Fighting Sleep at Night: Brain Correlates and Vulnerability to Sleep Loss.

OBJECTIVE: Even though wakefulness at night leads to profound performance deterioration and is regularly experienced by shift workers, its cerebral correlates remain virtually unexplored. METHODS: We assessed brain activity in young healthy adults during a vigilant attention task under high and low sleep pressure during night-time, coinciding with strongest circadian sleep drive. We examined sleep-loss-related attentional vulnerability by considering a PERIOD3 polymorphism presumably impacting on sleep homeostasis. RESULTS: Our results link higher sleep-loss-related attentional vulnerability to cortical and subcortical deactivation patterns during slow reaction times (i.e., suboptimal vigilant attention). Concomitantly, thalamic regions were progressively less recruited with time-on-task and functionally less connected to task-related and arousal-promoting brain regions in those volunteers showing higher attentional instability in their behavior. The data further suggest that the latter is linked to shifts into a task-inactive default-mode network in between task-relevant stimulus occurrence. INTERPRETATION: We provide a multifaceted view on cerebral correlates of sleep loss at night and propose that genetic predisposition entails differential cerebral coping mechanisms, potentially compromising adequate performance during night work.

The human circadian metabolome.

The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest-activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ~15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.

Somno-Art Software identifies pathology-induced changes in sleep parameters similarly to polysomnography.

Polysomnographic sleep architecture parameters are commonly used to diagnose or evaluate treatment of sleep disorders. Polysomnography (PSG) having practical constraints, the development of wearable devices and algorithms to monitor and stage sleep is rising. Beside pure validation studies, it is necessary for a clinician to ensure that the conclusions drawn with a new generation wearable sleep scoring device are consistent to the ones of gold standard PSG, leading to similar interpretation and diagnosis. This paper reports on the performance of Somno-Art Software for the detection of differences in sleep parameters between patients suffering from obstructive sleep apnea (OSA), insomniac or major depressive disorder (MDD) compared to healthy subjects. On 244 subjects (n = 26 healthy, n = 28 OSA, n = 66 insomniacs, n = 124 MDD), sleep staging was obtained from PSG and Somno-Art analysis on synchronized electrocardiogram and actimetry signals. Mixed model analysis of variance was performed for each sleep parameter. Possible differences in sleep parameters were further assessed with Mann-Whitney U-test between the healthy subjects and each pathology group. All sleep parameters, except N1+N2, showed significant differences between the healthy and the pathology group. No significant differences were observed between Somno-Art Software and PSG, except a 3.6±2.2 min overestimation of REM sleep. No significant interaction 'group'*'technology' was observed, suggesting that the differences in pathologies are independent of the technology used. Overall, comparable differences between healthy subjects and pathology groups were observed when using Somno-Art Software or polysomnography. Somno-Art proposes an interesting valid tool as an aid for diagnosis and treatment follow-up in ambulatory settings.

Performance of Somno-Art Software compared to polysomnography interscorer variability: A multi-center study.

The visual scoring of gold standard polysomnography (PSG) is known to present inter- and intra-scorer variability. Previously, Somno-Art Software, a cardiac based sleep scoring algorithm, has been validated in comparison to 2 expert visual PSG scorers. The goal of this research is to evaluate the performances of the algorithm against a pool of scorers. Sixty PSG and actimetry recording nights, representative of clinical practice (healthy subjects and patients suffering from obstructive sleep apnea [OSA], insomnia or major depressive disorder), were scored by 5 different sleep scoring centers and by the Somno-Art Software. Intra-class correlation coefficient (ICC) and Wilcoxon Signed-Rank Test were calculated between each scorer and the average value of the 6 scorers, including Somno-Art Software. In addition, epoch-by-epoch agreement between scorers were analyzed. Somno-Art Software estimation of sleep efficiency, wake, N1+N2, N3 and REM sleep fit within the interscorer range for the full dataset and the subgroups, except for underestimating N3 sleep in OSA patients. Additionally, Somno-Art Software overestimated sleep latency compared to the average scoring for insomniacs (+4.7 ± 1.6min). On the full dataset, Somno-Art Software had good (0.75 < ICC<0.90) or excellent (ICC>0.90) ICC scores for all sleep parameters except N3 sleep (moderate score, 0.50 < ICC<0.75). For the 4-stages epoch-by-epoch agreement, Somno-Art Software was slightly below that of the visual scorers except for the healthy sub-group where an overlap was demonstrated. Somno-Art Software sleep scoring shows a good interscorer reliability in the range of the 5 visual polysomnography scorers.

