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

1 minute drops during 1 minute Experiment of 16th December, 1909. 2.12 p.m Rotating object 10 2.30 ,, Rotating object + tone + metronome 5 Zot \ ys Rotating object + tone 0 ris Bei Rotating object EAN 7 Sie as Rotating object + tone Q 0 5 ee Rotating object 8 Experiment of 21st D r, 1909. P «x 2.25 p.m Rotating object 12 2.47 ° ,, Rotating object + tactile sti- mulation 3 Dart, Rotating objeg&+ tone 0 312. Rotating ob 8 SrA ee Rotatin ject + tone 0 oe eee Rotati ject 8 leri of 22nd December, 1909. 2.37 p.m ting object 9 Zino. m Otating object + tone + thermal stimulus at 50°C. 7 34 $ Rotating object + tone 0 3. V Rotating object 11

The stimulus to a conditioned alimentary reflex is provided by a rotating object, while a given tone serves as its conditioned in- hibitor. Tactile and thermal stimulations of the skin and the sounds of a metronome serve as different extra stimuli. The above three experiments show that during the time when the’ extra stimuli (metronome, tactile, or thermal) were acting upon the animal the conditioned inhibition was partially removed, revealing the underlying excitation.

In connection with these observations considerable interest is attached to the following experiment on the same dog, in which it was the intention to introduce an odour as still another dis-inhibiting agent. For this purpose the dog was transferred into another room fitted with a special box for graduating the intensity of odours. The apparatus itself, in addition to its visual effect and the sound of its electric motor, acted upon the animal by blowing a continuous current of air. All these agencies introduced a whole complex of new extra stimuli into the experiment, even without the addition of the odour. The new complex of extra stimuli dis-inhibited the inhibitory combination, but this effect gradually declined as time went on, disappearing completely in an hour and a half after the experiment was started. The following experiment was performed on the day following the last experiment.

The first application of the camphor dis-inhibited the combination, while on the second application this extra stimulus had already lost its dis-inhibiting effect. This rapid disappearance of the effect of the extra stimuli introduced by the new apparatus, and again by the use of the camphor, is the most usual case with extra stimuli which bring about dis-inhibition. The dog employed in this particular experiment was an old laboratory animal and had previously been subjected to numerous extraneous agencies, so that different changes produced now only a transient effect, the animal speedily becoming indifferent to them. This is why the introduction of new con- ditions into this experiment produced a dis-inhibition right from the very start and „ever any inhibition of the positive conditioned reflexes.

Results were quite different in the case of another dog used by Dr. Nikolaev. This dog was fresh to the laboratory and may have possessed also a type of nervous organization which was more easily subjected to inhibition. In this dog a rotating object was used for a conditioned alimentary stimulus, and a tone for its conditioned inhibitor. A metronome provided the extra stimulus. the 18th February, beginning of the next experiment, the metronome was a alone during one minute, the subsequent course of the eyfeNament being shown on the opposite page.

which ser an extra stimulus, did not produce during its first applicati) e result which would be expected from dis-inhibition applied along with the positive conditioned stimulus used singly produced a complete inhibition (12.14 p.m.). It follows, therefore, that the zero value of the reflex in the first case—inhibitory com- | bination + metronome—was not really due to the internal inhibition remaining undisturbed but was due to external inhibition resulting from a very powerful extraneous reflex in response to the first ap- plication of the metronome. As a result of several repetitions of the stimulus of the metronome with the inhibitory combination on the 16th February and an application at the beginning of the experiment of 18th February, the stimulus of the metronome was no longer able to produce so powerful an alien reflex and therefore its inhibitory

Salivary Time Stimulus during 30 seconds Secretion in drops during 30 seconds 11.15 a.m. Rotating object 9 Lida, Rotating object + tone + metronome 5 L589 &;; Rotating object 4. 11.54 _,, Rotating object 3 12.9 p.m. Rotating object + tone + metronome 2 12.14 ,, Rotating object 5 iby Ga sts Rotating object + metronome 3 12.34 ; |. Rotating object N 12.40 ,, Rotating object +tone XA effect upon the positive conditioned O practically disappeared (12.27 p.m.). Hocwever, its dis- ROY (Dy effect was still

