Investigating light sensitivity in bipolar disorder (HELIOS-BD).

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.

An online behavioral self-help intervention rapidly improves acute insomnia severity and subjective mood during the coronavirus disease-2019 pandemic: a stratified randomized controlled trial.

STUDY OBJECTIVES: Stressful life events, such as the coronavirus disease-2019 (COVID-19) pandemic, can cause acute insomnia. Cognitive behavioral therapy for acute insomnia is effective but is both time and resource-intensive. This study investigated if an online behavioral self-help intervention, which has been successfully used alongside sleep restriction for acute insomnia, reduced insomnia severity and improved mood in acute insomnia. This study also assessed good sleepers to explore if a "sleep vaccination" approach was feasible. METHODS: In this online stratified randomized controlled trial, 344 participants (103 good sleepers and 241 participants with DSM-5 acute insomnia) were randomized to receive the intervention/no intervention (good sleepers) or intervention/intervention after 28 days (poor sleepers). Insomnia severity was assessed using the ISI (primary outcome), and anxiety and depression using the GAD-7/PHQ-9 (secondary outcomes) at baseline, 1 week, 1 month, and 3-month follow-up. RESULTS: In people with acute insomnia, relative to baseline, there were significant reductions in ISI (dz = 1.17), GAD-7 (dz = 0.70), and PHQ-9 (dz = 0.60) scores at 1-week follow-up. ISI, GAD-7, and PHQ-9 scores were significantly lower at all follow-up time points, relative to baseline. Subjective diary-derived sleep continuity was unaffected. No beneficial effects on sleep or mood were observed in good sleepers. CONCLUSIONS: An online behavioral self-help intervention rapidly reduces acute insomnia severity (within 1 week), and benefits mood in people with acute insomnia. These beneficial effects are maintained up to 3 months later. Although the use of the intervention is feasible in good sleepers, their subjective sleep was unaffected. CLINICAL TRIAL REGISTRATION: Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic; prospectively registered at ISRCTN on 8 April 2020 (identifier: ISRCTN43900695).

Effect of 60 days of head down tilt bed rest on amplitude and phase of rhythms in physiology and sleep in men.

Twenty-four-hour rhythms in physiology and behaviour are shaped by circadian clocks, environmental rhythms, and feedback of behavioural rhythms onto physiology. In space, 24 h signals such as those associated with the light-dark cycle and changes in posture, are weaker, potentially reducing the robustness of rhythms. Head down tilt (HDT) bed rest is commonly used to simulate effects of microgravity but how HDT affects rhythms in physiology has not been extensively investigated. Here we report effects of -6° HDT during a 90-day protocol on 24 h rhythmicity in 20 men. During HDT, amplitude of light, motor activity, and wrist-temperature rhythms were reduced, evening melatonin was elevated, while cortisol was not affected during HDT, but was higher in the morning during recovery when compared to last session of HDT. During recovery from HDT, time in Slow-Wave Sleep increased. EEG activity in alpha and beta frequencies increased during NREM and REM sleep. These results highlight the profound effects of head-down-tilt-bed-rest on 24 h rhythmicity.

Nutritional interventions in treating menopause-related sleep disturbances: a systematic review.

CONTEXT: Sleep disturbances are a core symptom of menopause, which refers to the permanent cessation of menstrual periods. Nutritional interventions may alleviate menopause-related sleep disturbances, as studies have shown that certain interventions (eg, tart cherry juice, or tryptophan-rich foods) can improve relevant aspects of sleep. OBJECTIVE: The aim of this systematic review was to examine the effect of nutritional interventions for menopause-related sleep disturbances, in order to inform the subsequent development of specific interventional trials and assess their potential as a treatment for menopause-related sleep disturbances. DATA SOURCES: Published studies in English were located by searching PubMed and PsycArticles databases (until September 15, 2022). DATA EXTRACTION: Following full-text review, a final total of 59 articles were included. The search protocol was performed in accordance with PRISMA guidelines. DATA ANALYSIS: A total of 37 studies reported that a nutritional intervention improved some aspect of sleep, and 22 studies observed no benefit. Most (n = 24) studies recruited postmenopausal women, 18 recruited menopausal women, 3 recruited perimenopausal women, and 14 recruited women from multiple groups. The majority of the studies were of low methodological quality. Due to the heterogeneity of the studies, a narrative synthesis without meta-analysis is reported. CONCLUSION: Despite the large heterogeneity in the studies and choice of intervention, the majority of the identified studies reported that a nutritional intervention did benefit sleep, and that it is mainly subjective sleep that is improved. More high-quality, adequately powered, randomized controlled trials of the identified nutritional interventions are necessary. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021262367.

