Principles of General Physiology

The complexity turned out to be less than was expected, so far as the response itself was concerned. The production is easy under the right conditions. The complexity depends on the inhibition produced by events taking place independently, all of which exert their influence on the newly-formed reflex and must be duly controlled. There are two fundamental mechanisms concerned. Firstly, that of temporary association, by which external phenomena are brought into connection with reactions of the organism. And secondly, that of analysers.

The first, as we have seen in the preceding chapter, is a general property of nerve centres, but becomes more and more complex and modifiable in the course of the evolution of the higher centres. Pavlov makes use of it in a definite manner, which I will endeavour to make plain. In the lower centres, the reflexes are of remarkable regularity, as will have been seen in the previous part of the present chapter. They can, as a rule, be reckoned upon to follow a particular stimulus without fail. They are, in fact, "unconditioned." In the higher centres, the result that follows a particular stimulus depends upon a much greater number of conditions, sometimes no obvious result happens at all. Various " temporary combinations " are formed and we have " conditioned " reflexes. It is unnecessary to remark that the difference is really only one of degree, since no reflex can be said to be absolutely unconditioned.

Now, one of the most essential relationships between the organism and the outer world is that of food. In course of evolution, the means by which the presence of food becomes known increase in number and complexity with the differentiation of receptors. Thus, sometimes one, sometimes another phenomenon of the outer world becomes a sign of food and the impossibility of other than temporary connections is obvious. It is a case of the telephone exchange again, an illustration used also by Pavlov (1910, p. 9).

How are these temporary combinations made ? How is the conditioned reflex formed ? It is this : if a new, indifferent, external stimulus is many times present along with one which has already a definite response, the subsequent presentation of the new stimulus alone causes the reflex to be given. The reflex arc has now taken into connection with itself an additional afferent neurone, but not for an indefinite time and unconditionally, as we shall see presently. At the risk of some degree of repetition, it seems advisable to give an illustration. A dog, when given food, secretes saliva, as is well known. Suppose that every time the food is given, a particular bell is rung. After a number of repetitions of the combination of bell and food, the sound of the bell alone is found to cause secretion of saliva. A conditioned reflex to the sound of the bell has been formed. This is a very simple case, but the investigation of the various influences to which it is subject leads to a great deal of valuable information.

The work of Pavlov and his collaborators has, in fact, been hitherto concerned with such a comparatively simple case. The salivary glands have many advantages for the purpose. They can work alone, not being parts of a complicated system. The observation of the effect can be made quantitative, by recording the number of drops of saliva secreted. The operation necessary to make a salivary fistula is very simple and does not interfere with the normal state of the animal.

When food is taken into the mouth, stimulation of the various receptors in the mucous membrane brings about reflex secretion. This is the primitive, unconditioned reflex, present even without the higher parts of the brain. But it can be modified, as every one knows. The sight, or even thought, of food may excite secretion ; this is " psychical " secretion and it requires the highest parts of the brain. Fear may prevent the secretion, so that dry food cannot be swallowed. Now it is just this aspect that can be made into conditioned reflexes. Any phenomenon of the outer world, for which the animal in question possesses appropriate receptors, can be brought into temporary association with salivary secretion, so that it becomes an exciter of secretion, if only it has been frequently presented at the same time with the unconditioned reflex stimulus, food in the mouth.

The study is concerned with the different kinds of stimuli, their mutual effect on one another, and so on. Since a number may be present at one time, there is a great variety of possibilities of inhibition, of which Pavlov distinguishes two kinds, external and internal. All kinds of external phenomena may give rise to external inhibition. During the course of the formation of a conditioned reflex, especially in the early stages, a very slight outside disturbance may prevent its proper production. Thus, Dr Anrep informs me that he was engaged in the production of a conditioned reflex to a particular metronome beat. It was in the winter time and, just as he presented the food, the laboratory servant began to scrape away the snow at the entrance of the building. The effect of the intended stimulus was at once done away with ; the dog's attention was diverted, as the psychologist would put it, and the experiment spoiled for a time. As regards internal inhibition, it is found that a conditioned reflex, say salivary secietion on the sound of a bell, if repeated several times without the subsequent presentation of food, loses its effect, its proper consummation not being arrived at. This is merely temporary internal inhibition, since the reflex returns of itself after a rest.

