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

intervals efGyme. This procedure was performed in separate experime r all the remaining positive places. The positive and _ the Ç bve conditioned stimuli were allowed to act in every case during 30 seconds. The following table summarizes the series of experiments on this animal : The first vertical column gives the number of the places stimu- lated ; the succeeding vertical columns indicate the magnitude of inhibitory after-effect corresponding to these places. The upper hori- zontal row gives the length of the interval from the end of the inhibitory stimulus to the beginning of the stimulation of any given place.

It is thus seen that in the case of conditioned inhibition the inhibitory process initiated at a definite point spreads over the whole analyser, diminishing in intensity with distance from the primarily inhibited place, and reaching its maximum strength for the whole analyser only by the end of a period of 30 seconds ; Avni the inhibitory process undergoes a gradual diminution in simul- taneously over the whole analyser. The only exceyt$xf which must be made to this general rule is that at the plac ch is subjected to the primary inhibition the intensity of th itory after-effect does not increase gradually, but is maxi m the start.

rigid precautions to avoid casual extra, s stimuli, since these would invariably exert a disturbing influgnce’causing sometimes inhibition of the positive reflexes and so Bhs dis-inhibition. Dr. Anrep’s experiments were, however ed in our special laboratory. The three series of e fments, upon the movement of dif- ferential inhibition, e Kental extinction and conditioned inhibi- tion, all clearly dem ate that the inhibition first spreads from its point of initiat@a over the whole analyser and then gradually recedes. The bls of this process, however, are seen to differ considerably, dceording to the type of internal inhibition. In Dr. ee g yp

Krasnogorsky’s experiments on differential inhibition the irradiation of inhibition occurs instantaneously, and the inhibitory after-effect attains its maximum after a zero interval: it is only the concentra- tion of inhibition in this case which proceeds in a measurable interval of time. In Dr. Kogan’s experiments with extinctive inhibition the irradiation of inhibition was progressive, and the nearer places under- went the maximum secondary inhibition much sooner than the more remote places. The phase of concentration in the extinctive inhibi- tion, however, was four to five times longer in duration than the phase of irradiation. It is possible that this difference of rate between the irradiation of these two forms of inhibition depends upon the intensity of inhibition developed. Dr. Krasnogorsky usually repeated the primary inhibitory stimulus several times, regardless of the fact that it produced its full effect at once, while Dr. Kogan confined himself to the first zero. The differences in the case of conditioned inhibition are much more complicated and important. Dr. Anrep showed that the conditioned inhibition, like the differential inhibition in Dr. Krasnogorsky’s experiments, irradiated simultaneously, although in a varying degree, over the entire analyser ; after this, in contradistinction from Dr. Krasno- gorsky’s results, the inhibition increased gradually up to a certain maximum strength during a definite period, and at all places simul- taneously. The gradual diminution in intensity of the inhibition also occurred simultaneously over the entire an r. Thus con- ditioned inhibition differs from differential } ition and from experimental extinction in that the entire ser simultaneously reveals, though in different degrees, an } itory after-effect; an actual progression or regression of th imum inhibitory after- effect cannot be observed.

phenomenon, already indicate part by some previous workers. . He observed that both positive’ and negative conditioned reflexes established to tactile sti ion of different places on one side of the body are reproduge taneously and with extreme accuracy to tactile stimulation IN; Corresponding places on the other side. The irradiation and tration of the inhibitory after-effect once ini- tiated on one E i eee and equally involves the other side. This interest fact will be discussed further on in these lectures.

A seriG@)o experiments analogous to those carried out on the BANS. of inhibition over the cutaneous analyser were conducted a with the acoustic analyser, and these also confirmed the hypothesis ‘that the peripheral end of the analyser can be regarded as projected geometrically upon the cortex of the hemispheres. In these experi- ments different musical tones, the beat of a metronome, a-d a hissing sound served as conditioned stimuli [experiments of Drs. Manuilov and Ivanov-Smolensky]. The reflex to one of these conditioned stimuli was subjected to primary experimental extinc- tion, and the effect upon the reflexes to the remaining stimuli was observed. The following is an account of the experiments of Dr. Ivanov-Smolensky on this subject.

