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

10.45 ,, Weak buzzing 2 Slowly raises itself from the loops and takes food nder the usual conditions of life. we were fortunate to have at our ive type of animal, the special features appertain to every single anj In investigating this pro disposal an unusually of which will be discu in the succeeding lectures. (This dog was used for the experi ts described towards the end of the fourteenth lecture, p. 247). en constant conditions, the dog was remarkable

for the K of its highest nervous activity as expressed in the form of conditioned reflexes, and fully merited its nickname of “ an animated instrument.” The dog had ten different conditioned reflexes. There were six positive ones—to a buzzer, metronome, whistle, increase in illumination of the room, appearance of a small — toy horse ; and four negative ones—to a different rate of metronome, a diminution in the illumination of the room, the appearance of a square, and the appearance of a toy rabbit approximately of the same size and colour as the toy horse. For some time prior to the following experiments the buzzer had not been used, while out of the differentiated stimuli the metronome had been employed practically exclusively. The auditory stimuli usually, and in the early experiments always, gave a secretion 30 to 50% greater than that given by the visual stimuli. After two years’ work in the laboratory with this dog the positive conditioned reflexes showed some tendency to diminish and began to vary in their relative inten- sity, as frequently happens in the case of continuous and prolonged use of the same conditioned stimuli. During this state of the animal we could find all the definite transition stages of the cortical activity which were described earlier in this lecture as different phases of the progressive diffusion of the inhibitory process over the hemi- spheres. Each of these phases either lasted during the whole course of a single experiment or else, under the action of different influences produced experimentally, changed into some other_fhase [experi- ments by Dr. Speransky]. The only phase w outa not be observed, in this dog was the ultza paradoxont Y the conditions were not such as to favour the appearance of ase as the animal

never became very drowsy. The experi taken from different periods of the work are shown on the ite page. When the reflexes deviated ve h from normal they were strengthened and corrected by th od discussed in the fourteenth lecture, namely, by shoving interval between the beginning of the conditioned stimulus gad tts reinforcement. The spontaneous transition from one phas another in the two last experiments was most probably d O; ated reinforcement. We had, however, two special method NS: disposal by the use of which we could produce an recs interchange of phases. One of these methods

consisted in the lication of the completely differentiated inhibi- tory rate Khe metronome. Most probably the effect of this inhibitor Gy ulus was due to concentration of the diffuse inhibi- tion. í Salivary Time Conditioned stimulus during | Secretion in 0 seconds drops during 30 seconds | Experiment showing paradoxical phase and its transition into | the normal phase. Experiment showing complete @phibition and transition into the na phase. The second method consisted in the application of an extra stimulus, viz. the entry of the experimenter into the animal’s room. The following experiments serve as examples of the effect of each method :

The phase of complete inhibition with absence of the secretory and motor reactions is transformed in the above experiment first into the paradoxical, and then into the normal, phase by the application of the inhibitory rate of the metronome. Salivary Time Conditioned stimulus during | Secretion Remarks 30 seconds drops d The presence x experimenter in the room with the dog The questio ether all these different stages in the activity of the hemi res can be arranged in a definite order, and if so in what kind order, must remain for the present entirely open. A Bas of all the experiments at our disposal shows that the

sequence of the different phases was fairly variable, and it is not clear, therefore, whether the different states of the hemispheres in different animals are strictly successive or whether they may occur ` as parallel events. Only further experimentation can explain why a given phase undergoes transition directly into one or another of the remaining phases. It is hardly possible to doubt that all these different states of the hemispheres bear a strong resemblance to the different stages of what is generally known as hypnotism. The relation between the experimental results described here and hypnotism as observed in man will form the subject of the last lecture.

The different types ef nervous system.—Pathological disturbances of the cortex, result of functional interference. WE have been dealing up to the present with the normal activity of the cerebral cortex. It was noticed in passing, however, that the experiments to which our animals were subjected led in some instances to chronic disturbances of this normal activity. This was especially liable to occur in the early stages of our work, since in planning the experiments we had at first not even the slightest idea as to the limitations and the natural resistance of the cortex. The present lecture wiil be devoted to a description of those disturbances in the higher nervous activity which are of a purely functional origin, and not due to surgical interference or trauma. From some of these disturbances the animal recovers gradually and spontaneously under the influence of rest alone, on discontinuance of the disturbing experiments ; in other cases the disturbances are so persistent as to require special therapeutic measures. In aa i ces we were able to make observations during the actual gS f transition from the normal physiological state of the cor o a pathological state, and then to study its therapy. nin ogical state of the hemispheres in different individual RS rom the action of injurious influences varies greatly. RO; the same injurious influence causes severe and prolonged)dSsorders in some dogs; in others the disorders are only sliggt and fleeting ; while yet other dogs remain practically unaffecd{eJ. In many cases the deviation from normal produced by théPgame causative agent assumes in dif- ferent dogs quite differe pects. The type and the degree of pathological disturb t develops from some definite cause was found in all ca be determined primarily by the character of the individuakn AW system of the animals. Therefore, before

