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

zero effect. W, (however, in another experiment it was tested 10 minutes aft similar reinforcement a positive effect was ex- hibited. Ex6ejly similar results were obtained when acid instead of food w@y‘administered at the first zero, the reflex being again gee previously mentioned intervals of time. The following ` are the actual figures of some of the experiments: The conditioned stimulus on its first application on a particular day gave 6 drops in twenty seconds; the stimulus was reinforced immediately after complete extinction ; tested after 10 minutes it gave 3 drops in twenty seconds. On the following day the experiment was repeated under precisely similar conditions. The stimulus gave, to start with, 7 drops during 20 seconds, and tested twenty minutes after rein- forcement at the first zero of extinction gave no trace of any secretory effect. The experiments were now performed with administration of acid after the extinction of the alimentary conditioned reflex to its first zero. In the first experiment the reflex measured at the start 5 drops in twenty seconds. Tested 10 minutes after administration of acid following the first zero it gave 2 drops. On the following day the conditioned stimulus again gave 5 drops at first, but tested twenty minutes after administration of acid following the first zero it re- mained without any secretory effect. The maximum of the dis- inhibiting effect in both cases was reached, of course, much earlier

‘than ten minutes from the administration of food or acid following the first zero. The error in our older experiments was due to an obvious fallacy.. The comparison of the rate of recovery in the two cases had been made between the effect of the special reinforcing agent and the effect of the much weaker extraneous reflexes evoked by different auditory, visual, tactile and other stimuli which generally have. only a short after-effect, while the comparison sh been made with the dis-inhibiting effect of other extrane g e.g. chemical ones, which have as long an S oop has food.

The error was facilitated by the fallacious co ion that the unconditioned stimulus underlying the conditidgs one must stand in some special relation to the latter, co special powers of re-establishment after extinction. The res these recent experi- ments inclines us more and more to Relies that the inhibitory process arises in the nerve cells themse and not in the connecting path between those cells excited @ythe conditioned stimulus and those excited by the special nditioned stimulus employed. Otherwise it is difficult to re the fact of the identical restorative action of the acid and f

The second probablq eror I wish to describe is still undergoing. investigation, but | it myself to discuss it now, on the one hand on account of the éme importance of the point involved, and on ause it illustrates once more the exceptional difficulties presented in this research to the establishment of exact facts. It will be remembered that in the second lecture we discussed the essentials necessary for the establishment of conditioned reflexes. After establishing that the action of the originally neutral but potentially conditioned stimulus must overlap that of the un- conditioned stimulus, we insisted also that the former must precede, by however short a time, the commencement of the latter. When the unconditioned stimulus was applied 5-10 seconds before the neutral stimulus it was found impossible to develop a conditioned reflex even by 300-400 repetitions, whereas by the usual method any conditioned reflex can be established in the average dog by so few as 3-20 repetitions. It was natural to suppose that the strong unconditioned stimulus acting on some part of the cortex evoked in virtue of external inhibition such a profound inhibitory state in the rest of the cortex that all stimuli reaching these parts became ineffective. Such a state may be compared with that of a man preoccupied with some definite activity, who remains “deaf” and “blind” to anything occurring round about him—a familiar psychical phenomenon which is accepted from a physiological point of view as undoubtedly corresponding with an objective reality. The plausibility of the above reasoning made us confident of its validity until recently, when our point of view changed. The question was raised as to the mechanism by means of which an early reinforcement of the conditioned stimulus, t.e. Spiering of its isolated action, obstructs the development Əðhibition in the cortical cells acted upon by the conditione ulus. In investi- gating this problem with a modification of the’experiments we came unexpectedly on a new fact, viz. that i unconditioned stimulus is administered before the pre-estapts conditioned stimulus the

conditioned reflex becomes inhi became directed to the exact mparable case where, instead of a pre-established conditioned shulus, we deal with a neutral agent which is intended for t evelopment of a conditioned reflex. The effect of the uncong d stimulus on both is precisely the same, since it exhibits in e case’ the properties of an external inhibitor. In contrast wi e observations an introduction of a small modification Gs time relations between the unconditioned stimulus an@esither of the other two causes the hitherto neutral agent to re conditioned properties and the conditioned stimulus to be et€esthened in its pre-established ones. This contrast reminds