Separate conditioned alimentary reflexes were established, and | equalized, to four different tones produced by a Max-Kohl’s tone- | variator. These tones were chosen in two pairs, separated by an | interval of Approximately three octaves—the lower tones having | vibration frequencies of 123 and 132 respectively, and the upper tones of 1036 and 1161 respectively. Similar reflexes were also established. to a hissing sound, and to the sound of a metronome beating at a rate of one hundred per minute. In the course of the experiments one of the conditioned reflexes was extinguished to zero, and then all the remaining reflexes were tested in different experiments, either immediately or after intervals of 1, 3, 5, 7, 10,

12 or 15 minutes. All the reflexes were found to undergo secondary inhibition, but in a varying degree. A part of the results, of these experiments is given in the table on page 166. ~\ The table shows that on the extinction of one of AN belong- ing to the lower pair the reflex to the other tone e same pair reaches the maximum inhibition somewhat agai remains at this maximum longer, and recovers fro inhibition more slowly, than the reflexes to either of her tones. On the extinction of one of the high tones, thg r to the other high tone reaches the maximum inhibition m apidly, remains longer at this level, and recovers from the inhNeftory after-effect more slowly than the reflexes to either of t, wer tones. On the extinction of any of the tones the secon hibition of the reflexes to hissing and to the metronome is INA espects less than that of the reflexes to the tones. On th N hand, after extinction of the reflex to hissing or to the mekgydome an intense secondary inhibition of all the reflexes to ton obtained.

It is obvio at only the experiments with extinction of tones can beGoraht forward. as evidence of a definite geometrical projection of the acoustic peripheral receptor upon the cortical part of the analyser. The fact that extinction of the reflexes to the metronome and to hissing produces intense inhibition of the reflexes to tones, whereas extinction of the reflexes to tones results only in comparatively weak inhibition of the reflexes to the metronome and hissing may perhaps be accounted for by the greater strength and by the more mixed character of the latter stimuli.

It is highly probable that irr Siation and concentration of inhibi- tion, which takes place as dela in the cutaneous and acoustic analysers, follow a similar Q@yse also in the case of other analysers. However, the experim determination of the relationships in these cases is at PENN tremely difficult or even impossible owing to purely technic O acles. If in the future these obstacles should be overcome RAY laws governing the spread of inhibition be determined ,fgpall the: analysers, an. experimental method would be provid f the study of the internal structure of-the different analysen€.

Irradiation and concentration of nervous processes in the cerebral hemispheres (continued): (b) Irradiation and concentration of inhibition over the entire cortex ; (c) Irradiation and concentration of excitation. In the last lecture it was shown how internal inhibition, initiated in a single definite point of the cortical part of an analyser, rapidly irradiates. over the whole analyser, after which it is slowly concen- trated upon its initial point. Furthermore, it was found that the progress of irradiation of internal inhibition can be traced step by step within the analyser.

In the present lecture we shall trace the progress of inhibition from one analyser to another over the whole cerebral cortex. Experi- ments bearing upon this process have been conducted for all the forms of internal inhibition recognized up to the present. It was mentioned in the description of differential inhibition that when the inhibition is initiated in one analyser it eet in other analysers as well, in the form of an inhibitory aft t Ain a series of experiments by Dr. Beliakov it was f that dif- ferential inhibition of a small intensity does TEN in € in its after-

primarily developed, but that when the inten of the inhibition is - great the inhibitory after-effect involve analysers as well. However, secondary inhibition of oth Gri is in every case much weaker than that of the analys which the differentiation was primarily developed. A aon will be described to illustrate these relations : effects any other analyser than the one in as inhibition was was established to a tone of n’s whistle ; from this a pitch of one semitone lower was tiated. A second positive conditioned alimentary reflex was w#ablished to a noiselessly rotating object. The reflex to the*&@itory stimulus gave an average secretion of 11-12 drops duri€g) 0 seconds, and the reflex to the visual stimulus

