Effects of sleep injuries

The word 'experiment' will be used in a restricted sense, in order to make a clear conceptual distinction between the phenomenology of sleep and the work on the neurophysiological mechanisms of the sleep-wake cycle. ‟The name of the experimenter is given to someone who uses simple or complex investigation procedures to vary or modify, for any purpose, natural phenomena and make them appear in circumstances or conditions in which nature does not present them to him. In this sense, 'observation' is the examination of a natural phenomenon and 'experiment' is the examination of a phenomenon modified by the examiner" (see Bernard, 1865, p. 29). In this chapter, we will summarize the results of experiments in which coma, lethargy or insomnia, or any change in the sleep-wake cycle,

a) The ascending reticular formation

This line of research is closely related to the physiology of the ascending reticular system. We therefore refer to Bremer's article of the same name, whose main conclusions we will briefly summarize as an introduction to this part.

It was later seen that even the behavioral aspects of the awakening reaction can be reproduced with the stimulation of the reticular formation, in animals without narcosis and free in their movements (see Moruzzi, 1972, for the literature). These are phasic, short-lived effects.

The next step taken by Moruzzi and Magoun (v., 1949) was to suggest the hypothesis that the ascending reticular system was continuously, i.e. tonically, active and that its influence on the brain must be above a certain critical level to maintain vigil. The interruption of this ascending influence would be the cause of the coma that appears in the cat after the section of the midbrain, in the cerveau isolé preparation by Bremer (see is c). This syndrome would also be observed in humans after a lesion of the midbrain produced by trauma. Less complete disruptions of the midbrain, combined with hypothalamic lesions, would produce lethargy, thus explaining von Economo's observations. The demonstration that a continuous, 'tonic' activity was present in the reticular system was obtained following two different lines of research: a) reproduction of the syndrome of Corna del cerveau isolé with interruption of the ascending reticular projections (see Magoun, 19632; see Moruzzi, 1972, for literature); b) demonstration by microelectrode recording of the existence of a continuous, irregular discharge in reticular neurons.

A third step forward was made by C. Batini and others (see, 1959), when they demonstrated that a behavioral and electroencephalographic syndrome of insomnia, thus opposed to the coma syndrome of cerveau isolé, could be obtained by dissecting the brainstem a few millimeters backward, at the pontine level. This 'trigeminal mid pontine preparation' is characterized by desynchronized EEG and alert eye behavior. This observation and many others made following different research paths (see Moruzzi, 1963, 1972; see Bonvallet, 1966, for the literature) led to the conclusion that in the brainstem there is also a system that can be called ‛ deactivating', because it is antagonistic to the ascending reticular system which we have seen instead to be activating. These are populations of neurons with EEG synchronizing and hypnogenic effects.

In summary, at the end of the 1940s a unitary explanation of apparently unrelated observations, such as those of von Economo and Berger, appeared possible. This result was due to the demonstration of an ascending reticular system with an activating, tonic and phasic influence on the brain. Finally, at the end of the 1950s, the classic hypnogenic effects obtained with electrical stimulation (see Chapter 4) could be related in some way to the deactivating influences exerted by other structures of the brainstem.

b) The deactivating regions of the brainstem

All of these results were obtained in acute experiments and the chronic effects of brainstem sections were used only as a control. Chronic experimentation began to be used especially during the sixties. These experiments led to important results for the problem of the origin of the sleep-wake cycle. The demonstration that two opposing influences are exerted on the brain led to the hypothesis that the cycle itself, i.e. the alternation of sleep and wakefulness, could originate in the brainstem.

The history of chronic decerebration experiments is long (see Moruzzi, 1972, for the literature). However, we will only discuss the results obtained by J. Villablanca (v., 1966) on cats in which the brainstem had been separated from the brain with a section made at a higher level, i.e. just in front of the superior colliculi (decerebration collicular). These tall midbrain cats were followed for an extended period of time. It is, of course, impossible to define any state observed in brainless animals as sleep or wakefulness. All we can say is that, after chronic decerebration, it is possible to observe behaviors resembling those of the normal animal during sleep and wakefulness. After 15-20 days the cats were found crawling or sitting or even attempting to walk; the lids were open and the pupils dilated. These were manifestly symptoms of wakefulness and this impression was reinforced by the fact that these periods alternated with states characterized by bodily manifestations of sleep. Villablanca (ibid .) made a distinction between a state characterized by the closing of the eyelids, by the lifting of the nictitating membrane, and, above all, by the fluctuation of the pupil diameter (fluctuating miosis) - which corresponds to the synchronized sleep of the intact animal - and a state characterized by the narrowing extreme of the pupils (fissured myosis) and by the generalized collapse of the postural tone, which corresponds to the desynchronized sleep of the intact animal. The periods characterized by the reversible disappearance of decerebrate rigidity are usually called 'cataplexic episodes', from the name of a clinical syndrome that we will examine later.

The main result obtained by Villablanca with his experiments is not the demonstration that fragments of sleeping or waking behavior can be observed in the absence of the brain - this had already been seen by others before him - but rather the demonstration that it is both the sleep-wake cycle and the rhythmic alternation of the two stages of sleep can arise when the brainstem is separated from the brain. Of course, only the cranial nerves and spinal cord are available for sleep and waking manifestations when the brain is absent. But it is a fundamental achievement to have demonstrated that rhythms of this type can arise, in a brainless animal, in the brainstem.

The obvious explanation for these results, if we overlook the problem of paradoxical sleep, is that there is an alternation of activity between two systems: the ascending or activating reticular system and the deactivating regions of the caudal part of the brainstem. Recent research has allowed us to locate at least two of these deactivating regions: 1) the region of the solitary tract, which is endowed with phasic activities, as demonstrated by lesion and stimulation experiments (see Moruzzi, 1963; see Bonvallet, 1966, for literature); 2) the nuclei of the raphe, which are tonically active, as demonstrated by prolonged insomnia produced by their lesion (see Jouvet and Renault, 1966). These are two independent systems, and this is demonstrated by the fact that it is still possible to produce synchronization of PHEO and miosis by stimulation of vagoaortic afferent fibers leading to the region of the solitary bundle. This deactivating effect is also present when the raphe crossing has been interrupted by a sagittal section (see Puizillout and Ternaux, 1974).

c) Alternation of activities and reciprocal connections between antagonistic systems

Chronic experiments on the cerveau isolé show, on the other hand, that a sleep-wake cycle can also arise in an isolated brain, after a complete section of the midbrain. Bremer's classic experiments were clever and the main result was the discovery that the sleep-wake cycle was present after the section of the cervical cord at C 1 , i.e. when the brain was still connected to the brainstem ( encéphale isolé ), while the period disappeared, and was replaced by a 'permanent' coma after the section of the midbrain ( cerveau isolé). Manifestly either the abolition of the flow of sensitive and sensory impulses through the cranial nerves, as Bremer had originally suggested (see, 1937 and 1938), or the suppression of an ascending influence arising between the two sections could explain such differences evident between these two acute preparations. We now know that the elimination of the tonic influence of the ascending reticular system is responsible for the acute cerveau isolé coma.