us of another set of facts—the relation between the development of a secondary conditioned reflex and the development of conditioned inhibition, the case in which under identical external conditions, but with a small change in the time relations between the two stimuli, there develops in the one case a process of excitation, in the other - case a process of inhibition. All these observations concerning the action of the unconditioned stimulus point to the view (which involves a considerable modification of our original conception), that the mechanism of development of a conditioned reflex and the mechanism of external inhibition are somehow similar, and that the process of external inhibition bears some relation to the development of new connections between different cortical elements. If the analogy between external inhibition and the development of con- ditioned reflexes holds good, it should be expected that in the case where the unconditioned stimulus slightly precedes the Action of the neutral agent there would in the very beginning be an opportunity for formation of a link between their respective cortical points, leading to the formation of an unstable conditioned reflex. This reflex would, however, rapidly undergo inhibition on repetition of the superimposed stimulation. The first preliminary experiments have fully confirmed our supposition. We had already noticed that administration of the unconditioned stimulus immediately preceding the pre-established conditioned one led only gradually to a definite diminution of the reflex, a diminution which was the rapid and the more profound the smaller the intensity of th ditioned stimulus. Remembering this, we applied the simil mbination of the unconditioned stimulus with the hithert tral stimulus, but repeated this combination only a very fe es, to avoid the

development of the inhibitory process. I cases the expected result was obtained. The hitherto on ulus when now tested alone revealed undoubted conditione operties [experiments of Mlle. Pavlova and Drs. Kreps, Podko , Prorokov and Koupalov]. Considering now after these pr ary experiments the results obtained in the much -earlie riments by Dr. Krestovnikov (p. 27), we found that oN stimuli were tested by him for a conditioned effect only very large number of repetitions of the unconditioned WEO slightly preceding the neutral agent ;

moreover, even Wn these circumstances the stronger neutral stimuli when tested&\Sngly had at the first test some secretory effect. This secretory t, however, was explained as a casual and not a true conditioned effect—a brilliant illustration of the danger of too hasty generalizations. We imagined that if it were a true conditioned reflex it would increase in intensity on repetition of the combination, and not diminish and finally vanish, as happens in these experiments. It is possible also that we were misled by the

As before remarked, the problem here dealt with is being worked out in all its implications, under the strictest control and with the help of the knowledge which has been gained in the last few years. If the preliminary experiments described above should be fully upheld, an important fact in the physiology of the cortex will be disclosed—namely, that new connections can be established in the cortex, not only in the areas of optimal excitability, but also in those areas which are in one or another phase of inhibition.

In the present lecture it has been my aim not so much to dwell on the details of the different experiments as to lay the strongest emphasis upon the fundamental peculiarities of the method of conditioned reflexes. I believe that the wealth of facts discussed in all the preceding lectures is in itself a sufficient indication that the whole problem is worthy of an intense scientific research, which should result in accumulation of a great number of valuable data. I have not, therefore, hesitated to expose in the present lecture some of the weaknesses in our own scientific venture. Full realization of the difficulties seems to me preferable to digregarding them. Moreover, it has been my desire to forewarn f orkers in this field of the extraordinary complexity and th culties which they are bound to encounter.

On the whole, looking back upon im Quw field of physiological research I find it full of fascinatio cially since it satisfies two of the fundamental cravings human intellect—striving to. . realize. ever new and new rth to protest against the pretension of finality in truth we have aleady gained. In this domain there will for long remain an Conse breadth of uncharted ocean com- pared with the small oe of the known. The experimental results obtained with animals in their application to man.

In applying to man the results of investigation of the functions of the heart, digestive tract and other organs in the higher animals, allied as these organs are to the human in structure, great reserve must be exercised and the validity of comparisons must be verified at, every step. Obviously even greater caution must be used in attempting similarly to app:y our recently acquired knowledge concerning the higher nervous activity in the dog—the more so, since the incomparably greater development of the cerebral cortex in man is pre-eminently that factor which has raised man to his dominant position in the animal world. It would be the height of presumption to regard these first steps in elucidating the physiology of the cortex as solving the intricate problems of the higher psychic activities in man, when in fact at the present stage of our work no detailed application of its results to man is yet permissible.

