Sleep Homeostasis, Adenosine, Caffeine, and Narcolepsy

Abstract

Many functional aspects of wakefulness and sleep, including excessive daytime sleepiness, vigilance, attention, sleep structure, and quantitative measures derived from the electroencephalogram (EEG) are tightly controlled by two interacting processes: (1) a circadian program providing temporal context to most physiological processes including sleep and (2) a homeostatic process keeping track of “sleep pressure.” Sleep homeostasis is conceptualized in the two-process model of sleep regulation [1] as the build-up of sleep pressure (or “sleep need”) during wakefulness and the dissipation of sleep pressure during sleep. The homeostatic regulation of rest/sleep is a common principle in invertebrates, fish, and mammals [2]. In humans, we think today that the circadian system opposes homeostatic changes in sleep pressure, to enable healthy people to stay awake and alert throughout a normal waking day despite accumulating sleep pressure associated with wakefulness [3]. Vice versa, circadian clock and sleep homeostasis interact to permit healthy individuals to remain asleep during the night despite the waning of sleep need. When wakefulness is prolonged (“sleep deprivation”) and sleep pressure exceeds an average “reference value,” subjective and objective measures of sleepiness increase, vigilance deteriorates, and attention is impaired. Moreover, theta activity in the waking EEG, as well as slow-wave sleep (SWS; nonREM sleep stages 3 and 4) and EEG slow-wave activity (SWA; spectral power within 0.75–4.5 Hz) are enhanced in recovery sleep. Particularly, SWA (or “delta activity”) in nonREM sleep is predictably correlated with the duration of preceding wakefulness. This physiological measure constitutes the classical, highly reliable marker of sleep homeostasis, which served to delineate the basic concepts of the two-process model of sleep regulation [1,4]. The neurobiological mechanisms underlying nonREM sleep homeostasis remain incompletely understood.