Publications by authors named "Antoine U Viola"

30 Publications

  • Page 1 of 1

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

Clocks Sleep 2019 Dec 11;1(4):517-531. Epub 2019 Dec 11.

Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94305, USA;

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/clockssleep1040040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445844PMC
December 2019

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

Sci Rep 2019 12 2;9(1):18073. Epub 2019 Dec 2.

Sleep Disorders Center & CIRCSom (International Research Center for ChronoSomnology), University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-54311-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889287PMC
December 2019

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

Sci Rep 2019 Aug 22;9(1):12379. Epub 2019 Aug 22.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-48856-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704152PMC
August 2019

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

Sci Rep 2018 01 17;8(1):970. Epub 2018 Jan 17.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-17022-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772468PMC
January 2018

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

Sci Rep 2017 08 8;7(1):7620. Epub 2017 Aug 8.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-07060-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548856PMC
August 2017

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

Sci Rep 2017 07 17;7(1):5620. Epub 2017 Jul 17.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-05695-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514145PMC
July 2017

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.

Sleep Med 2016 05 17;21:47-56. Epub 2016 Feb 17.

Index Ventures, Geneva, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2016.01.015DOI Listing
May 2016

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

Ann Neurol 2015 Aug 30;78(2):235-47. Epub 2015 Jun 30.

Center for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.24434DOI Listing
August 2015

Dawn simulation light: a potential cardiac events protector.

Sleep Med 2015 Apr 26;16(4):457-61. Epub 2015 Feb 26.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2014.12.016DOI Listing
April 2015

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

Behav Brain Res 2015 Mar 27;281:258-66. Epub 2014 Dec 27.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012 Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2014.12.043DOI Listing
March 2015

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

PLoS One 2014 1;9(12):e113734. Epub 2014 Dec 1.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113734PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249976PMC
September 2015

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

Behav Brain Res 2014 Sep 2;271:23-9. Epub 2014 Jun 2.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2014.05.050DOI Listing
September 2014

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

J Biol Rhythms 2014 Apr;29(2):119-30

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0748730414524898DOI Listing
April 2014

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

Front Behav Neurosci 2014 6;8:59. Epub 2014 Mar 6.

Centre for Chronobiology, Psychiatric University Hospital of the University of Basel Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2014.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944366PMC
March 2014

Genetic polymorphisms of DAT1 and COMT differentially associate with actigraphy-derived sleep-wake cycles in young adults.

Chronobiol Int 2014 Jun 13;31(5):705-14. Epub 2014 Mar 13.

Institute of Pharmacology and Toxicology, University of Zürich , Zürich , Switzerland .

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/07420528.2014.896376DOI Listing
June 2014

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

Chronobiol Int 2013 Oct 10;30(8):988-97. Epub 2013 Jul 10.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/07420528.2013.793196DOI Listing
October 2013

The human circadian metabolome.

Proc Natl Acad Sci U S A 2012 Feb 31;109(7):2625-9. Epub 2012 Jan 31.

Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1114410109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289302PMC
February 2012

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

J Clin Endocrinol Metab 2012 Mar 21;97(3):E433-7. Epub 2011 Dec 21.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstrasse 27, CH-4012 Basel, Switzerland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2011-2391DOI Listing
March 2012

Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism.

Neurobiol Aging 2012 May 14;33(5):1010.e17-27. Epub 2011 Dec 14.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3(5/5)) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3(5/5) participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3(4/4) participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2011.10.024DOI Listing
May 2012

Short-term complexity of cardiac autonomic control during sleep: REM as a potential risk factor for cardiovascular system in aging.

PLoS One 2011 Apr 22;6(4):e19002. Epub 2011 Apr 22.

Centre for Chronobiology, University of Basel, Basel, Switzerland.

Introduction: Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects.

Methods: A polysomnographic study was performed in 12 healthy young (21.1±0.8 years) and 12 healthy older subjects (64.9±1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1-2 (S1-2), Stage 3-4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCE(min) measuring the minimum amount of information that cannot be derived from the knowledge of previous values.

Results: Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCE(min). In the older group, SE(3) and CCE(min) were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCE(min). This decrease of entropy measures was more evident during REM sleep.

Conclusion: Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019002PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081328PMC
April 2011

PER3 polymorphism and cardiac autonomic control: effects of sleep debt and circadian phase.

Am J Physiol Heart Circ Physiol 2008 Nov 3;295(5):H2156-63. Epub 2008 Oct 3.

Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom.

A variable number tandem repeat polymorphism in the coding region of the circadian clock PERIOD3 (PER3) gene has been shown to affect sleep. Because circadian rhythms and sleep are known to modulate sympathovagal balance, we investigated whether homozygosity for this PER3 polymorphism is associated with changes in autonomic nervous system (ANS) activity during sleep and wakefulness at baseline and after sleep deprivation. Twenty-two healthy participants were selected according to their PER3 genotype. ANS activity, evaluated by heart rate (HR) and HR variability (HRV) indexes, was quantified during baseline sleep, a 40-h period of wakefulness, and recovery sleep. Sleep deprivation induced an increase in slow-wave sleep (SWS), a decrease in the global variability, and an unbalance of the ANS with a loss of parasympathetic predominance and an increase in sympathetic activity. Individuals homozygous for the longer allele (PER3(5/5)) had more SWS, an elevated sympathetic predominance, and a reduction of parasympathetic activity compared with PER3(4/4), in particular during baseline sleep. The effects of genotype were strongest during non-rapid eye movement (NREM) sleep and absent or much smaller during REM sleep. The NREM-REM cycle-dependent modulation of the low frequency-to-(low frequency + high frequency) ratio was diminished in PER3(5/5) individuals. Circadian phase modulated HR and HRV, but no interaction with genotype was observed. In conclusion, the PER3 polymorphism affects the sympathovagal balance in cardiac control in NREM sleep similar to the effect of sleep deprivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00662.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614578PMC
November 2008

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

Scand J Work Environ Health 2008 Aug 22;34(4):297-306. Epub 2008 Sep 22.

Surrey Sleep Research Centre, Clinical Research Centre, Egerton Road, Guildford, United Kingdom.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5271/sjweh.1268DOI Listing
August 2008

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

Sleep 2008 Aug;31(8):1159-67

Surrey Sleep Research Centre, Guildford, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542962PMC
August 2008

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

Sleep 2008 May;31(5):608-17

Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398752PMC
http://dx.doi.org/10.1093/sleep/31.5.608DOI Listing
May 2008

PER3 polymorphism predicts sleep structure and waking performance.

Curr Biol 2007 Apr 8;17(7):613-8. Epub 2007 Mar 8.

Surrey Sleep Research Centre, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2007.01.073DOI Listing
April 2007

Sleep as a tool for evaluating autonomic drive to the heart in cardiac transplant patients.

Sleep 2004 Jun;27(4):641-7

Laboratoire des Régulations Plvsiologiques et des Rythmes Biologiques chez l'Homme, Strasbourg Cedex, France.

Study Objectives: The aim of this study was to investigate the autonomic drive to the heart in cardiac transplant patients (CTP) using heart rate (HR) and HR variability (HRV) analysis during non-rapid eye movement (NREM)-rapid eye movement (REM) sleep cycles, in particular during arousal associated with the emergence from slow wave sleep (SWS). In healthy subjects, this arousal is characterized by a pronounced HR surge, and HRV is lower during SWS than during the subsequent "active" sleep stage 2 and REM sleep.

Participants: The participants were 24 adults, 14 CTP (men, n = 11; women, n = 3; mean age, 62.2 +/- 2.2 years; time after transplantation, 4-14 years) and 10 control subjects (men, n = 7; women, n = 3; mean age, 61.0 +/- 1.8 years).

Design: The subjects underwent polygraphic sleep, cardiac, and respiratory recordings during an experimental night. HR was measured during the arousal. HRV was estimated from the R-R intervals in 5-minute stationary segments preceding and following arousal, ie, during SWS and active sleep stage 2 from the first 2 complete NREM-REM sleep cycles.

Results: In controls, HR increased during arousal associated with the emergence from SWS during the 2 sleep cycles (P < .05). Sleep-stage-dependent increases of all HRV indexes were observed in the 2 sleep cycles. Concerning CTP, 5 of them displayed a smaller HR increase at arousal, whereas 9 other patients had no HR variation. This distinction between the 2 groups of CTP was confirmed by HRV analysis. The patients with HR reactivity to arousal presented significant sleep-stage-dependent increases in global HRV and sympathetic HRV indexes, whereas the nonreactive group was characterized by an inability of HRV to change with sleep-stage alternation. Sympathetic HRV indexes were significantly higher in the reactive patients than in nonreactive patients, but high frequency power reflecting parasympathetic activity did not differ. However, the absolute HRV indexes were greatly decreased in both groups of patients compared to controls.