The " analysers " are what have been called sense organs, or mechanisms of sensation, whose function it is to separate and distinguish the complicated phenomena of the outer world. Many of the facts already worked out by physiologists belong to Pavlov's category of conditioned reflexes. When, for instance, a certain combination of stimuli, arising from the retina and from the eye muscles, has several times been found to coincide with the touch stimuli of an object of a given sizej the combination becomes the conditioned stimulus of the actual size of

the object. As we shall see in more detail in the following chapter, the analys a consists of something more complex than the peripheral receptors alone, ole includes these, but is continued to their central connections in the brain, ai of these latter are often very complex, reaching to the highest centres. As ;els FIG. 158. DIAGRAM OF FIRST STAGES OF CENTRAL ANALYSIS AND INTEGRATION OF The outer (lotted lines mark the lateral Ixmndaries of the spinal cord. The centre line is the middle of the cord. The letters, T, P, C, U, refer to synapses with cells concerned with touch, pain, cold, and heat respect h civ. The lines represent bundles of nerve filirt-s.

example, Fig. 158, which is a diagram given by Head of the partial analysis and reintegration, in the lower centres of the spinal cord and the bulb, of the three different sets of receptors in the skin and the underlying structures of the hand, maybe glanced at. The meaning of the names "protopathic," "epicritic," and "deep" sensibility will be explained later (page 514). For the present, we may take the first as being associated with pain, the second with the fine, discriminating, higher receptors of touch, heat, and cold, and the last as the Pacinian and similar receptors, connected with the muscular sense and pressure.

It will be clear that the method of conditioned reflexes presents great opportunities of testing the delicacy of the appreciation of external forces. The dog has been found, in this way, to be able to distinguish small differences of the pitch of musical notes. For example, a note of 100 vibrations per second has been made into a conditioned stimulus by presentation along with food, so that on hearing this note by itself, secretion results. But no effect is produced by a note of 104 vibrations, nor by one of 96. A similar conditioned reflex to electrical stimulation of a spot on the skin ceases to appear when the electrodes are moved 1 cm. away.

This differentiation is found to be brought about by inhibition, that is, by exclusion of all parts of the analyser with the exception of a limited region. The co-operation of inhibition in the formation of conditioned reflexes may be seen thus : an electrical current sufficiently strong to give signs of pain when applied to the skin, is made the signal of a conditioned reflex when applied to a particular spot. It is found now that it gives signs of pain no longer, but, if moved 1 cm. away, there is no secretion but there are signs of pain. In practice, of course, it is necessary to shave the spot and mark it for future accurate localisation.

We may here pause for a moment to note the difference between the spinal and the higher centres in regard to nociceptive reflexes. We saw that these reflexes are prepotent in the former case, but the conditioned reflex in the ca«e quoted above has obtained the mastery over one. Nocuous skin stimuli can even be made into a conditioned stimulus for the feeding reflex, but not when applied over bone, nor when acid in the mouth is the stimulus for the unconditioned reflex instead of food. So that nocuous stimuli are more difficult to deal with, even by the higher centres, and the mastery over them is only a qualified one.

A spot which has been made the signal for a conditioned reflex, by presentation of food along with the stimulation of the spot, is called an " active " spot. It is necessary to distinguish between an "inactive" and an "indifferent" spot. The latter name is given to spots which have not been used as signals for any particular purpose ; while an " inactive " spot is one which has been made, by stimulation, the signal for non-presentation of food ; that is, as it were, a reflex for "no food," and is associated with absence of salivary secretion.