describing the„diérent pathological states it is important to say a few words. t the different individual types of nervous system found in dogs. The systematic investigation of the higher definite criteria which when expanded in the future will lead up to an exact definition of the different types of nervous system of individual animals. Such criteria when perfected should greatly assist the development of a strictly scientific experimental investi- gation of the hereditary transmission of different aspects of nervous activities in animals.1 At present, however, I shall not go beyond a general classification of our dogs. Two definite types, which may be regarded as extremes, stand out with special prominence.

The first type was met with practically from the beginning of our investigation, and the researches on animals belonging to this type led in our early experiments to much confusion. At a time when we were still quite unfamiliar with the subject of conditioned reflexes, we met in some of the experiments with considerable diffi- culties on account of a drowsiness, which developed from the use of certain conditioned stimuli and under certain conditions of experi- mentation, and which we were not able to overcome. We thought to get rid of this drowsiness by choosing for our experiments dogs which outside the experimental conditions were very lively. Animals were selected which were extremely vivacious, always sniffing at everything, gazing at everything intently, and reacting quickly to the minutest sounds. Such animals when they get acquainted with men, which they do very quickly and easily, often become ae

by their continuous demonstrativeness. They can never b Men 4 keep quiet either by orders or by a mild physical pu was, however, soon found that these very animals ane in the stand and limited in their movements, and ei when left alone in the experimental room, were the ents ei drowsy, so that their conditioned reflexes quickly djahaished or even dis- appeared altogether, in spite of frequent(réy$rcement by food or acid. Indeed, our repeated stimuli w y had not yet acquired stable positive conditioned propertie mediately and in a most unequivocal fashion, produced dregvsthess and even sleep in dogs which at the commencement ea were wide awake.

1 Experiments which have unicated briefly at the Edinburgh International Congress of ee (1923) upon hereditary facilitation of the development of so a reflexes in mice have been found to be very complicated, di rin and moreover extremely difficult to control. They are at present ®ging subjected to further investigation under more stringent conditio present the question of hereditary transmission of conditioned Ss nd of the hereditary facilitation of their acquirement

In some animals this happened even when they were not placed in the stand during the experiments, but were left free on the floor, the experimenter remaining quietly in the room ; nevertheless the dogs on administration of a conditioned stimulus soon got sleepy, closed their eyes and finally lay down on the floor. This often happened immediately after the reinforcement of a conditioned stimulus. At first we despaired of achieving anything with these animals; later we learned how to get over the difficulties. In dogs of this type many conditioned reflexes must be developed concur- rently, and with a great variety of stimuli; no stimulus must be repeated more than once in a single experiment, and long pauses between the applications of the various stimuli must be avoided ; not only excitatory but also inhibitory reflexes must be developed. In short, when we make rapid and considerable variations in the experimental environment such dogs become quite satisfactory subjects for the experiments. It is an interesting point, but one which cannot be pursued here, whether this type represents a higher or lower stage of nervous development.

Until a rigid scientific classification is fully established for all the various types of central nervous system I think we may be per- mitted to make use of the ancient classification of the so-called temperaments. The animals just described must be regarded in the light of the ancient classification as belonging to the n° sanguine ”’ type. - Under quick changes of stimuli they are oigo c and highly reactive, but with the slightest monotony of Kphvironment they become dull, drowsy and inactive. S