Validation of Somno-Art Software, a novel approach of sleep staging, compared with polysomnography in disturbed sleep profiles.

Study Objectives: Integrated analysis of heart rate (electrocardiogram [ECG]) and body movements (actimetry) during sleep in healthy subjects have previously been shown to generate similar evaluation of sleep architecture and continuity with Somno-Art Software compared to polysomnography (PSG), the gold standard. However, the performance of this new approach of sleep staging has not yet been evaluated on patients with disturbed sleep. Methods: Sleep staging from 458 sleep recordings from multiple studies comprising healthy and patient population (obstructive sleep apnea [OSA], insomnia, major depressive disorder [MDD]) was obtained from PSG visual scoring using the American Academy of Sleep Medicine rules and from Somno-Art Software analysis on synchronized ECG and actimetry. Results: Inter-rater reliability (IRR), evaluated with 95% absolute agreement intra-class correlation coefficient, was rated as "excellent" (ICCAAAvg95% ≥ 0.75) or "good" (ICCAAAvg95% ≥ 0.60) for all sleep parameters assessed, except non-REM (NREM) and N3 sleep in healthy participants (ICCAAAvg95% = 0.43, ICCAAAvg95% = 0.56) and N3 sleep in OSA patients (ICCAAAvg95% = 0.59) rated as "fair" IRR. Overall sensitivity, specificity, accuracy, and Cohen's kappa coefficient of agreement (κ) on the entire sample were respectively of 93.3%, 69.5%, 87.8%, and 0.65 for wake/sleep classification and accuracy and κ were of 68.5% and 0.55 for W/N1+N2/N3/rapid eye movement (REM) classification. These performances were similar in healthy and patient population. Conclusions: The present results suggest that Somno-Art can be a valid sleep-staging tool in both healthy subjects and patients with OSA, insomnia, or MDD. It could complement existing non-attended techniques measuring sleep-related breathing patterns or be a useful alternative to laboratory-based PSG when this latter is not available.

PER3 polymorphism predicts sleep structure and waking performance.

Circadian rhythmicity and sleep homeostasis interact to regulate sleep-wake cycles [1-4], but the genetic basis of individual differences in sleep-wake regulation remains largely unknown [5]. PERIOD genes are thought to contribute to individual differences in sleep timing by affecting circadian rhythmicity [6], but not sleep homeostasis [7, 8]. We quantified the contribution of a variable-number tandem-repeat polymorphism in the coding region of the circadian clock gene PERIOD3 (PER3) [9, 10] to sleep-wake regulation in a prospective study, in which 24 healthy participants were selected only on the basis of their PER3 genotype. Homozygosity for the longer allele (PER3(5/5)) had a considerable effect on sleep structure, including several markers of sleep homeostasis: slow-wave sleep (SWS) and electroencephalogram (EEG) slow-wave activity in non-rapid eye movement (non-REM) sleep and theta and alpha activity during wakefulness and REM sleep were all increased in PER3(5/5) compared to PER3(4/4) individuals. In addition, the decrement of cognitive performance in response to sleep loss was significantly greater in the PER3(5/5) individuals. By contrast, the circadian rhythms of melatonin, cortisol, and peripheral PER3 mRNA expression were not affected. The data show that this polymorphism in PER3 predicts individual differences in the sleep-loss-induced decrement in performance and that this differential susceptibility may be mediated by its effects on sleep homeostasis.

Author Correction: Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evidence That Homeostatic Sleep Regulation Depends on Ambient Lighting Conditions during Wakefulness.

