional a chronic functional lesio of which produces ana whole cortex, and two ways. First, it is possible that the excitation evoked by stimuli acting upon the area of cortical disturbance now rapidly passes over into inhibition. Such a transition into inhibition is at first restricted to the immediate area around the original point of cortical disturbance but ultimately irradiates to involve the whole of the cortex. Second, it is possible that the stimuli act upon the area of cortical disturbance as injurious agents, so that, exactly as in the case of any injurious agents acting on any other part of the body, the entire cortical activity becomes inhibited on account of external inhibition.

In either case it is obvious that the localized disturbance of the- acoustic analyser is again the result of a clash between excitation and inhibition. Besides those cases which have been related in the present and in the preceding lectures many others have been observed in which a similar clashing of the two antagonistic nervous processes led sometimes to a temporary, sometimes to a more prolonged distur- bance of the normal activity of the cortex, in the form of a lasting predominance of one or the other process. In many cases these pathological disturbances could not be remedied by any of the measures which were applied. These abnormal conditions developed either during the establishment of very difficult differentiations— especially in the case of successive compound stimuli [experiments of Dr. Ivanov-Smolensky, Dr. Eurman and Dr. Zimkina]—or on immediate transition from inhibitory cutaneous stimuli togsditatory ones—especially when the differentiation depended u rate of stimulation of one and the same place on in the latter case the experiments were perfor and aggressive type of animal [experiments r. Federov] the general excitation reached such an intensit it became impossible to. continue the experiments. The “ek as, however, cured by

prolonged administration of bromides by disuse of both positive and negative tactile stimuli. In a ‘gg of more inhibitable type [experiments of Dr. Petrova] t key developed under similar. con- ditions an abnormal focus, to rearen strictly localized, in the cutaneous analyser, just AN e experiments of Dr. Rickman with the acoustic analyser positive stimulation of this point - invariably led to a diftuge spreading of inhibition which persisted throughout the givep experiment or even during a few subsequent days. Further riments with this dog were prevented. on account of its g ill of nephritis.

With regard to the pathology of the cortex, there remain to be mentioned another set of cases in which the disturbances verge almost impreceptibly into the normal. These cases are the result of a permanent congenital weakness of the nervous system of the animal, which under definite conditions is rendered abnormal, while a more resistant nervous system remains normal. However, before describing these it is necessary, for the sake of clearness, to discuss briefly those external stimuli which. directly lead to inhibition of the cortical elements. These are of three kinds—monotonously recurring weak stimuli, very strong stimuli and unusual stimuli. All these can result either from the appearance of some new stimulus or from a new grouping of old stimuli. The conditions of our lives as well as of the lives of animals provide many occasions for the action of such stimuli, and it is not necessary to give any special examples. The biological significance of the development of cortical inhibition in response to such stimuli can easily be perceived. If stimuli of considerable strength, and especially continually changing stimuli, determine—as they must do in order to maintain the delicate equilibration of the organism in its surroundings—an alert state of the cortex, then it is quite reasonable to suppose that weak and monotonous stimuli which do not call forth any activity should tend towards inhibition so as to rest the cortical elements and give them time for recovery after a preceding activity. The inhibitory influence

of very strong stimuli can be regarded as a refle “ passive self- defence,” as, for instance, in the case of hypno he immobility of the animal makes it less noticeable to the e , and thus abolishes or diminishes the aggressive reaction of enemy. It has been seen that the presence of something un also leads to a limitation of movement, which again may Q ‘survival value ” for the animal, since in the new conditio sual reactions might not be appropriate and might lead to ¥gme injury. Of course in the case of a new, even small, change ie environment, two reflexes appear —a positive one, the inve Gatory reflex, and a negative one, which might be described as ex of caution and restraint. Whether these two reflexes areWi@épendent or whether the second is a sequence to the first and res rom external inhibition or negative induction cannot be setka

A big flood which occurred in Petrograd on the 23rd September, 1924, afforded us an opportunity to observe in our dogs prolonged neuro-pathological disturbances which developed as a result of the extremely strong and unusual external stimuli consequent on the flood. The kennels of the animals which stood on the ground at about a quarter of a mile’s distance from the main building of the laboratory were flooded with water. During the terrific storm, amid the breaking of the waves of the increasing water against the walls of the building and the noise of breaking and falling trees, the animals had to be quickly transferred by making them swim in little groups from the kennels into the laboratory, where they were kept on the first floor, all huddled up together indiscriminately. All this produced a very strong and obvious inhibition in all the animals, since there was no fighting or quarrelling among them whatever, otherwise a usual occurrence when the dogs are kept to- gether. After this experience some of the dogs on their return to the kennels showed no disturbance in their conditioned reflexes. Other dogs—those of the inhibitable type—suffered a functional disturbance of the cortical activities for a very considerable period of time, as could be disclosed by experiments upon their conditioned reflexes.