Our second type of dog is also very O e, and must be placed at the other end of the classical serie emperaments. In every new and slightly unfamiliar set o undings such animals are extremely restrained in their n ents. They slink along close to the wall in a cringing fashion often at the smallest movement or sound from outside—a Vai or a threatening movement—they immediately cower to t oor. Everybody who sees such an Q yudge it a great coward. These animals

rimental surroundings and the associated ly, but when they become thoroughly familiar with the new coYritions they make invaluable subjects for experi- mentation.* pe animal described at the end of the last lecture as “a livi @itrument ” belonged to this type. Such animals do not eee stands when the experimental conditions remain more or less constant ; on the contrary their conditioned reflexes, especially the inhibitory ones, remain extremely stable ‘and regular. We are engaged at present in our laboratory with a most exaggerated repre- sentative of this type. This dog—a bitch—was born at the institute and was always treated with the utmost gentleness; When she was about twelve months old she was occasionally brought into the laboratory, and during every experiment in the stand only very few stimuli were given. When brought to the laboratory five years after its first introduction this dog still behaved in exactly the same manner as on the first occasion, and until quite recently never got used to the laboratory conditions in the slightest degree. She slinks along behind the experimenter on the way to the experimental rooms, always with her tail between her legs. On meeting members of the staff (some of whom constantly try to make friends with her and pet her) she invariably and quickly dodges them, draws back and squats down on the floor. She reacts in the same manner to every slightly quicker movement or slightly louder word of her master, and behaves towards all of us as if we were her most dangerous enemies from whom she constantly and most severely suffers. In spite of all this, when she at last got used to her own experimental room many extremely regular and constant positive and negative conditioned reflexes were developed. This was so unexpected by us that the animal was flatteringly given the name of “ LON. It would not be an exaggeration to bring this animal una type of “ melancholic.” I shall return to this animal lat@y~Both the above types are obviously extremes. In the firgy\¢ke excitatory process predominates in the extreme, and in the ge the inhibitory. Both, therefore, are limited types, with, so to XS , & narrow scope of vital expression.

The first needs a contig and novel succession of stimuli, which may indeed often be algenfh the natural surround- ings ; the other, on the contrary, room ney uniform conditions of life and therefore suffers from bejag Thable to react to a sufficient number of stimuli to ensure a legend development of its nervous It has, no doubt, occu o some that these two types present a contradiction to the of the identity of sleep and internal inhibition, in that the with a predisposition to excitation tends

to fall asleep ngaggo conditions of our experiments, while the type with a pre sition to inhibition remains fully awake. If, the cortical elements serves as an impetus to a development of an inhibitory process, it.is easy to understand that in the first type the excess of excitability of the cortical elements leads to their precipitate functional exhaustion, and so, when the cortical elements are exposed to prolonged: monotonous stimuli, especially favours a development of inhibition which irradiates widely over the whole cortex. Only a quick succession of new stimuli acting upon different groups of nerve cells can neutralize the tendency of this type of animal towards inhibition. In the second type, on the other hand, though the in- hibition of the motor area of the cortex is so easily initiated (passive defence reflex) the inhibition does not irradiate over a wide area, some considerable parts of the cortex remaining unaffected; the parts which remain in an active state resist the diffuse spread of inhibition, i.e. sleep, and thereby make possible the restitution of the active state of the whole cortex as soon as the cause which initiated the initial inhibition has disappeared. In the first case the biologically unprofitable tendency is checked by the excitatory effect of a quickly changing environment, in the second by the restriction of the actual spread of inhibition in the cortex. In fact the limitation of the irradiation of the inhibition in the latter case seems to be a special protective mechanism of an otherwise defective nervous system.

There is a parallel to such limitation in the case of a man who has - trained himself to sleep even while walking, t.e. to lim the inhibition to the cortex, so that it does not descend to the cortical areas. In between the extremes just described caye found numerous intermediate types which present a greate nce between excita- tion and inhibition, types on the whole adapted to the natural conditions of life and therefore biology more resistant. Those that approximate to the first type@re ely and active, and in most cases aggressive ; those that ah finito to the second type are quiet and restrained. I re er in particular one dog of the latter type whose re was in many respects extraordinary.

I have never noticed it down on the floor while it waited for the experiment afte NEE tched from the kennel to the laboratory. It reacted as if isinterested in what happened around, and did not enter No flier friendly or antagonistic relations with any- body, even its Yster. In its stand it never showed any signs of drowsiness. Oi its positive or negative conditioned reflexes were considerable excitation. I succeeded in disturbing the placid calm of this animal by making most extraordinary sounds with a toy trumpet and having a frightful animal mask over my face. The dog lost all its usual restraint, began to bark determinedly and tried to get at me—a most “ phlegmatic ” but powerful type.