Contrasting Effects of Sleep Restriction, Total Sleep Deprivation, and Sleep Timing on Positive and Negative Affect.

Laboratory-based sleep manipulations show asymmetries between positive and negative affect, but say little about how more specific moods might change. We report extensive analyzes of items from the Positive and Negative Affect Scale (PANAS) during days following nights of chronic sleep restriction (6 h sleep opportunity), during 40 h of acute sleep deprivation under constant routine conditions, and during a week-long forced desynchrony protocol in which participants lived on a 28-h day. Living in the laboratory resulted in medium effects sizes on all positive moods (Attentiveness, General Positive Affect, Joviality, Assuredness), with a general deterioration as the days wore on. These effects were not found with negative moods. Sleep restriction reduced some positive moods, particularly Attentiveness (also General Positive), and increased Hostility. A burden of chronic sleep loss also led to lower positive moods when participants confronted the acute sleep loss challenge, and all positive moods, as well as Fearfulness, General Negative Affect and Hostility were affected. Sleeping at atypical circadian phases resulted in mood changes: all positive moods reduced, Hostility and General Negative Affect increased. Deteriorations increased the further participants slept from their typical nocturnal sleep. In most cases the changes induced by chronic or acute sleep loss or mistimed sleep waxed or waned across the waking day, with linear or various non-linear trends best fitting these time-awake-based changes. While extended laboratory stays do not emulate the fluctuating emotional demands of everyday living, these findings demonstrate that even in controlled settings mood changes systematically as sleep is shortened or mistimed.

Pre-Sleep Cognitive Arousal Is Unrelated to Sleep Misperception in Healthy Sleepers When Unexpected Sounds Are Played during Non-Rapid Eye Movement Sleep: A Polysomnography Study.

BACKGROUND: It is well-established that environmental noise can disrupt sleep, and cause a mismatch between subjective and objective sleep, which is known as "sleep misperception". Naturalistic studies indicate that pre-sleep cognitive arousal and sleep misperception are associated in the context of noise. However, it is not known if this is the case when ecologically valid noises are specifically played during non-rapid eye movement (NREM) sleep, which is susceptible to noise-related disruption. The present study evaluated if pre-sleep cognitive arousal was associated with sleep misperception in healthy normal sleepers, when unexpected ecologically valid common nocturnal noises were played during NREM sleep. METHODS: Eighteen healthy sleepers (Mage = 23.37 years, SDage = 3.21 years) participated. Sleep was measured objectively on three consecutive nights using polysomnography, in a sleep laboratory environment, and subjectively, through participant estimates of total sleep time (TST). Night 1 was a baseline night where no noises were played. On Night 2, noises, which were chosen to be representative of habitual nocturnal noises heard in home environments, were played to participants via in-ear headphones after 5 min of objective sleep. RESULTS: Unexpectedly, habitual pre-sleep cognitive arousal was not associated with subjective-objective TST discrepancy on Night 2. CONCLUSIONS: These results suggest that in healthy sleepers, when ecologically valid noises are played unexpectedly during NREM sleep in an unfamiliar sleep laboratory environment the subjective experience of sleep is not associated with pre-sleep cognitive arousal, or negatively impacted by noise exposure.

Sex differences and sex bias in human circadian and sleep physiology research.

Growing evidence shows that sex differences impact many facets of human biology. Here we review and discuss the impact of sex on human circadian and sleep physiology, and we uncover a data gap in the field investigating the non-visual effects of light in humans. A virtual workshop on the biomedical implications of sex differences in sleep and circadian physiology led to the following imperatives for future research: i) design research to be inclusive and accessible; ii) implement recruitment strategies that lead to a sex-balanced sample; iii) use data visualization to grasp the effect of sex; iv) implement statistical analyses that include sex as a factor and/or perform group analyses by sex, where possible; v) make participant-level data open and available to facilitate future meta-analytic efforts.

Individual differences and diversity in human physiological responses to light.

