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STUDY OBJECTIVES: This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. METHODS: A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. RESULTS: A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. CONCLUSIONS: Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303. CITATION: Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med. 2022;18(3):789–800.

Objectives Rotating shift work is associated with adverse outcomes due to circadian misalignment, sleep curtailment, work-family conflicts, and other factors. We tested a bright light countermeasure to enhance circadian adaptation on a counterclockwise rotation schedule. Methods Twenty-nine adults (aged 20–40 years; 15 women) participated in a 4-week laboratory simulation with weekly counterclockwise transitions from day, to night, to evening, to day shifts. Each week consisted of five 8-hour workdays including psychomotor vigilance tests, two days off, designated 8-hour sleep episodes every day, and an assessment of circadian melatonin secretion. Participants were randomized to a treatment group (N=14), receiving intermittent bright light during work designed to facilitate circadian adaptation, or a control group (N=15) working in indoor light. Adaptation was measured by how much of the melatonin secretion episode overlapped with scheduled sleep timing. Results On the last night shift, there was a greater overlap between melatonin secretion and scheduled sleep time in the treatment group [mean 4.90, standard deviation (SD) 2.8 hours] compared to the control group (2.62, SD 2.8 hours; P=0.002), with night shift adaptation strongly influenced by baseline melatonin timing (r 2 =-0.71, P=0.01). While the control group exhibited cognitive deficits on the last night shift, the treatment group’s cognitive deficits on the last night and evening shifts were minimized. Conclusions In this laboratory setting, intermittent bright light during work hours enhanced adaptation to night work and subsequent readaptation to evening and day work. Light regimens scheduled to shift circadian timing should be tested in actual shift workers on counterclockwise schedules as a workplace intervention.

Objective: To examine the relationship between headaches, naps, and nocturnal sleep in women with chronic migraine (CM) using micro-longitudinal data from diaries and actigraphy. Methods: 20 women with CM and 20 age and sex-matched healthy controls (HC) completed self-report questionnaires, electronic diaries, and wrist actigraphy over a 4-week period. Between-group comparisons were conducted with naps (frequency and duration) as the primary variable of interest. Within-group analyses were conducted on the CM group using hierarchical linear mixed models to examine the temporal relationships between headache severity, sleep behaviors, and sleep parameters. The primary variables of interest were naps (number and duration) and nocturnal sleep efficiency (diary and actigraphy). Results: The CM group reported significantly more days with naps (25.85%) compared to the HC group (9.03%) during the study period (p = .0025). Within-group analyses in CM revealed that greater headache severity was associated with longer nap duration (p = .0037) and longer nap duration was associated with lower sleep efficiency measured using diaries (p = .0014) and actigraphy (p

Circadian clocks drive cyclic variations in many aspects of physiology, but some daily variations are evoked by periodic changes in the environment or sleep-wake state and associated behaviors, such as changes in posture, light levels, fasting or eating, rest or activity and social interactions; thus, it is often important to quantify the relative contributions of these factors. Yet, circadian rhythms and these evoked effects cannot be separated under typical 24-h day conditions, because circadian phase and the length of time awake or asleep co-vary. Nathaniel Kleitman's forced desynchrony (FD) protocol was designed to assess endogenous circadian rhythmicity and to separate circadian from evoked components of daily rhythms in multiple parameters. Under FD protocol conditions, light intensity is kept low to minimize its impact on the circadian pacemaker, and participants have sleep-wake state and associated behaviors scheduled to an imposed non-24-h cycle. The period of this imposed cycle, Τ, is chosen so that the circadian pacemaker cannot entrain to it and therefore continues to oscillate at its intrinsic period (τ, ~24.15 h), ensuring circadian components are separated from evoked components of daily rhythms. Here we provide detailed instructions and troubleshooting techniques on how to design, implement and analyze the data from an FD protocol. We provide two procedures: one with general guidance for designing an FD study and another with more precise instructions for replicating one of our previous FD studies. We discuss estimating circadian parameters and quantifying the separate contributions of circadian rhythmicity and the sleep-wake cycle, including statistical analysis procedures and an R package for conducting the non-orthogonal spectral analysis method that enables an accurate estimation of period, amplitude and phase.