Another group of dogs belongs to a more excitable type, and may be regarded as corresponding to the “ choleric ” type of the ancient classification. Inhibitory conditioned reflexes in these animals are less stable. It is obvious that a large number of animals cannot be placed definitely in any one of these four types, but broadly speaking all the dogs which we used could be divided into two groups—those with an excessive or moderate tendency to excitation, and those with an excessive or moderate tendency to inhibition.

After this digression I can now proceed to the description of the functional disturbances in the cortical activities which were either observed accidentally or produced experimentally. The first observation was made under the following conditions. As was men- tioned in the third lecture, a conditioned alimentary reflex can be developed to a most severe electrical stimulus applied to the skin— a stimulus which would normally evoke the inborn defence reaction but to which the animal now responds by an alimentary reaction, turning its head towards the place where the food appearg, licking its lips and producing a secretion of typical “ time saliva [experiments of Dr. Eroféeva, p. 29]. In the case is being described the development of this reflex had bee use of a very weak current, which was gradually j until finally it was extremely powerful. The reflex developed in this way remaine

tioned alimentary for many months. The electric current was occasionallyegr by cauterization or mechanical injury of the skin, both ing the same reflex. The animal remained perfectly TAR ughout a long period of the experiments, but after a cer ime this peculiar conditioned stimulus, similarly to any ot gan to acquire inhibitory proper- ties, the onset of the sé y effect becoming more and more removed from the begi Kids of the conditioned stimulus. On rare occasions the electri timulus had been applied to places other than the one for @kich the reflex had been originally developed. Now, however, Wrésolved to generalize the reflex by a systematic application. stimulus to new places. For some time the elec-

trical stimulus continued, when applied to the different places of the skin, to produce the same conditioned alimentary reflex without any interference of a defence reaction. A limit, however, was suddenly reached. When a still further place was added to those. already successfully generalized everything underwent an abrupt and complete change. No trace of the alimentary reaction was left : instead only a most violent defence reaction was present. Even an extremely weak current, which before the development of the ali- mentary conditioned reflex remained entirely without effect, now when applied to the original place of stimulation or to any other brought about the most violent defence reaction. The experiment was repeated on two other dogs. In one of them the outburst of excitation occurred on the application of the stimulus of the electric current to a ninth new place. In the other the application to a thirteenth new place did not yet bring about any explosion of excita- tion. When, however, the electric stimulus was applied in the same experiment to several of these places on the same day, and not, as before, to a single place only, the same explosive change occurred. In all three dogs nothing could be done to restore at once the alimentary reflex to the electrical stimulus. The animals became restless and excited in an extreme degree, which they had never been before. In one dog it was only after an interval of three months that it was possible to start a fresh development of the original alimentary conditioned reflex to the stimulus of th oy ptric current. This was a much more difficult operation than bate, ut the reflex _ was finally restored. In the other two dogs a, Sen longer interval did not help. Obviously the nervous syste been brought into a chronic pathological state.

At the sO of these experiments, unfortuņately, we had not begun G account of the type of nervous system of our dogs. G Possibly on account of the %ecial nature of the stimulus used in these experiments all these f id not attract sufficient attention on our part ; but some ti fterwards the same phenomenon was observed under more conditions of experimentation. The experiments in que ére made to determine the limits of the analysis of shapeg ilferent objects [experiments of Dr. Shenger- Krestovnikova] projection of a luminous circle on to a screen

ad become well established a differentiation between d an ellipse with a ratio of the semi-axes 2:1, of the same luminosity and the same surface area, was obtained by the usual method of contrast. A complete and constant differentia- tion was obtained comparatively quickly. The shape of the ellipse was now approximated by stages to that of the circle (ratios of the semi-axes of 3 : 2, 4: 3 and so on) and the development of differenti- ation continued through the successive ellipses. The differentiation proceeded with some fluctuations, progressing at first more and more quickly, and then again slower, until an ellipse with ratio of semi-axes 9:8 was reached. In this case, although a considerable degree of discrimination did develop, it was far from being complete. After three weeks of work upon this differentiation not only did the discrimination fail to improve, but it became considerably worse, and finally disappeared altogether. At the same time the whole behaviour of the animal underwent an abrupt change. The hitherto quiet dog began to squeal in its stand, kept wriggling about, tore off with its teeth the apparatus for mechanical stimulation of the skin, and bit through the tubes connecting the animal’s room with the observer, a behaviour which never happened before. On being taken into the experimental room the dog now barked violently, which was also contrary to its usual custom ; in short it presented all the symptoms of a condition of acute neurosis. On testing the cruder differentiations they also were found to be destroyed, even the one with the ratio of the semi-axes 2:1. A fresh dev@lopment of the latter differentiation up to its previous exactn sa twice as slowly as at first, but during the re-establi nt of this crude differentiation the animal gradually became er, returning