Nevertheless, inasmuch as the higher nervous activity exhibited by the cortex rests, undoubtedly, on the same foundationgy man’ as in the higher animals, some very general and a ow evences can even now be drawn from the latter to the former. e future it may confidently be expected that a full and detid knowledge of at least the elementary facts of this activity a e obtained as regards both normal and pathological states.. ilarities between the manifestations of this activity in man! animal being more obvious under normal conditions, I shalkdismiss these briefly, dis- cussing in more detail certain pathologiggl cases. '

It is obvious that the different s of habits based on training, education and discipline of any re nothing but a long chain of conditioned reflexes. We all how associations, once established and acquired between d stimuli and our responses, are per- sistently and, so to spéak) automatically reproduced, sometimes even although we fight.against them. For instance, in the case of games and various, of skill, it is as difficult to abolish all sorts of superfluous ents as to acquire the necessary movements ;

and it is equally difficult to overcome established negative reflexes, t.e. inhibitions. Again, experience has taught us that a difficult task should be approached by gradual stages. We know also how different extra stimuli inhibit and discoordinate a well-established routine of activity, and how a change in a pre-established order dislocates and renders difficult our movements, activities and the whole routine of life. Again, we know how weak and monotonous stimuli render us languid and drowsy, and very often lead to sleep. We are also well acquainted with different cases of partial alertness in the case of normal sleep, for example a sleeping mother next to her sick child. . All these phenomena are analogous to those constantly met with in our animals as described in the preceding lectures, and there is no point in further discussing them in the present lecture. The discussion of pathological cases, however, will prove instructive. Contemporary medicine distinguishes ‘‘ nervous ” and “‘ psychic ” disturbances—neuroses and psychoses, but this distinction is, of course, only arbitrary. No real line of demarcation can be drawn between these two groups: it is impossible to imagine a deviation of higher activities from normal without a functional or structural disturbance of the cortex. The distinction between “nervous ” and “ psychic ” affections is a distinction made on grounds of greater or smaller complexity and subtlety in the disturbance of the nervous activity. Our experiments definitely show the validity of such a distinction.

So long as we deal with animals in ich the patho- logical disturbance results from functional inger ces including violent changes in the conditions of life (such r dogs experienced in the great flood in Petrograd), or on ac of small operations on the cortex, we can grasp the mec m of these disturbances more or less satisfactorily and expre terms of neuro-physiology. Such disturbances would come un classification of “‘ neuroses\”’ But if the disturbances are the%esults of extirpation or destruction by scar of large parts of the ex we encounter great difficulty in picturing the mechanism Gre resulting disturbance in the nervous activity, and we dep ore largely upon various suppositions which still remain A erified and controlled. Such disturbances would be classi “psychoses.” Obviously this difference in our attitude iXdjpe entirely to the much greater complexity of the disturhayge in the latter cases, and to the inadequacy of present- day phate analysis. We shall not discuss any conjectured subjek phere of our animals, but shall consider both cases

simply as disturbances in the normal cortical activity—smaller and more elementary in the former and more extensive and more. com- plicated in the latter cases. In the dog two conditions were found to produce pathological disturbances by functional interference, namely, an unusually acute clashing of the excitatory and inhibitory processes, and the influence of strong and extraordinary stimuli. In man precisely similar conditions constitute the usual causes of nervous and psychic dis- turbances. Different conditions productive of extreme excitation, such as intense grief or bitter insults, often lead, when the natural reactions are inhibited by the necessary restraint, to profound and prolonged loss of balance in nervous and psychic activity. So, too, neuroses and psychoses may develop as a result of different powerful stimuli, e.g. extreme danger to oneself or to near friends, or even the spectacle of some frightful event not affecting one directly. At the samé time we know that the same influence may produce a profound disturbance in some individuals and show no trace of effect on others, according to the power of resistance of the nervous system in each case. Exactly the same difference is observed also in dogs, which show a great variation in regard to the production of patholo- gical disturbances. We had dogs in which one of the most efficacious methods of evoking nervous disturbances, namely, a direct transition from an inhibitory to an excitatory rate of stimulation of the same place of the skin, failed to produce the slightest effect a a great number of repetitions on many days. In others distur otcurred. eventually after many repetitions, while in some i s produced by a single juxtaposition of the stimuli. In th e manner the great flood, which, as was mentioned previous\\4ed to a profound disturbance, obviously analogous to tr c neurosis in man, produced this effect only in some ofthe dogs, namely, those of an extremely inhibitable type. |

different forms of disturbance, ding on the type of nervous system of the animal. In ith the more resistant nervous system it leads to a predo ce of excitation ; in dogs with the less resistant nervous , to a predominance of inhibition. So far as can be judged o basis of casual observation I believe that these two ame eZ the pathological disturbance of the cortical activity in anim re comparable to the two forms of neurosis in man—in HAN eMreudian terminology neurasthenia and hysteria—-

