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

In the first example the subject of the experimen Aa dog which has already been mentioned in previous lectur - 231). A tone of 256 d.v. was used as a positive conditi alimentary stimulus, while ten neighbouring tones up an © own the scale were differentiated [experiments of Dr. Bier The second ple is taken from experiments upon a dog which had many SS ionally constant alimentary conditioned reflexes. In this case the dissociation between the motor and the secretory response was more permanent and occurred even in experiments in which the causative inhibitory stimulus was not used.

A fresh reflex, to the appearance of a grey screen, was established and a series of experiments were performed, in each of which the new stimulus was repeated many times in succession at short intervals. It was now observed that on application of any of the old stimuli, though the conditioned secretion was often still considerable, the animal did not touch the food. presented to it in reinforcement [experiments by Dr. Rosenthal]. Salivary Time Conditioned stimulus Secretion in Remarks during 30 seconds drops during 30 seconds

SEOs, Flashes of lamp 7 | The animal does not SA Me Sound of bubbling 7 touch the food 3.24 E Buzzer | This condition was independent of any application of the grey screen in the particular experiment and lasted for a considerable time. During the experiment the dog remained almost motionless, but there were no obvious signs of sleep. Food pyesented to the animal in the same stand and under precisely the g pnvironmental conditions, but without a previous appiicata, f a conditioned stimulus, was taken with avidity.

The following chance observation bel phenomena. A dog which served for iments with conditioned alimentary reflexes, and which howed any dissociation of the secretory and motor compqopeħts of the reflex, nor any signs of sleep while in the stand, was ge for the very first time in front of a large audience for the_ptepose of a demonstration. The un- familiarity of the surrou s had a big effect upon the animal; it shivered slightly, an as though spellbound. On administra- tion of the conditi stimulus the normal secretory effect was id not take the food, and in a relatively short

time fell into I See sleep in its stand, right in front of the audience, with completsyelaxation of the skeletal muscles. Evidently in this case the WWerful, unusual and protracted extraneous stimulus Pow t first a partial inhibition affecting only the motor area of the cortex; then the inhibition spread over the whole cortex and descended also to the lower parts of the brain. The experiment on the whole is similar to those by which so-called animal hypnotism is usually demonstrated. For example, a rapid immobilization of an animal held on its back also leads to an inhibition which spreads to a varying degree in different animals. In some cases a complete or partial catalepsy is produced (immobility of the body, but with movements of the eyes, head and neck); in others it leads to the development of profound sleep. In our laboratory this was observed on several occasions. An extremely unruly animal, for example, vigorously resisting the preparations for the experiment, would be rapidly immobilized by a powerful grasp, associated of course with considerable mechanical stimulation, and would fall asleep in its stand almost immediately.

We see in this manner that a partial as well as a complete sleep can be produced by weak and protracted neutral stimuli, by short but vigorous stimuli, and by negative as well as positive conditioned stimuli. I shall have an opportunity of discussing certain further details in the next lecture. The above experiments demonstrate that the extent of the spread in the brain of the diffused inhibition can be small or great, and that there may exist different transition stages in the depth of the inhibi- tion, or, in other words, different intensities of the diffuse ighibition (sleep). Ņ

In the eighth lecture I discussed the mechanism the case of simultaneous conditioned stimuli, a sti analyser is overshadowed by a stimulus from a gestion was put forward that this overshadowi upon the different strengths of the stimuli analysers (p. 141). Experiments pies since been performed entirely uphold this suggestion. ee, we intentionally produced a considerable change in the strength of6ur usual conditioned stimuli, the auditory being made weak d the others either remaining unchanged or being made Ñ ) there was a definite reversal of

the relations previously o ed, the auditory stimuli now partici- pating in the He AA EN mpound to a smaller extent than the other stimuli, t.e. on i ed application of an auditory stimulus a much smaller AE obtained than on application of any other stimulus OAN o the compound. The following are some of In one dog a compound simultaneous conditioned stimulus consisted of a tactile and an auditory component, the auditory being considerably weakened. The compound stimulus, when well estab- lished, gave 4-44 drops of saliva during 20 seconds’ isolated action. When used separately the auditory component gave a secretion of 1-14 drops and the tactile 24-5 drops [experiments of Dr. Rickman].