tiations now occurred even more quickly t efore. The 9:8 ellipse at its first application was comple obese from the circle, but from the second applicati ards no trace of a dis- crimination was obtained, and the ep again entered a state of extreme general excitation with the“Same results as before. No further experiments were perfo with the animal. Some of the different stages of these expeyi s are given on page 292. In the first experiment n below the ellipse with ratio of the semi-axes 4:3 was f criminated. In the second experiment the ellipse with the raWigf) : 8, in its first stage of development, gave only 1 drop of salary secretion. After repeating it in the course of the succeedi o weeks its effect, as shown in the third of the

experiments i below, became equal to that of the circle. After a this even the ellipse with a ratio of 2:1 failed to become fully discriminated, as shown in the fourth experiment ; and only in the fifth of the given experiments, performed 1} months later, did it After these eyperiments we paid considerable attention to urbances in the cortical activity and began to study It became obvious that under certain conditions of excitation with inhibition led to a profound dis-

turbance of the usual balance between these two processes, and led in a greater or less degree and for a longer or shorter time to patho- logical disturbances of the nervous system. In the first example, with the development of an alimentary reflex to the strong electric stimulus, it was the inborn defence reflex which had to be inhibited ; in the second example, with the visual stimuli, as we know already from the seventh lecture, the differentiation which had to be estab- lished also depended on a development of inhibition. In both cases a balance of the two antagonistic processes was satisfactorily main- tained until a certain critical stage was reached, when, under the stress of the delicate antagonistic relations of the stimuli, the further adjustment of the balance became impossible and finally gave way to an undisputed predominance of one of them (as will be shown later), producing a pathological state.

In further experiments dogs were intentionally selected which possessed different types of nervous system, in order to find out _ the different pathological disturbances which would be produced by functional (2.e. non-surgical) interferences with the cortical activity. The first of these experiments [Dr. Petrova] were performed on two dogs, representatives, as judged by their general behaviour, of the two extreme types of nervous system. These dogs were those already described in the lecture upon sleep, the drowsiness, which they exhibited at first, being successfully removed by the adminja{xation in rapid succession of six different conditioned reflexes wi terval of 5 seconds between the beginning of the condj d and the unconditioned stimuli (p. 254). Besides abolishin ep the experi- ments provided very clear and definite TA of the essential differences between the types of nervous or of the two dogs, successfully corroborating the ings) eir respective types which was previously made by generak observation. In the course of the experiments the conditioned exes, which to begin with were practically simultaneous, wes transformed into long-delayed reflexes with an interval of eo es between the conditioned and the unconditioned on Sesion of the reflexes was

performed gradually nging the length of isolated action of the conditioned stim y 5 seconds daily ; correspondingly the so-called latent aa C the reflexes—i.e. the interval of time between the begi g of the conditioned stimulus and the onset of the salivary, END o the « gradually more and more prolonged. All six KÝ ere being treated in this manner at the same time. The dog with a predominant tendency to inhibition mastered the problem of developing the longer delay straight ahead, and without any nervous disturbances ; the dog with a predominant tendency to excitation reacted to the problem in a quite -different manner. When the delay of the reflexes reached two minutes the animal began to enter into a state of general excitation, and with a further prolongation of the delay to 3 minutes the animal became quite crazy, unceasingly and violently moving all parts of its body, howling, barking and squealing intolerably. All this was accompanied by an unceasing flow of saliva, so that although the secretion increased during the action of the conditioned stimuli all traces of the delay completely disappeared. Obviously the development of the inhibitory phase of delay required by many conditioned reflexes at one time was too difficult a problem for the excitable nervous system of this dog. It should be added that certain difficulties in the way of a successful development of a balance between the two antagonistic processes, difficulties in the form of hyper-excitation, were met with in many dogs, but in no other dog did this general excitation reach so great an intensity. However, the problem set to this animal was much more than usually complicated, since it was required to set up a balance of the two antagonistic processes in many points of the hemispheres at one and the same time. Eventually there was nothing to be done, other than to relinquish the exper\ments in this form. It is interesting that the problem which so fa: d impossible of resolution by the nervous system of this Was nevertheless quite satisfactorily achieved when another mega experimentation was employed. We restricted our work XO: e of the conditioned stimuli only.