We examined whether ambient lighting conditions during extended wakefulness modulate the homeostatic response to sleep loss as indexed by. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA) in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e., sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800 K), and once under either white light (WL: 250 lux, 2800 K) or blue-enriched white light (BL: 250 lux, 9000 K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.

Light therapy with boxes or glasses to counteract effects of acute sleep deprivation.

Sleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition. Individuals were randomly exposed to 10,000 Lux light box, 2,000 Lux LED blue-enriched glasses, and control (ambient dim-light at 8 lux). Alertness, cognition and mood were assessed throughout the night and following morning. Five women and 13 men (mean 24.78 year old) presented with a progressive and increasing alteration of alertness, cognition, and mood during each sleep deprivation. A rebound was observed at 8 am resulting from the circadian drive overriding cumulative sleep homeostatic effects. Morning light significantly improved sleepiness and sustained attention from 5 to 7 am. These effects were comparable between devices and significantly different from control. Both devices were overall well and similarly tolerated. Early morning light therapy in the condition of sleep loss may have broad practical applications to improve sleepiness, sustained attention and subsequent risk of accidents.

Early morning executive functioning during sleep deprivation is compromised by a PERIOD3 polymorphism.

STUDY OBJECTIVES: To contrast the effects of total sleep deprivation (TSD) on executive and non-executive function in volunteers homozygous for either the short or long variant of a variable number tandem repeat polymorphism in PERIODS, which is a genetic marker for susceptibility to the negative effect of sleep loss on waking performance. DESIGN: Following two laboratory nights of baseline sleep, both groups underwent an approximately 40-hour constant routine, performing brief tests of executive, memory, attention, and motor function every 2 hours. SETTING: Clinical Research Centre. PARTICIPANTS: Fourteen PER3(4/4) (homozygotes for shorter variant of the gene) and 10 PER3(5/5) (homozygotes for longer variant) healthy, young adults (mean 25.0 +/- 1.0 years). INTERVENTIONS: Total sleep deprivation (approximately 40 hours) following baseline sleep. MEASUREMENTS AND RESULTS: Hormonal assays established that melatonin levels, which reflect circadian phase, reached their midpoint around 04:00 in both genotypes. Cognitive performance deteriorated across the night, and was similar for both genotypes throughout, except 2-4 h after the midpoint of the melatonin rhythm. Only at this time-point and only on tests of executive function (e.g., 3-back, paced visual serial addition task) did PER3(5/5) participants perform reliably worse. Covariance analyses controlling for genotype dependent differences in homeostatic sleep pressure derived from principal component analysis of baseline sleep latency, slow wave sleep and wake after sleep onset largely removed these early morning differences in executive function. CONCLUSIONS: This PER3 polymorphism differentially influences the effects of sleep deprivation on executive and non-executive function in the early morning. These effects appear to be mediated through homeostatic sleep pressure.

Inter-individual differences in habitual sleep timing and entrained phase of endogenous circadian rhythms of BMAL1, PER2 and PER3 mRNA in human leukocytes.

STUDY OBJECTIVES: Individual sleep timing differs and is governed partly by circadian oscillators, which may be assessed by hormonal markers, or by clock gene expression. Clock gene expression oscillates in peripheral tissues, including leukocytes. The study objective was to determine whether the endogenous phase of these rhythms, assessed in the absence of the sleep-wake and light-dark cycle, correlates with habitual sleep-wake timing. DESIGN: Observational, cross-sectional. SETTING: Home environment and Clinical Research Center. PARTICIPANTS: 24 healthy subjects aged 25.0 +/- 3.5 (SD) years. MEASUREMENTS: Actigraphy and sleep diaries were used to characterize sleep timing. Circadian rhythm phase and amplitude of plasma melatonin, cortisol, and BMAL1, PER2, and PER3 expression were assessed during a constant routine. RESULTS: Circadian oscillations were more robust for PER3 than for BMAL1 or PER2. Average peak timings were 6:05 for PER3, 8:06 for PER2, 15:06 for BMAL1, 4:20 for melatonin, and 10:49 for cortisol. Individual sleep-wake timing correlated with the phases of melatonin and cortisol. Individual PER3 rhythms correlated significantly with sleep-wake timing and the timing of melatonin and cortisol, but those of PER2 and BMAL1 did not reach significance. The correlation between sleep timing and PER3 expression was stronger in individuals homozygous for the variant of the PER3 polymorphism that is associated with morningness. CONCLUSIONS: Individual phase differences in PER3 expression during a constant routine correlate with sleep timing during entrainment. PER3 expression in leukocytes represents a useful molecular marker of the circadian processes governing sleep-wake timing.

Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality.

OBJECTIVES: Specifications and standards for lighting installations in occupational settings are based on the spectral sensitivity of the classical visual system and do not take into account the recently discovered melanopsin-based, blue-light-sensitive photoreceptive system. The authors investigated the effects of exposure to blue-enriched white light during daytime workhours in an office setting. METHODS: The experiment was conducted on 104 white-collar workers on two office floors. After baseline assessments under existing lighting conditions, every participant was exposed to two new lighting conditions, each lasting 4 weeks. One consisted of blue-enriched white light (17 000 K) and the other of white light (4000 K). The order was balanced between the floors. Questionnaire and rating scales were used to assess alertness, mood, sleep quality, performance, mental effort, headache and eye strain, and mood throughout the 8-week intervention. RESULTS: Altogether 94 participants [mean age 36.4 (SD 10.2) years] were included in the analysis. Compared with white light (4000 K), blue-enriched white light (17 000 K) improved the subjective measures of alertness (P<0.0001), positive mood (P=0.0001), performance (P<0.0001), evening fatigue (P=0.0001), irritability (P=0.004), concentration (P<0.0001), and eye discomfort (P=0.002). Daytime sleepiness was reduced (P=0.0001), and the quality of subjective nocturnal sleep (P=0.016) was improved under blue-enriched white light. When the participants' expectation about the effect of the light treatments was entered into the analysis as a covariate, significant effects persisted for performance, alertness, evening fatigue, irritability, difficulty focusing, concentrating, and blurred vision. CONCLUSIONS: Exposure to blue-enriched white light during daytime workhours improves subjective alertness, performance, and evening fatigue.

Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement.

Sleepiness and cognitive function vary over the 24-h day due to circadian and sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks associated with these variations remain to be fully established. Using functional magnetic resonance imaging (fMRI), we investigated brain responses associated with circadian and homeostatic sleep-wake-driven dynamics of subjective sleepiness throughout day and night. Healthy volunteers regularly performed a psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep pressure). When sleep deprived, arousal-promoting thalamic activation during optimal PVT performance paralleled the time course of subjective sleepiness with peaks at night and troughs on the subsequent day. Conversely, task-related cortical activation decreased when sleepiness increased as a consequence of higher sleep debt. Under low sleep pressure, we did not observe any significant temporal association between PVT-related brain activation and subjective sleepiness. Thus, a circadian modulation in brain correlates of vigilant attention was only detectable under high sleep pressure conditions. Our data indicate that circadian and sleep homeostatic processes impact on vigilant attention via specific mechanisms; mirrored in a decline of cortical resources under high sleep pressure, opposed by a subcortical "rescuing" at adverse circadian times.

Differential impact in young and older individuals of blue-enriched white light on circadian physiology and alertness during sustained wakefulness.

We tested the effect of different lights as a countermeasure against sleep-loss decrements in alertness, melatonin and cortisol profile, skin temperature and wrist motor activity in healthy young and older volunteers under extendend wakefulness. 26 young [mean (SE): 25.0 (0.6) y)] and 12 older participants [(mean (SE): 63.6 (1.3) y)] underwent 40-h of sustained wakefulness during 3 balanced crossover segments, once under dim light (DL: 8 lx), and once under either white light (WL: 250 lx, 2,800 K) or blue-enriched white light (BL: 250 lx, 9,000 K) exposure. Subjective sleepiness, melatonin and cortisol were assessed hourly. Skin temperature and wrist motor activity were continuously recorded. WL and BL induced an alerting response in both the older (p = 0.005) and the young participants (p = 0.021). The evening rise in melatonin was attentuated under both WL and BL only in the young. Cortisol levels were increased and activity levels decreased in the older compared to the young only under BL (p = 0.0003). Compared to the young, both proximal and distal skin temperatures were lower in older participants under all lighting conditions. Thus the color temperature of normal intensity lighting may have differential effects on circadian physiology in young and older individuals.

Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations.

The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.

Assessing sleep architecture and continuity measures through the analysis of heart rate and wrist movement recordings in healthy subjects: comparison with results based on polysomnography.

OBJECTIVE: The objective of the study was to evaluate the reliability of a new methodology for assessing sleep architecture descriptors based on heart rate and body movement recordings. METHODS: Twelve healthy male and female subjects between 18 and 40 years of age, without sleep disorders and not taking any drug or medication that could affect sleep, were recorded continuously during five consecutive nights. Together with the standard polysomnography, heart rate was recorded with a Holter and wrist movements by actimetry. Of the 60 recorded nights, 48 artifact-free nights were analyzed by two independent and well-trained visual scorers according to the rules of the American Academy of Sleep Medicine. Sleep stages were assigned to every 30-s epoch. In parallel, the same nights were analyzed by the new methodology using only heart rate and actimetry data, allowing a 1-s epoch sleep stage classification. Sleep architecture was measured for 48 nights, independently for the two manual scorings and the automatic analysis. RESULTS: Over 42 nights, the intra-class correlation coefficient, used to assess the consistency or reproducibility of quantitative measurements made by different observers, was classified as excellent when all 12 descriptors were combined. Analyses of the individual descriptors showed excellent interclass correlation for eight and good for four of the 12. CONCLUSION: The automatic analysis of heart rate and body movement during sleep allows for the evaluation of sleep architecture and continuity that is equivalent to those obtained by manual scoring of polysomnography. The technique used here is simple and robust to allow for home sleep monitoring.

L-arginine: an ultradian-regulated substrate coupled with insulin oscillations in healthy volunteers.

OBJECTIVE: Coupled oscillations of 50-110 min in insulin and glucose have been found previously in healthy men under continuous enteral nutrition. Because L-arginine induces insulin release as glucose does, we tested the hypothesis that L-arginine can also display such an ultradian rhythm. RESEARCH DESIGN AND METHODS: Seven healthy male subjects participated in one experimental night during which blood was sampled every 10 min from 2300 to 0700. Plasma glucose, C-peptide, and L-arginine levels were measured simultaneously. The insulin secretion rate (ISR) was calculated from plasma C-peptide levels by a deconvolution procedure. RESULTS: Plasma glucose followed the recognizable profiles, with oscillations closely linked to similar changes in the ISR. Pulse analysis of L-arginine profiles revealed significant oscillations linked to glucose and ISR oscillations, with the highest cross-correlation coefficients at time lag 0 ranging from 0.380 to 0.680 for glucose and L-arginine and from 0.444 to 0.726 for ISR and L-arginine (P < 0.01). The mean period of L-arginine oscillations was 77.2 +/- 6.2 min, and their mean amplitude was 19.9 +/- 1.7%, similar to that of glucose (17.0 +/- 1.9%), when expressed as the percentage of mean overnight levels. CONCLUSIONS: This newly discovered ultradian rhythm of L-arginine and its coupling with glucose and ISR oscillations sheds new light on the regulation of L-arginine, the substrate of numerous metabolic pathways, including nitric oxide synthesis. These oscillations may be of significance in conditions of hyperinsulinemia or abnormal glucose tolerance.

Sleep processes exert a predominant influence on the 24-h profile of heart rate variability.