In another dog the compound simultaneous conditioned stimulus was made up of a 100 candle-power lamp together with the sound of a musical tone which was considerably damped. The compound stimulus when fully established gave 7-8 drops of saliva during 30 seconds ; the visual stimulus applied singly gave 5 drops, and the auditory gave 24 drops. In an exactly similar manner a thermal cutaneous stimulus of 0° C., which was employed with a very weak tone to form a compound simultaneous conditioned stimulus, gave when applied singly a much greater effect than the tone [experiments of Dr. Gantt and Dr. Koupalov].

Thus we see that the difference in the intensity of the reflexes evoked by the various conditioned stimuli belonging to the different analysers is determined by the strength of the stimulus and not by any functional difference in the nervous elements of the analysers. These experiments give us a method of comparing the intensity of stimuli which belong to different analysers. Bearing these facts in mind we can begin to study the different stages through which the diffused inhibition passesy SE The starting-point for these investigations vagy by a case of a pathological state of the nervous system had been brought about experimentally by means of a ey “ functional (non- surgical) interference.” Experiment produced pathological states of the nervous system will t with fully in succeeding lectures ; in the present lecture se describe only the experiment which induced us to pursue E5 further investigation of normal

animals. Positive conditioned ntary reflexes [experiments by Dr. Rosenkov] were establi to the sound of a whistle, beats of a metronome, rhythm Ctile stimulation of the skin at a rate of 24 per minute, Xshes of an electric lamp; several negative reflexes were a stablished by differentiation, including one to tactile stimulé#pn of the same skin area at the rate of 12 per minute. The follo table gives the figures for the normal effect of the On the basis of the previous discussion we may take the strength of the stimuli in order from strong to weak as whistle, metronome, tactile stimulation and lamp.

The experiment now proceeded as follows: In between the different positive stimuli the differentiated tactile’stimulus of 12 per minute was introduced, being applied during 30 seconds and | followed without any interval by the positive tactile stimulus of . 24 per minute which was also continued for 30 seconds and then | reinforced as usual. This seemingly small factor produced an | extraordinary effect. On the day following this experiment and on

the succeeding nine days all conditioned reflexes had disappeared excepting only for a very occasional small secretion. This period was followed by a series of definite successive changes in the condi- tioned activity of the brain. The first of these extremely peculiar changes is illustrated by the next experiment. EAN The experiment sho Qly the reverse of what was observed during the normal stata J the animal. The strong stimuli have either no effect or ondaa very small one ; the weak stimuli have a greater effect th rmal. All positive stimuli were, of course, reinforced. Th€N§State of the cortex we called the paradoxical

| phase. The paradoxical phase in this dog continued for fourteen | This was called the phase of equalization, since all the stimuli | | became equal in their effect. The.phase of equalization lasted for ct q seven days and was then succeeded by still another phase during which the effect of stimuli of medium strength was greatly increased ; q the effect of the strong stimulus was slightly diminished, while the | weak stimulus had no effect. After seven days more, all the reflexes had returned to their normal value. In the succeeding experiments on the same problem, in order to be quite certain, we used different intensities of one of the positive stimuli. The results obtained were | | exactly comparable with the results of the previous experiments. | ql It thus became obvious that the difference in the reaction to stimuli i in all these different phases is determined by the relative strength of the stimuli. I In the manner just described was secured t that the cellular structures of the cortex un | stages of transition between complete inh#aion and normal excita- | bility, stages which are divulged by t&>peculiar reactions of the | cortical elements to the stimuli rent strengths. After the study of these transition stages én obviously pathological state, the question arose whether ineeae stages would be found normally we during the transition from jhe“dlert state to sleep and the reverse. | It was thought probabl the pathological case just described | consisted only in ane ation and prolongation of events which in the normal N re transient and not so evident, just as was psy. Special experiments conducted in this |

| the case with il direction led AAt positive result. -The following are some oe Twen) eighbouring tones had been differentiated from the ENN as a positive stimulus. This dog had also, among many others, two positive conditioned reflexes, differing greatly in intensity, to a weak and to a loud crackling sound. The following table gives the normal intensity of these two reflexes : Salivary Time Conditioned stimulus during Secretion in 30 seconds drops during 30 seconds 2.10 p.m. Loud crackling sound 124 220E, Weak crackling sound 44

The actual experiments proceed as follows. By repeated applica- tion of the differentiated tones the animal is rendered definitely drowsy ; the weak crackling sound is now applied. The secretory effect is absent. The dog awakens during the reinforcement with food, which it begins to eat. The next application of the weak crackling sound evokes a secretion which is yet small. The reflex is again reinforced. A third application of the weak crackling sound produces a normal, or in some cases even a supernormal, secretory effect, and the reflex is again reinforced. The strong crackling sound is applied next ; its effect is either less than or equal to the last effect of the weak sound. It is only somewhat later, when the alert state has been fully recovered, that the strong crackkigg sound evokes its full normal effect, and that the nem titative relations between the two reflexes become restore e following gives one of the actual experiments : KS