gave an wae 7-8 drops. The results of a series of experiments upon the irradiation of differential inhibition are illustrated by the following table : Salivary Stimulus applied Secretion in during 30 seċonds drops during | 30 seconds inhibitory semitone ha en repeated twice with an interval of tested half a mi N iter had lost more than 50% of its effect, (experiment 6 th June). After a greater summation of the inhibi- tory after, by four successive repetitions of the semitone with interva minutes between them, the reflex to the visual stimulus

tested half a minute later (in the experiment of 11th June) showed a diminution of 60%, while the inhibition of the reflex to the auditory stimulus (tested in the experiment of 14th June) was nearly complete. _ Similar results are obtained with extinctive inhibition, as shown in a series of experiments by Dr. Gorn. In these experiments, owing to the introduction of certain modifications into the technique, the irradiation of the inhibitory process was even more clearly exhibited, especially as regards the earlier removal of its after-effect from the secondarily involved analysers. The following are some of the experiments : Separate conditioned alimentary reflexes were established in a dog to the tone c’ sharp of a pneumatic tuning-fork and to flashes of three electric lamps, each of 16 candle-power.

Stimulus | Time applied Salivary Secretion in drops during during 30 seconds 30 seconds The conditioned reflex to light was in these experiments subjected to extinction, and the inhibitory after-effect was tested upon the reflex to the auditory stimulus. The reflex to the visual stimulus itself, after extinction up to the point of two consecutive zeros, showed the first signs of spontaneous recovery only after an interval of 234 minutes (15th December, 2.31 p.m.). The reflex to the auditory stimulus, on the other hand, when tested immédiately after a similar extinction of the visual reflex was diminished in strength by only 60% (26th January, 1912, 2.524 p.m.), and when tested in the third experiment after a pause of 24 minutes it was quite free of any inhibitory after-effect (27th October, 1911, 1.52 p.m.). It is thus seen that the inhibition irradiated from the visual to the acoustic analyser—never, however, producing a full inhibitory after- effect, and quickly retreating from it. That the rapid removal of the inhibitory after-effect from the acoustic analyser in these experi- ments was not due to a smaller intensity of the primary inhibition within the visual analyser is proved by the following details. In the case of the visual stimulus the interval between the repetitions (24 minutes) led to a progressive diminution of the reflex through all the stages of extinction, whereas in the acoustic analyser an identical interval sufficed for a complete restoration of the reflex. Moreover, when in the second experiment the extinction of the visual reflex had led to a reduction of the secretion to 34 drops as against the usual o 74 minutes the strength

served only to check the progress of the dimin of the reflex, and did not result in any ciable restoration (2.43 p.m.), while the acoustic analyser after that interval already completely free from any inhi y after-effect. Neither was the difference between the res of the primarily and the secondarily extinguished reflex to any peculiarities of the cortical elements of the visual auctor cells, as was proved by experiments in which the tone Was subjected to the primary extinc- tion, and the effect of s ary inhibition was observed on the visual analyser. The ns between the rates of recovery from the inhibition in the rily and secondarily extinguished analysers in these experi ere exactly the same as before, and there is

no need, therefd o give separate tables. It can now reasonably be assumech Got in the secondarily extinguished. analyser we deal r the x <i of the irradiated inhibition, and that its recessional the single cutaneous analyser (concentration of inhibition). ! Experiments on irradiation of extinctive inhibition over the | entire cortex of the hemispheres were performed with a great number | of variations. For example, two conditioned reflexes were developed ! in the analyser which was subjected to primary extinction (e.g. | visual analyser), and the inhibitory effect of experimental extinction