the first with exaggeration of the excitatory and weakness of the inhibitory process, the second with a predominance of the inhibitory and weakness. of the excitatory process. There are grounds for considering the first type as having a more resistant nervous system which (at least in some cases) is able to perform a large amount of coordinated activity, while the weaker type of nervous system is quite incapable of adaptation to the ordinary conditions of life. The first type also goes through periods of weakness, and this can easily be understood, since for the most part such individuals are continuously excited, active, profligate of nervous activity—and the nervous exhaustion must, of course, be made good. This type may be regarded as having a longer period in the sequence of activity and rest of the nervous system as compared with the normally balanced brain, the periods of excitation and inhibition being more accentuated. Though the second type may exhibit violent attacks of excitation this does notimply greater vigour of their nervous system : , the excitation is generally without aim and without result—so to speak, crudely mechanical. In the observations made on dogs we obtained, I believe, some indication as.to the origin and character of this excitation. We had one dog [experiments of Dr. Frolov] of a very inhibitable type, or, as it would be more commonly described, a very cowardly and submissive animal. This animal served for experiments upon gastric secretion, and in the courge of the experi- ments it had to remain in the stand for many in succession. It never went to sleep while in the stand: t remaining very quiet it preserved a fully alert posture, I oving slightly and sometimes carefully shifting its legs. This\state of the animal was not semi-cataleptic, since it invariab onded to the call of its name.

When it was taken from t id and freed from the loops and leash, this dog invariably cgentev€d into astonishing fits of ex- citation, howling, throwing on vigorously about, sometimes upsetting the stand and falling‘wi the table. This excitation (which by the way was not cau desire for micturition or defaecation) could not be OPPN O) way, whether by shouting, petting or by striking the a , which became absolutely unrecognizable. A few minutes cise in the yard restored it to its normal state, ` the animal leadtw€ the way of itself into the experimental room, jumping u the stand and again standing motionless. The same

behavio Ly s sometimes observed in other dogs, but never in so RS tèd a form. These wild attacks of excitation may possibly be regarded as a brief outburst of positive induction following a prolonged and intense inhibition. A similar explanation may also be suggested for the fits of excitation in neurosis of the second type in which the inhibitory tendency prevails. The possible partici- pation of another cause also is suggested by experiments [by Dr. Podkopaev] on another dog. This dog was a quiet animal with a well-balanced nervous system, not very alert, which did not jump into the stand of itself, but when placed in the stand stood quietly and never slept. The positive and negative conditioned reflexes were very constant and precise. The dog had several conditioned

- reflexes established to stimulation of places along one side of the ` now to appear on the successive stimulation of other inhibit body, a stimulus on a definite place on the hind leg being a positive alimentary stimulus and all the rest negative. All these reflexes had developed rapidly and were very precise. During the application of the tactile stimuli the animal had always remained quiet, not making any local or general movements ; even the positive motor alimentary reaction was very weak, and the dog was slow in taking the food. The development of the negative reflexes had been begun at the front paw—the most remote from the positive place. Suddenly and quite unexpectedly -the stimulation of the front paw began to be accompanied by a motor reaction in the form of rapid twitching of the stimulated extremity. Sometimes the twitching assumed the rhythm of the tactile stimulus. Such local motor reactions began

in closer and closer proximity to the place of positive ifitance, the reaction at the same time becoming more vigorous extensive and involving all extremities. The head and n mained motionless, not participating in the activi the extremities. Salivary secretion was of course absent. however, the place on the thigh nearest to the positive one wa\ pow also made positive the motor reaction to the simula of this place vanished entirely. The same happened also to motor reaction for other places when they were transforme im negative into positive ones —with the exception only of the pedo remote places which, though

acquiring the positive secret ect, continued to evoke the local motor reaction in a muc kened form. The fact that this phe- nomenon made its app ce not during the establishment, but only after the Se enc of the differentiation—this and its localized form n it probable that the disturbance was of spinal origin, occurri account of a partial functional disconnection of the cortical cutaneous analyser from the lower centres. A similar explanation may be advanced for analogous cases in man.

We have a number of further observations which recall some more or less well-known forms of nervous disturbance in man. I shall remind you of the dog [experiments of Dr. Rickman (p. 302)] which was brought into a state in which it could not withstand any, strong conditioned stimuli—immediately entering into an inhibitory state so that a conditioned activity could be elicited only by the use of very weak stimuli. It is permissible to draw a parallel, of course only as regards the mechanism, between the case of this dog and the cases of many years of sleep in human patients—for example, of a young girl described by Pierre Janet and of an adult man as observed in one of the Petrograd hospitals for nervous disorders. The patients in both cases were lying in a continuous sleep, entirely motionless, did not speak a word and had to be fed artificially and kept clean. Only during the stillness of the night, when the daily bustle of life with its strong and varied stimuli quieted down, had the patients a chance of exhibiting some activity. The patient of Pierre Janet was observed to eat and even write during the night. It was reported of the Petrograd case that sometimes during the night he got out of bed. When this patient, at the age of 60, after nearly twenty years of continuous sleep, began to improve and could speak, he recounted that he often heard and saw everything occurring ground him, but had no strength either to move or to‘speak AVA these cases obviously presented an extreme weakening of | ervous system— especially of the cortex—which quickly le er the influence of any strong stimuli to a development of co e inhibition, i.e. sleep.