@ Salivary Time Conditioned stimulus ai & Secretion in during 30 TK ds drops during In some experiments repetition of these stimuli instead of leading to a temporary predominance of the effect of the weaker stimulus resulted only in an equalization of the effects of the strong and weak crackling sounds. Evidently during the gradual dispersion of sleep under the action of repeated brief feedings the cortical elements pass through the paradoxical phase and the phase of equalization. It follows that these experiments are exactly comparable to the pathological case which was previously described, excepting that the change which took under normal conditions a few minutes required in the pathological case many days. :

In another dog a slight drowsiness developed on account of too prolonged experimentation. This was accompanied by a complete obliteration of the differences in the intensities of the reflexes to the different stimuli, so that all the positive conditioned reflexes now became equal. With the help of injections of a suitable dose of caffeine the dog was brought back to its usual condition of wake- fulness, and with this all the normal relations between the intensities of the different conditioned reflexes returned. Both experiments [by Dr. Zimkin] are given below :

Time Conditioned stimulus applied Secretion in during 30 seconds drops during 30 segonds 12.50 p.m Loud beats of metronome AN § 1257 ee Lamp 74 LA te Loud buzzing sound 8 | P hee Weak buzzing ~P 8 On the following day the sin ORR ived subcutaneously 8 cc. of a 2% solution of caffeine ew inutes before the experiment. At the time of the eae Nahe was fully alert. Load beats of metronome Weak buzzing sound Weak beats of metronome Loud buzzing sound In the animal which was previously mentioned in this lecture as showing dissociation of the secretory and motor reactions, it was often observed that during the period of this dissociation the weakest conditioned stimulus (the lamp) was the only one which evo] ed on some occasions a strong salivary reflex, sometimes even bringing about both reactions—a normal secretion and motor response, and acceptance of the food on reinforcement. It is thus seen that a paradoxical phase could be observed also in these cases of a limited extent of diffusion of the inhibition [experiments by Dr. Rosenthal] .

A further and quite peculiar condition was observed in some cases of intense drowsiness which fell just short of changing into complete sleep. When positive conditioned stimuli had nearly lost their effect, well-developed negative stimuli, on the other hand, acquired definite excitatory properties. The following is an example of such an experiment by Dr. Shishlo : Positive conditioned alimentary reflexes were established to tactile stimulation of the shoulder and of the thigh, and to a thermal cutaneous stimulus of 45° C. ; a very constant negative conditioned stimulus was also established to a tactile stimulation of a definite skin area on the back. The effect of the positive tactile stimuli ranged normally from 15-18 drops during one minute. The thermal conditioned stimulus began relatively soon to induce wsiness and sleep. The experiment to be described commend ith an application of the thermal cutaneous stimulus which S rowsiness. The experiment then proceeded as follows :

Time Conditioned stimulus during ee ` S in Remarks one minute o Š a e minute 12.29 p.m. Tactile stimulation of i \ The dog re- shoulder | mains drowsy $209). 35 Tactile stimulatio igh 2 ` in spite of re- 12.50 Tactile stimu t ack ; | inforcement (inhibitor 12 of the- reflexes A similar conversi of negative stimuli into Aa ones was also on several ogdesjons observed in pathological conditions. This effect is given thetame of the ulira-paradoxical phase.

It thus es evident that during the transition from the alert state to complete sleep the hemispheres pass through several different stages. Since sleep is nothing but a widely distributed internal inhibition, we should expect at least some of these stages to appear during the ordinary inhibitory after-effect, which was discussed at length in the earlier lectures upon internal inhibition. So far only one case has been investigated, namely, conditioned inhibition, and this would appear to realize our expectation [experiments by Dr. Bikov] :