, of one of these reflexes was observed upon both of them and also upon reflexes belonging to other analysers. Recovery from the of initiation of thé inhibition exactly in the same manner as within inhibitory after-effect was found first’ of all in secondarily extin- guished reflexes belonging to other analysers. Shortly afterwards recovery occurred in the secondarily extinguished reflex belonging to the visual analyser itself, and finally, but after a much longer time, the reflex which underwent the primary extinction became freed from the inhibitory after-effect. The difference in the length of time necessary for the recovery of the two reflexes belonging to the primarily inhibited visual analyser clearly points to a regional localization of reflexes within the analysers, such as was already suggested in the preceding lecture.

Experiments performed with irradiation of conditioned inhibition gave, on the whole, very similar results. One definite additional stimulus was used as a common conditioned inhibitor for conditioned reflexes belonging to different analysers, each of the conditioned i stimuli in turn being repeated with the additional N and remaining in the compound always without reinforce > so that the compound conditioned stimulus developed inhi ye properties The actual experiments were conducted as follow st one of the conditioned stimuli was applied, and its secr XD effect recorded. Next the conditioned inhibitor was TE mbination with the same or another conditioned sion dN the combination was

repeated several times in succession. ally, the effect of the first conditioned stimulus applied singl again tested at different intervals of time after the last ap ion of the inhibitory combina- tion. When the positive refle d was the one employed in the | inhibitory combination, it ound to be considerably inhibited, and was only slowly f Qm the inhibitory after-effect ; when, however, the inhibitor bination was made with a stimulus from inhibited, and raf\Ny recovered its original strength. It is thus ` seen that © ory after-effect was very powerful and prolonged

in the analyser of the reflex subjected to the primary conditioned inhibition, but was only weak and of short duration in other analysers. In a series of experiments conducted by Dr. Degtiareva separate conditioned alimentary reflexes were established to a metronome (M) and to flashes of electric lamps (L). A noiselessly rotating object (R) was used as a conditioned inhibitor common to both positive stimuli. The application of the conditioned stimuli both singly and in the inhibitory combination was always continued during one minute, and the amount of saliva secreted during this time was recorded. The following experiments give the final result of the determination of the minimal interval which was necessary for complete recovery of the conditioned reflexes from ` their secondary inhibition.

Salivary Time . Stimulus Secretion in drops during one minute These experimen ow that after five repetitions of the inhibi- tory combinati Which the metronome formed part, the minimum period ba Hy a Ve the complete recovery of the positive reflex to the metron was 7 minutes (experiment of 13th May, 4.46 p.m.). On the hand, the minimum period required for the complete eens of the reflex to the metronome after five repetitions of the inhibitory combination of rotating object plus visual stimulus was only 15 seconds (experiment of 16th May, 4.35} p.m.).

Finally, we have studied the irradiation of that form of internal inhibition which develops during the first phase of reflexes with a long delay. Owing to the peculiar character of this type of internal inhibition, occurring as part of a diphasic phenomenon, it might naturally be expected to exhibit peculiarities with regard to its after-effect, and such was actually found to be the case. The results obtained in experiments with different dogs varied considerably, and only in a certain number of cases could the irradiation of the inhibition easily be followed over the entire cortex. The experi- ments were performed in the following manner. The stimulus for the delayed reflex was continued only during the first part of the inhibitory phase of the delayed reflex, and was then followed either immediately or after some interval of time by a conditioned stimulus from another analyser ; the strength of this stimulus had previously been determined, and was now again tested to find the magnitude of the inhibitory after-effect. Some of these experiments are given below.

