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

of the investigatory reflex is based on the development of inhi- bition, and is in all details analogous to extinction of conditioned reflexes. If the agent which is responsible for the investigatory reflex ceases, on repetition at frequent intervals of time during one single experiment, to call forth the corresponding motor reaction, a pro- longation of the interval in the same experiment restores the reaction exactly as in the case of extinguished conditioned reflexes. Similarly, a definite investigatory reflex which has only just disappeared on account of repetition of the stimulus becomes temporarily re-estab- lished by an application of some new extra stimulus calling forth

- another investigatory reflex. It follows, therefore, that the ex- tinguished investigatory reflex undergoes dis-inhibition exactly as do the underlying positive reflexes in cases of internal inhibition. If the investigatory reflex to a definite agent is repeatedly evoked in the course of a number of days it permanently disappears, just as does a systematically non-reinforced conditioned reflex. Finally, such an extinguished investigatory reflex can be temporarily re- established by administration of stimulants (caffeine) exactly, for example, as in the case of conditioned differentiated reflexes (p. 127). The inhibition of the investigatory reflex invariably leads to drowsi- ness and sleep (even more easily than the inhibition of conditioned reflexes). In the following experiments by Dr.Chechoulin the develop- ment of inhibition and sleep in the case of the igseptigatory reflex was studied by means of conditioned stimuli.

The dog used for these experiments had reflex established to a whistle. Hissing, b of the skin and other stimuli were all bring about the investigatory reien itioned alimentary ing, tactile stimulation ied for the first time to Conditioned Kgalivary : Time stimulus applied retion in Latent period Remarka ; during 30 secon ops during | in seconds (og) 30 seconds Now, beginnagfrom 4.21 p.m., the bubbling sound was repeatedly applied durjégyperiods of 30 seconds and at intervals of 2 minutes. During t. st three applications there were movements of orienta- tion. Jya. in the direction of the sound, and these movements

gradually became weaker. With the fourth application the first signs of drowsiness made their appearance. Up to the eighth repetition the sleep was interrupted at different moments of the stimulation. During the eighth and ninth stimulations all movements of the animal disappeared. At 4.43 p.m. the sound of bubbling was applied for 10 seconds, and then the whistle was added and kept on for 30 seconds. This brought about neither motor nor secretory reaction and the sleep continued. Administration of food awakened the animal; it took the food but even after that it still remained drowsy. The experiment with the conditioned stimulus continued as follows :

Conditioned Salivary Time stimulus applied Secretion in | Latent period Remarks during 30 seconds | drops during | in seconds 30 seconds 4.53 p.m. Whistle 24 8 Reinforced 525E Whistle pan 7 Reinforced It should be remembered that this dog was never observed to fall asleep in its stand during the usual experiments with conditioned reflexes. In the succeeding experiments new agents bringing about — an investigatory reflex were repeated up to the point of sleep, or sometimes only until the stage of disappearance of the motor reaction. Twenty-one days after the experiment recorded above tagih stimo lation of the skin was used as the extra stimulus for the oO gatory reflex, the experiment proceeding as follows :

Conditioned stimuli Secretion Time of in drops different duration The conditioned reflex in th Ceh experiment was twice reinforced after only five seconds of Ne on of the stimulus in order to main- tain the normal streng e reflex to the end of the experiment. Starting from EO an application of the tactile cutaneous stimulus was made @aring 30 seconds and similar applications were repeated at inter, of one minute. During the first three applica- tions the ani ned its head towards the place on the skin where

the tactile stimulus was applied. During the fourth and fifth repeti- tions there were no movements. at all, but there was no drowsiness of the animal. Now, at 4.324 p.m., the tactile stimulus was applied singly during 10 seconds, after which the whistle was added to it and both stimuli were continued together during 30 seconds. Fifteen seconds after the beginning of the action of the whistle there was a commencement of salivary secretion, but during the whole remaining period of stimulation only 2 drops were recorded. The experiment continued as follows :