One of the dogs has already been mentioned in these lectures [experiments by Dr. Speransky]—a strong healthy animal, but very easily subjected to inhibition, with all conditioned refle ormally of considerable magnitude, very constant and very e so long as the environing conditions were’ kept rigidly co . This dog had ten alimentary conditioned reflexes, six positon four negative (differentiations). Out of the positive reflexQ ee were auditory and three visual. The buzzer, which was ngest of the auditory stimuli, evoked the largest secretion. en) three visual reflexes were equal in their secretory effects ok smaller by about one-third than the auditory. A week after t ood the dog was brought in to the experimental room and ed in its stand. The animal was abnormally restless and a ghditioned reflexes were practically absent, and, though usu ery ready for food, the animal now would not touch the d even turned its head away. During three days while th&aflimal was purposely left without food its general behaviour Quring the experiments remained unaltered. On considering varjowspossible interpretations we reached the conclusion that this ex inary behaviour of the animal must still be an

after-effect of the flood, and the following method of combating the disturbance was adopted : Instead of leaving the animal alone during | the experiment the experimenter now remained in the same room Pa. with it, while I myself conducted the experiment from the outside. All the reflexes showed an immediate restoration in the first experi- | ment and the animal took the food with avidity, but it was sufficient | for the experimenter to leave the animal alone for all the abnormal symptoms to recur. In order to re-establish the reflexes permanently | | it was necessary to adopt the above course, of alternately leaving i | and entering the room, for a considerable period of time. On the | eleventh day of this treatment a conditioned stimulus which had not I been employed since before the flood was now for the first time again | employed, namely, the buzzer, which was the strongest stimulus, | and which before the flood constantly evoked the largest secretion. | After the application of the buzzer all the remaining conditioned reflexes almost completely disappeared, the animal again declined | the food, became very restless and continuously stared at the floor. | Under the influence of the same special stimulus, namely, the presence | of the experimenter in the room with the animal, the reflexes were | again gradually restored, but repetition of the buzzer after an interval | of five days produced the disturbance afresh. The buzzer was then | applied only when the experimenter was in the room with the animal, but even so, normal relations only returned gradually and very

| slowly. .On many occasions a phase of equalizatio the reflexes | was observed after administration of the ieee eflexes often | diminishing and the animal declining the f Perfectly normal reflexes were at last obtained after forty-s ee of experimenta- | tion, 7.e. two months after the flood. Fo made the following | experiment. A small stream of wate Noy allowed to trickle silently | beneath the door into the animal’s Qor. The water formed a small pool on the floor next to the re) e on which the dog stood in its stand. This experiment, whic Q) represented in full on page 315, was conducted in the @yce of the experimenter from the animal’s room. &

Several eS en the reflexes were perfectly normal and the buzzer Sah not been used for a considerable | length of time, Cis fresh application of the buzzer gave a reflex which was af gyeater intensity than the reflexes to the other stimuli, but on re g the stimulus of the buzzer once every day for several the secretory effect gradually diminished, and finally the buzzer became not only entirely ineffective of itself, but its applications now led also to a diminution of all the other reflexes. It is of interest that at this stage of the experiment the presence not

Metronome, 120 per 154 minute TOA Strong illumination 9 : of room Takes the food with 10:36, Buzzer 17 avidity 10.46 ,, Appearance of a 9 circle 10.5977, Whistle 15 HALS, Metronome, 80 per . 0 — minute (inhibitory) EP20 Metronome, 120 per 124 Takes the food with minute avidity 11.30 ,, Appearance of a 0 — square (inhibitory) 11.41 ,, Api PA S of a 9 ) Takes the food with 11.50, Buzzer 17 Ja ereny A small stream of | water is ¥llowed to tri iselessly 11.59 E oe pote animal’s and form a ol on the floor e animal jumps up quickly, gazes 12.2 p.m Strong illumination restlessly at the of the room O floor, tries to get EZ ie, Metronome, 120 per KO off the stand and minute O breathes heavily 1215 Whistle 0 The conditioned 12.25 <5, Buzzer 0 stimuli serve only 12.32 ,, Appearance of 0 to increase the circle Qy general excitation; N the animal declines | O the food only of the TAG ter in the animal’s room but even of his clothes

placed some we D of sight (ċ.e. olfactory stimulus) was sufficient e Evidently under the effect of an extremely powerful and unusual stimulus the cortical cells, which in this dog already had a tendency to inhibition, now permanently became still more susceptible to inhibition. Stimuli to which the dog had already for a considerable time been indifferent (the general environment of the experiment), and also strong agencies which had acted before as powerful condi- tioned stimuli (buzzer), produced a strong inhibitory effect upon the cortical elements, the resistance of which was now diminished. Minutest components of the extraordinary stimulus of the flood were sufficient to evoke the same abnormal reaction.

