Adenosine and functional A 1 adenosine receptor (A 1 AR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral A 1 AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [ 18 F]CPFPX positron emission tomography was used to quantify A 1 AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A 1 AR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in A 1 AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A 1 AR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in A 1 AR availability. Sleep deprivation resulted in a higher A 1 AR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in A 1 AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A 1 AR availability might be causal for individual responses to sleep loss.S leep loss is known to impair almost every aspect of cognition, such as learning (1), long-term memory consolidation (2), attention and psychomotor vigilance (PVT) (3), and executive functions (4), including decision making (5) and emotional control (6). Sleep deprivation further typically alters the frequency distribution of the waking electroencephalogram (EEG) as an indicator of alertness corresponding to cognitive performance (7). However, large interindividual differences exist in the degree of cognitive performance decline during sleep deprivation (3). In a trait-like process, some individuals keep high-level performance during sustained wakefulness, whereas others suffer from severe performance loss (3). The neuro-molecular mechanisms in the brain responsible for these different vulnerabilities are still largely unknown. Caffeine, commonly consumed for fighting fatigue, promotes wakefulness via adenosine receptor antagonism. It seems likely that the adenosinergic system is a neurochemical link between performance and sleep (8). Adenosine is contributing to the homeostatic process of sleep-wake regulation (for review, see refs. 9-12). As has been shown in cats and rats, extracellular adenosine concentration fluctuates rhythmically in many brain regions, such as the basal forebrain, increasing during wakefulness and decreasing during sleep: it thereby induces sleep after wake extension and is in turn restored to baseline levels after recovery sleep (13). For additional information on adenosine, see...

Sleep deprivation (SD) could amplify the temporal fluctuation of spontaneous brain activities that reflect different arousal levels using a dynamic functional connectivity (dFC) approach. Therefore, we intended to evaluate the test-retest reliability of dFC characteristics during rested wakefulness (RW), and to explore how the properties of these dynamic connectivity states were affected by extended durations of acute sleep loss (28/52 hr). We acquired resting-state fMRI and neuropsychological datasets in two independent studies: (a) twice during RW and once after 28 hr of SD (n = 15) and (b) after 52 hr of SD and after 14 hr of recovery sleep (RS; n = 14).Sliding-window correlations approach was applied to estimate their covariance matrices and corresponding three connectivity states were generated. The test-retest reliability of dFC properties demonstrated mean dwell time and fraction of connectivity states were reliable. After SD, the mean dwell time of a specific state, featured by strong subcortical-cortical anticorrelations, was significantly increased. Conversely, another globally hypoconnected state was significantly decreased. Subjective sleepiness and objective performances were separately positive and negative correlated with the increased and decreased state. Two brain connectivity states and their alterations might be sufficiently sensitive to reflect changes in the dynamics of brain mental activities after sleep loss. K E Y W O R D Sacute sleep deprivation, dynamic connectivity states, light sleep/drowsiness, resting-state fMRI, test-retest reliability

Sleep of sufficient duration is crucial for cognitive performance. For adults a habitual sleep duration of ≥7 hr has been recommended to maintain health (Hirshkowitz et al., 2015; Watson et al., 2015). However, today's lifestyle often entails shortened sleep due to obligations both in private and in working life. Over time, such shortened sleep can result in a chronic sleep deficit. Cognitive domains seem to be differentially affected by sleep deficits. While sustained attention is greatly affected by both

Sleep structure is highly stable within individuals but different between individuals. The present study investigated robustness of the individual sleep structure to extended total sleep deprivation. Seventeen healthy men spent a baseline night (23:00-07:00 hours), 58 h of sleep deprivation and a 14-h recovery night (17:00-07:00 hours) in the laboratory. Intraclass correlation coefficients showed that the agreement between baseline and recovery with respect to the proportion of the different sleep stages increased as a function of recovery sleep duration. High values were reached for most of the sleep stages at the end of 14 h of recovery sleep (intraclass correlation coefficients between 0.38 and 0.76). If sleep duration of the recovery night is extended to 14 h, sleep stage distribution resembles that of a baseline night underlining the robustness of the individual sleep structure.