Time applied during in drops pa ee Remarks 30 seconds 2.45 p.m. | Whistle | 5 i! Reinforced The experiments show that on repetition the motor component of the investigatory reflex gradually diminished, and that, on con- tinuing the repetitions further, drowsiness developed and became more and more profound, although in some experiments before drowsiness appeared the stimulus remained, during a certain interval of time, apparently without effect. Nevertheless, superimposition of a conditioned stimulus upon the extraneous stimulus showed that during the whole period of this apparent ineffectiveness the investigatory agent was exerting an inhibitor woe (the experiment with the tactile stimulus as extra lús). This in- hibition of the conditioned stimulus was not du ternal inhibition, for, so far from producing inhibition of t nditioned reflexes, a weakened investigatory reflex actually hibits them (compare

the sixth lecture for the action of the LDestigatory reflex upon the two phases of delayed'‘conditione s). It is obvious therefore that inhibition and sleep corel a result of the repetition of the investigatory reflex, in the for case leading to a diminution and in the latter to a crore of the conditioned reflex (the experi- ment with the bubblin ). The same is ve shown also when the experiments are conducted on pup FE aide of Dr. Rosenthal]. On mono-

tonous repetitiQn Jof a stimulus under constant environmental conditions thgspuppies fall asleep very quickly and often with sur- prising si eity. It is, I think, a common experience that man, when y to an intensive mental life, usually falls into drowsiness and sleep when subjected to the accompanying monotonous stimuli, however unfortunate such drowsiness or sleep may be as to place and as to time. This means, of course, that the definite cortical elements which react to such protracted external stimuli become functionally fatigued and pass into a state of inhibition, which in the absence of a counteraction by an excitation of other places, spreads over the hemispheres and leads to sleep. The extreme rapidity with which the cellular structures of the cortex undergo functional fatigue and become subjected to inhibition can be contrasted with the persistence of function of the cellular structures of the spinal cord and medulla under identical conditions. Experiments by Dr. Zeliony in our laboratory showed that while in a normal dog an in- vestigatory reflex to a definite sound quickly vanished, the same sound in a dog with extirpated cortex, under identical conditions, called forth an investigatory reflex in a stereotyped. manner and for an unlimited number of times.

To return again to conditioned reflexes. The development of inhibition with its ultimate expression in the form of sleep is due to functional fatigue of the cellular structures of the cortex. This is borne out by the following observations which were made repeatedly in our laboratory. In dogs in which any analyser had been surgically damaged, positive conditioned stimuli related to this analyser could scarcely be continued even for a very short time singly, gake they tended quickly to assume inhibitory properties ; quiteXos eA they never excited any preliminary positive action at all, @yehaved as inhibitory stimuli from the start. This phenom Ni especially constant and easy of demonstration in the D) the damaged cutaneous analyser.’ After extirpation of Bey coronarius and ecto-sylvius anterior (see Fig. 8), positive gx8s to tactile stimula- tion of the extremities, pelvis and sh@ul@@r became replaced for several months by inhibitory reflexes at the reflexes were now truly inhibitory was proved by thefact that positive conditioned reflexes related to other pele) owed their full normal effect before the application of a Gig imulus, but diminished in their positive effect or lost it age after the application of the tactile conditioned stimulus. os) same time tactile stimuli quickly and easily produced sleep eef in dogs which never before the operation fell asleep in respo tactile stimuli. These facts often assumed the following extre y impressive form. A tactile conditioned stimu- lus which KN lied to the part of the cutaneous surface related

| to the damaged portion of the analyser would lead to inhibition and sleep, but the same stimulus applied to the skin corresponding | to the non-damaged portion of the analyser would give a full positive effect, leaving the animal fully alert [experiments of Dr. Krasnogorsky, Dr. Rosenkov and Dr. Archangelsky]. To the same group of obser- vations belong those made in our laboratory during the period of shortage in Russia a few years ago. The semi-starved animals could not be used for experiments with conditioned reflexes, since all positive conditioned stimuli assumed inhibitory properties, and the dogs invariably developed sleep exactly in conjunction with the application of the conditioned stimuli. Obviously the general mal- 1 nutrition of the dog had powerfully affected the functional resistance of the cortical elements [experiments of Dr. Frolov, Dr. Rosenthal and others].

