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

Whe conditioned stimuli for the two reflexes were taken from th e analyser, the estab- lishment of the conditioned defence re d to a prolonged diminu- tion in the magnitude of the con alimentary reflex. More- over, when both the alimentar efence stimuli were related to different points of the utaneganalyser, it was found that after the establishment of the Ki oned defence reflex a diminution in the strength of the cond¥aghéd alimentary reflex was found only for those alimentary pq rest to the one which had been given properties as a cn stimulus to the defence reflex, the reflexes for more remo entary points retaining their full magnitude. Now, if the a inhibition had been confined. to the centres of

the uncond ed reflexes, such relations would not have been found in the caft\al analysers. These observations render it highly prob- phenomenon, of the same nature as negative induction, and that external inhibition can, therefore, be identified with internal inhi- bition. It may be noted that the nearest point associated with the alimentary reflex did not under these circumstances manifest any. properties peculiar to the point for the defence reaction, and no motor defence reaction ever accompanied the alimentary reflex. . At present a series of experiments is being conducted with the object of securing more direct evidence on this point.

There can be no doubt that the phenomenon of mutual induction described above provides a physiological basis for the large group of contrast phenomena.-described in connection with the physiology of the sense organs. Here, therefore, we are confronted with a further illustration of the successful application of the objective method to the study of problems hitherto considered to be exclusively within the domain of subjective investigation. Interaction of irradiation and concentration with induction.

THE last three lectures were devoted to the irradiation of excitation and inhibition in the cerebral cortex and to their mutual induction. Trradiation and concentration on the one hand, and induction on the other, were dealt with separately, as if they were completely independent. In actual fact, however, it is plain that these processes are superimposed on and interact with one another. Cases of the apparently isolated existence of irradiation and concentration of either excitation or inhibition without the simultaneous presence of induction can only be regarded as exceptional, and must be inter- preted either as being an expression of some definite phase of the development of these processes, or as an individual peculiarity of the nervous organization of the experimental animal. It is probable, also, that, at least in some cases, the interpretation of experiments upon irradiation and concentration was simplified artificially, since at first the existence of mutual induction was not thought of. More- over, in the initial phases of our investigation whole problem presented such overwhelming and chaotic c ity that many sides of the subject were intentionally ignor e had to disregard. many points, and had to obviate special O problems, replac- ing dogs which for some reason were ble or presented. complex relations difficult to trace. At th nt time, however, as a result of many years’ experience, spegi ention can be directed to any new fact or any new peeling observed in any individual animal, and such peculiarities now raie/fresh problems for investigation.

The mutual relations radiation and concentration of the two nervous processes wi eir mutual induction are exceedingly complex, and a co e knowledge of their interrelations has not yet been attaing: he data available on this subject.at present do not lend themgelv}s to systematic arrangement, but there is sufficient material to @erit consideration. Positive conditioned reflexes were established to tactile stimulation of two places on the thigh (1 and 2), one on the abdomen (3), one on the chest (4), and one on the shoulder (5); a place on the fore leg of the animal was completely differentiated from the others, and acted, therefore, as an inhibitory stimulus. All the positive stimuli were equalized as regards the magnitude of their effect. The actual experiments were conducted in the following manner. At the beginning of each experiment the normal magnitude of the secretory reaction for a given positive stimulus was determined ; further on in the experiment the effect of the same positive stimulus was tested. again, either immediately or at various intervals of time after the termination of the inhibitory stimulus. This process was repeated with all the rest of the positive stimuli, the whole series of experi- ments taking a period of about five months for completion. The results are summarized in the’ two following tables, in which the magnitudes of the positive conditioned reflexes for the different places are expressed)as percentages of their normal value, as deter- mined in every experiment prior to the use of the inhibitory stimulus.

of stimulatio ile the upper horizontal row indicates the interval of time between the end of the inhibitory and the beginning of the positive stimulus. The first table represents the average figures for the total number of experiments during the whole period of investiga- tion ; the second table gives the average figures only for the last month of the investigation, the intervals of 5 and 15 seconds having been employed during the latter period only.

