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

The animal became qui S and even began to get sleepy during the experiment noQ hen kept in the stand but also when kept free on the floor. & oe conditioned stimuli were now applied again, but with eS seconds’ delay. Once more the isolated action of each condit¢Jyed stimulus was gradually prolonged from day to day until the Sd of 3 minutes was reached. On this occasion definite ones reflexes were developed without any disturbances. Duri e 14-2 minutes after the beginning of the conditioned stim aN animal was asleep, but towards the end of the second minute or at the very beginning of the third it quickly roused up its relaxed posture and a very sharp alimentary motor aş as secretory reaction appeared. The final stage of riments was described in the fifteenth lecture (p. 261).

In this manner, with the help of suitable periods of rest and by patient practising of the reflexes, that satisfactory balance of the two pro- cesses, which failed to appear at the first attempt was achieved. The differences in the nervous systems of the two dogs was thus made clear and we could now proceed with the main object of our experiments. This time, however, the investigation was carried out in a manner slightly different from that of those accidentally observed cases which were described previously. The effect of different forms of inhibition (differentiation, conditioned inhibition and extinction) was tested upon long-delayed reflexes. We hoped that as a result of such a complex presentation of different inhibiting influences a disturbance of the normal relations between the two antagonistic nervous processes would occur, as had already happened in the first establishment of the long-delay. Such a disturbance of the balance between the two processes did not, however, occur. What did happen was that these experiments, with the various forms of internal inhibition, always brought out more and more forcibly the essential differences between the two dogs. The development. of every new inhibition was accompanied in the excitable dog by a temporary period of excessive general excitation, while the other dog evinced practically no difficulties. Since we failed to produce a disturbance of the equilibrium in the manner described we had recourse to the procedure which had proved successful with the dog previously described. We therefore commenced a d&yelopment of a conditioned alimentary reflex to an electric sti $ applied to the skin. This reflex was fully established and ised with some intervals for a considerable length of time.

© hronic functional disturbance of the nervous system occurred 9) h dogs even without the application of the electric stimulus (> places. It is probable that this disturbance of the normal Kalare between excitation and inhibition was favoured by the cong of the inhibitory activity already established. The new important point is that the disturbance of the normal soe of the nervous system found an opposite expression in t ae) imals : in the excitable dog it was

the inhibitory reflexes suffered, in the other it-was the excita- | tory reflexes, and o h later the inhibitory ones. The following is a detailed descripttefi of these experiments. the excitable Q o metronome, buzzer, bubbling sound, and tactile stimulati QP the thigh ; and negative reflexes to a combination of a hissing sound with the metronome (the hissing sound preceded the metronome by 5 seconds), and to a tactile stimulation of the shoulder (differentiation). All the positive conditioned reflexes were. delayed for three minutes.

(before the development of the conditioned reflex to the electric stimulus). Salivary Secretion in drops during 3 Conditioned stimulus applied successive Time A during 3 minutes 4 minutes from the beginning of the condi- tioned stimulus In reference to this experiment it should be mentioned that in ‘excitable dogs the commencement of conditioned stiptuli, especially account, in the case of delayed reflexes, there i en observed an initial short dis-inhibition of the inhibitory p (3.54 p.m.). The development of the conditioned TRE the electric stimulus pril it was already fully established. During the whole ee, the electric stimulus had . been given any considerable st all the forms of inhibition remained practically unaffecte n August the electric current was considerably increased OG onea and now the delayed reflexes

became disturbed and the itioned inhibition became incomplete. In order to diminish afibitory stress all conditioned stimuli excepting the buzze e now allowed to act for 30 seconds only, instead of three es, before reinforcement. In spite of this, and in spite of disuse of the “alimentary” electric stimulus, the gradual * ening of all inhibitory processes continued. The delay dis red altogether ; the hissing, which, when preceding by 5 “ s the action of the metronome had established an

inhibitory combination, now itself acquired excitatory properties, i.e. became a conditioned stimulus of the second order. Even the differentiation of the tactile stimuli was now considerably dis- inhibited. 3.15 p.m. Bubbling, 30 seconds 5 Bot ee, Tactile stimulation of thigh, 30 seconds 8 3.40 ,, Tactile stimulation of shoulder (inhibitory), In the case of the inhibitable dog the conditioned stimuli were the same. The following experiment illustrates the conditioned reflexes as they were before the development of the reflex to the

Dia mmi Tactile shies ice of thigh Slos Tactile ES n of oan (inhibitory) ,0, 0O The developmen}, of the conditioned reflex to the electric stimulus was begun in this also towards the end of March. The reflex developed easj d soon reached a magnitude of 7 drops during 30 DEN é defence reaction occasionally returned when the current was increased in strength, but finally it disappeared alto- gether and was entirely replaced by a typical alimentary reaction. It was soon noticed on repeating the already established reflex to the electric current that its secretory effect began to diminish, while the secretory effect of other stimuli had practically disappeared, being pre- sent only at the beginning of the experiment and in a very weak form.

