Further studies however have shown that these apparently in effective stimuli actually produce a considerable inhibition of that part of the brain on which they act. This state of inhibition lasts for some time and is of a measurable intensity. The transition of the cortex into an inhibitory state is very rapid in the case of conditioned stimuli which are not associated with some definite activity of the animal, and the inhibition is very profound. This inhibition remains as an after-effect and readily undergoes sum mation with the effect of any other inhibitory stimuli which may chance to affect the brain. The inhibition in these cases not only becomes more intense but it also begins to involve other areas of the brain, areas which were not affected in the first instance but which now lose their excitability on account of this spreading inhibitory influence ; on stimulation of these areas with appro priate conditioned stimuli, they give either no reflex effect or a greatly diminished one. A great number of conditions are known in which various conditioned stimuli acquire inhibitory properties and which on administration set up a state of diminished ex citability and inhibition in the brain. On repetition of these in hibitory stimuli, a stage is reached when no conditioned reflex response can be obtained.
Such a state of widely spread inhibition is easily produced and is the common and everyday occurrence of sleep. The fundamental condition for the appearance and development of inhibition which is localised in some definite part of the brain is exactly the same as that of sleep. From the point of view of conditioned reflexes, the brain is never active as a whole. Areas of inhibition are inter mixed with areas of excitation, and these always antagonise the tendency of the inhibition to spread over the whole brain. Even when the inhibition has attained a mastery over the brain, there may always remain areas which will be in an excitatory state, which is however not strong enough to keep the animal in a state of alertness.
Thus sleep is nothing but a state of inhibition which is always present in some areas of the brain, but which has now become diffused continuously (with practically no intervening fields of excitation) over the entire cortex and which has descended also to some of the lower parts of the brain. The development of inhibition is very rapid in the case of conditioned stimuli which do not lead to some activity ; it must however be considered as only a special instance of a more general case, since a state of inhibition can also develop when the stimuli are associated with and followed by the respective activity.
In the case of a varied activity, although no given point of the cortex attains such a profound depth of inhibition, yet the great number of inhibitory points leads to a widely distributed in hibitory state even without an intensive irradiation, and this also descends to affect some of the lower centres of the brain. A great number of quickly changing stimuli following in succession and leading to some activity of the animal may often exert a very prolonged and powerful resistance to the general dissemination of inhibition, thus delaying the onset of sleep. A well-established rhythm in the changes from wakefulness to sleep may facilitate this wide-spreading of the inhibition leading to sleep.
Since, as we know, the spread of inhibition is a gradual process, involving first a smaller and then a greater area, we should expect to find various transition stages between the fully alert state and complete sleep. Such transition stages actually exist, and they have been studied in considerable detail by observing the condi tioned reflexes of the animal. Sleep in animals often exhibits the following peculiar form. As in fully developed sleep, the activity of the hemispheres is absent, all conditioned stimuli remain with out effect, and different extraneous stimuli, unless exceptionally powerful, fail to evoke any reaction. Nevertheless the animal preserves an entirely alert posture; it stands with wide-open eyes, head up, extremities extended, not seeking support ; sometimes it remains motionless for minutes and sometimes for hours. On changing the position of an extremity, the extremity retains the new position. Presentation of food gives no reaction, and the animal continues to remain still. As the result of careful obser vations of man and animals, it may be said that this transition state from the alert state to sleep is always present before the development of complete sleep, though only in a fleeting form.
A similar demarcation of excitable areas which have undergone complete inhibition may exist also between different large areas of the cortex itself, producing what may be called localised sleep. This form is frequently seen and can be produced experimentally. For instance, secretory activities may be present and of normal magnitude, while all motor activities are already inhibited. The inhibition in such a case must have spread over the motor area of the cortex so that the excitation induced by the conditioned stimulus could reach the glands but not the muscles. The above observations demonstrate that the extent of the spread of the diffused inhibition in the brain may be small or great, and that there may exist different transition stages in the depth of the inhibition or, in other words, different intensities of the diffused inhibition, sleep. Bearing in mind the fact that in alertness the strength of the conditioned reflex is determined, ceteris paribus, by the strength of the stimulus, we can proceed to study with some degrees of definiteness the different stages through which the diffused inhibition develops.