In the examples enumerated up to the present we have had only cases of transition of inhibition into sleep, but the reverse can also take place, sleep passing into inhibition. To take an example A conditioned reflex delayed by 3 minutes has been established. The animal is placed in the stand and is fully alert, but so soon as the conditioned stimulus is applied the animal becomes drowsy and. no salivary secretion is evoked during the whole 3 minutes. When food is given at the end of the third minute the animal takes it but slowly and reluctantly. The stimulus is repeated several times in the same experiment with the usual variations of t Qal between the applications; at each stimulation the dog mes more alert and the secretion appears at first towards th of the 3rd minute. On further repetition of the stimulation t cretion augments and | finally the three-minute period of stim n divides itself approxi- | mately into two equal parts. In fon part there is no secretion,

although the animal remains cS ert ; in the second part there is a copious secretion, and at t d of the stimulation the animal takes the food promptly ang-gats it with avidity. In this case the | widely irradiated inhibiti ep), which appeared in the beginning | on account of the pr nce of the inhibition initiated during the first part of the an of the conditioned stimulus, gets gradually concentrated intf/a restricted inhibition. This concentrating of the inhibition is broud about through the influence of the progressively

increasing e tion determined by the second part of the action of the KA oned stimulus and by the dis-inhibitory effect of rein- It sometimes happens that the reverse, namely a pure replacement of inhibition by sleep, is obtained with the long delay of 3 minutes, or even with delays so short as 30 seconds. The animal, which has previously kept fully alert in its stand during the experiment, now. falls asleep, each time exactly at the beginning of the action of the conditioned stimulus. The eyes close, the head droops, the whole body relaxes and hangs on the loops of the stand, and the animal emits an occasional snore. After the lapse of a definite period of time—in the short delay 25 seconds or in the case of the long delay 14-2 minutes—the animal quickly and spontaneously awakens and exhibits a sharp alimentary motor and salivary reaction. It is clear that in this case an inhibition which is generally concentrated becomes replaced by diffused inhibition, 7.e. sleep.

Finally, it can also be shown [experiments of Dr. Foursikov] that a summation of two distinct and different inhibitions leads to sleep. For example, the dog has a well-established long-delayed conditioned. reflex to a metronome: the length of the delay is 3 minutes. No salivary secretion occurs during the first two minutes of the stimulation, but at the end of the second minute the secretion appears, and reaches a maximum towards the end of the third minute. An extraneous stimulus of a weak hissing sound is now made to accompany the conditioned stimulus. The hissing sound dis-inhibits the inhibitory phase of the reflex, while a small motor reaction in the form of an investigatory reflex towards the hissing? served.

The conditioned reflex is reinforced. On a repetitio p this com- bination not only does the investigatory a Ci hissing disappear, but the alimentary reflex also, nge animal becomes obviously drowsy. This experiment can o interpreted in the following way: The investigatory r a hissing undergoes extinction on its- first application, a , therefore, the hissing sound initiates an inhibitory nn This inhibitory process summates with the inhibitory ph he delayed reflex and streng- thens it to such an extent tha excitatory phase of the reflex is never allowed to develop, .b eplaced by general drowsiness of the animal. That this is rue interpretation of the experiment appears abundantly į sequel. On the next repetition of the conditioned stimulus, without the addition of the weak hissing sound, a regular ed reflex, with its two phases well pronounced, is obtained, a repeating after this the combination of the metronom + ith the hissing sound the conditioned reflex again

disappears and obvious drowsiness takes its place. The following are the actual figures of the experiment : In this connection I conceive it useful to draw attention to the following interesting point. It is evident that the above éxperiment, together with that of Dr. Chechoulin mentioned previously (p. 256), reveals still another phase in the action of extra stimuli upon con- ditioned reflexes. A powerful extra stimulus, as will be remembered from the sixth lecture, at first brings about through the investigatory reflex a complete inhibition of the delayed reflex. Qn repetition, when the investigatory reflex considerably weake rings about only dis-inhibition of the first phase of the Iela fex Finally, as we have just learned, the extra stimulus K gain inhibits the reflex, but now by another mechanism : it mes itself a stimulus for a direct initiation of an inhibition i Koania A weak extra stimulus, as was just shown by th riment of Dr. Foursikov, brings about at first a weak and ¢rasHtory investigatory reflex and so leads on its very first splice dis-inhibition of the delayed reflex (4.52 p.m.). Afterw > the weak extra stimulus itself initiates a second, and nove inhibition.