The terminology used in the intedgretation of the foregoing phenomena may seem to be ne arbitrary, but it is not possible at a time when the ferns in wha is still beyond our retained and could be well seen in the exp Ko) oe 18th February powers of analysis to avoid su erms in what is necessarily a schematic representation of ep plex nervous processes involved. Our terms serve to deerit the actual state and succession of events. e inhibitory combination can further be those stimuli which determine a permanent . 46). The following experiment by Dr. Nikolaev ement :

A rotating object serves for the conditioned alimentary stimulus, while a tone serves for its conditioned inhibitor. Salivary Time Stimulus during 1 minute aap thar s aur Tate? 1.47 p.m. Rotating object 10 v§ | Rotating object + tone 0 yA +5 Rotating object 10 ZO Ws. 10 cc. of 5% solution of sodium carbonate introduced in two doses into the dog’s mouth — 2.44 , Rotating object +tone i 2.5 2:5090, y Rotating object + tone 0 n eave Rotating object | 6

In this case the inhibitory after-effect of sodium carbonate, given 4 minutes before, caused a definite dis-inhibition of the reflex (2.44 p.m.). If an inhibitory combination is applied early within the time of the after-effect left by a very strong extra stimulus, for example a concentrated solution of quinine, no dis-inhibition is obtained. This corresponds exactly with the case of the metronome in the experiment on page 84. However, the dis-inhihiting effect of quinine can be exhibited as clearly as in the cas K e metronome, simply by throwing in the inhibitory combin at a later stage, when the strength of the after-effect of the g&n of the quinine has had time to diminish. On account of omplete accord of the two sets of experiments the descri oe the experiments with quinine need not be given. @)

All the experimental eviden ch has been dealt with in this lecture establishes conclusivel t the nervous processes on which conditioned inhibition depe are identical in character with those of extinctive ON, he fundamental condition for their development is the s Qpr ely that there shall be no reinforcement by the unconditiogo Neie, In both cases the process develops gradually, being{strgrgthened by repetition. Moreover, the inhibitory after-effect dges Mót limit itself to the particular positive conditioned reflex whig Cndergoes experimental extinction or conditioned

inhibiti t in both cases extends to other conditioned reflexes as oN Suen even those which are of heterogeneous origin. The final point of resemblance is that in both cases the inhibitory process can be rapidly though temporarily removed, the inhibited reflexes undergoing dis-inhibition on account of external inhibition resulting from alien reflexes to extra stimuli of small intensity. The only point of difference is that in extinctive inhibition it is the positive conditioned stimulus taken by itself which changes its positive significance to an inhibitory one, while in the case of con- ditioned inhibition the positive conditioned ‘stimulus becomes involved in a new complex and changes its character in conjunction with an additional stimulus. |

WE shall now consider the third type of internal inhibition, which has been termed inhibition of delay. It is obvious from the preyious discussion that a considerable choice is allowed in the establishment of conditioned reflexes as regards the time interval between the beginning of the conditioned stimulus and the moment at which it is reinforced by the unconditioned reflex. This interval can be made very short, 1-5 seconds, or even a fraction of a second, provided that the beginning of the conditioned stimulus precedes the moment of application of the unconditioned stimulus. Alternatively, the length of time of the isolated action of the conditioned stimulus. can be made comparatively long, extending over several minutes. The re- flexes which develop with these two different methods, i.e. with short and with prolonged duration of action of the conditioned stimulus, present great differences with respect to their general properties and their latent periods. These two typés of reflex are designated respectively simultaneous—or to be as Ce almost simultaneous—reflexes, and delayed reflexes. Ge duration of the isolated action of the conditioned stimulus pe ee impor-

tance, since, in the first place, it determi we shail see later, the eventual character of every conditione x, and secondly, because it forms the basis of development t type of inhibition which In all conditioned reflexes hich the interval between the beginning of the conditionegẹstimulus and the moment of its rein- forcement is short, say econds, the salivary reaction almost immediately follows ginning of the conditioned. stimulus. On the other hand AN Peflexes which have been established with a longer interval Fetyreen the two stimuli the onset of the salivary response is delayed, and this. delay is proportional to the length of

the interval Breen the two stimuli and may even extend to several Delayed reflexes can be established in various ways. One way is to start by the preliminary establishment of an almost simultaneous reflex—i.e. one in which the conditioned response appears quickly, say 1-3 seconds after the beginning of the conditioned stimulus— and to develop the delay gradually. By retarding the moment of the application of the unconditioned stimulus about five seconds each day a corresponding and progressive delay is easily obtained, and we can stop finally at a convenient interval when the required length of delay has been reached.