nervous activity which has ofte described, in the neuro- pathological literature, for prs g had a narrowly localized chronic functional lesion of th tical part of the acoustic analyser, any stimulation of the dera pie of the analyser by an appropriate agent leading to inhibiti the entire cortex. We are aware of many states of the system in man in which a perfectly normal activity cas maintained only so long as the man is not affected by ange Aaetimes almost a negligible, component—even

the remotest hi f those strong stimuli which originally evoked the nervo turbance Finall want to remind you of the case, described in the nine- teen cture, of periodical visual illusion in one of our dogs (p. 327). This was probably due to distortion of the effect upon the cortex of the external visual stimuli by locàl, internal stimuli originating in. the extending scar. Many similar cases of illusions in man are probably due to the interference of similar cortical stimuli of internal local origin.

Though our research abounds in cases of pathological disturbances which are comparable to those observed in man, I do not feel either safe or justified in proceeding in my comparison beyond the above observations, and these should not be taken as in any sense explaining the incaleulably complex symptoms observed in man, but only as showing that a comparison of a general nature can even now be . made. Similar comparisons between experimental animals and man can be made also in respect to therapeutic measures—general and

pharmacological. It has been stated already that rest and inter- ruption of experiments in many cases helped in the restoration of normal conditions. Several interesting details must, however, be described. One of our dogs was brought into an extremely excitable state by a clash of the inhibitory with the excitatory process [experiments of Dr. Petrova]. All forms of inhibition were disturbed, all negative conditioned stimuli acquiring positive properties. On application of any of the conditioned stimuli—those formerly positive as well as those formerly negative—the animal entered into a state of pronounced excitation which, as generally happens, was accompanied by severe hyperpnoea. The disuse of ne tioned reflexes did not improve the condition of the anita yper- pnoea continued and the positive reflexes remaine Sxessive. It was then resolved to use only those of the aN timuli which were physiologically weak, i.e. the visual and tX Ge, and to discard the auditory, which as a rule in our expe k Sii strong. The beneficial result of this treatment TO diate. The animal became quiet, hyperpnoea RRETA and the magnitude of the salivary effect returned to normal. Ar some time it became pos- sible gradually to introduce a the stronger positive stimuli without upsetting the result treatment. Furthermore, after several days a pre-establis erentiation of the tactile stimuli according to place (on easiest forms of internal inhibition)

Carn full vigour, and this without any signs of excitation on theq@art of the animal. This is an instructive case, showing how a dm WiTution in the strength of stimuli affecting the hemispheres d a diminution of the excessive excitability of the cortical elements. Of course, in the treatment of neurotic conditions in the human subject similar therapeutic measures are very widely adopted. I shall describe also another case which seems to me very in- structive from the point of view of therapy. In this instance we are concerned with a dog which was entirely out of the ordinary run and which had an obviously abnormal reaction to cutaneous stimuli, a reaction associated with a strong excitation of the cortex [experiments of Dr. Prorokov (p. 183)]. On application of the ugual tactile stimulus to the skin of the thigh the animal immediately began to wriggle its hind quarters, stamp its hind legs, throw up its head in a peculiar manner and make peculiar little noises, sometimes yawning. On administration of food and while it was being eaten the reaction disappeared. Contrary to our expectation the presence of this reaction did not in any way interfere with the development of a conditioned reflex to the tactile stimulus, a phenomenon which usually occurs in the presence of some extraneous motor reactions in animals, e.g. retraction of the extremities or local twitching of the platysma muscle. In the case under discussion, however, a conditioned reflex developed very quickly, and, what was quite exceptional, this tactile cutaneous salivary conditioned reflex was even stronger in intensity than the reflexes to the most powerful auditory stimuli. Similarly, the motor alimentary reaction—which usually replace the peculiar special reaction somewhere towards the middle of Ais lated action of the cutaneous conditioned stimulus—was ¢ erably stronger than the motor reaction observed with any ot ditioned stimulus. Furthermore, the usual period of “ O ’ excitation observed as an after-effect following roinforo a ith food was the most intense and the most prolonged in e of the tactile cutaneous stimulus.