Caffeine Intake Alters Recovery Sleep after Sleep Deprivation.

BACKGROUND: Caffeine is a well-known psychostimulant reputed to alleviate the deleterious effects of sleep deprivation. Nevertheless, caffeine can alter sleep duration and quality, particularly during recovery sleep. We evaluated the effects of acute caffeine intake on the duration and quality of recovery sleep following total sleep deprivation (TSD), taking into account daily caffeine consumption. METHODS: Forty-one participants performed a double-blind, crossover TSD protocol (38 h of continuous wakefulness) with acute caffeine or placebo. Caffeine (2.5 mg/kg) or placebo was administered twice during continuous wakefulness (last treatment 6.5 h before bedtime for the recovery night). Polysomnographic measurements were recorded using a connected headband. RESULTS: TSD was associated with a rebound in total sleep time (TST) on the recovery night (+110.2 ± 23.2 min, p < 0.001). Caffeine intake decreased this recovery TST (-30.2 ± 8.2 min p = 0.02) and the N3 sleep stage duration (-35.6 ± 23.2 min, p < 0.01). Caffeine intake altered recovery sleep continuity (increased number of long awakenings), stability (higher stage transition frequency), and organization (less time spent in complete sleep cycle) and decreased the delta power spectral density during NREM sleep. On the recovery night, habitual daily caffeine consumption was negatively correlated with TST in caffeine and placebo conditions and positively correlated with wake after sleep onset (WASO) duration and with the frequency of long (>2 min) awakenings in the caffeine condition only. CONCLUSIONS: Acute caffeine intake during TSD affects nighttime recovery sleep, with an interaction with daily consumption. These results may influence advice on caffeine intake for night-shift workers. (NCT03859882).

Cognitive performance during exposure to moderate normobaric hypoxia after sleep restriction: Relationship to physiological and stress biomarkers.

INTRODUCTION: Exposure to moderate levels of simulated hypoxia has subtle cognitive effects relative to ground level, in healthy individuals. However, there are few data on the cognitive consequences of the combination of hypoxia and partial sleep deprivation, which is a classic military or civilian operational context. In this study, we tested the hypothesis that exposure to moderate hypoxia while sleep-restricted impairs several domains of cognition, and we also assessed physiological parameters and salivary concentrations of cortisol and alpha-amylase. METHOD: Seventeen healthy males completed two sessions of cognitive tests (sustained attention using the PVT psychomotor vigilance task and executive functions using the Go-NoGo inhibition task and N-Back working memory task) after 30 min (T + 30') and 4 h (T + 240') of exposure in a normobaric hypoxic tent (FIO2 = 13.6 %, ≃ 3,500 m) (HY). This was completed after one night of sleep restriction (3 a.m. to 6 a.m. bedtime, SRHY) and one night of habitual sleep (10 p.m. to 6 a.m. bedtime, HSHY) (with cross-over randomization). The two nights sleep architecture and physiological parameters (oxygen saturation (SpO2) and heart rate (HR) during T + 30' and T + 240'sessions were analyzed. Salivary cortisol and alpha-amylase (sAA) concentrations were analyzed before hypoxia, after the T + 30' and T + 240' cognitive sessions, and after leaving the hypoxic tent. RESULTS: Sustained attention (RT and number of lapses in the PVT) and executive functions (Go-NoGo and 1-Back and 2-Back parameters, as inhibition and working memory signatures) were impaired in the SRHY condition compared to HSHY. SpO2 and HR were higher after 4 h compared with 30 min of hypoxia in the HSHY condition, while only HR was statistically higher in the SRHY condition. In SRHY, salivary AA concentration was lower and cortisol was higher than in HSHY. A significant increase in sAA concentration is observed after the cognitive session at 4 h of hypoxia exposure compared to that at 30 min, only in the SRHY condition. There are significant positive correlations between reaction time and the corresponding heart rate (a non-invasive marker of physiological stress) for the executive tasks in the two sleep conditions. This was not observed for salivary levels of sAA and cortisol, respective reliable indicators of the sympathoadrenomedullary system and the hypothalamic-pituitary adrenocortical system. CONCLUSION: Exposure to moderate normobaric hypoxia (≃ 3500 m / ≃ 11,500 ft simulated) after a single night of 3-hour sleep impairs cognitive performance after 30 min and 4 h of exposure. The key determinants and/or mechanism(s) responsible for cognitive impairment when exposed to moderate hypoxia with sleep restriction, particularly on the executive function, have yet to be elucidated.

Combined Effects of Moderate Hypoxia and Sleep Restriction on Mental Workload.