Another method of establishing a delayed reflex is to pass directly from an almost simultaneous reflex to one with a long delay, leaving out all intermediate stages. As a result of this modification in tech- nique the mode of formation of the delayed conditioned reflex is ‘considerably altered. The reflex, however well established as a simultaneous reflex, disappears at first altogether—or, to use an expression commonly employed by some of my collaborators, there follows a prolonged period of zeros. Eventually, however, some conditioned secretion of saliva does appear, but not until just before the moment when the unconditioned stimulus is usually applied. On continuing the experiments with the chosen interval of time the secretion progressively increases, and at the same time its commence- ment shifts further along towards the beginning of the conditioned stimulus and finally settles at a definite intermediate position between the commencement of the conditioned stim d its reinforcement. Q

In both the foregoing methods the experiment rt with the establishment of simultaneous reflexes which hen changed either at once or by gradual stages into delaye es. It has been found impracticable, in the great majorit imals, to develop a delayed reflex without first establishi corresponding simul- - taneous reflex, since, as will be desert a later lecture, the dogs under these conditions quickly becgme*subjected to drowsiness and sleep so that the experimental ation of conditioned reflexes becomes difficult if not imposyp) For this reason the method has received little attention in vestigations,

The following exa Q a delayed reflex is taken from a paper by Dr. Zavadsky nl ete out a considerable number of experi- ments upon. internalGghibition of delay. The sound of a whistle is employed as a c -oned, stimulus to acid ; the isolated action of the whistle is nued during an interval of 3 minutes and is then reinforced by acid, the sound being continued for some time longer So as to overlap the action of the unconditioned stimulus. Salivary Secretion in drops during Time Conditioned | successive periods Stimulus of 30 seconds of the isolated action of the conditioned

The rate of formation of a delayed reflex is subject to great variation. In the first place, the individual character of the animal’s nervous system plays an important part. In some dogs the estab- lishment of the reflex is rapid, while in others the beginning of the salivary secretion persistently refuses to separate itself from the beginning of the conditioned stimulus, and the development of delay is very slow. In some animals an indication of a developing delay can be observed in the course of a single day and after only a few delayed reinforcements ; in others there is no indication of the conditioned delay even after a month of persistent work. In the type of dog in which the formation of delay is rapid, it ixnfound that the delay frequently passes into sleep at an early ef the isolated action of the conditioned stimulus. On this a t it is necessary when carrying out a systematic investigatio dogs of this charac- ter to restrict the experiments to sh ayed reflexes, which means that we must be content wi cording only the small secretion of saliva during the cong) vely short time of isolated action of the conditioned stingylts“as compared with the larger secretion accompanying a pro caved action of the stimulus.

Another influence affegaing@ the development of delay in the conditioned reflex eae the type of conditioned stimulus used. Tactile and thermal Py ion of the skin and visual stimuli lead. to a quicker form of delay than auditory stimuli, but other things being eqgfilNiActile, thermal and visual stimuli give a smaller total conditioné’€ffect. These facts are illustrated in the following experimen a Dr. Iacovleva : PrelinG@ y to the development of long-delayed reflexes three shore ved conditioned alimentary reflexes were established by

repeating the isolated action of the stimuli during 30 seconds, followed by reinforcement. The stimuli corresponding to the three .. reflexes were the sound of a metronome, a tactile stimulus, and the flash of a lamp. Conditioned Latent in divisions of the Time Stimulus period graduated tube during applied during in the isolated action 30 seconds seconds of the conditioned stimulus 10.15 a.m. Lamp 3 30 All 10.25 7; Tactile 2 30} reflexes are 10.3557 Metronome 2 53) reinforced.

During the year which intervened between this experiment and the experiment of 24th April, 1925, which is given next, the three reflexes had been used repeatedly in other investigations and had been gradually converted into reflexes of longer delay. The isolated action of the conditioned stimulus had been first prolonged to one minute and then to two minutes, and each reflex had been reinforced Conditioned Latent in graduata, f ` Stimulus period tube pe; : Secs. Time applied for in during @keNsolated

In the cases of the tactile isual stimuli the delay is more precise, the reflex respons 1% more perfectly separated itself from the beginning of t nditioned stimulus and being more perfectly related to thé tire of administration of the unconditioned stimulus. Another factot ich exerts a great influence upon the develop- ment of a orged reflex is the amount of practice which has been eS reflex during the preliminary stage of short delay ; a long practised short delay sometimes operates as a persistent obstacle to the development of a longer delay.

