Sleep

1. Historical introduction

A little more than half a century has passed since C. von Economo (v., 1918) reported that in epidemic lethargic encephalitis, or sleeping sickness, the lesions are localized above all in the region of the midbrain that surrounds the Silvio aqueduct and in the 'hypothalamus. The interpretation he gave of his observations (see Von Economo, 1929) was wrong, but he was certainly right when he thought that the nervous structures damaged by the epidemic disease had critical importance in regulating the sleep-wake cycle.

Not many years later WR Hess (v., 1927) found that sleep could be obtained, in the cat without narcosis and free in its movements, with appropriate electrical stimulations of the medial region of the thalamus. Despite the possibility of errors (see chapter 4), this line of research had a profound influence on the development of sleep physiology. It was the first demonstration that physiological sleep can be achieved with localized electrical stimulation of the brain, and the results needed to be repeatedly confirmed by stimulating other regions of the diencephalon and brainstem. Furthermore, Hess's experiments paved the way for a fruitful line of research in which the study of behavior was associated with different types of electrophysiological stimulation and recording. Of course, it was impossible to locate, in those times, any relationship between von Economo's observations and Hess's experiments. Everything felt so different: case reports and animal experiments, injuries and stimulations, lethargy, and physiological sleep.

The discovery by H. Berger (v., 1929) that the electrical activity of the cerebral cortex could be recorded, in man, through cranial integuments (electroencephalogram, EEG) opened the era of electrophysiological studies in man and animals in the absence of narcosis. Berger himself made a major contribution to sleep studies when he showed that the human EEG exhibits slow, large voltage oscillations during this state, thus eliminating from discussion the naïve assumption that higher centers should be silent when there is no consciousness. He also demonstrated that this type of electrical activity is markedly different from the rapid low-voltage waves (β-waves) that characterize active wakefulness; and also by the slow oscillations of potential at 10/s (α waves) that appear during the relaxed vigil. Finally, Berger found that both α-waves and sleep rhythms could be abolished by sensitive or sensory stimulation and replaced by β-waves: two phenomena designated, respectively, Berger's arrest reaction and electroencephalographic awakening. All these effects were generalized and therefore not limited to the cortical area corresponding to the stimulated sensory modality. Their abrupt onset then prevented the recognition of links with the tonic phenomena responsible for maintaining vigil. It will be up to ED Adrian (v., 1934) to explain Berger's observations on the basis of models of activity of cortical neurons. He suggested the

Two lines of research arose from these early works. The line of 'phenomenological investigation', essentially based on observations, became extremely fruitful with the introduction of electroencephalographic and microelectrode recording techniques in Mammals without narcosis, free in their movements. It led to the demonstration that during sleep, in cats (see Klaue, 1937) and in humans (see Dement and Kleitman, 1957), periods characterized by EEG desynchronization are present and to studies on the relationships between this phase of sleep, called desynchronized sleep or paradox, and dreams ( ibid.). The investigations on the behavior of single units of the cerebral cortex must be situated along the same lines of phenomenological research (see Evarts, 1962 and 1964); and also the electrophysiological works on postural tone (see Jouvet, 1962), on spinal reflexes (see Pompeiano, 1965, 1966 and The neurophysiological ..., 1967) and on sensory transmission during desynchronized sleep (see Pompeiano, Sensory inhibition ..., 1967).

The second line of research, 'experimental investigation', is based on the study of changes in the wake-sleep cycle produced by lesions or by stimulation. Many aspects of this field of investigation have been examined by F. Bremer in the article ascending reticular system. Suffice it to recall here the research on the encéphale isolé and on the cerveau isolé(see Bremer, 1935, 1937, and 1938), the work of G. Moruzzi and HW Magoun (see, 1949) on the ascending lattice system, and the experiments of DB Lindsley et al. (see, 1949 and 1950) on the effects of reticular lesions; and finally the demonstration of the existence in the lower part of the brainstem of a deactivating system, probably hypnogenic (see Moruzzi, 1963, for the literature). The ascending reticular system has made it possible to give a unitary explanation of observations that are apparently unrelated to each other, such as those we referred to in the first part of this introduction.

The most recent experimental developments concern the neurochemical study of the brainstem structures that control the wake-sleep cycle and the electrophysiological investigation of the behavior of single nerve cells of the pons and cerebral cortex.

2. Sleep phenomenology

The study of the neurophysiological and neurochemical mechanisms of the sleep-wake cycle, which will be treated in the following chapters, must be preceded by the description of the phenomena that are observed when no attempt is made to modify sleep or wakefulness or their rhythmic alternation. ‟The name of observer is given to one who applies simple or complex investigation procedures to the study of phenomena which he does not modify and who, consequently, collect them as nature offers him" (see Bernard, 1865, p. 29 This is always the first approach in any field of natural sciences.

Half a century ago the only avenue open to researchers was the study of animal behavior and this line of attack is still followed in much research in comparative physiology and in a field of the natural sciences, ethology. Animal behavior is mainly based on movements or positions, therefore on the phasic and tonic activity of skeletal muscles and the corresponding motor neurons. Modern developments in electrophysiological techniques have made it possible to study the behavior not only of large populations of cerebral neurons (electroencephalography), but also of the activity of single nerve cells in the animal without narcosis, free in its movements. However, the aim of the research is always the same, whether we study the behavior of muscle fibers or that of brain neurons. We simply observe what is happening, making no attempt to influence the physiological sleep-wake cycle. Naturally some experimentation, in the strict sense of the word (see chapter 3), is also inevitable in this type of research. Indeed, it can be useful to specifically ask nature a few questions, as we do, for example, when we observe the effects of sensitive or sensory stimuli. The fundamental point, however, is that there is no attempt to modify the physiological rhythm of the alternation between sleep and wakefulness. Our aim is only to carefully describe natural phenomena and their relationships over time. it is unavoidable even in this type of research. Indeed, it can be useful to specifically ask nature a few questions, as we do, for example, when we observe the effects of sensitive or sensory stimuli. The fundamental point, however, is that there is no attempt to modify the physiological rhythm of the alternation between sleep and wakefulness. Our aim is only to carefully describe natural phenomena and their relationships over time. it is unavoidable even in this type of research. Indeed, it can be useful to specifically ask nature a few questions, as we do, for example, when we observe the effects of sensitive or sensory stimuli. The fundamental point, however, is that there is no attempt to modify the physiological rhythm of the alternation between sleep and wakefulness. Our aim is only to carefully describe natural phenomena and their relationships over time.