These experiments show that when the positive stimulus is applied immediately after the termination of the inhibitory stimulus its effect is invariably increased, when it is applied after an interval of 15 seconds its effect is below normal, and when applied towards the end of 30 seconds its effect is minimal ; only towards the end of the 5th minute is complete recovery of its normal effect obtained (first table). Thus the application. of the inhibitory stimulus is followed in the first place by an effect of positive induction ; this is succeeded by an irradiation of inhibition, which gradually disappears so that the effect of the positive stimulus returns to normal again. A similar replacement of positive induction by an inhibitory after- effect might also have been noticed by the reader in experiments given in the previous lecture, when the phenomenon of positive induction was first described (see especially experiment on page 193).

Returning to the experiment described above, the following particulars should be noted. While the magnitude of positive induction increased somewhat towards the later period of the investigation (second table), the inhibitory after- t diminished, both as regards its duration (being now confin hin an interval of two minutes), and as regards the extent irradiation (being more obvious at the two positive places ne o the inhibitory one). The latter phenomenon is a repetition fact which has already been discussed in the earlier mire ae connection with the after-

In the lecture on the irion of inhibition attention was drawn to an observation made %7 Dr. Kogan, that in one of his dogs the complete extinction tactile conditioned stimulus in one place was always im ly succeeded by an increased excita- bility—+.e. REAS ction—in the place which was furthest a single n engajnforcement (i.e. the first step in extinction) of a condition gO alimentary reflex was investigated. Conditioned flexes were established in a dog to tactile stimulation

of several places on one side of the body, all of which were spaced out along a line commencing in front at the lower part of the fore limb, extending along the whole length of the trunk, and finishing at the lower part of the hind limb. All the places were equalized as regards the magnitude of the positive conditioned effect. Every experiment commenced by stimulating some definite place, in order to determine the normal magnitude of the reflex. The stimulation of the same or another place (at a distance of 1, 43 or 89 cms.) was now applied without reinforcement ; then the particular place which had been stimulated first in the experiment was tested again at intervals of from 45 secs. to 12 mins. The experiment was concluded by testing any of the remaining places, in order to confirm the normal positive effect for the given day. Experiments were conducted with intervals of 4-5 days, in order to ensure a more or less stationary condition of the inhibition with respect to its after-effect. However,

this expectation was not fulfilled, since the inhibition became more and more centred around the cortical point of its origin as the experi- ments proceeded, and on this account it is necessary to represent the general results in the form of three tables for three consecutive series of experiments. In the dog on which these experiments were carried out, the magnitude of the positive conditioned effect was so constant that it was possible to utilize each separate experiment instead. of taking the mean of several experiments. In tke tables given on page 208 the magnitude of the reflex is r tod in percentages of the normal positive effect for each day. intervals of 45 secs., 1 and 3 mins. are given only in the table, since only at this period of the experiments did the of saliva after administration of the non-reinforced conditi stimulus stop in time enough to allow of a determinatj the after-effect of extinction at earlier periods. O

It is seen from these tables that Sue beginning of the experi- ments (first table) the inhibition d to the furthermost place and was still obvious 12 minutes the extinction. Later (second table) the inhibition became fy d within a distance of 43 cm., and after 4 minutes was aller intensity than the inhibition occurring in the precega Ch: le after so long as 12 minutes. It can further be observed fr he second table that at the remoter places there was BN, in the later intervals, an increase, instead of a decrease, of t ect as compared with its normal magnitude. Finally, in oom phase (third table), the inhibitory after-effect

could be observed only in the primarily extinguished place, and this at variable periods of time, whereas in the remaining places, with the exception during the first minute of the remotest place, there was either an increase above the normal, or a return to the normal magnitude of the positive effect. The increased positive effect was most probably due to positive induction, which could be detected first at the places more remote from the starting-point of the inhibi- tion, but only after a considerable period of time following extinction:

