title: Effects of chronic and acute sleep deprivation on sleep-wake regulation and cognition
Creators: name: Hennecke, Eva
Publisher: name: UNSPECIFIED
Year: 2021

description: Recuperative sleep contributes substantially to cognitive performance. Sleep deficits are associated with impaired cognitive functions and consequently augment the probability for errors and accidents. Shift workers are especially at risk for sleep deficits because they rather sleep at adverse circadian times and thus are exposed to light or noise during sleep opportunities. However, great inter-individual differences exist in the vulnerability to sleep deprivation effects. Moreover, cognitive functions are differentially affected by sleep deficits. Progress in the understanding of the before mentioned parameters has the potential to improve work safety by establishing personnel selection and assistance systems accordingly. The following thesis was written in the scope of the scientific junior group “Chronic sleep loss: from molecular neuroimaging to safety and health in space” (SomnoSafe) at the Institute of Aerospace Medicine of the German Aerospace Center (DLR). The three publications of this cumulative dissertation are based on two elaborative cooperation projects with the Institute of Neuroscience and Medicine (INM-2) of the Forschungszentrum Jülich. Given that sleep during space missions is shortened and disturbed (Whitmire et al., 2010), the present work aims at contributing to the understanding of the effects of chronic and acute sleep deficits on sleep-wake regulation, cognition and their inter-individual differences. Concerning sleep-wake regulation and cognition, the first publication focuses especially on adenosinergic mechanisms, the second publication on sleep structure and the third publication on possible interaction effects of chronic and acute sleep deprivation. A promising approach in elucidating inter-individual differences in sleep-wake behavior is the investigation of the adenosinergic system. Adenosine dampens cerebral nervous activity. It accumulates during wakefulness and is depleted during sleep in rodents and cats (Porkka-Heiskanen et al., 2000). Thus, adenosine is thought to be the neuromolecular correlate of the need for deep sleep that increases during wakefulness and decreases during sleep as measured with polysomnography. The first publication focuses on human cerebral A1 adenosine receptor (A1AR) availability during and after recovery from extended wakefulness. A1AR was quantified by [18F]CPFPX positron emission tomography scans after 52 hours of wakefulness and after a 14-h recovery sleep opportunity and compared to reference data from a well-rested sample. The results show increased human cerebral A1AR availability during extended sleep deprivation and a reduction of A1AR to baseline levels after recovery sleep. On the individual level, high A1AR availability during sleep deprivation was associated with higher cognitive performance and lower sleep pressure. Thus, differences in endogenous adenosine and receptor availability might account for the individual sleep loss responses. The second publication explores the physiology of extended recovery sleep and recovery processes after prolonged wakefulness. After an adaptation and a baseline night, participants were sleep deprived for 58 hours and had a 14-h sleep opportunity thereafter. Sleep was recorded with polysomnography. We analyzed and compared the proportion of sleep stages between baseline and recovery sleep on an hourly basis. Our results revealed, that the sleep stage proportions of the two nights approximate as a function of sleep duration. In accordance with predictions of the two process model (Borbély, 1982), slow-wave activity was already recovered after approximately 10 hours of recovery sleep. Interestingly, intraclass correlation coefficients for the sleep parameters further increased thereafter, suggesting ongoing recovery processes. For most sleep parameters, the individual sleep structure could be reestablished after 14 hours of recovery sleep. The results emphasize the robustness of the individual sleep structure and give insights in recovery from prolonged wakefulness. Cognitive performance during chronic and acute sleep deprivation and recovery from sleep loss effects is addressed in the third publication. A question that has not previously been answered is whether chronic sleep loss followed by one recovery night, predisposes individuals to impaired neurocognitive functioning during a subsequent period of additional acute sleep deprivation. Therefore, we investigated single and combined effects of sleep restriction, acute sleep deprivation and recovery sleep on performance (verbal and spatial working memory, declarative memory). Chronic and acute sleep deprivation were separated by one recovery night. Our study design mimicked possible sleep-wake scenarios of shift-workers on earth as well as of astronauts on the International Space Station, where chronic sleep restriction effects might be paired with acute sleep deficits in case of special operations. After an adaptation night and two baseline nights, participants underwent 5 nights of chronically restricted sleep to 5 hours time in bed (TIB; chronic sleep restriction group) or 5 nights of normal sleep with 8 hours TIB (control group). After one night of normal sleep (8 hours TIB), there was a night of acute sleep deprivation (38 hours) for both groups and a final 10-h recovery night. During wakefulness, participants performed a cognitive test battery at 3-hourly intervals. Declarative memory was tested with paired-associate lists, verbal and spatial working memory was measured with N-back tasks. The results show that declarative memory recall and verbal working memory were unaffected by chronic sleep restriction. Spatial working memory performance, however, was impaired during chronic sleep restriction. Individuals with prior sleep restriction showed also stronger impairments of spatial working memory during acute sleep deprivation than individuals of the control group. Thus, we found interaction effects of chronic and acute sleep loss for this cognitive domain despite one intervening recovery night. Furthermore, chronic sleep restriction effects were partly initially covert and revealed during acute sleep deprivation. This finding is of special importance as recovery sleep might provide individuals with a false sense of complete recuperation. The results of our investigations give new insights into the adenosinergic contribution to homeostatic sleep-wake regulation. For the first time in humans, we provide evidence for increasing and decreasing adenosine receptor availabilities in accordance with wakefulness and sleep. With the second publication we further show recovery processes in addition to those predicted by the homeostatic sleep-wake regulation. The third publication provides evidence for longer lasting effects of chronic sleep deprivation on performance. Our findings underline the importance of adequate sleep and recovery periods. Especially, the complex interplay between inter-individual differences in sleep-wake regulation and cognition as well as the danger of insufficient recovery of cognitive functions after recovery sleep need further investigation. The factors should further be considered with regard to employee selection and the development of assistance systems. The cumulative dissertation consists of two parts. Part 1 constitutes the synopsis. The first chapter details the theoretical background of the publications. An introduction to sleep, cognition and sleep deprivation effects on cognition is given. Chapter 2 explains the methods applied in the two laboratory sleep studies, on which the three publications are based. Chapter 3 gives an overview on each of the three publications. Chapter 4 provides a comprehensive general discussion. Part 2 of the dissertation consists of the references to the original publications.