The dog upon which the experiments described in detail at the beginning of the present lecture were performed had also passed through the experience of the flood, with resulting disturbances, which, though based on a similar predisposition to inhibition, assumed a somewhat different character from those observed in the first dog. Two experiments are given below, the one performed the day before the flood (22nd September, 1924), the other on the third day after the flood (26th September, 1924).

(The experiments by Dr. Rickman upon the same dog, given in the first part of this lecture, were performed, it will be remembered, much later than this, December 1925—March 1926.) the food, but the positive conditioned reflexes were diminished and the maximum secretory effect was obtained by the negative stimulus (2.55 p.m.—ultra-paradoxical phase). Experiments were now per- formed in which for a very long time the inhibitory rate of the metronome was not used. The positive reflexes were satisfactory and approached the normal, but even now on a single fresh application of the inhibitory stimulus, in any experiment, all condi- tioned reflexes were greatly diminished or even abolished, not only |

in the given experiment but during several succeeding days. The following are two examples : Salivary Time Conditioned stimulus applied Secretion in during 30 seconds drops during 30 seconds 11.41 a.m: Weak tone 6 11.46 ,, Metronome, 120 per minute 74 | Lik i Metronome, 60 per minu 0 | (inhibitory) | TESORI Strong tone O 0 12.1 p.m. Buzzer x 3 120 Te. Electric lamp 0 TAA B Metronome, 120 minute l4 Ii During the period of re of the conditioned reflexes when |l the inhibitory stimulus not used all the different phases of | transition between te inhibition and the normal positive | effect were observed. the beginning the recovery was favoured | by the usual God of interrupting the experiments for a few days and short the isolated action of all the conditioned stimuli.

one or two reflexes in the beginning of an experiment were generally very weak, and all the rest failed altogether. The animal grew lethargic and persistently declined the food. As a final measure the - experiments were conducted with the animal kept free on the floor instead of in its stand. The beneficial effect of this method lies partly in the removal of the inhibitory influence of the stand, and partly in the introduction of additional excitatory impulses from the muscles and joints. The measure proved efficacious. The reflexes began gradually to return and progressively gained in strength. The animal accepted the food and normal relations became finally re-established. The administration of the negative stimulus led during the first seven days to a disappearance of the reflexes for the rest of that particular experiment. This inhibitory effect was not so apparent at the beginning of the experiment on the following day. In the course of the succeeding two weeks the prolonged inhibitory after-effect gradually disappeared and the inhibitory stimulus could now be practised during a single experiment more often. The differentiated inhibitory stimulus was repeated several times in every experiment, and concentration of the inhibition was accelerated by the immediate application of the corresponding positive stimulus. But it was only after two months of experi- mentation with the animal on the floor, and eight months after the flood, that it was found possible to return to A" experi-

It is thus seen that the powerful and un from the flood increased the susceptibility to inhibition to so great an extent that ev omparatively minute intensification of inhibition from the ide, in the form of a conditioned inhibitory stimulus, reid impossible for a long time any existence of positive condigio reflexes under ordinary ex- perimental conditions. ae All these experiments clegrl}bring out the fact that a develop- ment of a chronic phn state of the hemispheres can occur

from one or other of t ses: first a conflict between excitation and inhibition which ortex finds itself unable to resolve ; .second the action of ex ky powerful and unusual stimuli. I have still Ces the pathological state of another animal TR EAN Dr. Vishnevsky], but unfortunately I cannot state definitely er its present state depends only upon a congenital dalo 16h has been accentuated by its general conditions of life —age, pregnancy and so on—or whether it was produced as a result of the flood, as in the case of the two preceding animals. This animal was described in the preceding lecture (p. 287) as belonging to an extremely inhibitable type. Previously to the flood it had been left

for a long time without observation, and it was not until four months ) after the flood that experiments with the dog were resumed. It has already been mentioned that a long time before the flood this dog served for a considerable number of valuable experiments. Now, in spite of all the therapeutic measures which have been applied, the animal still cannot be employed for experiments upon our usual problems. All that I can do, therefore, in the present lecture is to describe its condition. The scope of the normal life of the animal, at any rate under laboratory conditions, has narrowed down considerably. In the laboratory it reacts to the minutest stimuli either by a passive defence reaction (an investigatory reflex which is immediately followed by inhibition of all movements and even refusal of food) or, as an exception to its type, it sleeps. Only in two ways can any return to normal conditions of life be brought about in this dog: either there must be adopted a quick transition from the conditioned stimulus to its reinforcement with food (within 1-2 seconds from its beginning), or else the experiments must be conducted with the animal on the floor and with the experimenter constantly moving about in the same room. In the AA case the animal trots after the experimenter during the whole experi- ment, but even so the reinforcement of the Toa stimulus must not be too much delayed. Both methods e provement in the same manner, the animal now ceasing to r o small changes in the environment in the same way that it-<N¢@”before, so that it y stimuli of unusual strength. Conditioned reflexes beging, uxdér these conditions, to return.