The following experiment presents several points of interest (Pavlov, 1912, pp. 330-331). Along a series of spots on the hind leg, there were arranged five devices for producing mechanical stimulation of the skin. The stimulus was equal in all. The upper four were made " active," that is, were accompanied by secretion of saliva. The lowest one was made "inactive," that is, whenever it was stimulated, no food was presented. Suppose, for the sake of example, that stimulation of each of the upper four for thirty seconds is accompanied by the production of 10 drops of saliva, while that of the fifth gives none. Stimulate the inactive spot, and then, thirty seconds later, stimulation of any one of the upper four spots will be found ineffective. At one minute interval, activity begins to return and in order from above down. Thus, the following numbers of drops were obtained, 5, 3, 1, 0. After two minutes, 10, 8, 5, 2. After three to four minutes, 10, 10, 10, 4 ; and complete return to normal after five to six minutes. Inhibition, therefore, spreads over a wide area of the analyser and disappears from the more distant parts first.

Those conditioned reflexes in which the time element enters are also very instructive. Suppose that the sound of a bell is not at once accompanied by the presentation of food, but only after two minutes' interval ; and that this succession is repeated until the conditioned reflex is formed. It is then found that the sound of the bell is not at once followed by secretion, but only after the interval of two minutes has elapsed. Now, during the time between the stimulation and the reflex, it is clear that something must be going on in the centres, but that its manifestation is inhibited. This can be shown by the application of some external indifferent stimulus during the interval, when the saliva immediately appears. It is to be understood that this indifferent agent is not one that produces secretion

of itself and, in fact, if it is presented along with the active stimulus, the effect of the latter is inhibited. It is to be supposed, therefore, that when it causes secretion in the above experiment, it must inhibit the process which was itself inhibiting the appearance of saliva. We have inhibition of inhibition, as described above (page 416). A variation of this experiment was made as follows. It was actually done owing to a misunderstanding of instructions. A metronome beat and the giving of food occurred together every ten minutes. Afterwards the signal alone was given. If it occurred at ten minutes' interval, saliva appeared, but not if at shorter intervals.

A conditioned stimulus can be made an inhibitory one. Suppose that a sound and a light are made, each for itself, active, that is, associated with presentation of food, but that, when both occur together, no food is presented, that is, the combination is made inactive. Then one must inhibit the other. Moreover, one may be presented alone and be followed by secretion, and, while the active stimulus is still present, the other, also active by itself alone, may be presented. The secretion stops, because the combination of the two is inactive.

Pavlov (1912, p. 329) states the following rule with regard to the spread of stimuli in the cortex. As they arrive, they spread at first and irradiate, then collect together, fix and concentrate. This law shows itself very clearly in the phenomena of inhibition (1912, p. 330). Suppose that a number of various stimuli have been made signals for activity of the salivary gland. They act also when combined together. But if one of them is made feeble by inhibition, the others are also extinguished, if tested at once. But if the test is not made until several minutes later, it will be found that the activity has returned to all, except to the one previously inhibited, which remains for a much longer time ineffective.

Since, during a conditioned reflex, the whole of the cortex, except the part in action, is inhibited, it follows that, if^the stimulus is not followed by presentation of food, so that internal inhibition of this part also takes place, there is a tendency to total inhibition and to sleep. Sleep itself, indeed, may be associated with food and be excited by a conditioned stimulus. A lullaby may be regarded as the conditioned stimulus to send a child to sleep.

Removal of an area of the cortex damages permanently any conditioned reflex in which that area had been concerned. It was found that when a certain large skin area had been made a conditioned stimulus for the feeding reflex, the removal of parts of the frontal lobes abolished the conditioned reflex from a particular, sharply defined area of skin. On stimulation of the ineffective skin area, there is, however, a strong inhibition of the effect from an active area. It leads, also, very quickly to drowsiness and sleep. Removal of occipital lobes prevents the obtaining of conditioned reflexes from individual visible objects, although it is still possible from various intensities of illumination. Other cases might be given in which parts of the brain had been removed, resulting in abolition of the power of obtaining certain kinds of conditioned reflexes, but retaining that of others. An animal might thus be spoken of as an idiot, incapable of education, so far as certain systems were concerned, but rational in other systems.

It will be clear, from some incidental facts mentioned, that an opportunity is presented for the investigation of the phenomena of hypnosis and of sleep. As a working hypothesis, we might suppose that hypnosis is associated with a condition of active inhibition, sleep as that condition of inactivity of the parts of the brain associated with consciousness which follows on inhibition, if no further excitatory stimuli are supplied. It may be regarded as a zero state, neither excitation nor inhibition ; all excitatory stimuli being first removed by inhibition, which itself then also disappears.

