ABSTRACT
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.
Subject(s)
Depressive Disorder, Major , Sleep Apnea, Obstructive , Humans , Polysomnography , Sleep , Sleep Apnea, Obstructive/diagnosis , SoftwareABSTRACT
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.
Subject(s)
Depressive Disorder, Major , Sleep Apnea, Obstructive , Humans , Polysomnography , Reproducibility of Results , Sleep Apnea, Obstructive/diagnosis , Sleep Stages , SoftwareABSTRACT
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.
ABSTRACT
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.
Subject(s)
Circadian Rhythm/physiology , Phototherapy/instrumentation , Sleep Deprivation/therapy , Work Schedule Tolerance/physiology , Adult , Affect/physiology , Attention/physiology , Cognition/physiology , Cross-Over Studies , Eyeglasses , Female , Humans , Male , Phototherapy/methods , Sleep Deprivation/diagnosis , Sleep Deprivation/physiopathology , Treatment Outcome , Wakefulness/physiology , Young AdultABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Attention/physiology , Brain/physiology , Circadian Rhythm/physiology , Sleep/physiology , Adult , Arousal/physiology , Cognition/physiology , Female , Humans , Male , Psychomotor Performance/physiology , Reaction Time/physiology , Sleep Deprivation/physiopathology , Wakefulness/physiology , Young AdultABSTRACT
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.
Subject(s)
Circadian Rhythm/radiation effects , Light , Sleep Deprivation/physiopathology , Sleepiness , Wakefulness/radiation effects , Adult , Age Factors , Aged , Attention/physiology , Attention/radiation effects , Circadian Rhythm/physiology , Cross-Over Studies , Female , Humans , Hydrocortisone/blood , Male , Melatonin/blood , Middle Aged , Motor Activity/physiology , Motor Activity/radiation effects , Skin Temperature/radiation effects , Sleep/physiology , Wakefulness/physiology , Wrist/physiologyABSTRACT
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.
Subject(s)
Circadian Rhythm , Cognition/physiology , Hypothalamus/physiology , Sleep/physiology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Memory, Short-Term , Polysomnography , Young AdultABSTRACT
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.
Subject(s)
Healthy Volunteers , Heart Rate/physiology , Polysomnography/methods , Sleep Stages/physiology , Wrist , Actigraphy/methods , Adult , Electronic Data Processing , Female , Humans , Male , Reproducibility of ResultsABSTRACT
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.
Subject(s)
Arousal/genetics , Attention/physiology , Brain/physiopathology , Circadian Rhythm/genetics , Period Circadian Proteins/genetics , Reaction Time/genetics , Sleep Deprivation/genetics , Adult , Arousal/physiology , Brain Stem/physiopathology , Circadian Rhythm/physiology , Female , Functional Neuroimaging , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/physiopathology , Polymorphism, Genetic , Prefrontal Cortex/physiopathology , Psychomotor Performance/physiology , Reaction Time/physiology , Sleep Deprivation/physiopathology , Sleep Deprivation/psychology , Thalamus/physiopathology , Young AdultABSTRACT
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.
Subject(s)
Arousal/radiation effects , Heart Rate/radiation effects , Light , Adult , Arousal/physiology , Electrocardiography , Heart Rate/physiology , Humans , Hydrocortisone/analysis , Male , Saliva/chemistry , Young AdultABSTRACT
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.
Subject(s)
Cognition/physiology , Light , Memory, Short-Term/physiology , Sleep/physiology , Adult , Affect/physiology , Attention/physiology , Cross-Over Studies , Humans , Male , Psychomotor Performance/physiology , Sleep Stages/physiology , Surveys and Questionnaires , Time Factors , Wakefulness/physiology , Young AdultABSTRACT
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.
Subject(s)
Adenosine Deaminase/genetics , Circadian Rhythm/physiology , Memory, Short-Term/physiology , Sleep, REM/physiology , Adult , Electroencephalography , Female , Genotype , Humans , Male , Polymorphism, Genetic , Wakefulness/physiology , Young AdultABSTRACT
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.
