Total sleep deprivation is known to have significant detrimental effects on cognitive and socio-emotional functioning. Nonetheless, the mechanisms by which total sleep loss disturbs decision-making in social contexts are poorly understood. Here, we investigated the impact of total sleep deprivation on approach/avoidance decisions when faced with threatening individuals, as well as the potential moderating role of sleep-related mood changes. Participants (n = 34) made spontaneous approach/avoidance decisions in the presence of task-irrelevant angry or fearful individuals, while rested or totally sleep deprived (27 h of continuous wakefulness). Sleep-related changes in mood and sustained attention were assessed using the Positive and Negative Affective Scale and the psychomotor vigilance task, respectively. Rested participants avoided both fearful and angry individuals, with stronger avoidance for angry individuals, in line with previous results. On the contrary, totally sleep deprived participants favored neither approach nor avoidance of fearful individuals, while they still comparably avoided angry individuals. Drift-diffusion models showed that this effect was accounted for by the fact that total sleep deprivation reduced value-based evidence accumulation toward avoidance during decision making. Finally, the reduction of positive mood after total sleep deprivation positively correlated with the reduction of fearful display avoidance. Importantly, this correlation was not mediated by a sleep-related reduction in sustained attention. All together, these findings support the underestimated role of positive mood-state alterations caused by total sleep loss on approach/avoidance decisions when facing ambiguous socio-emotional displays, such as fear.

Sleep loss is associated with sleepiness, sustained attention, and memory deficits. However, vulnerability of higher cognitive processes (i.e. decision making) to sleep debt is less understood. Therefore, a major challenge is to understand why and how higher cognitive processes are affected by sleep debt. We had established in mice correlations between individual decision-making strategies, prefrontal activity, and regional monoaminergic levels. Now, we show that acute sleep debt (ASD) disturbs decision-making processes and provokes brain regional modifications of serotonin and dopamine that could explain why ASD promotes inflexible and more risk-prone behaviors. Finally, we highlight, for the first time, that in a large group of healthy inbred mice some of them are more sensitive to ASD by showing inflexible behavior and decision-making deficits. We were also able to predict mice that would be the most vulnerable to ASD depending of their behavior before ASD exposure.

Introduction: Sleep extension has been associated with better alertness and sustained attention capacities before, during and after sleep loss. However, less is known about such beneficial effect on executive functions (EFs). Our aim was to investigate such effects on two EFs (i.e., inhibition and working memory) for subjects submitted to total sleep deprivation and one-night of recovery. Methods: Fourteen healthy men (26–37 years old) participated in an experimental cross-over design with two conditions: extended sleep (EXT, 9.8 ± 0.1 h of Time In Bed, TIB) and habitual sleep (HAB, 8.2 ± 0.1 h TIB). During these two conditions subjects underwent two consecutive phases: Six nights of either EXT or HAB followed by 3 days in-laboratory: baseline (BASE), TSD (38 h) and after recovery (REC). EFs capacities were assessed through Go-NoGo (inhibition) and 2N-Back (working memory) tasks. Both EFs capacities were measured at different time (BASE/TSD/REC: 09:30, 13:00, 16:00; TSD: 21:00, 00:00, 03:00, 06:30). Results: In both conditions (HAB and EXT), TSD was associated with deficits in inhibition (higher errors and mean reaction time from TSD 09:30 until the end; p < 0.05) and working memory (lower corrects responses from TSD 06:30 or 09:30; p < 0.05). We observed no significant differences between HAB and EXT conditions on EFs capacities during BASE, TSD, and REC periods. Conclusion: Six nights of sleep extension is neither efficient to reduce core EFs deficits related to TSD nor to improve such capacities after a recovery night. These results highlight that sleep extension (six nights of 10 h of TIB) is not effective to limit EFs deficits related to TSD suggesting a disconnection inside cognition between executive and sustained attention processes. Clinical Trials: NCT02352272.

Introduction: It is widely admitted that both total sleep deprivation (TSD) and extended task engagement (Time-On-Task, TOT) induce a cognitive fatigue state in healthy subjects. Even if EEG theta activity and adenosine both increase with cognitive fatigue, it remains unclear if these modifications are common mechanisms for both sustained attention and executive processes. Methods: We performed a double-blind counter-balanced (placebo (PCBO) and caffeine (CAF) - 2× 2.5 mg/kg/24 h)) study on 24 healthy subjects (33.7 ± 5.9 y). Subjects participated in an experimental protocol including an habituation/training day followed by a baseline day (D0 and D1) and a total sleep deprivation (TSD) day beginning on D1 at 23:00 until D2 at 21:00. Subjects performed the psychomotor vigilance test (PVT) assessing sustained attention, followed by the executive Go-NoGo inhibition task and the 2-NBack working memory task at 09:15 on D1 and D2. Results: We showed differential contributions of TSD and TOT on deficits in sustained attention and both executive processes. An alleviating effect of caffeine intake is only observed on sustained attention deficits related to TSD and not at all on TOT effect. The caffeine dose slows down the triggering of sustained attention deficits related to TOT effect. Discussion: These results suggest that sustained attention deficits induced by TSD rely on the adenosinergic mechanism whereas TOT effect observed for both sustained attention and executive would not.

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).

(1) Background: Caffeine is a psychostimulant that is well known to mitigate the deleterious effects of sleep debt. Our aim was to assess the effects of acute caffeine intake on cognitive vulnerability and brain activity during total sleep deprivation (TSD), taking into account habitual caffeine consumption. (2) Methods: Thirty-seven subjects were evaluated in a double-blind, crossover, total sleep deprivation protocol with caffeine or placebo treatment. Vigilant attention was evaluated every six hours during TSD using the psychomotor vigilance test (PVT) with EEG recordings. The influence of habitual caffeine consumption was analyzed by categorizing subjects into low, moderate, and high consumers. (3) Results: The PVT reaction time (RT) increased during TSD and was lower in the caffeine condition vs. the placebo condition. The RT was shorter in the low-caffeine consumers compared to moderate and high consumers, regardless of conditions and treatments. The TSD-related increase in EEG power was attenuated by acute caffeine intake independently of habitual caffeine consumption, and the individual alpha frequency (IAF) was lower in the high-consumption group. The IAF was negatively correlated with daytime sleepiness. Moreover, a correlation analysis showed that the higher the daily caffeine consumption, the higher the RT and the lower the IAF. (4) Conclusions: A high level of habitual caffeine consumption decreases attentional performance and alpha frequencies, decreasing tolerance to sleep deprivation.