The following ENS perties of inhibition and sleep also uphold our view as eir identity. In the preceding lectures abundant eviden given to establish the fact of irradiation and concentration of theAnhibitory process within the mass of the cerebral cortex, and % s shown that the development of the inhibition was extren(ly’ slow, being measured: by minutes. Moreover, it varios pect to rate in different animals and under different conditions. There is no question but that sleep also does not develop instantly. We know from our own experience how drowsiness and sleep overtake us only gradually, and how sometimes they spread only slowly and with difficulty; and some investigators, indeed, have endeavoured to study experimentally the problem of the gradual involving of the activity of the different sense organs, and its more complex mental concomitants. We know also how variable is the rate of transition in human beings between sleep and waking, and the same variability has been observed in our experimental animals. Moreover, during our lectures it has constantly been mentioned how inhibition, which at first develops with difficulty, gets reproduced with greater and greater ease upon practice and repetition and by using different forms of inhibition. Exactly in — the same manner, extra stimuli, and conditioned stimuli which upon repetition bring about a state of sleep, with practice bring about this state more ard more easily.

The following is of special interest. As was discussed previously, inhibition induces excitation. Corresponding with this, in some animals in which the inhibitory phase of a delayed reflex.is replaced by sleep, this appearance of sleep is on some occasions preceded by a short period of a slight but definite general excitation of the animal. The phenomenon is still more obvious and constant when sleep is induced under the action of a repeated and prolonged ee extra

‘stimulus. It was often observed in the experiments by Dg: nthal, that, when the neutral stimulus evoked definite ess in a puppy, and before the animal completely fell P, it passed through a fleeting phase of excitation, mov, out uneasily, scratched itself, and barked without any ojyiots reason, holding its nose up into the air. A similar state of excitation preceding in initial stages of anaesthesia gquit also perhaps be interpreted from this point of view.

be taken as sufficient NS f the view that sleep and internal do not know, up to t resent, of a single fact in all our researches which contradic Gays conception. It is to be deplored, however, that we have On no reliable graphic method of registration of sleep, as is well known, often occurs c n. Itis legitimate to graphic registration of the position of the head of the animal. A perfection of some such method for the graphic registration of sleep is greatly to be desired, so that the whole evidence regarding sleep can be expressed in an exact quantitative manner.

The details of our normal everyday existence are in full agreement with the foregoing interpretation of sleep. Our daily work, for some of us a round of exceeding monotony and for others extremely rich and varied, in either case must in the end determine an appearance of sleep. A prolonged stimulation of one and the same point in the cortex leads to a great and profound inhibition, and this irradiates widely so as to involve the whole of the cortex and the lower parts | of the brain. In the case of a varied activity, although no given

point of the cortex attains such a profound depth of inhibition, yet | the great number of inhibitory points leads to a widely distributed inhibitory state even without wide irradiation, and this also descends to affect some of the lower centres of the brain. Of course a great number of quickly changing stimuli following in succession may | often exert a very prolonged and powerful resistance to the general dissemination of inhibition over the hemispheres, thus delaying the onset of sleep. A well-established rhythm in the changes from wake- fulness to sleep and from sleep to wakefulness may determine a beginning of sleep even without a sufficient functional fatigue of the cellular structures of the cortex. Both cases have,had sufficient illustration in our experiments, in the analogous ey between | the excitatory and inhibitory processes.

Transition stages between the alert state and complete sleep : hypnotic stages. In the last lecture an abundant array of facts was brought forward showing that sleep is nothing but internal inhibition which has become diffused continuously (i.e. without intervening fields of excitation) over the entire cortex and has descended also to some of the lower parts of the brain. Since, as we know, the spread of inhibition is a gradual process involving first a smaller and then a greater area we should expect to find. different extensities as well as different intensities of sleep or, in other words, transition stages between the fully alert state and complete sleep. Such transition stages actually exist ; we had many opportunities to observe them and to produce them experimentally.