Finally, I have evidence that the delay for a stimulus of one and the same character develops at a different rate according as the stimulus is continuous or intermittent. In the former case the It can be seen that the reflex response in the case of reflexes with a prolonged delay consists of two phases, an initial phase of inactivity and a subsequent phase of activity, and we must now inquire into the nature of, these phases. Does this first and com- paratively long period of inactivity mean that the excitatory process is undergoing a progressive summation so that it can evoke an obvious activity when it has reached the necessary intensity ? Or is the excitatory process sufficiently strong from the beginning, but unable to produce any secretory effect beċause it is temporarily

The first possibility must be ruled out straightway on the evidence already given with regard to the formation of delayed. reflexes, for seeing that in the case of a short delay the conditioned stimulus can evoke a conditioned., reflex with great ease, there seems to be no reason why the same stimulus when more prolonged. should, require a greater period of summation. Any suggestion that this first phase of inactivity is gaused through fatigue can also easily be eliminated. If, owing t ite olated action of the conditioned stimulus, fatigue did devel X should expect a gradual diminution of the positive effect of t ditioned stimulus : this, however, is not observed. On th trary, although the beginning of the secretion gets delaye ertheless the secretion increases progressively in amount vee delayed reflex is developed by the first method. With the seco ethod, in which the isolated action of the conditioned sti Sus is prolonged from the start, although the positive effect digappears at first altogether, it reappears after a while and then th tion increases steadily until it settles at a constant maxim :

There remains AN y the supposition that the initial phase of inactivity is due KY excitatory process being temporarily inhibited. That this is ro, interpretation is evidenced by the fact that the existene an excitatory process in a concealed form during the period yh delay can easily be demonstrated: if during the extra stimulus which has not hitherto been associated in any way with an activity of the salivary glands, we shall immediately elicit a secretion of saliva which is frequently copious and which is always accompanied by the motor reaction peculiar to the conditioned stimulus which was used; in other words, the conditioned reflex becomes revealed throughout the entire duration of the conditioned stimulas in a single positive phase instead of in two phases— negative and positive. The following are some experiments by Dr. Zavadsky bearing upon this question :

Tactile stimulation of the skin is used as a conditioned stimulus for acid. The conditioned stimulus is allowed to act for a period of 3 minutes and is then reinforced, being still continued so as to overlap the action of the acid. The sound of the metronome which is used in the following experiment has had hitherto no relation to any secretory reflexes and has of itself been unable to evoke any secretion of saliva. These experiments of Dr. Zavadsky are important as revealing a new and unexpected phenomenon. The established conditioned stimulus had no positive effect by itself during 1-1} minutes, but the neutral stimulus which was added to it for the first time immediately disclosed the regular positive conditioned re- flex. It is obvious that we have come across a fresh case of dis-inhibition.

During the last three lectures considerable stress has been laid on the phenomenon of dis-inhibition and many examples have been given. I would plead as my excuse the great importance of an adequate conception of the rôle played by this phenomenon in the physiology of the hemispheres, although of course the study of the lower parts of the nervous system presents many instances of analogous phenomena. So far, however, as the interpretation of the intimate mechanism of dis-inhibition goes we are completely in the dark, and it can only be hoped that accumulation of experi- mental evidence may at some future date throw light on its nature.

I wish now to call your attention again to the first of the two experiments just described. It can clearly be seen that the stimulus of the metronome when added to the tactile stimulus not only elicited a flow of saliva during the initial phase of inactivity, but also caused a considerable diminution in the. salivar eA cretion during the active phase. While the tactile stimulus apg singly elicited a secretion during the second 14 minutes ra from 29-46 drops, the addition of the metronome reduced thi drops. There must, therefore, be a double effect on the f the extra stimulus— dis-inhibitory in the initial phase, u of inactivity ; inhibitory in the succeeding phase, usually of a) ity

If different extra PRR ro Dhi Sera inhibition are allowed to act upon delayed eae reflexes, various definite and regular modifications@re Sa in the course followed by the delay. The extra st 1 which were used in this connection for one experimental ays ve been arranged in the following groups according to the i ce they exerted upon delay : ITT. Besly rotating objects; the sound of a: metronome ; tactile , ulation of the skin (the conditioned stimulus to the delayowNreflex being in this animal.a similar tactile stimulation of