It is, however, only neh to delay reinforcement until 5-10 seconds from the ate Os the conditioned stimulus for the animal quickly to grow Qis and even fall asleep over its plate while taking the food, truly extraordinary state of the nervous system may be PAN as a state of extreme exhaustion— a perfect example of Ta Oed faiblesse irritable. The disturbance obviously has its sea ice cortical elements, since the delicate reactions of the ae. Gys analysers are essentially an intrinsic function

of the cerebral c A more detailed investigation of this dog is being ow he present time. Pathological disturbances of the cortex, result of surgical interference : (a) General disturbances of the cortical activity. (b) Disturbances of the acoustic analyser. HavinG attained, on entirely objective lines, to a measure of under- standing concerning at least the main aspects of the physiological activity of the cortex, we naturally became interested to apply the method of conditioned reflexes to the study of cortical localization of functions in an endeavour to determine the importance of different parts of the brain for the normal functioning of the cortex as a whole. Experiments in this direction were planned even in the early stages of our research (see my communication at the International Medical Congress at Madrid, 1903). The only method so far available for such a study consists in observing the effects of partial destruction or complete extirpation of different parts of the cortex. This method naturally suffers from fundamental disadvantages, since it involves the roughest forms of mechanical interference and the crude dis- membering of an organ of a most exquisite structure and function. Imagine that we have to penetrate into the activipyef an incompar- ably simpler machine fashioned by human haps d that for this purpose, not knowing its different parts, i d of carefully dis- mantling the machine we take a saw an away one or another fraction of it, hoping to obtain an exac wledge of its mechanical working! The- method usually PR to the study of the hemi- spheres or other parts of the çe nervous system is essentially as primitive as this. Hamman chisel, the saw and the drill ; these are the instruments whi must be used to open up the strong protective skull. The tear through the several layers of enveloping oteategfe rans rupturing many blood-vessels,

and finally, we inju destroy whole lumps of the delicate nervous tissue in diff Q) Ynechanical ways—concussion, pressure and incision. But is the marvellous functional resistance and the peculiar REN of.the living substance, that, in spite of all these gross ma Ny ations, within the lapse of only a single day it is some- tim i@possible without special and exact investigations to observe anything abnormal in animals submitted to cerebral operations. Accordingly, even by these primitive methods, some insight into the functions of the cortex can be gained. But the obvious usefulness of these crude methods should on no account satisfy the physiologist. . He should strive to apply new advances of technical science and to seek ever new and more appropriate methods for the study of the exquisite mechanism of the hemispheres. Naturally the methods available for the investigation of the cortex at present, by means of extirpation of different parts, can but lead to entangled patho- logical states, and even the most guarded deductions with regard to the constitution of the cortex cannot therefore be ensured against a high probability of error. Indeed, since the special function of the cortex is to establish new nervous connections and so to ensure a perfect functional correlation between the organism and its environ- ment, every disturbance of any part of it will be reflected upon the whole mechanism. Besides this direct influence of the operative procedure, which may reasonably be expected with time to diminish spontaneously, there is another very serious complication of the operation which appears later on—namely, the development of a scar at the place of cerebral lesion which now becomes a source of irritation and leads to further destruction of the surrounding parts. On the one hand the scar, owing to its mechanical irritation of the

surrounding normal parts of the brain, sets up recurrent Aen distortion and rupture, it progressively disintegrates t ispheres. I have been unfortunate in attempting to impr e operative technique, having made, as I now think, a ron In order to obviate haemorrhage during the operatio ed to remove in the dogs, long before the operation Cy, rain, the temporal muscles which cover the skull; this Res in a partial atrophy of the bones of the skull, so that th ould now be opened, often without the loss of a single drop gf bréod. But the dura mater in these cases also undergoes cons le atrophy, becomes dry and brittle, so that in most casesG impossible to make use of it to close up the cerebral ron As a result the wound was left after the operatiops ect communication with the more ex- ternal tissues, which lẹdgo the formation of a very. hard scar ulti- mately penetratin Gyd growing into the cerebral tissue. Almost every animal thas operated upon suffered from attacks of con- _