However, the effect of positive Yaduction gradually makes itself felt at places nearer to the starting point of the inhibition, and appears earlier after the incipien tinction. In other words, both as regards time and space, owtive induction gradually overcomes and supersedes the inhiktgd The experimengsyust described present some interesting details. Firstly, they ey iar the extreme sensitivity of the cortical elements : the effect of a single non-reinforcement exercising over a large region% f the cortex a profound influence lasting for a consider- able Geto than 12 minutes). Secondly, they afford a further

example of the extreme delicacy and lability of physiological processes in the cerebral hemispheres : a relatively small influence repeated at intervals so long as 4-5 days causes a profound change in the general course of events (rapid diminution of inhibitory after-effect). Lastly, it can easily be observed that the state of different cortical points manifests a definite rhythmic undulation, both with respect to time and to distribution of inhibition. Thus in the third table the primarily extinguished place was alternately under the influence of, and free from, inhibition during 12 minutes, and a similar rhythmic oscillation was also observed in space, namely, in the distribution of excitation and inhibition in the cerebral cortex at any given moment. This fact, which is of considerable importance, will be referred to frequently in the further course of these lectures. It should be regarded as a natural result of the interaction and mutual adjustment of the two opposite nervous processes of excitation and inhibition— just as the waves of the third degree on a blood pressure curve represent the result of the interaction of pressor and depressor influences.

In some further experiments on the same dog, in which extinction was not restricted to a single non-reinforcement but was carried to the first zero, a similar undulation was observed, but only at the place nearest to the one undergoing extinction. No such undula- tions were apparent at more remote places. The resu f these experiments are presented in the following table: XO Inhibitory after-effect of extinction to the- ffgs®zero : magnitude of the reflex tested at different time inhibitory stimulus (expressed as per

It is possible that the steady level of the reflex at the remoter place, which remained unaltered for 7 minutes (8th to 15th minutes), could be regarded as some expression of an undulation, especially since it corre- sponded to the period of a wave of inhibition at the nearest place. Dr. Andréev has observed similar undulations in another dog. In these experiments four apparatuses for tactile stimulation of the skin were arranged along the hind limb of the animal from the upper part of the thigh to the lower part of the leg. These places are indicated in order from above downwards by the numbers 0, 1, 2 and 3, and were spaced at equal distances of 15 cms. from one another. Stimulation of any one of the three lower places served as a positive conditioned alimentary stimulus, while stimulation of the upper place was differentiated, and acted, therefore, as an inhibitory stimulus. The differentiation, however, in this dog was not very stable. In the general course of the experiments the intervals between successive stimulations were always 7 minutes. Each experi- ment began with the conditioned stimulus of a buzzer or a metronome. This was followed by two positive tactile stimuli, which were applied to any of the active places, and these were followed by the positive tactile cutaneous stimulation which was being specially tested in the given experiment. All these stimuli were applied with intervals of 7 minutes. The uppermost apparatus evoking inhibition was used next. After this, and this time at different intexygls varying in the different experiments from 0 to 10 minutes, BRON tile stimulus which immediately preceded the inhibitory, ulus was again applied and the inhibitory after-effect dete&xined.. The following table represents the results of these exPRN ents, the magnitude of the reflexes being calculated as a per fe of the normal positive effect, for which the mean value of t B e tactile cutaneous reflexes which preceded the inhibitory &imulus was taken. Each figure given in the table is an averag hree observations.

The complex relations occurring in these experiments can be more readily followed on the following chart : It is evident that the effects upon the different pos KK Y inces of the irradiating inhibition initiated by the stimulation @j Brace No. 0 showed more points of variance than of resem The chief point which they had in common was the ENO: nS inhibitory after-effect in all three places sooner or ~Q Or: | a maximum and then disappeared. A further poi sjua was that all three places simultaneously revealed Swo waves of inhibition, the crest of. one occurring at an inter} of sixty seconds following the termination of the eee, Oo and the second after an interval of five minutes. ney e resemblance ended; all the other features presented i rable differences. At the place

nearest to the inhibitory here was, immediately on the termina- tion of the inhibitors pds a slight increase of excitability, t.e. an effect of positiye uction. In the remaining two places the inhibitory after-é was revealed immediately. ‘The second wave of inhibition a ces 1 and 2 was greater than the first, but at place 3 the RS ve was expressed only slightly, while during the first wave the inhibition was complete. Moreover, numerous secondary fluctuations were observed at places l and 2. At place 3, on the other hand, the only fluctuation was a rather considerable weakening of the inhibition during the first half of the fourth minute. If this had not been present, the course of the inhibitory after-effect would have been as regular as in the cases examined previously in the ninth and tenth lectures. At place 3, again, just as in previous observations, the period of development of the inhibi- tion was several times less than the period of its recession, while at places 1 and 2 the time taken to reach the maximum of inhibition was either equal to, or even less, than the time required for the com- plete restoration of the normal excitability. Lastly, when the gross value of the total inhibitory after-effect was computed by adding together all the percentages of inhibition calculated from the table, it was found that the inhibition exerted its fullest effect at place 3, a smaller effect at place 2, and the least effect at place 1.