The following serves as an illustration of this period of the experiments : Secretion in Time Conditioned stimulus during 3 minutes drops during successive minutes 3.25 p.m. Buzzer 0, 0, 2 3.39 oe Metronome 0, 0,5 3.47 ,, Buzzer 0, 0,0 Sa Tactile stimulation of thigh 0,0, 0 4.20 _,, Tactile stimulation of shoulder (inhibitory) 0, 0,0 4.25 ,, Bubbling 0, 0,0 4.37 ,,. Metronome 0, 0,0 4.48 ,, Buzzer 0, 0,0 The animal started at this time to lose weight became very dull. All experiments were therefore interrupte considerable time, and the dog was given plenty of food AAG) cod-liver oil. It soon picked up weight, and its general ess also increased.

After this period of interruption all the Gre delayed conditioned reflexes excepting the one to the bu ere shortened to delays of 30 seconds. The ultimate resu ined, however, unchanged. No more than indications of the positive reflexes were obtained. The electrical stimulus still ev@y a considerable secretion, but on increasing its strength t eflex again diminished and finally disappeared altogether. e other positive conditioned reflexes had long since disap 4nd now all the forms of internal inhibi- tion began gradua disappear also, a salivary secretion being

The folloyin?“experiment illustrates this condition and shows that the sfsgf@us for the long-delayed reflex (buzzer) produced a positive t during the formerly inhibitory phase and had no Salivary Time Conditioned stimulus Secretion in : drops 12.48 p.m. Tactile stimulation of thigh (positive), 30 seconds 0 ROS So Tactile stimulation of shoulder (inhibitory), 30 seconds 0 | ee ae Bubbling (positive), 30 seconds | 1.20: ;, Metronome (positive), 30 seconds 0 1.40. _,, Buzzer (positive long delayed), 3 minutes 3, 2,0 rol Tactile stimulation of thigh (positive), 30 seconds 0 BF ee, Tactile stimulation of shoulder (inhibitory), 30 seconds 0 2A Bea Metronome (positive), 30 seconds 0 2.42 ~;, Hissing +metronome (inhibitory), 30 seconds 0 Zo. ta Metronome (positive), 30 seconds 0

The positive effect of the formerly inhibitory stimuli did not de- pend upon a weakening of the inhibitory process but was determined by disturbances in the excitatory process, appearing in the form of the ultra-paradoxical phase of the cortical elements (see p. 275). The general condition of the dog during this period of the experi- ments was quite satisfactory. It was found in other e iments that the differentiation and the conditioned me e also weakened, giving place to a salivary secretion.

The experiments just described show that a two dogs, with different types of nervous system, prolong sturbances of the higher nervous activity which N we Saban identical injurious influences took quite different d a In the excitable dog the inhibitory function of the corti e ee became extremely weakened. In the quiet dog it was owes of the corresponding cells (since the stimuli were identi} which became extremely weak. In other words, two quite differ ypes of neurosis were produced,

The experimentally Rp neuroses were in both cases extremely persistent andre and even after:a break in the experiments they WAS, O tendency to improve. It was now re- solved in the case of thë excitable dog to employ a valuable thera- peutic agent, na K oronides, since in our early experiments [Drs. Nikiforovsky Deriabin] a strengthening of inhibition was EN ved under the action of bromides in cases where the internal inhibition was weak. Therefore, after the state of neurosis had continued for several months the animal was given 100 cc. of 2% solution of potassium bromide daily in the form of an enema. It was soon observed that all the forms of internal inhibition began quickly to re-establish themselves and in a definite sequence. The

first to recover completely was the tactile differentiation ; this was © followed by the conditioned inhibition, and finally by the delay. All the reflexes had returned to normal by the tenth day of the treatment. It must be noted that as a result of administra of bromides there was no diminution in the magnitude of ud sitive reflexes. On the contrary they were extremely constan rding to these and all our previous experiments bromides Na nc not be regarded as sedatives diminishing the excitabili the central nervous system: they simply regulate the g y of the nervous system by strengthening the intensity of ike inhibition.

Bromides were administered eleven days only, but the cure of the neurosis was permanent the remaining 24 months neurosis of the “ phlegm all reflexes remained normal for ur experimentation. The state of dog was not improved by the adminis- tration of bromides, other therapeutic measures which were tried. The animal erefore left alone for a very long time, and little attention Wasypaid to it. At the end of this period we were surprised to fiad that the animal had spontaneously and completely recovered. hall come across further experiments with this dog in the n cture.