If the cerebral cortex is completely removed, no conditioned reflexes can be formed at all. It appears, then, that the cortex is the organ for appropriate adjustment to the varied combinations and changes in the outer world. As regards the methods to be used in these researches, it will be obvious, from what has been said as to the interference of chance phenomena with the establishment of a conditioned reflex, that a properly fitted laboratory, in which all

extraneous stimuli are excluded, is a necessity. On this point, the article by Pavlov (1911) may be consulted. Pavlov's address given at the Physiological Congress at Groningen (Pavlov, 1913), and his paper (1912) should be read. A research by Orbeli (1909) may be referred to as an example of some of the kinds of work done already in Pavlov's laboratory. Many of the facts described above were given me by Prof. Babkin and Dr Anrep, who had taken part in numerous experiments.

The contrast between the effects produced by reflex stimulation of nerves and those produced by direct stimulation of efferent nerves is due to the passage through synaptic membranes in the former case. The increased delay in the case of reflexes is not owing to a need of time to make the synapse conducting, nor for " amoeboid " movement of cell processes into contact, but to actual passage through a resistance. The discharge does not, as a rule, cease when the stimulus ceases, but lasts for a varying time afterwards. This after-discharge can be cut short by inhibition, and very sharply.

Repeated subminimal stimuli are capable of evoking a reflex ultimately. In some cases, as that of the scratch reflex, a single induction shock, however strong, will not do so. Two reflexes making use of the same final common path may reinforce one another. This, together with inhibition, plays an important part in reactions to " constellations " of stimuli. If the skin area for the scratch reflex is stimulated at two different points with subminimal intensity, both stimuli act on the whole centre and produce the reflex by "immediate spinal induction."

After a period of inhibition, there is frequently an increased excitability, which is not shown when the stimulus is merely removed for a period equal to that of the inhibition. This rebotmd is not, therefore, due to rest alone. The synapse between an axis cylinder and the cell body or dendrites of another neurone will only allow impulses to pass in the direction named, and not from the cell body back to the axis cylinder of another neurone. This has been proved experimentally in the case of motor neurones, but there is evidence to show that the synapses of dorsal root fibres (sensory) with cells in the spinal cord is permeable in both directions.

The phenomenon of the refractory period is well marked in reflexes. In the case of the motor neurones used as final common path by the scratch reflex and also by the flexion reflex, the long refractory period must be situated in some neurone on the afferent side, since the latter reflex is not rhythmic. When the contraction of a group of muscles, necessary for a particular reflex, can be opposed by that of an antagonistic group, it is found that along with contraction of the one group there is relaxation, by inhibition of the centre, of the other group. This is the phenomenon known as reciprocal innervation, and was appreciated by Descartes in the case of the eye muscles. The seat of the inhibitory component of the reflex appears to be either at the synapse with the motor neurone of the final common path, or in an intermediate neurone very close to this.

In some cases, where smooth muscle is the effector, there is reciprocal innervation of peripheral origin. Thus, stimulation of the efferent nerve to the muscles causes contraction of one muscle and inhibition of its antagonist. The claw of the crayfish and the dilatation of the pupil may be mentioned. Under natural conditions, a reflex arc is played upon by various afferent impulses, some inhibitory, and the discharge depends on the algebraic sum of l. whole, as shown in double reciprocal innervation.

When the relative intensities of the excitatory and inhibitory stimuli are very nearly balanced, a rhythmic discharge results. In the case of the leg, this is alternating on the two sides, so that stepping is produced. Explanations suggested will be found in the text. The effects of strychnine and of chloroform in converting inhibition into excitation, and vice versa, show themselves in reflexes dealt with by reciprocal innervation. This action is not exercised on the final common path itself, but either at the synapses of different neurones with it, or in some previous synapses, as in fact follows from the seat of the inhibition itself, as stated above. The effect of the conversion of inhibition into excitation by tetanus toxin in willed movements and the suffering it causes is described in the text.