In our experiments we came across not only the usual form of sleep, which is evidenced by an absence of the normal function of the cortex and a relaxation of the skeletal muscles (closure of the eyes, drooping of the head, sagging limbs, and body limply: hanging in the loops of the stand), but also a quite different for far, at any rate, as could be judged by the condition of the sk uscles. In this form the activity of the hemispheres is bsent: all

conditioned stimuli remain without effect, and nt extraneous stimuli, unless exceptionally powerful, fail t ke any reaction. Nevertheless the animal preserves an alert posture ; it stands with wide open immovable eyes! up, extremities -ex- tended, not seeking support in the Ros remaining motionless sometimes for minutes and sometimésfor hours. On changing the position of an extremity such ity retains the new position. The flexor reflex evoked by to the planta assumes the character of a contracture. The pr ion of food brings no reaction and the animal continues t, Nn quite still. This form of inhibition was noticed only in a ll number of dogs, and up to the present we are not in a pogiiion to define the special conditions of experi- mentation or th Cial peculiarities of the nervous system which

has made most careful observations upon the transition of dogs from the alert state to sleep, and he finds that the condition just described is present in all dogs, though usually only in a fleeting form. It seems that the physiological interpretation of this state should not present any great difficulty: we are dealing with a complete inhibition confined exclusively to the cortex, without a concurrent descent of the inhibition into the centres regulating equilibrium and maintenance of posture (centres of Magnus and de Kleijn) ; in other words the animal is in a state of catalepsy. Thus in this form of sleep the plane of demarcation between the inhibited regions of the brain and the regions which are free from inhibition seems to pass just beneath the cerebral cortex. A similar demarcation of

-excitable areas from areas which have undergone complete inhibition may exist also between different large areas of the cortex itself, producing what may be called a localized sleep. This form of sleep was met with frequently, and we are now able to produce it experi- . mentally as well. On the first occasion it was observed as follows [experiments of Dr. Voskressensky]: A dog in which work had hitherto proceeded without any interference by sleep began to show signs of drowsiness—due to its being frequently left in the stand in the experimental room for hours at a stretch without any applica- tion of conditioned or any other stimuli. Obviously the monotony of the stimulation by the constant surroundi finally to a development of an intense inhibition involvi ally the whole of the brain. The inhibitory effect of the KEren became so strong that the mere introduction of the into the experimental room had an immediate and obvious i ry effect which became. still more pronounced after the was placed in the stand. It had to be roused up in all m f ways to keep it from falling fast asleep before the Pas s for the experiment had been completed (a matter of only, fèw minutes). When the experimenter left the room and close door in order to start the experiment from outside, and t out losing a minute began to apply one or another conditi Simul, the normal conditioned reflex was fully present ; c fonal secretion of saliva was obtained and the animal immediately took the food. When, however, after leaving the room erval was made of 4-5 minutes before the application of the SQ imal, this stimulus now produced the following re- markgievresult The conditioned secretory effect was present and

the salivary secretion was sharply augmented on food being presented ; the animal however did not take the food, which in order to effect adequate reinforcement had to be placed in its mouth. During this time no relaxation of the skeletal muscles could be observed. When an interval of ten minutes was made after leaving the room no conditioned alimentary reflex could be obtained, and the animal was found fast asleep with a relaxed musculature and occasional snoring. Only one possible explanation of these observations suggests itself. The inhibition must have spread in the first place only over the motor area of the cortex, so that excitation could be initiated by a condi- tioned stimulus belonging to any other analyser and could spread to the salivary gland but not to the muscles—with a resulting one- sided alimentary reflex lacking its motor component, Later the inhibition spread over the whole mass of the cortex and over the- lower parts of the brain, bringing about complete sleep with a re- laxation of the skeletal muscles. In this experiment the stages of a gradually developing sleep were brought about under the influence of the protracted action of neutral stimuli upon the hemispheres, but more usually this effect appeared as the result of numerous applications within a single experiment of negative or positive conditioned stimuli, especially if, in the latter case, either the intensity of the stimulus was weak or the period of application prolonged. The following two examples may serve in illustration :