Pathological disturbances of the cortex; result of functional interference (continued). In the present lecture we shall discuss further experiments and observations upon the pathological states of the cerebral cortex. The inquiry is one of particular interest, not only on account of the special attention devoted to this subject at the present time, but also on account of several fortuitous occurrences. It has become . possible to trace how, as a result of different injurious influences,

the activity of the cortex gradually and by scarcely noticeable stages deviates from normal and becomes pathological ; often also the pathological states can be made use of for inquiry into nervous processes taking place under purely. physiological conditions, since under pathological conditions different aspects of the nervous processes which are screened off from us by the unified and balanced complexity of the normal physiological state become dissociated or accentuated. In the lecture upon the hypnotic states occurring under normal conditions it was mentioned that the mostewĝeresting of these were subjected to experimental investigati Si y after they had previously been observed in exagger form in a pathological case.

In one of our dogs which, it will be remagfadr aforoa (p. 270), had several positive and negative ERE pol Oe, a tactile stimula- tion at the rate of 24 per minute ha Tan as a positive stimulus and a stimulation at the T per minute as a negative one: moreover, as usually under neral conditions, the relative intensity of the positive reflex yas directly determined by the relative strength of their congsfe stimuli. In one of the experi- ments the positive rate of ctile stimulation was made to follow the inhibitory rate wi ra) ny interval of time. This apparently small modification ok te experiment was sufficient to create a pathological distyrygnce of the cortical activities in this dog. At first, for a few , all positive conditioned reflexes disappeared completely ;, as followed by a series of different modifications

in the strength of the reflexes, a state of affairs which lasted for many days, the relation between the magnitudes of the reflexes and the intensities of the stimuli gradually changing from one phase to another. The entire disturbance lasted for 54 weeks, after which the reflexes returned to normal. Obviously this dog falls into one group with the inhibitable dog (described at the end of the preceding lecture), in which functional interferences with the cortical activities produced a profound nervous disturbance which was accompanied by a disappearance of all positive conditioned reflexes for many months. In the dog just described the same type of disturbance was produced, but lasted for only thirty-six days, within which period the activity of the cortex passing through different stages finally returned to normal.

It becomes clear on considering all the pathological cases so far described, that the underlying cause of their development is in every instance the same. Broadly we can regard these disturbances as due to a conflict between the processes of excitation and inhibition which the cortex finds difficult to resolve. Besides these pathological cases we have at our disposal others which present features of perhaps even greater interest, firstly on account of certain intrinsic peculiarities, secondly on account of peculiar features in the mode of their origination. The case which is to be described first was studied from day to dayduring many months, and in view of the considerable inter sid resents the description will be given in detail [experiment, XS r. Rickman]. The experiments were carried out on a dog was exceedingly inhibitable. The animal had served in t oratory for different experiments for a very long time, an ad among others an inhibitory alimentary conditioned to a metronome rate of 60 beats per minute, while a rate o eats per minute served as a positive stimulus. The so of the various positive reflexes was definitely related to the stréwéth of their respective conditioned stimuli. The inhibitory Qitioned reflex, which at the time of the experiments had b peated 266 times, was constant and precise, being so AS ated that its inhibitory after-effect upon the positive refl eO s very short. The strength of the reflexes during this age period is represented in the table shown on the opposite page. ,

The d onged to a group which can be called “ expert at au view of the fact that in this group all the types of internal inhibition develop with great ease and precision. We now — determined to investigate in further experiments the degree of stability of the inhibitory process in this dog. For this purpose it was decided to transform the negative conditioned stimulus into a ` positive one by the method which is usually the most effective, namely, repeated reinforcement of the inhibitory stimulus without any intermediate introduction of the positive stimuli (see p. 198). However, the destruction of the inhibition in this dog proceeded extremely slowly. The hitherto inhibitory stimulus was followed by reinforcement 4-7 times in succession on each of three successive

Tp f f Salivary Motor reaction Time Conditioned stimulus applied Secretion in and general during 20 seconds drops during behaviour 20 seconds - 10.37 a.m. Metronome, 120 per minute 8 Lively ali- 10.45 ,, Electric light 4 mentary 10.49 ,, Strong tone 6 reaction 10.56 ,, Metronome, 60 per minute 0 The dog re- mains mo- tionless Lively ali- ILO Buzzer 9 IED 4; Weak tone 34 ) meray days. The first sign of any destruction of the inhibiti s observed at the seventeenth application with reinforcemenŃ \n the form of a very small secretion without any accompanys O)imentary motor reaction. At the twenty-seventh reinforce e salivary secretion was already considerable. No definite ances in the other positive stimuli could be observed at th period, excepting a certain tendency to equalization of the secre effect of strong and weak positive conditioned stimuli. Th periment of the 14th December on page 304 shows the strengt Die reflexes at this time.