Aircraft pilots face a high mental workload (MW) under environmental constraints induced by high altitude and sometimes sleep restriction (SR). Our aim was to assess the combined effects of hypoxia and sleep restriction on cognitive and physiological responses to different MW levels using the Multi-Attribute Test Battery (MATB)-II with an additional auditory Oddball-like task. Seventeen healthy subjects were subjected in random order to three 12-min periods of increased MW level (low, medium, and high): sleep restriction (SR, <3 h of total sleep time (TST)) vs. habitual sleep (HS, >6 h TST), hypoxia (HY, 2 h, FIO2 = 13.6%, ~3500 m vs. normoxia, NO, FIO2 = 21%). Following each MW level, participants completed the NASA-TLX subjective MW scale. Increasing MW decreases performance on the MATB-II Tracking task (p = 0.001, MW difficulty main effect) and increases NASA-TLX (p = 0.001). In the combined HY/SR condition, MATB-II performance was lower, and the NASA-TLX score was higher compared with the NO/HS condition, while no effect of hypoxia alone was observed. In the accuracy of the auditory task, there is a significant interaction between hypoxia and MW difficulty (F(2-176) = 3.14, p = 0.04), with lower values at high MW under hypoxic conditions. Breathing rate, pupil size, and amplitude of pupil dilation response (PDR) to auditory stimuli are associated with increased MW. These parameters are the best predictors of increased MW, independently of physiological constraints. Adding ECG, SpO2, or electrodermal conductance does not improve model performance. In conclusion, hypoxia and sleep restriction have an additive effect on MW. Physiological and electrophysiological responses must be taken into account when designing a MW predictive model and cross-validation.

MATB for assessing different mental workload levels.

Multi-Attribute Task Battery (MATB) is a computerized flight simulator for aviation-related tasks, suitable for non-pilots and available in many versions, including open source. MATB requires the individual or simultaneous execution of 4 sub-tasks: system monitoring (SYSMON), tracking (TRACK), communications (COMM), and resource management (RESMAN). Fully customizable, the design of test duration, number of sub-tasks used, event rates, response times and overlap, create different levels of mental load. MATB can be combined with an additional auditory attention (Oddball) task, or with physiological constraints (i.e., sleep loss, exercise, hypoxia). We aimed to assess the main characteristics of MATB design for assessing the response to different workload levels. We identified and reviewed 19 articles for which the effects of low and high workload were analyzed. Although MATB has shown promise in detecting performance degradation due to increase workload, studies have yielded conflicting or unclear results regarding MATB configurations. Increased event rates, number of sub-tasks (multitasking), and overlap are associated with increased perceived workload score (ex. NASA-TLX), decreased performance (especially tracking), and neurophysiological responses, while no effect of time-on-task is observed. The median duration used for the test is 20 min (range 12-60) with a level duration of 10 min (range 4-15). To assess mental workload, the median number of stimuli is respectively 3 events/min (range 0.6-17.2) for low, and 23.5 events/min (range 9-65) for high workload level. In this review, we give some recommendations for standardization of MATB design, configuration, description and training, in order to improve reproducibility and comparison between studies, a challenge for the future researches, as human-machine interaction and digital influx increase for pilots. We also open the discussion on the possible use of MATB in the context of aeronautical/operational constraints in order to assess the effects combined with changes in mental workload levels. Thus, with appropriate levels of difficulty, MATB can be used as a suitable simulation tool to study the effects of changes on the mental workload of aircraft pilots, during different operational and physiological constraints.

Relationship between Habitual Caffeine Consumption, Attentional Performance, and Individual Alpha Frequency during Total Sleep Deprivation.

(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.

An ecological approach to clinically assess nightmares in military service members with severe PTSD.

BACKGROUND: Trauma-related nightmares (TRNs) are distressing events which contribute to insomnia severity, chronicity and treatment resistance of PTSD. Therefore, recording TRNs is a crucial technical challenge in order to understand their physiopathological patterns and their impact on sleep. However, TRNs are difficult to record during a single night in a sleep laboratory, which, moreover, is likely to be considered by patients as a protective sleep environment that is therefore not representative of home sleep conditions. METHOD: In the present study, we investigate if objective sleep measures acquired at-home using two ambulatory devices is of clinical value by correlating with PTSD patients' complaints about sleep and nightmares. A secondary objective is to relate awakenings associated with TRNs to sleep stages and to provide new insights into the use of electrodermal activity (EDA) as a potential physiological marker of TRNs. Sixty veterans and active-duty service members were assessed by questionnaires and recorded for 5 consecutive nights in their homes. RESULTS: Our approach firstly identified positive correlations between subjective and objective sleep parameters (total sleep time, sleep-onset latency and TRNs frequency). We also developed a method of synchronization between the two ambulatory devices that allowed us to match 200 TRNs (reported by event marker push button) with sleep stages corresponding to 91 nights and 37 patients. Most awakenings associated with TRNs occurred during NREM sleep (65.5% versus 34.5% during REM sleep). Our results also reveal significant differences in the frequency of EDA peaks 10 min before the reported events, with a lower frequency in REM (13.7 peaks) than in NREM (24.8 peaks) awakenings associated with TRNs. This EDA peaks frequency in REM sleep is not statistically different from that in REM sleep preceding awakenings that are not associated with TRNs. CONCLUSION: The development of wearable devices to collect physiological parameters is of interest in clinical practice to improve our knowledge of sleep and trauma-related nightmares in patients with PTSD.