The most natural interpretation of these complex relations between the cortical excitation and the irradiated inhibition is that the induced increase of excitability produced the greatest effect nearest the point primarily inhibited ; for this reason the undulating character of the struggle between the two opposing processes was seen most clearly in the neighbourhood of this cutaneous area. That ‘the underlying excitatory process was actually greategt in this place is obvious from the definite result of positive i ey which was observed immediately on the termination of th bitory stimulus at this point alone. In remoter places the i i ion was exhibited in a practically unimpeded form, first incre radually in strength, and then undergoing a prolonged w, ing until the normal positive effect was restored. It m noted, however, that the individual figures which were av LW exhibited for the first place variations much wider than f Are intermediate place, and still wider than those for the r Qt place. It is possible that the ‘minor differences between urves for the different places should to a certain extent b ted to this. On the other hand, it is possible that the inc ney in the separate figures was in itself a true expression greater fluctuations of the excitability in the nearest place, as pared with the remoter ones.

The foll Katy experiments by Dr. Podkopaev, which were per- formed on a Oeon dog, give another striking illustration of the great Or exity of the relations in question. Apparatuses for tactile stimulation of the skin were arranged in linear order along one side of the body of this dog.as follows: No. 0 on the front paw, No. 1 on the shoulder, No. 2 on the chest, No. 3 on the abdomen, and No. 4 on the thigh. A positive conditioned alimentary reflex was established by stimulation of the front paw (No. 0) ; the remain- ing places (Nos. 1, 2, 3 and 4) were rendered inhibitory, and made equal in their action. Immediately after the application of any of the inhibitory stimuli, the place producing a positive reflex was tested, its normal effect having previously been determined at the beginning of the experiment. The experiments to determine the effect of each inhibitory place upon the positive ones were performed without any stereotyped order in the choice, first one and then another being taken. The results cannot, therefore, be attributed to any regular changes in the experimental conditions during the course of the experiments.

The following table contains the data for each of three separate experiments with each inhibitory stimulus, together with the mean figures. The effect of the positive stimulus is expressed as a per- centage of its normal magnitude. It should be remembered that the excitatory effect of place No. 0 was in all cases tested immediately after applying one or other,of the inhibitory stimuli. tion oføfplace No. S This table demonstra early that the intensity of excitation at the positive ze E es considerably, depending on which of the inhibitory stimulNsäs previously applied. When the nearest or the remotest pegas the one previously stimulated, a definite effect of posit@§ ‘induction was readily observed: the secretory

activity i aed considerably as compared with the normal, the | latent period became shorter, and frequently the alimentary motor reaction became increased in intensity. Moreover, the effect of | positive induction resulting from stimulation of the remotest place | was somewhat greater than that resulting from stimulation of the nearest one. No influence was observed from stimulation of place i No. 3, and the effect of stimulation of place No. 2 showed no regu- | larity, being at one test inhibitory, at another test giving rise to positive induction, and at a still further test giving neither effect. The similarity between the figures for the three separate determina- tions in these experiments (excluding those for place No. 2) was su | great that there can be no grounds for doubting the accuracy of the | average figures, and the figures relating to place No. 3 can be taken, || therefore, as evidence of the existence of an intermediate zone in which neither the inhibitory after-effect nor induction was in the | ascendant. | We must now consider what this experiment teaches us with | regard to the intimate functional activity of the cortex. If it is || assumed that the linear arrangement of the places on the skin corresponds with a similar arrangement of projection points in the || cortex, the result obtained above should: be regarded as striking | evidence of an undulatory distribution -of cortical excitability. On this view the cortical area over which a nervous process spreads must be regarded as an alternation of regions with eightened and with diminished excitability, in which now the ex ory and now the inhibitory process predominates. These ents cannot, however, be regarded otherwise than as su We, and the whole hypothesis of the wave-like progression of a&gNation and inhibition cannot be accepted without further an re direct experimental proof, especially since it involves so portant and far-reaching

| The data brought forward lou lecture tend to show that the | changés in excitability of diffe points of the cortex caused by | external stimuli, and esp those of an inhibitory character, | proceed in a wave-like r, both in regard to time for a given | single place, and in yrd to space for different cortical points | simultaneously. is nothing surprising in this phenomenon, | considering that spread of the nervous processes on the one | hand and th iGputual induction on the other are established facts.