Conclusion: HR reactivity during arousal associated with the emergence from SWS, corroborated by HRV surrounding arousal, may suggest a partial improvement of the sympathetic drive to the heart in some CTP, with no indication of increased parasympathetic activity. Other signs of reinnervation have to be identified to validate this hypothesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sleep/27.4.641DOI Listing
June 2004

Age-related changes in cardiac autonomic control during sleep.

J Sleep Res 2003 Sep;12(3):173-80

Laboratoire des Régulations Physiologiques et des Rythmes Biologiques chez l'Homme, Strasbourg, Cedex, France.

Aging is commonly associated with decreased sleep quality and increased periodic breathing (PB) that can influence heart rate variability (HRV). Cardiac autonomic control, as inferred from HRV analysis, was determined, taking into account the sleep quality and breathing patterns. Two groups of 12 young (21.1 +/- 0.8 years) and 12 older (64.9 +/- 1.9 years) volunteers underwent electroencephalographic, cardiac, and respiratory recordings during one experimental night. Time and frequency domain indices of HRV were calculated in 5-min segments, together with electroencephalographic and respiratory power spectra. In the elderly, large R-R oscillations in the very-low frequency (VLF) range emerged, that reflected the frequency of PB observed in 18% of the sleep time. PB occurred more frequently during rapid eye movement sleep (REM) sleep and caused a significant (P < 0.02) increase in the standard deviation of normal R-R intervals (SDNN) and absolute low-frequency (LF) power. With normal respiratory patterns, SDNN, absolute VLF, LF, and high frequency (HF) power fell during each sleep stage (P < 0.01) compared with young subjects, with no significant sleep-stage dependent variations. An overall decrease (P < 0.01) in normalized HF/(LF + HF) was observed in the elderly, suggesting a predominant loss of parasympathetic activity which may be related to decreased slow-wave sleep duration. These results indicate that two distinct breathing features, implying different levels of autonomic drive to the heart, influence HRV in the elderly during sleep. The breathing pattern must be considered to correctly interpret HRV in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1046/j.1365-2869.2003.00353.xDOI Listing
September 2003

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

Diabetes Care 2003 Jan;26(1):168-71

Laboratoire des Régulations Physiologiques et des Rythmes Biologiques chez l'Homme, Strasbourg Cedex, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/diacare.26.1.168DOI Listing
January 2003

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

J Biol Rhythms 2002 Dec;17(6):539-47

Laboratoire des Regulations Physiologiques et des Rythmes Biologiques chez l'Homme, 67085 Strasbourg, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0748730402238236DOI Listing
December 2002

Ritanserin, a serotonin-2 receptor antagonist, improves ultradian sleep rhythmicity in young poor sleepers.

Clin Neurophysiol 2002 Mar;113(3):429-34

Laboratoire des Régulations Physiologiques et des Rythmes Biologiques chez l'Homme, Institut de Physiologie, 4, rue Kirschleger, 67085 Cedex, Strasbourg, France.

Objectives: To determine the effect on sleep electroencephalographic (EEG) activity of ritanserin, a serotonin-2 (5-HT2) receptor antagonist in young poor sleepers.

Methods: Eight male subjects underwent two randomized night studies after receiving either a placebo or 5 mg ritanserin administered in the morning. The overnight variations in the delta (0.5-4.0 Hz) and sigma (12.25-15.0 Hz) frequency bands were characterized using a peak analysis which provided a quantitative evaluation of the time-courses in EEG activity.

Results: In subjects under ritanserin, slow wave sleep duration and the number of non-rapid eye movement (NREM)-REM sleep cycles were significantly enhanced (P<0.01). The number of peaks in delta activity occurring in the normal 80-120 min range was significantly (P<0.05) increased. Using a delta peak analysis, 4 periods containing or not a significant peak were identified in each subject. A significant increase in delta activity was observed in the areas under the averaged curves during the second and the third periods (P<0.05), while sigma activity decreased under ritanserin during the first, second and third periods (P<0.05).

Conclusions: These results demonstrate that ritanserin increases delta activity, possibly by opposing the inhibitory control of 5-HT2 receptor family. It restores sleep ultradian rhythmicity and improves sleep quality in young poor sleepers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s1388-2457(02)00014-7DOI Listing
March 2002
-->