Exposure to light affects our physiology and behaviour through a pathway connecting the retina to the circadian pacemaker in the hypothalamus - the suprachiasmatic nucleus (SCN). Recent research has identified significant individual differences in the non-visual effects of light,mediated by this pathway. Here, we discuss the fundamentals and individual differences in the non-visual effects of light. We propose a set of actions to improve our evidence database to be more diverse: understanding systematic bias in the evidence base, dedicated efforts to recruit more diverse participants, routine deposition and sharing of data, and development of data standards and reporting guidelines.

Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic in self-reported good and poor sleepers (Sleep COVID-19): study protocol for a randomised controlled trial.

BACKGROUND: Theoretical models of insomnia suggest that stressful life events, such as the COVID-19 pandemic, can cause acute insomnia (short-term disruptions to sleep). Early interventions may prevent short-term sleep problems from progressing to insomnia disorder. Although cognitive behavioural therapy for insomnia (CBT-I) is effective in treating insomnia disorder, this can be time and resource-intensive. Further, online interventions can be used to deliver treatment to a large number of individuals. The objective of this study is to investigate if an online behavioural intervention, in the form of a leaflet, which has been successfully used alongside CBT-I for acute insomnia, can reduce symptoms of acute insomnia in poor sleepers. METHODS: A total of 124 self-reported good and poor sleepers will be enrolled in an online stratified randomised controlled trial. After baseline assessments (T1), participants will complete a 1-week pre-intervention sleep monitoring period (T2) where they will complete daily sleep-diaries. Poor sleepers (n = 62) will be randomly allocated to an invention or wait-list group, where they will receive the intervention (T3), or will do so after a 28-day delay. Good sleepers (n = 62) will be randomly assigned to an intervention or no intervention group. All participants will complete a 1-week post intervention sleep monitoring period using daily sleep diaries (T4). Participants will be followed up at 1 week (T5), 1 month (T6) and 3 months (T7) post intervention. The primary outcome measure will be insomnia severity, measured using the Insomnia Severity Index. Secondary outcome measures will include subjective mood and subjective sleep continuity, measured using sleep diaries. Data will be analysed using an intention-to-treat approach. DISCUSSION: It is expected that this online intervention will reduce symptoms of acute insomnia in self-reported short-term poor sleepers, and will also prevent the transition to poor sleep in good sleepers. We expect that this will demonstrate the feasibility of online interventions for the treatment and prevention of acute insomnia. Specific advantages of online approaches include the low cost, ease of administration and increased availability of treatment, relative to face-to-face therapy. TRIAL REGISTRATION: ISRCTN43900695 (Prospectively registered 8th of April 2020).

Sleepiness is a signal to go to bed: data and model simulations.

STUDY OBJECTIVES: Assess the validity of a subjective measure of sleepiness as an indicator of sleep drive by quantifying associations between intraindividual variation in evening sleepiness and bedtime, sleep duration, and next morning and subsequent evening sleepiness, in young adults. METHODS: Sleep timing and sleepiness were assessed in 19 students in late autumn and late spring on a total of 771 days. Karolinska Sleepiness Scales (KSS) were completed at half-hourly intervals at fixed clock times starting 4 h prior to participants' habitual bedtime, and in the morning. Associations between sleepiness and sleep timing were evaluated by mixed model and nonparametric approaches and simulated with a mathematical model for the homeostatic and circadian regulation of sleepiness. RESULTS: Intraindividual variation in evening sleepiness was very large, covering four or five points on the 9-point KSS scale, and was significantly associated with subsequent sleep timing. On average, a one point higher KSS value was followed by 20 min earlier bedtime, which led to 11 min longer sleep, which correlated with lower sleepiness next morning and the following evening. Associations between sleepiness and sleep timing were stronger in early compared to late sleepers. Model simulations indicated that the directions of associations between sleepiness and sleep timing are in accordance with their homeostatic and circadian regulation, even though much of the variance in evening sleepiness and details of its time course remain unexplained by the model. CONCLUSION: Subjective sleepiness is a valid indicator of the drive for sleep which, if acted upon, can reduce insufficient sleep.

Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic (Sleep COVID-19): structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary aim of the present study is to examine the efficacy of an online intervention for poor sleep in the context of an ongoing stressful major life event, by assessing if this intervention can reduce insomnia severity at short-term (one week post-intervention) and long-term (one and three months post-intervention) follow-up time points. It is hypothesised that the intervention will: 1) reduce insomnia severity in poor sleepers, compared to wait-list control poor sleepers, and good sleepers; 2) reduce subjective symptoms of anxiety and depression in all groups, and 3) prevent the transition to acute insomnia in good sleepers. TRIAL DESIGN: This study is a cluster randomised controlled trial. PARTICIPANTS: Both healthy good sleepers, who do not report having any current sleep problems, and individuals who report having sleep problems, will be recruited for the present study. This is a single-site study (Northumbria University). This study will be delivered using the internet and there are no geographic restrictions. Individuals who self-report as poor sleepers will meet DSM-5 criteria for acute insomnia, which is where individuals: 1) have difficulties in falling asleep, staying asleep, or awakening too early for at least three nights per week, for a time period of between two weeks and three months; and 2) report experiencing distress or impairment caused by sleep loss. Both 1) and 2) must have occurred despite the individual having had an adequate opportunity for sleep during this time period. Good sleepers will be individuals who do not have current sleep problems. All participants must have a sufficient level of English comprehension to understand and complete study measures. Individuals cannot participate if they report having chronic sleep problems (where they have existed for more than three months immediately prior to providing consent), nor will individuals who are actively seeking treatment for their sleep problems irrespective of how long they have had the sleep problem. Individuals also cannot participate if they have a self-reported history of head injuries, or if they have a self-reported diagnosis of schizophrenia, epilepsy or personality disorder, as the distraction techniques involved in the insomnia intervention may increase rumination in individuals with these conditions, and influence the effectiveness of the intervention. INTERVENTION AND COMPARATOR: Participants who receive the intervention will be provided with an online version of a self-help leaflet. A printed version of this leaflet has been successfully used in previous treatment studies, which have been conducted by our research group. Participants will be encouraged to download, save or print out this leaflet, which will be provided in PDF format. There will be no restrictions on use and participants will be encouraged to refer to this leaflet as often as they wish to. Briefly, this self-help leaflet aims to improve sleep by identifying and addressing sleep-related dysfunctional thinking by providing education about sleep, providing techniques to distract from intrusive worrisome thoughts at night, and providing guidelines for sleep-related stimulus control. The comparator is a wait-list control (i.e. where they will receive the intervention after a one month delay) group. MAIN OUTCOMES: The primary outcome measure will be insomnia severity, as measured using the Insomnia Severity Index (Bastien, Vallières, & Morin, 2001), assessed immediately prior to the intervention and at one week, one month and three months post-intervention, compared to baseline. Secondary outcome measures will include subjective mood, measured using the 7-item Generalised Anxiety Disorder Questionnaire (GAD-7; Spitzer, Kroenke, Williams, & Lowe, 2006)) and 9-item Patient Health Questionnaire (PHQ-9; Kroenke, Spitzer, & Williams, 2001), assessed immediately prior to the intervention, and one week, one month and three months post-intervention, compared to baseline. Additionally, subjective sleep continuity, derived from sleep diaries (Carney et al., 2012), will be compared pre and post-intervention. RANDOMISATION: This study will operate as a cluster randomised controlled trial. Good sleepers will be randomised into an intervention or a no-intervention group, with a 1:1 allocation. Poor sleepers will be randomised into an intervention or wait-list control group, with a 1:1 allocation. Randomisation will be conducted automatically using Qualtrics study software, where block sizes will be equal and randomisation will be computer-generated. BLINDING (MASKING): Participants will not be blinded to group assignment. The outcomes will be assessed by a blinded investigator. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The minimum sample size is 60. A total of 30 poor sleepers will be randomised to the intervention or wait-list control group. A total of 30 good sleepers will be randomised to the intervention or no intervention group. TRIAL STATUS: Recruitment for this study has yet to start. It is anticipated that recruitment will begin in August 2020 and end in April 2022. The current study protocol is version 1.0 (20 July 2020) TRIAL REGISTRATION: This study was prospectively registered in the ISRCTN registry (registration number ISRCTN43900695 , date of registration: 8 April 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Applications in sleep: How light affects sleep.

