Abstract
Disturbances of the sleep-wake cycle are highly prevalent and diverse. The aetiology of some sleep disorders, such as circadian rhythm sleep-wake disorders, is understood at the conceptual level of the circadian and homeostatic regulation of sleep and in part at a mechanistic level. Other disorders such as insomnia are more difficult to relate to sleep regulatory mechanisms or sleep physiology. To further our understanding of sleep-wake disorders and the potential of novel therapeutics, we discuss recent findings on the neurobiology of sleep regulation and circadian rhythmicity and its relation with the subjective experience of sleep and the quality of wakefulness. Sleep continuity and to some extent REM sleep emerge as determinants of subjective sleep quality and waking performance. The effects of insufficient sleep primarily concern subjective and objective sleepiness as well as vigilant attention, whereas performance on higher cognitive functions appears to be better preserved albeit at the cost of increased effort. We discuss age-related, sex and other trait-like differences in sleep physiology and sleep need and compare the effects of existing pharmacological and non-pharmacological sleep- and wake-promoting treatments. Successful non-pharmacological approaches such as sleep restriction for insomnia and light and melatonin treatment for circadian rhythm sleep disorders target processes such as sleep homeostasis or circadian rhythmicity. Most pharmacological treatments of sleep disorders target specific signalling pathways with no well-established role in either sleep homeostasis or circadian rhythmicity. Pharmacological sleep therapeutics induce changes in sleep structure and the sleep EEG which are specific to the mechanism of action of the drug. Sleep- and wake-promoting therapeutics often induce residual effects on waking performance and sleep, respectively. The need for novel therapeutic approaches continues not at least because of the societal demand to sleep and be awake out of synchrony with the natural light-dark cycle, the high prevalence of sleep-wake disturbances in mental health disorders and in neurodegeneration. Novel approaches, which will provide a more comprehensive description of sleep and allow for large-scale sleep and circadian physiology studies in the home environment, hold promise for continued improvement of therapeutics for disturbances of sleep, circadian rhythms and waking performance.
Highlights
Disturbances of the sleep-wake cycle are highly prevalent and diverse
When we only consider recent observational studies in which sleep in participants without sleep complaints were assessed by polysomnography, the consensus conclusion across these cross-sectional studies is that sleep efficiency/continuity is a significant determinant of reported sleep quality and the feeling of being refreshed upon awakening (Akerstedt et al 2016; Kaplan et al 2017a, b; Della Monica et al 2018)
Long and short sleepers differ in their ‘preferred’ or ‘tolerated’ level of sleepiness. Whether and how this relates to homeostatic aspects of sleep regulation or to the longer circadian biological night observed in long sleepers remain unclear (Aeschbach et al 2003)
Summary
Sleep is a major determinant of well-being, mental and physical health and understanding sleep-health relations, and sleep disorders are dependent on adequate quantification of sleep. The sleep experience can be reported as sleep quality and sleep depth At another level sleep is a state of the brain and the body which in humans and animals can be quantified by objective behavioural criteria such as immobility and arousal thresholds and by a wide range of physiological variables. Quantification of specific electrophysiological phenomena such as slow waves and sleep spindle oscillations (Dijk et al 1993; Lazar et al 2015), muscle tone (Brunner et al 1990a; Jeppesen et al 2018) or heart rate variability (Yang et al 2018; Viola et al 2008a) and changes thereof across the sleep episode or in response to pharmacological and non-pharmacological sleep manipulations have provided new insights into the sleep process. Analyses of the temporal characteristics of the EEG have revealed phenomena such as phase locking between slow oscillations and sleep spindles (Klinzing et al 2016) and ultra-slow oscillatory processes in spindle activity with periods of approximately 50–75 s (Lecci et al 2017; Lazar et al 2018)
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