Glycaemic Effects of a 156-km Ultra-trail Race in Athletes: An Observational Field Study.

BACKGROUND: Ultra-trail running races pose appreciable physiological challenges, particularly for glucose metabolism. Previous studies that yielded divergent results only measured glycaemia at isolated times. OBJECTIVES: We aimed to explore the impact of an ultra-endurance race on continuously measured glycaemia and to understand potential physiological mechanisms, as well as the consequences for performance and behavioural alertness. METHODS: Fifty-five athletes (78% men, 43.7 ± 9.6 years) ran a 156-km ultra-trail race (six 26-km laps, total elevation 6000 m). Participants wore a masked continuous glucose monitoring sensor from the day before the race until 10 days post-race. Blood was taken at rest, during refuelling stops after each lap, and after 24-h recovery. Running intensity (% heart rate reserve), performance (lap times), psychological stress, and behavioural alertness were explored. Linear mixed models and logistic regressions were carried out. RESULTS: No higher risk of hypo- or hyperglycaemia was observed during the exercise phases of the race (i.e. excluding stops for scientific measurements and refuelling) compared with resting values. Laps comprising a greater proportion of time spent at maximal aerobic intensity were nevertheless associated with more time > 180 mg/dL (P = 0.021). A major risk of hyperglycaemia appeared during the 48-h post-race period compared with pre-race (P < 0.05), with 31.9% of the participants spending time with values > 180 mg/dL during recovery versus 5.5% during resting. Changes in circulating insulin, cortisol, and free fatty acids followed profiles comparable with those usually observed during traditional aerobic exercise. However, creatine phosphokinase, and to a lesser extent lactate dehydrogenase, increased exponentially during the race (P < 0.001) and remained high at 24-h post-race (P < 0.001; respectively 43.6 and 1.8 times higher vs. resting). Glycaemic metrics did not influence physical performance or behavioural alertness. CONCLUSION: Ultra-endurance athletes were exposed to hyperglycaemia during the 48-h post-race period, possibly linked to muscle damage and inflammation. Strategies to mitigate muscle damage or subsequent inflammation before or after ultra-trail races could limit recovery hyperglycaemia and hence its related adverse health consequences. TRIAL REGISTRATION NUMBER: NCT05538442 2022-09-21 retrospectively registered.

Ultradian sleep cycles: Frequency, duration, and associations with individual and environmental factors-A retrospective study.

OBJECTIVE: Sleep varies between individuals in response to sleep-wake history and various environmental factors, including light and noise. Here we report on the intranight variation of the ultradian nonrapid eye movement-rapid eye movement (NREM-REM) sleep cycle in 369 participants who have contributed to different laboratory studies from 1994 to 2020 at the Centre for Chronobiology, Basel, Switzerland. RESULTS: We observed a large interindividual variability in sleep cycle duration, including NREM and REM sleep episodes in healthy participants who were given an 8-hour sleep opportunity at habitual bedtime in controlled laboratory settings. The median sleep cycle duration was 96 minutes out of 6064 polysomnographically-recorded cycles. The number and duration of cycles were not normally distributed, and the distribution became narrower for NREM sleep and wider for REM sleep later in the night. The first cycle was consistently shorter than subsequent cycles, and moderate presleep light or nocturnal noise exposure had no significant effects on ultradian sleep cycle duration. Age and sex significantly affected NREM and REM sleep duration, with older individuals having longer NREM and shorter REM sleep particularly in the end of the night, and females having longer NREM sleep episodes. High sleep pressure (ie, sleep deprivation) and low sleep pressure (ie, multiple naps) altered ultradian sleep cycles, with high sleep pressure leading to longer NREM sleep in the first cycle, and low sleep pressure leading to longer REM sleep episodes. Positive correlations were observed between N2 and NREM duration, and between N1 and REM duration. Weak intrasleep REM sleep homeostasis was also evident in our data set. CONCLUSIONS: We conclude that ultradian sleep cycles are endogenous biological rhythms modulated by age, sex, and sleep homeostasis, but not directly responsive to (moderate levels of) environmental cues in healthy good sleepers.

Circadian and homeostatic sleep-wake regulation of secretory immunoglobulin A (sIgA): Effects of environmental light and recovery sleep.