Five positive conditioned reflexes were established—to a metro- -nome, a loud tone, the same tone damped down, the appearance of a disc of cardboard, and tactile stimulation of the skin. A conditioned inhibition was developed to a combination of a sound of bubbling with the action of the tactile stimulus. The mean figures of the secretory effect of the five positive stimuli, averaged from a great number of experiments, were in the above-mentioned order of the stimuli—metronome 22, loud tone 184, soft tone 164, disc 134, and tactile stimulus 10 drops during 30 seconds. The conditioned in- hibition having been firmly established, all the conditioned stimuli in turn were tested 10 minutes after the application of the inhibitory combination. The metronome gave 163, the loud tone 16, the damped tone 20, and the disc 18 drops. Taking into consideration the possible interferences of irradiation of inhibition and of induction, the only- point of importance in the present. connection is tha GN th effect of

the weaker tone was considerably above normal; that of the stronger tone was below normal. This reversal e effect of the strong and weak tones can be regarded as ASH e of a paradoxical both stimuli therefore were obviously d to the same point of the cortex. This investigation is ent being continued with other types of internal inhibition In the lecture upon mutual i tion a suggestion was made that external inhibition might be-slue to negative induction, t.e. to an inhibition which is ey cortical areas neighbouring on the area of excitation. Oa in another fashion, it was suggested that the intimate anism underlying external inhibition is identical with i fen internal inhibition. It was hoped to

test this aul determining whether external inhibition causes similar chan% n the reactions of the cortex to those which have just been ibed in the case of internal inhibition. For the purpose of BN tigation a stimulus was needed which would produce a protracted effect of external inhibition, and use was made of the introduction into the animal’s mouth of rejectable substances which, as was mentioned previously, produces a prolonged after-effect. The experiments were performed upon two dogs, both of which had well-established alimentary conditioned reflexes.

In the first dog [experiments by Dr. Prorokov], after introduction of a solution of sodium carbonate, strong and weak conditioned stimuli were tested immediately on termination of the secretion due , to the alkali itself. It was found that at first all the conditioned reflexes were inhibited to the same extent, but that within the next 15-20 minutes the reflexes to the weak stimuli returned to normal or even exceeded the normal value, while the strong stimuli were either equal in effect to the weaker ones or even gave a considerably . smaller effect. In the experiment given below a solution of sodium carbonate was introduced into the dog’s mouth at 9.41 a.m.

Time Conditioned stimulus tion in drops during 30 seconds during Under the usual conditions without administration Q alkali the effect of the buzzer was about 8 drops duri seconds, while the effect of the tactile stimulus was 4 s during 30 In a second dog [experiments by Dr. an there were, how- ever, somewhat different results. sete introduction of the rejectable substance into the dog’s m@utiand the termination of the resulting secretion, all the condi d stimuli, when tested at frequent intervals up to the end of þe experiment, showed an equali- zation in their effect. Concur this there was observed as the experiment continued @)- e diminution in the strength of the reflexes. In control iments performed previously the re- flexes were proportio he strength of the stimuli, the stronger buzzer giving the lar effect and the lamp the smallest. In the following ee Se solution of sodium carbonate was introduced into the dog’s at 11 a.m., and the resulting secretion of saliva

Salivary Secre- Time Conditioned stimulus tion in drops during 30 seconds during 30 seconds Although the results obtained in the two dogs would appear to corroborate the suggestion that internal and external inhibition are fundamentally one and the same process, yet the complexity of the problem necessitates a repetition and greater variation of the experi- _ ments with more critical attention to other possible interpretations of the results. In the course of our investigation we became greatly interested in the effect upon conditioned reflexes of different narcotics in the first stages of their action, in complete narcosis, and again during the period of recovery. Urethane and chloral hydrate were used for this purpose. In the case of the action of narcotics as compared with the effect of inhibition a different sequence of events was observed : there was a gradual weakening of all conditioned reflexes, the weak conditioned stimuli naturally becoming y ae before the strong ones. This state was given the of the narcotic phase. The following experiment is tak om a research by Dr. Lebedinsky : Q

Positive conditioned reflexes were So lished to loud buzzing, metronome, weak buzzing, tactile ore and intermittent flashes of an electric lamp. With reg the intensities of their effect the stimuli followed in the orf@given. The animal, after being placed in the stand, eS 10.9 a.m. two grammes of chloral hydrate dissolved in 150 water in the form of an enema. The experiment proceeds © in the table on the opposite page. We thus see th the development of narcosis the effect of all the stimuli E ive diminished, and on return to the alert state the stimulørogressively recovered their normal conditioned effect. They exception, out of the twenty stimuli, was presented

Thus in different healthy animals under different conditions there were found many different phases of transition in the reactions of the cortex to conditioned stimuli. An obvious question arises as to how far all these different phases, including also the narcotic phase, Salivary Time Conditioned stimulus | Secretion in during 30 seconds drops during 30 seconds 10.14 a.m. Metronome 11 Dog takes the food, yawns and stands shakily 16.21. .,, Lamp 34 Takes the food ; hangs down. in the loops of the stand