Subject(s)
Light , Period Circadian Proteins/genetics , Sleep/genetics , Adult , Case-Control Studies , Electroencephalography , Homozygote , Humans , Male , Polymorphism, Genetic , Sleep, REM/genetics , Young AdultABSTRACT
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.
Subject(s)
Adenosine Deaminase/genetics , Circadian Rhythm/physiology , Polymorphism, Single Nucleotide , Psychomotor Performance/physiology , Sleep Deprivation/physiopathology , Sleep/physiology , Adult , Analysis of Variance , Cross-Over Studies , Female , Gene Frequency , Genotype , Humans , Male , Melatonin/metabolism , Memory/physiology , Reaction Time/physiology , Saliva/chemistry , Surveys and Questionnaires , Time Factors , Wakefulness/physiology , Young AdultABSTRACT
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.
ABSTRACT
Accumulating evidence suggests that dopamine plays a key role in sleep-wake regulation. Cerebral dopamine levels are regulated primarily by the dopamine transporter (DAT) in the striatum and by catechol-O-methyl-transferase (COMT) in the prefrontal cortex. We hypothesized that the variable-number-tandem-repeat (VNTR) polymorphism in the 3'-untranslated region of the gene encoding DAT (DAT1, SLC6A3; rs28363170) and the Val158Met polymorphism of COMT (rs4680) differently affect actigraphy-derived rest-activity cycles and sleep estimates in healthy adults (65 men; 45 women; age range: 19-35 years). Daytime sleepiness, continuous rest-actigraphy and sleep diary data during roughly 4-weeks were analyzed. Nine-repeat (9R) allele carriers of DAT1 (n = 48) more often reported elevated sleepiness (Epworth sleepiness score ≥10) than 10-repeat (10R) allele homozygotes (n = 62, p < 0.02). Moreover, male 9R allele carriers showed higher wrist activity, whereas this difference was not present in women ("DAT1 genotype" × "gender" interaction: p < 0.005). Rest-activity patterns did not differ among COMT genotypes. Nevertheless, a significant "COMT genotype" × "type of day" (workdays vs. rest days) interaction for sleep duration was observed (p = 0.04). The Val/Val (n = 36) and Met/Met (n = 24) homozygotes habitually prolonged sleep on rest days compared to workdays by more than 30 min, while Val/Met heterozygotes (n = 50) did not significantly extend their sleep (mean difference: 7 min). Moreover, whereas the proportion of women among the genotype groups did not differ, COMT genotype affected body-mass-index (BMI), such that Val/Met individuals had lower BMI than the homozygous genotypes (p < 0.04). While awaiting independent replication and confirmation, our data support an association of genetically-determined differences in cerebral dopaminergic neurotransmission with daytime sleepiness and individual rest-activity profiles, as well as other sleep-associated health characteristics such as the regulation of BMI. The differential associations of DAT1 and COMT polymorphisms may reflect the distinct local expression of the encoded proteins in the brain.
Subject(s)
Actigraphy , Activity Cycles/genetics , Catechol O-Methyltransferase/genetics , Dopamine Plasma Membrane Transport Proteins/genetics , Motor Activity/genetics , Polymorphism, Genetic , Sleep/genetics , Wakefulness/genetics , 3' Untranslated Regions , Adult , Age Factors , Body Weight , Female , Gene Frequency , Healthy Volunteers , Heterozygote , Homozygote , Humans , Male , Minisatellite Repeats , Phenotype , Young AdultABSTRACT
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.
Subject(s)
Circadian Rhythm/radiation effects , Cognition/radiation effects , Dyssomnias/therapy , Health Status , Hydrocortisone/metabolism , Melatonin/metabolism , Photoperiod , Phototherapy , Saliva/metabolism , Adult , Affect/radiation effects , Analysis of Variance , Biomarkers/metabolism , Dyssomnias/metabolism , Dyssomnias/physiopathology , Dyssomnias/psychology , Europe , Humans , Male , Seasons , Sleep/radiation effects , Time Factors , Treatment Outcome , Wakefulness/radiation effects , Young AdultABSTRACT
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.