Secretory Immunoglobulin A (sIgA) builds the first line of the human immune defense. It is not clear whether the power of this defence line is constant across the 24-h day, depends on sleep pressure levels and can be influenced by external lighting conditions. Thus, in 10 healthy young volunteers, we retrospectively analyzed saliva samples for sIgA levels under strictly controlled laboratory conditions across 40 â€‹h of extended wakefulness under two lighting conditions (dim light 8 lx and blue-enriched light 250 lx, 9000 â€‹K) to test for circadian and homeostatic sleep-wake influences. We compared the temporal profile of sIgA with the circadian time course of melatonin and cortisol along with subjective sleepiness levels, assessed in the same study by Gabel et al. (2017). The 40-h time course of sIgA exhibited a clear circadian modulation with peak values in the mornings coinciding with the individuals' habitual rise-time. In addition, sIgA levels progressively increased throughout the 40 â€‹h of extended wakefulness and were temporally correlated with subjective sleepiness but not with subjective ratings of tension and discomfort. In contrast to the circadian profile of melatonin and cortisol, sIgA levels were not significantly altered by the lighting conditions. Unexpectedly, sIgA levels in the morning after recovery sleep from 40 â€‹h of extended wakefulness rose considerably by more than an order of magnitude (10 times more) compared to morning levels after baseline sleep. We have evidence that diurnal sIgA levels in humans are regulated by the circadian timing system, and challenging the status of the sleep-wake homeostat (i.e. extended wakefulness) boosts human sIgA levels. Thus, besides a person's circadian phase position, the first line of human immune defense also strongly depends on the person's sleep-wake history and actual sleepiness levels. In sum, the fight against pathogenic microorganisms by a key immunological component (sIgA) is modulated by two fundamental processes implicated in human sleep-wake regulation.

Effect of artificial dawn light on cardiovascular function, alertness, and balance in middle-aged and older adults.

STUDY OBJECTIVES: When arising in the morning, many older people experience dizziness and difficulty maintaining proper balance, as the cardiovascular system is not able to compensate to the postural shift (standing) and maintain sufficient blood flow to the brain. Such changes in cardiovascular function are observed in young individuals exposed to a dawn simulation light. In this study, we examined whether exposure to a dawn simulation light could impact cardiovascular function and consequent changes in balance in middle-aged and older adults. METHODS: Twenty-three participants (67.3 ± 8.8 y), 12 of whom reported a history of dizziness in the morning, underwent two overnight stays in our laboratory. During both nights, they slept in complete darkness, except for the last 30 minutes of one of the nights during which a dawn simulation light was used. Continuous blood pressure (BP) and heart rate (HR) were monitored. Subjective and objective alertness, salivary cortisol, and mobile and standing balance were examined upon arising. RESULTS: Dawn simulation light decreased (33%) the amount of sleep before morning awakening, lowered BP (6.24 mmHg), and increased HR (0.93 bpm). Despite these changes in physiology, there was no significant impact of dawn simulation on subjective or objective alertness, measures of standing or ambulatory balance, morning cortisol awakening response, or cardiovascular function after awakening. CONCLUSION: While the dawn simulation did cause an increase in wake and a change in cardiovascular function prior to morning arousal in older adults, we could find no evidence of a functional change in either cardiovascular function or balance upon standing. CLINICAL TRIAL: Registered on Clinicaltrials.gov, #NCT02632318, https://clinicaltrials.gov/ct2/show/NCT02632318.

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.

Auditory psychomotor vigilance testing in older and young adults: a revised threshold setting procedure.

BACKGROUND: One of the most common ways to examine the daytime impact of sleep loss is the use of the psychomotor vigilance test (PVT). PVT metrics, including median reaction time (RT) and number of lapses, have been examined in a variety of studies in which both acute and chronic sleep times are manipulated. Most of these studies involve young, healthy individuals and use a visual stimulus. As light is a possible countermeasure to sleep loss, and sometimes incompatible with the use of visual PVT, PVT with auditory cues (aPVT) has been used. A threshold of 400 ms is commonly used to delineate lapses from normal RT in the aPVT. As aging can influence a variety of brain functions, we wanted to examine whether this lapse threshold was accurate for use in older adults. METHODS: Twenty-eight young and 19 healthy older participants performed a 10-min auditory PVT approximately 90 min before habitual bedtime. The occurrence of lapses was determined by five objective RT thresholds: (1) 400 ms, (2) 500 ms, (3) 2 × median, (4) mean + 2 × SD, and (5) method 4 without outliers. Results of these methods were compared with a triplicate visual inspection of RT histograms to determine RT outside of the expected log normal distribution. RESULTS: In both groups, methods 1, 4, and 5 performed poorly, while methods 2 and 3 were adequate, though method 3 was statistically superior. CONCLUSION: In both age groups, the use of twice the median as an objective threshold had the best concurrence with visual scoring.