Effects of Caffeine Intake on Cognitive Performance Related to Total Sleep Deprivation and Time on Task: A Randomized Cross-Over Double-Blind Study.

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.

Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms.

Several genetic polymorphisms differentiate between healthy individuals who are more cognitively vulnerable or resistant during total sleep deprivation (TSD). Common metrics of cognitive functioning for classifying vulnerable and resilient individuals include the Psychomotor Vigilance Test (PVT), Go/noGo executive inhibition task, and subjective daytime sleepiness. We evaluated the influence of 14 single-nucleotide polymorphisms (SNPs) on cognitive responses during total sleep deprivation (continuous wakefulness for 38 h) in 47 healthy subjects (age 37.0 ± 1.1 years). SNPs selected after a literature review included SNPs of the adenosine-A2A receptor gene (including the most studied rs5751876), pro-inflammatory cytokines (TNF-α, IL1-ß, IL-6), catechol-O-methyl-transferase (COMT), and PER3. Subjects performed a psychomotor vigilance test (PVT) and a Go/noGo-inhibition task, and completed the Karolinska Sleepiness Scale (KSS) every 6 h during TSD. For PVT lapses (reaction time >500 ms), an interaction between SNP and SDT (p < 0.05) was observed for ADORA2A (rs5751862 and rs2236624) and TNF-α (rs1800629). During TSD, carriers of the A allele for ADORA2A (rs5751862) and TNF-α were significantly more impaired for cognitive responses than their respective ancestral G/G genotypes. Carriers of the ancestral G/G genotype of ADORA2A rs5751862 were found to be very similar to the most resilient subjects for PVT lapses and Go/noGo commission errors. Carriers of the ancestral G/G genotype of COMT were close to the most vulnerable subjects. ADORA2A (rs5751862) was significantly associated with COMT (rs4680) (p = 0.001). In conclusion, we show that genetic polymorphisms in ADORA2A (rs5751862), TNF-α (rs1800629), and COMT (rs4680) are involved in creating profiles of high vulnerability or high resilience to sleep deprivation. (NCT03859882).

Impact of total sleep deprivation and related mood changes on approach-avoidance decisions to threat-related facial displays.

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Determination of the sleep-wake pattern and feasibility of NREM/REM discrimination using the non-invasive piezoelectric system in rats.

The piezoelectric cage-floor sensors have been used to successfully dissect sleep patterns in mice based on signal features related to respiration and body movements. We studied performance of the piezoelectric system to quantify the sleep-wake pattern in the rat over 7 days of recording compared with a visual electroencephalogram/electromyogram scoring, and under two light/dark (LD12:12 and LD16:8) photoperiods leading to change in the 24-hr sleep characteristics (N = 7 per group). The total sleep time (%/24 hr) over the 7 days recording and hourly sleep time over the last 24-hr recording were not statistically different between methods under the two photoperiods. Both methods detected higher total sleep time with the LD16:8 photoperiod compared with LD12:12 (p < .05), and correlated significantly (p < .001) at light and dark periods during each photoperiod. The accuracies for discrimination of sleep-wake patterns between methods were 81.9% and 84.9% for LD12:12 and LD16:8, respectively. In addition, spectral analysis of the respiratory signal given by piezo during all 10-s periods of the corresponding non-rapid eye movement and rapid eye movement sleep periods recorded by electroencephalogram/electromyogram resulted in selection of 36 features that could be inserted in an automated non-rapid eye movement sleep and rapid eye movement sleep classification, with 90% accuracy with the electroencephalogram/electromyogram visual scoring. The piezo system proved to be a reliable non-invasive alternative to electroencephalogram recording to study total sleep time in rat, with feasibility to discriminate between non-rapid eye movement and rapid eye movement sleep stages. This will be interesting in pharmacological or bio-behavioural studies evaluating sleep patterns or the restorative functions of sleep in the body and the brain.

Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882).

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).

Layer 2/3 Pyramidal Neurons Control the Gain of Cortical Output.

Initial anatomical and physiological studies suggested that sensory information relayed from the periphery by the thalamus is serially processed in primary sensory cortical areas. It is thought to propagate from layer 4 (L4) up to L2/3 and down to L5, which constitutes the main output of the cortex. However, more recent experiments point toward the existence of a direct processing of thalamic input by L5 neurons. Therefore, the role of L2/3 neurons in the sensory processing operated by L5 neurons is now highly debated. Using cell type-specific and reversible optogenetic manipulations in the somatosensory cortex of both anesthetized and awake mice, we demonstrate that L2/3 pyramidal neurons play a major role in amplifying sensory-evoked responses in L5 neurons. The amplification effect scales with the velocity of the sensory stimulus, indicating that L2/3 pyramidal neurons implement gain control in deep-layer neurons.