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BackgroundRecent surveys indicate that 85% of the adult population consume caffeine on a daily basis. Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly unexplored. The circadian timing system promotes wakefulness at the end of the biological day (“wake maintenance zone”) and promotes sleep after the onset of the endogenous melatonin secretion (“opening of sleep gate”). There is mounting evidence that circadian and sleep homeostatic mechanisms continuously interact at the neurobehavioral, hormonal and cerebral level. Furthermore, we have recent evidence that the strength of circadian wake-promotion and the timing of circadian rhythmicity differs according to a genetic predisposition in the adenosinergic system. Thus, we assume that the daily consumption of caffeine may substantially impact on both circadian and homeostatic sleep-wake processes at different systemic levels. General AimWe aim at quantifying the influence of regular caffeine intake and its cessation on circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being, neurobehavioral performance and associated cerebral mechanisms.Specific AimsRegular caffeine intake: We aim at investigating the effects of sleep-wake regulatory adaptations to regular caffeine consumption a) on night-time sleep structure and sleep intensity (electroencephalography, EEG), b) on circadian wake-promotion (nap sleep during the biological day) and circadian timing of hormonal rhythms, and c) on waking quality, as indexed by subjective ratings, objective measures of neurobehavioral performance, and cerebral mechanisms (EEG and functional magnetic resonance imaging [MRI]) (see 1.4). Cessation of regular caffeine intake: To investigate the response of sleep-wake regulatory mechanisms to a sudden change in the adenosinergic system on points a- c (as delineated above). Experimental Design/MethodsYoung healthy regular caffeine consumers will be asked to participate in a double-blind, placebo-controlled within-subjects design with three conditions: Regular caffeine intake, regular placebo intake, and cessation of regular caffeine intake. In the chronobiology laboratory, circadian sleep-wake promotion will be assessed by combining EEG and multimodal MRI techniques. Circadian timing will be assessed by salivary melatonin and cortisol rhythms. Sleep and waking quality will be quantified by continuous polysomnography, waking EEG, subjective ratings (sleepiness, mood, craving, withdrawal symptoms) and cognitive performance (vigilance and working memory). Each of the three laboratory parts will last 40 h under strictly controlled conditions (i.e., dim light, constant ambient temperature etc.). Subsequent to each laboratory condition, actimetry and sleep diaries will serve to assess sleep- and waking patterns in the field under caffeine vs. placebo conditions.Potential ValueThe project will substantially advance our knowledge about the impact of the commonly encountered caffeine consumption on the sleep-wake regulatory system. Circadian mechanisms might be crucially involved in the maintenance of a vicious circle of counteraction of sleepiness by caffeine, leading to impaired sleep, followed by daytime sleepiness. Furthermore, the project will substantially contribute to understand the complex interplay of sleep-wake regulatory mechanisms in response to acute or long-term changes in the adenosinergic system. Depending on the outcome of the results, our project may contribute important insights on recent societal changes in sleep-wake behaviour (e.g., shorter sleep duration and delayed sleep phase) and the related increase in people suffering from sleep problems.