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.

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.

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.

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.

The circadian regulation of sleep: impact of a functional ADA-polymorphism and its association to working memory improvements.

Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG) was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers), previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM) sleep and slow wave sleep concomitant with reduced power between 8-16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is linked to working memory independent of the timing of the sleep episode within the 24-h cycle.

Light modulation of human sleep depends on a polymorphism in the clock gene Period3.

Non-image-forming (NIF) responses to light powerfully modulate human physiology. However, it remains scarcely understood how NIF responses to light modulate human sleep and its EEG hallmarks, and if there are differences across individuals. Here we investigated NIF responses to light on sleep in individuals genotyped for the PERIOD3 (PER3) variable-number tandem-repeat (VNTR) polymorphism. Eighteen healthy young men (20-28 years; mean ± SEM: 25.9 ± 1.2) homozygous for the PER3 polymorphism were matched by age, body-mass index, and ethnicity. The study protocol comprised a balanced cross-over design during the winter, during which participants were exposed to either light of 40 lx at 6,500 K (blue-enriched) or light at 2,500 K (non-blue enriched), during 2h in the evening. Compared to light at 2,500 K, light at 6,500 K induced a significant increase in all-night NREM sleep slow-wave activity (SWA: 1.0-4.5 Hz) in the occipital cortex for PER3(5/5) individuals, but not for PER3(4/4) volunteers. Dynamics of SWA across sleep cycles revealed increased occipital NREM sleep SWA for virtually all sleep episode only for PER3(5/5) individuals. Furthermore, they experienced light at 6,500 K as significantly brighter. Intriguingly, this subjective perception of brightness significantly predicted their increased occipital SWA throughout the sleep episode. Our data indicate that humans homozygous for the PER3(5/5) allele are more sensitive to NIF light effects, as indexed by specific changes in sleep EEG activity. Ultimately, individual differences in NIF light responses on sleep may depend on a clock gene polymorphism involved in sleep-wake regulation.

Insights into behavioral vulnerability to differential sleep pressure and circadian phase from a functional ADA polymorphism.

Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss-related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was no longer present when sleep pressure was reduced by the application of multiple naps. Concomitantly, well-being was worse in the G/A genotype under sleep loss when compared to the nap protocol, and n-back working memory performance appeared to be specifically susceptible to sleep-wake manipulation in this genotype. When considering psychomotor vigilance performance, however, a higher sensitivity to sleep-wake manipulation was detected in homozygous participants, but specifically at the end of the night and only for optimal task performance. Although these data are based on a small sample size and hence require replication (12 G/A- and 12 G/G-allele carriers), they confirm the assumption that interindividual differences regarding the effect of sleep manipulation highly depend on the cognitive task and circadian phase, and thus emphasize the necessity of a multimethodological approach. Moreover, they indicate that napping might be suitable to counteract endogenously heightened sleep pressure depending on the neurobehavioral domain.

Time-on-task decrement in vigilance is modulated by inter-individual vulnerability to homeostatic sleep pressure manipulation.