Considerab culties arise, however, when a general rule govern- ing Peale between the two processes is looked for. At present we are still confronted with a series of unrelated facts, which do not explain why in some cases these undulations are present, in others absent; why in some cases the spreading inhibition is preceded. by a positive induction, and why in others the latter is not apparent. The available experiments, however, indicate that this variability is determined by the co-operation of three factors. These are, firstly, the functional peculiarities ofthe central nervous system of the experimental animal employed; secondly, the different stages of establishment of new connections in the cortex under the influence of external stimuli; and thirdly, the form in which such

connections are established, since, for example, the different types of internal inhibition are known to differ considerably as regards their intensity and stability. One of the most important problems in the future complete analysis of the relations in question must be the exact determination of the part played by each of these factors in the cortical activity at any given moment, taking into considera- tion the relative intensities of the nervous processes involved. Of course, the problem can to some extent be dealt with even at present. In the experiments which were described a tentative approach to a solution of this question could be noticed. This is even more clearly revealed in experiments which have been recently conducted and are still in progress. In the last four lectures it could be seen that the inhibition produced by a stimulus applied at a certain point spreads over the analyser, either immediately on the if ation of the inhibitory stimulus or after a short preliminary of positive induction. For the purpose of determining w appens during the actual application of the inhibitory gti¢fySus the following special series of experiments was carried ou n these experiments other points of the same or of other oo were tested, not on

the termination of the inhibitory Oo fion, as was’ hitherto the practice, but while the inhibitory s@f&yMlation was still in progress, i.e. the positive stimulus to be te as, so to speak, superimposed on the background of the in ry stimulus. The investigation was carried out on four di ogs by Dr. Podkopaev. first. The dog emplgyetLwas the same which served for the experi- ments upon the irracSaMon of inhibition after a single non-reinforce- ment of the ene stimulus and after extinction to zero. In the present egy iments extinction of the conditioned reflex to tactile sigen of a definite place of the skin was carried to zero.

The degree of inhibition was tested at two places, one at a distance of 1 cm. and the other at a distance of 89cm. The positive stimulus was applied at each place at the 30th second of action of the inhibi- tory stimulus and the combined stimulus was now continued. during a further 30 seconds. The stimulation of the nearer place when applied upon the background of the inhibitory stimulus gave 843% of the secretory effect, while that of the distant place gave 88%. In other words, the effect was practically the same at both places. It will be remembered that when the same places were stimulated immediately after the termination of the inhibitory stimulus, the nearer point gave 44% and the remoter point 664% (page 209). In order to appreciate these results more fully, it must be noted that in the case of the simultaneous stimulation of the inhibitory, and either of the positive places, the latent period of the reflex was considerably reduced, and the alimentary motor reaction was more sharply expressed than usually. Both these facts are unmistakable evidence of positive induction at all points of the analyser, except the one specially extinguished. The somewhat diminished secretory effect from the other places should undoubtedly be interpreted as the result of an algebraic summation of their effect with the effect of the extinguished place.

In a modification of these experiments another feature of special interest was revealed. The extinction to zero produced at a definite place of the skin was obtained by repeating the congitjoned stimulus without reinforcement at intervals of 2 minutes e process of extinction was continued to the third zero Oh the third zero stimulation of another place of the skin wag\superimposed on the , Stimulation of the inhibitory place. Th x effect obtained from the combined. stimulation was in th ity of cases equal to the usual effect of the positive stimul kèn singly. Thus it follows

that an intensification of inhib&ion still further diminished the inhibitory effect upon the surko)inding areas during the time the inhibitory stimulus lasted (enced induction). Another point is als yy brought out in these experiments. As was shown previo age 209), the reflexes at the two positive places in this d e still 50% inhibited two minutes after extinction of anc place to the first zero. But when the action of one or another of the positive places was superimposed upon the action of t ibitory stimulus at its third zero, again two minutes after th eding zero, there was no inhibitory after-effect from the