Adverse cardiovascular events are known to exhibit 24-h variations with a peak incidence in the morning hours and a nonuniform distribution during the night. The authors examined whether these 24-h variations could be related to circadian or sleep-related changes in heart rate (HR) and in HR variability (HRV). To differentiate the effect of circadian and sleep-related influences, independent of posture and of meal ingestion, seven normal subjects were studied over 24 h, once with nocturnal sleep from 2300 to 0700 h and once after a night of sleep deprivation followed by 8 h of daytime sleep from 0700 to 1500 h. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest). HRV was calculated every 5 min using two indexes: the standard deviation of normal R-R intervals (SDNN) and the ratio of low-frequency to low-frequency plus high-frequency power. Sleep processes exerted a predominant influence on the 24-h profiles of HR and HRV, with lowest HRV levels during slow wave sleep, high levels during REM sleep and intrasleep awakenings, and abrupt increases in HR at each transition from deeper sleep to lighter sleep or awakenings. The circadian influence was smaller, except for SDNN, which displayed a nocturnal increase of 140% whether the subjects slept or not. This study demonstrates that 24-h variations in HR and HRV are little influenced by the circadian clock andare mainly sleep-stage dependent. The results suggest an important role for exogenous factors in the morning increase in cardiovascular events. During sleep, the sudden rises in HR at each transition from deeper sleep to lighter sleep or awakenings might precipitate the adverse cardiac events.

Dawn simulation light: a potential cardiac events protector.

OBJECTIVE/BACKGROUND: Major cardiovascular events frequently increase in the morning due to abrupt changes in the sympatho-vagal cardiac control during the transition from sleep to wakefulness. These neural changes are translated into stepwise increases in cardiac functions, resulting in a potential cardiovascular stress. Here, we explored whether light can "optimize" heart rate and its neural control, by actively promoting a less steep transition from sleep to wakefulness, thus minimizing morning cardiovascular vulnerability. METHODS: Seventeen healthy young men were awakened 2-hours before their habitual wake-time. In a counterbalanced within-subject design, we applied a control condition (darkness during sleep and dim light during wakefulness) or dawn-simulation-light (DSL) starting 30-minutes before and ending 30-minutes after scheduled wake-up time. RESULTS: Our data reveal a significantly gradient reduction in heart rate during the transition from sleep to wakefulness, when applying DSL as compared to a control condition. Likewise, cardiac sympatho-vagal control smoothly increased throughout the 30-min sleep episode preceding scheduled wake-up under DSL and remained stable for the first 30-min of wakefulness. Interestingly, these effects were mostly driven by changes in the parasympathetic cardiac control. CONCLUSIONS: Our data demonstrate for the first time that a non-invasive strategy, as light exposure surrounding the wake-up process, can significantly reduce the deleterious sleep-to-wake evoked cardiac modulation in healthy young men awakened under conditions of increased sleep pressure. A translational approach of this light exposure, which closely resembles natural lighting conditions in the morning, may therefore act as a potential protector for cardiac vulnerability in the critical morning hours.

Dawn simulation light impacts on different cognitive domains under sleep restriction.

Chronic sleep restriction (SR) has deleterious effects on cognitive performance that can be counteracted by light exposure. However, it is still unknown if naturalistic light settings (dawn simulating light) can enhance daytime cognitive performance in a sustainable matter. Seventeen participants were enrolled in a 24-h balanced cross-over study, subsequent to SR (6-h of sleep). Two different light settings were administered each morning: a) dawn simulating light (DsL; polychromatic light gradually increasing from 0 to 250 lx during 30 min before wake-up time, with light around 250 lx for 20 min after wake-up time) and b) control dim light (DL; <8 lx). Cognitive tests were performed every 2 h during scheduled wakefulness and questionnaires were completed hourly to assess subjective mood. The analyses yielded a main effect of "light condition" for the motor tracking task, sustained attention to response task and a working memory task (visual 1 and 3-back task), as well as for the Simple Reaction Time Task, such that participants showed better task performance throughout the day after morning DsL exposure compared to DL. Furthermore, low performers benefited more from the light effects compared to high performers. Conversely, no significant influences from the DsL were found for the Psychomotor Vigilance Task and a contrary effect was observed for the digit symbol substitution test. No light effects were observed for subjective perception of sleepiness, mental effort, concentration and motivation. Our data indicate that short exposure to artificial morning light may significantly enhance cognitive performance in a domain-specific manner under conditions of mild SR.