Under sleep loss, vigilance is reduced and attentional failures emerge progressively. It becomes difficult to maintain stable performance over time, leading to growing performance variability (i.e., state instability) in an individual and among subjects. Task duration plays a major role in the maintenance of stable vigilance levels, such that the longer the task, the more likely state instability will be observed. Vulnerability to sleep-loss-dependent performance decrements is highly individual and is also modulated by a polymorphism in the human clock gene PERIOD3 (PER3). By combining two different protocols, we manipulated sleep-wake history by once extending wakefulness for 40 h (high sleep pressure condition) and once by imposing a short sleep-wake cycle by alternating 160 min of wakefulness and 80 min naps (low sleep pressure condition) in a within-subject design. We observed that homozygous carriers of the long repeat allele of PER3 (PER3 (5/5) ) experienced a greater time-on-task dependent performance decrement (i.e., a steeper increase in the number of lapses) in the Psychomotor Vigilance Task compared to the carriers of the short repeat allele (PER3 (4/4) ). These genotype-dependent effects disappeared under low sleep pressure conditions, and neither motivation, nor perceived effort accounted for these differences. Our data thus suggest that greater sleep-loss related attentional vulnerability based on the PER3 polymorphism is mirrored by a greater state instability under extended wakefulness in the short compared to the long allele carriers. Our results undermine the importance of time-on-task related aspects when investigating inter-individual differences in sleep loss-induced behavioral vulnerability.

Effects of artificial dawn and morning blue light on daytime cognitive performance, well-being, cortisol and melatonin levels.

Light exposure elicits numerous effects on human physiology and behavior, such as better cognitive performance and mood. Here we investigated the role of morning light exposure as a countermeasure for impaired cognitive performance and mood under sleep restriction (SR). Seventeen participants took part of a 48h laboratory protocol, during which three different light settings (separated by 2 wks) were administered each morning after two 6-h sleep restriction nights: a blue monochromatic LED (light-emitting diode) light condition (BL; 100 lux at 470 nm for 20 min) starting 2 h after scheduled wake-up time, a dawn-simulating light (DsL) starting 30 min before and ending 20 min after scheduled wake-up time (polychromatic light gradually increasing from 0 to 250 lux), and a dim light (DL) condition for 2 h beginning upon scheduled wake time (<8 lux). Cognitive tasks were performed every 2 h during scheduled wakefulness, and questionnaires were administered hourly to assess subjective sleepiness, mood, and well-being. Salivary melatonin and cortisol were collected throughout scheduled wakefulness in regular intervals, and the effects on melatonin were measured after only one light pulse. Following the first SR, analysis of the time course of cognitive performance during scheduled wakefulness indicated a decrease following DL, whereas it remained stable following BL and significantly improved after DsL. Cognitive performance levels during the second day after SR were not significantly affected by the different light conditions. However, after both SR nights, mood and well-being were significantly enhanced after exposure to morning DsL compared with DL and BL. Melatonin onset occurred earlier after morning BL exposure, than after morning DsL and DL, whereas salivary cortisol levels were higher at wake-up time after DsL compared with BL and DL. Our data indicate that exposure to an artificial morning dawn simulation light improves subjective well-being, mood, and cognitive performance, as compared with DL and BL, with minimal impact on circadian phase. Thus, DsL may provide an effective strategy for enhancing cognitive performance, well-being, and mood under mild sleep restriction.

Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3.

CONTEXT: Light exposure, particularly at the short-wavelength range, triggers several nonvisual responses in humans. However, the extent to which the melatonin-suppressing and alerting effect of light differs among individuals remains unknown. OBJECTIVE: Here we investigated whether blue-enriched polychromatic light impacts differentially on melatonin and subjective and objective alertness in healthy participants genotyped for the PERIOD3 (PER3) variable-number, tandem-repeat polymorphism. DESIGN, SETTING, AND PARTICIPANTS: Eighteen healthy young men homozygous for the PER3 polymorphism (PER3(5/5)and PER3(4/4)) underwent a balanced crossover design during the winter season, with light exposure to compact fluorescent lamps of 40 lux at 6500 K and at 2500 K during 2 h in the evening. RESULTS: In comparison to light at 2500 K, blue-enriched light at 6500 K induced a significant suppression of the evening rise in endogenous melatonin levels in PER3(5/5) individuals but not in PER3(4/4). Likewise, PER3(5/5) individuals exhibited a more pronounced alerting response to light at 6500 K than PER3(4/4) volunteers. Waking electroencephalographic activity in the theta range (5-7 Hz), a putative correlate of sleepiness, was drastically attenuated during light exposure at 6500 K in PER3(5/5) individuals as compared with PER3(4/4). CONCLUSIONS: We provide first evidence that humans homozygous for the PER3 5/5 allele are particularly sensitive to blue-enriched light, as indexed by the suppression of endogenous melatonin and waking theta activity. Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in the sleep-wake regulation.