Sleep is an active physiological state that plays a critical role in our physical and mental health and well-being. It is generated by a complex interplay between two oscillators, namely, the circadian oscillator and the sleep-wake homeostat. Sleep propensity is a function of wakefulness, that is, the longer one is awake the greater the homeostatic sleep pressure. Sleep onset occurs as a wake promoting circadian signal subsides, coinciding with an evening rise in melatonin and drop in core temperature. Light is one of the strongest time signals for the circadian oscillator. Poor sleep is a prevalent complaint today, attributable, in part, to our easy access to artificial light, especially after dusk. This non-visual effect of light is mediated by a multi-component photoreceptive system, consisting of rods, cones and melanopsin-expressing intrinsically-photosensitive retinal ganglion cells (ipRGC). Perhaps, with this available biological knowledge we can engineer artificial light to minimize its disruptive effect on sleep. We will highlight this by discussing circadian photoreception and its effect on sleep, in the blind population.

Sleep Timing in Late Autumn and Late Spring Associates With Light Exposure Rather Than Sun Time in College Students.

Timing of the human sleep-wake cycle is determined by social constraints, biological processes (sleep homeostasis and circadian rhythmicity) and environmental factors, particularly natural and electrical light exposure. To what extent seasonal changes in the light-dark cycle affect sleep timing and how this varies between weekdays and weekends has not been firmly established. We examined sleep and activity patterns during weekdays and weekends in late autumn (standard time, ST) and late spring (daylight saving time, DST), and expressed their timing in relation to three environmental reference points: clock-time, solar noon (SN) which occurs one clock hour later during DST than ST, and the midpoint of accumulated light exposure (50% LE). Observed sleep timing data were compared to simulated data from a mathematical model for the effects of light on the circadian and homeostatic regulation of sleep. A total of 715 days of sleep timing and light exposure were recorded in 19 undergraduates in a repeated-measures observational study. During each three-week assessment, light and activity were monitored, and self-reported bed and wake times were collected. Light exposure was higher in spring than in autumn. 50% LE did not vary across season, but occurred later on weekends compared to weekdays. Relative to clock-time, bedtime, wake-time, mid-sleep, and midpoint of activity were later on weekends but did not differ across seasons. Relative to SN, sleep and activity measures were earlier in spring than in autumn. Relative to 50% LE, only wake-time and mid-sleep were later on weekends, with no seasonal differences. Individual differences in mid-sleep did not correlate with SN but correlated with 50% LE. Individuals with different habitual bedtimes responded similarly to seasonal changes. Model simulations showed that light exposure patterns are sufficient to explain sleep timing in spring but less so in autumn. The findings indicate that during autumn and spring, the timing of sleep associates with actual light exposure rather than sun time as indexed by SN.

Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans.

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the 'gold standard' for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.

Machine-learning-derived sleep-wake staging from around-the-ear electroencephalogram outperforms manual scoring and actigraphy.

Quantification of sleep is important for the diagnosis of sleep disorders and sleep research. However, the only widely accepted method to obtain sleep staging is by visual analysis of polysomnography (PSG), which is expensive and time consuming. Here, we investigate automated sleep scoring based on a low-cost, mobile electroencephalogram (EEG) platform consisting of a lightweight EEG amplifier combined with flex-printed cEEGrid electrodes placed around the ear, which can be implemented as a fully self-applicable sleep system. However, cEEGrid signals have different amplitude characteristics to normal scalp PSG signals, which might be challenging for visual scoring. Therefore, this study evaluates the potential of automatic scoring of cEEGrid signals using a machine learning classifier ("random forests") and compares its performance with manual scoring of standard PSG. In addition, the automatic scoring of cEEGrid signals is compared with manual annotation of the cEEGrid recording and with simultaneous actigraphy. Acceptable recordings were obtained in 15 healthy volunteers (aged 35 ± 14.3 years) during an extended nocturnal sleep opportunity, which induced disrupted sleep with a large inter-individual variation in sleep parameters. The results demonstrate that machine-learning-based scoring of around-the-ear EEG outperforms actigraphy with respect to sleep onset and total sleep time assessments. The automated scoring outperforms human scoring of cEEGrid by standard criteria. The accuracy of machine-learning-based automated scoring of cEEGrid sleep recordings compared with manual scoring of standard PSG was satisfactory. The findings show that cEEGrid recordings combined with machine-learning-based scoring holds promise for large-scale sleep studies.