Two conditioned reflexes delayed for 30 seconds were established, the conditioned stimulus being in the first case flashes of electric lamps, and in the second tactile stimulation of the skin; a third conditioned reflex to a metronome was delayed for 3 minutts; the inhibitory phase of this reflex was equal to 14-2 minut S three reflexes were established with the help of acid. Q The result Oito definite. The inhibition evoked by the metronome, q first stage of its action has irradiated from the

acoustic analyser into both the visual and tactile cutaneous analysers, diminishing their reflexes by 60-70%. In another dog the results were almost completely reversed. The conditioned stimuli applied immediately after the inhibitory phase of the delayed reflex produced an increased positive effect. The reason of this difference was found without difficulty. In the first dog, when an interval of 2 minutes was introduced between the isolated action of the metronome and the application of the succeed- ing conditioned stimulus, the excitation phase of the delayed reflex never appeared during these 2 minutes. In other words, the inhibi- tory phase of the delayed reflex in this dog was effectively isolated from the excitatory phase. On this account, under the conditions of the experiments, the inhibition became obvious in its after-effect upon both the visual and tactile stimuli. In the second dog, on the other, hand, when. the same interval was introduced between the isolated action of the metronome and the application of the succeed- ing conditioned stimulus, the active phase of the reflex to the metronome became revealed during the interval. In this dog, therefore, under the conditions of the experiment, the effect of the positive conditioned stimuli falling within the positive phase of the delayed reflex was not diminished but considerably increased on account of summation of the two reflexes. In this second dog the excitatory process appeared earlier and was more powerful; in other words, the separation of the inhibitory Q f the delayed reflex from the excitatory phase was not comp t is interesting to note in this connection that in the first e inhibitory process in general predominated over the excitat e.

In this and the preceding lectur ave adduced numerous experiments illustrating the spr the inhibitory after-effect over the cerebral cortex, and. ce e that to some readers I have seemed to over-stress this poi However, such multiplication of experiments was. necessary_jn‘érder to emphasize sufficiently how often this phenomenon $ in simple and pure forms. The facts hitherto considered only the fundamental interrelations between the inhibit nd excitatory processes revealed by special

methods of e ntation, and often merely owing to special individual poo Nadities of the animal. In many cases these funda- mental int ations are obscured by various accessory elements which ro? the whole process much more complex. internal inhibition we were struck by the paradoxical and un- expected results of certain experiments [Dr. Krasnogorsky]. Dr. Krasnogorsky’s. experiments on the irradiation and concentration of differential inhibition within the cutaneous analyser were described in the preceding lecture (page 153). The preliminary test of a con- ditioned reflex to tactile stimulation of the skin at a place situated at a distance of 22 cm. from the place primarily inhibited elicited 8 drops of salivary secretion during 30 seconds, while a visual reflex gave a secretion of 5 drops. One minute after the last of three successive stimulations of the inhibitory place the visual reflex was found to be reduced to zero; in.other words, the inhibitory after- effect spreading from the tactile into the visual analyser had com- pletely overshadowed the excitatory effect of the visual stimulus. After ten minutes’ interval the inhibitory place was again stimulated, now four times in succession, and on testing the tactile reflex at the place 22 cms. away, one minute after the last inhibitory stimulus, it was found to be completely free from inhibition.

Similar phenomena have been recorded in experiments on con- ditioned inhibition conducted by Dr. Chebotareva. Several con- ditioned reflexes were established in a dog to stimuli belonging to different analysers. A conditioned reflex to a metronome, when applied in conjunction with a conditioned inhibitor in ee form of a visual stimulus, failed to elicit a single drop of saliva. Mies or two later the metronome applied singly (when, of c Ait was reinforced) produced its full secretory effect. Condi 4 reflexes to a tactile stimulus and to an odour of aN ever, when

It appears, therefore, from these NG that, contrary to our expectation, the reflexes R the inhibitory after- effect in the primarily inhibited anal sooner than in any other. However, on careful consideration ® records of the development of the various reflexes in the an , it became obvious that these apparently anomalous resulgs obtained only in cases when the secondarily inhibited refl elonging to other analysers were in the case of. old reflexes, when they had not been exercise a considerable time or were weak through having been sad with the help of stimuli of small intensity. Hence it follow t if a certain area which was originally under the BENS% ibition has become free from the inhibitory after-