The secretory reaction stablished to the rate of 60 beats of the metronome did aQ Never remain constant, but in spite of continued reinforohg quickly declined and at its thirtieth repetition fell to AS, oreover, it was now noticed that immediately after an applicat) the metronome at the rate of 60 practically none of the pogt reflexes could be elicited (18th December). Salivary Time Conditioned stimulus applied Secretion in during 20 seconds drops during 20 seconds 10.56 a.m. Metronome, 60 per minute 54 (formerly the inhibitory rate) 3T Electric lamp 5 11.10, Metronome, 120 per minute 5 LEETS Buzzer 8 24S Weak tone 5 als; Metronome, 120 per minute 54 FESS), Buzzer 7

showing the general disturbance of the conditioned = Showing the general disturbance of the conditioned reflexes. reaction ; takes the food with avidity Investiga- tory reflex At first turns the head away but subse- guently takes food Turns itself right away and de- clines food Takes the food after some delay Alimentary reaction ; takes the food at once In its general behaviour the animal appeared to be perfectly healthy and when free on the floor it consumed the same food as that offered during the experiment with great avidity, just as it did in the above experiment after the conditioned stimulus me before the metronome (12.4 p.m.).

In succeeding experiments, though some of the positive effect of the metronome rate of 60 per minute returned, its strong inhibitory effect upon other conditioned reflexes nevertheless continued as before. In all those experiments, however, in which the metronome was not used all the reflexes were perfectly normal, excepting that the weaker stimuli gave a somewhat smaller secretion towards the end of an experiment than usual. Experiment of 24th December, 1925 (without application of the metronome).

pe F f Salivary Motor reaction Time Conditioned stimulus applied Secretion in and general during 20 seconds drops during behaviour 20 seconds I have intentionally given several expepi s with the initially positive reflexes in order to show how, 1 atid how persistently . the normal relations were retained in rae the disturbing influence of the metronome during the inter between these particular experiments. On continuing th Syperiments further )the general relation between the tenth SO reflexes and the strength of the stimuli continued to b tained in all experiments in which the metronome was no . In those experiments, however, in which either of the reS the metronome—which themselves gave a secretion varying $ to 74 drops—was used there was invariably a disturbance of nditioned reflexes following within the given rbance in the form of complete inhibition or of

rate of 120 per minute often produced a greater disturbance than the formerly inhibitory rate of 60. The experiments given below are taken from this period of experimentation. | Conditioned stimulus Salivary : Time applied Secretion in Motor reaction and during 20 seconds drops during general behaviour a | 20 seconds Experiment of 28th December, 1925 (Phase of Equalization). 10.56 a.m. Buzzer 10 Alimentary reaction 1A TE EUA Electric lamp 6 Bs 5 AG es Metronome, 60 per 2 e ` minute TO A. Weaker tone 5 3, Er i237 Metronome, 120 per 44 Weak alimentary re- minute action Lt SR eee Strong tone 5 Alimentary reaction 11.40 _,, Buzzer 4h ” ie 11.47 _,, Electric lamp 54 - 53 Experiment of 5th January, 1926 (Narcotic Phase). 12.53 p.m. Metronome, 60 per 6 Delayed alimentary minute reaction It Electric lamp 34 Alimentary reaction |S Sa Strong tone 6 m be PALO Se Metronome, 120 per 3 i ys minute LISa Weak tone 0 eðk alimentary re- i xS action ; EPA o Buzzer 4l Alimentary reaction T3055 Electric lamp 0 Turns head away, -

declines food ieee ae Buzzer xO Definite alimentary Q reaction: takes ; food immediately 10.44 a.m. Strong tone Qy 8 Alimentary 10.49 ,, Electric la 3 3 UNERA See Metronom per $ Investigatory mi L2 ges We e 5 Lively alimentary VE ù 4} Weak alimentary TLI =, z tone 5 Lively alimentary PEZI S uzzer 24 Weak alimentary 1120... {lectric lamp 34 Lively alimentary 11.31 O Stropg tone 1 Alimentary Moreover, a new conditio AN eflex to a bubbling sound was estab- lished ; the stimulus eer in this dog to the group of strong stimuli. As a result of thig treatment the reflexes increased in strength and now e nGDiminution towards the end of an experiment.

After eleven d eat experimentation the rate of 120 beats | per minute L metronome was again tried : - | > Salivary Conditioned Secretion À Time stimulus applied in drops Motor i aien and general during 20 seconds during ehaviour 20 seconds Experiment of 26th January, 1926 (without the use of the metronome). In the last experiment, though the wate of the reflexes remained unchanged, a general diminu he strength of all the reflexes became apparent towardd, Ow of the experiment. In view of this tendency all the sti ere for several days rein- forced after a very much shorter d and the use of the metronome