Sleep EEG Derived From Behind-the-Ear Electrodes (cEEGrid) Compared to Standard Polysomnography: A Proof of Concept Study.

Electroencephalography (EEG) recordings represent a vital component of the assessment of sleep physiology, but the methodology presently used is costly, intrusive to participants, and laborious in application. There is a recognized need to develop more easily applicable yet reliable EEG systems that allow unobtrusive long-term recording of sleep-wake EEG ideally away from the laboratory setting. cEEGrid is a recently developed flex-printed around-the-ear electrode array, which holds great potential for sleep-wake monitoring research. It is comfortable to wear, simple to apply, and minimally intrusive during sleep. Moreover, it can be combined with a smartphone-controlled miniaturized amplifier and is fully portable. Evaluation of cEEGrid as a motion-tolerant device is ongoing, but initial findings clearly indicate that it is very well suited for cognitive research. The present study aimed to explore the suitability of cEEGrid for sleep research, by testing whether cEEGrid data affords the signal quality and characteristics necessary for sleep stage scoring. In an accredited sleep laboratory, sleep data from cEEGrid and a standard PSG system were acquired simultaneously. Twenty participants were recorded for one extended nocturnal sleep opportunity. Fifteen data sets were scored manually. Sleep parameters relating to sleep maintenance and sleep architecture were then extracted and statistically assessed for signal quality and concordance. The findings suggest that the cEEGrid system is a viable and robust recording tool to capture sleep and wake EEG. Further research is needed to fully determine the suitability of cEEGrid for basic and applied research as well as sleep medicine.

Functional decoupling of melatonin suppression and circadian phase resetting in humans.

KEY POINTS: There is assumed to be a monotonic association between melatonin suppression and circadian phase resetting induced by light exposure. We tested the association between melatonin suppression and phase resetting in humans. Sixteen young healthy participants received nocturnal bright light (∼9500 lux) exposure of continuous or intermittent patterns, and different durations ranging from 12 min to 6.5 h. Intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every bright light stimulus in an intermittent exposure pattern induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest that phase shifts and melatonin suppression are functionally independent such that one cannot be used as a proxy measure of the other. ABSTRACT: Continuous experimental light exposures show that, in general, the conditions that produce greater melatonin suppression also produce greater phase shift, leading to the assumption that one can be used as a proxy for the other. We tested this association in 16 healthy individuals who participated in a 9-day inpatient protocol by assessing melatonin suppression and phase resetting in response to a nocturnal light exposure (LE) of different patterns: (i) dim-light control (<3 lux; n = 6) or (ii) two 12-min intermittent bright light pulses (IBL) separated by 36 min of darkness (∼9500 lux; n = 10). We compared these results with historical data from additional LE patterns: (i) dim-light control (<3 lux; n = 11); (ii) single continuous bright light exposure of 12 min (n = 9), 1.0 h (n = 10) or 6.5 h (n = 6); or (iii) an IBL light pattern consisting of six 15-min pulses with 1.0 h dim-light recovery intervals between them during a total of 6.5 h (n = 7). All light exposure groups had significantly greater phase-delay shifts than the dim-light control condition (P < 0.0001). While a monotonic association between melatonin suppression and circadian phase shift was observed, intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every IBL stimulus induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest unique specificities in how light-induced phase shifts and melatonin suppression are mediated such that one cannot be used as a proxy measure of the other.

Significance of circadian rhythms in severely brain-injured patients: A clue to consciousness?

OBJECTIVE: To investigate the relationship between the presence of a circadian body temperature rhythm and behaviorally assessed consciousness levels in patients with disorders of consciousness (DOC; i.e., vegetative state/unresponsive wakefulness syndrome or minimally conscious state). METHODS: In a cross-sectional study, we investigated the presence of circadian temperature rhythms across 6 to 7 days using external skin temperature sensors in 18 patients with DOC. Beyond this, we examined the relationship between behaviorally assessed consciousness levels and circadian rhythmicity. RESULTS: Analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3 hours). We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised were closely linked to the integrity of circadian variations in body temperature. Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in 2 out of 8 patients. CONCLUSION: The study provides evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness. Our findings also make a case for circadian rhythms as a target for treatment as well as the application of diagnostic and therapeutic means at times when cognitive performance is expected to peak.