Sleep loss pervasively affects the human brain at multiple levels. Age-related changes in several sleep characteristics indicate that reduced sleep quality is a frequent characteristic of aging. Conversely, sleep disruption may accelerate the aging process, yet it is not known what will happen to the age status of the brain if we can manipulate the sleep conditions. To tackle this question, we employed an approach of brain age to investigate whether sleep loss would cause age-related changes in the brain. We included MRI data of 134 healthy volunteers (mean chronological age of 25.3, between the age of 19 and 39, 42 females/92 males) from five datasets with different sleep conditions. Across three datasets with the condition of total sleep deprivation (> 24 hours of prolonged wakefulness), we consistently observed that total sleep deprivation increased brain age by 1-2 years regarding the group mean difference with the baseline. Interestingly, after one night of recovery sleep, brain age was not different from baseline. We also demonstrated the associations between the change in brain age after total sleep deprivation and the sleep variables measured during the recovery night. By contrast, brain age was not significantly changed by either acute (3 hours’ time-in-bed for 1 night) or chronic partial sleep restriction (5 hours’ time-in-bed for 5 continuous nights). Taken together, the convergent findings indicate that acute total sleep loss changes brain morphology in an aging-like direction in young participants and that these changes are reversible by recovery sleep.SIGNIFICANCE STATEMENT:Sleep is fundamental for humans to maintain normal physical and psychological functions. Experimental sleep deprivation is a variable-controlling approach to engaging the brain among different sleep conditions for investigating the brain’s responses to sleep loss. Here, we quantified the brain’s response to sleep deprivation by using the change of brain age predictable with brain morphological features. In three independent datasets, we consistently found increased brain age after total sleep deprivation, which was associated with the change in sleep variables. Moreover, no significant change in brain age was found after partial sleep deprivation in another two datasets. Our study provided new evidence to explain the brain-wide effect of sleep loss in an aging-like direction.

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Introduction: Vigilance performance is experienced as effortful and relies on limited cognitive resources. Recent theories propose that effort allocation is regulated through a continuous cost-benefit analysis, in which effort is considered a cost that is weighed against potential benefits (e.g. monetary reward). The willingness to exert effort is higher when expected benefits are larger. Conversely, rewards are considered less attractive if more effort is required to obtain them (effort discounting). As vigilance performance is heavily affected by sleep deprivation (SD), it is important to examine how SD impacts on this cost-benefit weighting of effortful attention. Methods: Two methodological approaches were used to investigate this matter. First, we tested whether incentives improved vigilance performance, and whether this was altered after a night of SD. Participants (N=25) performed the Psychomotor Vigilance Task (PVT) under different incentive conditions (1, 5, or 15 cent/fast response [individually defined]). Subsequently, reward devaluation was measured using a discounting task in which participants indicated their preference for rewards that were available upon performance of different durations of PVT (1, 5, 10, 20 or 30 min). All tasks were performed once after a night of sleep, and once after SD (in counterbalanced order). During PVT performance, pupil diameter was monitored as a measure of attentional effort and arousal. Results: Overall, PVT performance improved in higher reward runs. This effect was accompanied by increased pupil size, indicating higher attentional effort. Although performance was poorer during SD for all runs, this SD-effect was most pronounced when rewards were low. Results form the discounting task showed that participants clearly devalued rewards that were contingent on longer task performance. Importantly, this discounting effect was steeper after SD. Conclusion: Findings from both tasks confirm that the allocation of attentional effort in vigilance performance is subject to a cost-benefit analysis, and that the subjective costs of vigilance are increased after SD. Support (If Any) MISALIGNED MEALS COMPROMISE REPRODUCTIVE SUCCESS IN MICE Butler MP, Swamy S, Kukino A Oregon Health & Science University, Portland, ORIntroduction: Shift work has deleterious effects on reproductive health and has been linked to irregular menstrual cycles, endometriosis, reduced fertility, increased miscarriage, and low birth weight. These effects may be due to disruptions of the circadian timing system. Therefore, we tested the hypothesis that mis-timed food, a common disruptive feature of shift work, would impair reproductive success in mice. Methods: Male and female Per2::Luc mice that carry a fusion protein of Per2 and luciferase were fed either during their active or inactive phases. Circadian desynchrony was verified by in vivo imaging of antiphase Per2 oscillations in the liver. Prior to pairing, estrus cycling was monitored in all females for three weeks. Males and females, balanced for ag...

The EEG alpha rhythm (8-13 Hz) is one of the most salient human brain activity rhythms. Spectral power in the alpha range in wakefulness and sleep varies among individuals based on genetical predisposition, yet knowledge about the underlying genes is scarce. The EEG alpha oscillations are related to cerebral energy metabolism and modulated by the level of attention and vigilance. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate (ATP) breakdown and acts as a sleep promoting molecule by activitating A1and A2Aadenosine receptors. We quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1adenosine receptor availability by positron emission tomography with18F-CPFPX, in a large sample of healthy volunteers carrying different alleles of gene variant rs5751876 ofADORA2Aencoding A2Aadenosine receptors. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37)= 2.35, p = 0.014, Wilk’s Λ = 0.467). Across considered brain regions an effect ofADORA2Agenotype on A1adenosine receptor binding potential was found (F(18,40)= 2.62, p = 0.006, Wilk’s Λ = 0.459) and after correction for multiple testing this effect was shown to be significant for circumscribed occipital region of calcarine fissures.A correlation between individual differences in oscillatory alpha power and adenosine receptor availability was found for the subgroup of female participants only. In conclusion: a genetic variation in the adenosinergic system affects individual alpha power, although a direct modulatory effect via the A1AR has been demonstrated for females only.