Objective Mindfulness-based interventions (MBI) have been shown to reduce subjective symptoms of insomnia but the effects on objective measures remain unclear. The purpose of this study was to examine sleep EEG microarchitecture patterns from a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Therapy for Insomnia (MBTI). Methods Sleep EEG spectral analysis was conducted on 36 participants with chronic insomnia (>6 months) randomized to 8-week MBSR, MBTI, or self-monitoring control (SM). Overnight polysomnography with 6-channel EEG was conducted at baseline, post-treatment, and 6-month follow-up. Spectral power averaged from channels C3/C4 across NREM epochs (excluding N1) was examined for within-group changes and relationships with self-report measures. Results Increases in absolute NREM beta (16–25 Hz) power were observed from baseline to post-treatment (p = .02, d = 0.53) and maintained at 6-month follow-up (p = .01, d = 0.57) in the combined MBI groups, and additionally in the gamma (25–40 Hz) range at follow-up for the MBTI group only. No significant changes in these frequency bands were observed for SM. Following mindfulness intervention, NREM beta was positively associated with Five-Facet Mindfulness (FFM) score (rho = 0.37, p = .091) and negatively associated with Insomnia Severity Index (rho = −0.43, p = .047). Conclusion These results in people with insomnia corroborate prior reports of increased high-frequency sleep EEG power associated with mindfulness training. This change in beta EEG pattern merits further evaluation as a potential marker of the effects of mindfulness meditation on sleep, especially given the paradoxical findings in the context of insomnia. Clinical Trial Registration clinicaltrials.gov , NCT00768781 .

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Study Objectives To investigate treatment models using cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) for people with obstructive sleep apnea (OSA) and comorbid insomnia. Methods 121 adults with OSA and comorbid insomnia were randomized to receive CBT-I followed by PAP, CBT-I concurrent with PAP, or PAP only. PAP was delivered following standard clinical procedures for in-lab titration and home setup and CBT-I was delivered in four individual sessions. The primary outcome measure was PAP adherence across the first 90 days, with regular PAP use (≥4 h on ≥70% of nights during a 30-day period) serving as the clinical endpoint. The secondary outcome measures were the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with good sleeper (PSQI 7) serving as the clinical endpoints. Results No significant differences were found between the concomitant treatment arms and PAP only on PAP adherence measures, including the percentage of participants who met the clinical endpoint. Compared to PAP alone, the concomitant treatment arms reported a significantly greater reduction from baseline on the ISI (p = .0009) and had a greater percentage of participants who were good sleepers (p = .044) and remitters (p = .008). No significant differences were found between the sequential and concurrent treatment models on any outcome measure. Conclusions The findings from this study indicate that combining CBT-I with PAP is superior to PAP alone on insomnia outcomes but does not significantly improve adherence to PAP.

Objective This observational pilot study examined objective circadian phase and sleep timing in chronic migraine (CM) and healthy controls (HC) and the impact of circadian factors on migraine frequency and severity. Background Sleep disturbance has been identified as a risk factor in the development and maintenance of CM but the biological mechanisms linking sleep and migraine remain largely theoretical. Methods Twenty women with CM and 20 age-matched HC completed a protocol that included a 7 day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. We compared CM vs HC on sleep parameters and circadian factors. Subsequently, we examined associations between dim-light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). Results CM and HC did not differ on measures of sleep or circadian phase. Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49, P = .039) and later sleep episode (r = .47, P = .037). In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine-related disability (r = .48, P = .042). These relationships remained significant after adjusting for total sleep time. Conclusions This pilot study revealed that circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity, which was not better accounted for by the amount of sleep. These findings support the plausibility and need for further investigation of a circadian pathway in the development and maintenance of chronic headaches. Specifically, circadian misalignment and delayed sleep timing could serve as an exacerbating factor in chronic migraines when combined with biological predispositions or environmental factors.

Sleep and circadian rhythm changes during adolescence contribute to increased risk across emotional, behavioral, cognitive, social, and physical health domains. This study examines if sleep and dim light melatonin onset (DLMO) are related to greater risk in these 5 health domains. Participants were 163 (93 female, age = 14.7 years) adolescents with an evening circadian preference from a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Sleep and circadian measures included weekday total sleep time (TST), bedtime, and shut-eye time assessed via sleep diary, the Children's Morningness-Eveningness Preferences scale, and DLMO. Health domains included self-reported emotional, cognitive, behavioral, social, and physical health. Later DLMO was significantly associated with shorter weekday TST, later weekday bedtime, and later weekday shut-eye time, as well as lower risk in the behavioral domain. At the trend level, later DLMO was related to fewer physical health problems. Earlier DLMO combined with a later bedtime, later shut-eye time, or shorter TST predicted greater risk in the cognitive domain. Later DLMO and shorter TST or a later bedtime predicted worse physical health. DLMO timing was not related to the emotional or social domain. There is evidence that a discrepancy between sleep behaviors and the endogenous circadian rhythm may be related to risk in the cognitive domain for adolescents with an evening circadian preference. Preliminary evidence also indicated that a delayed DLMO and shorter TST or a later bedtime may be related to vulnerability to physical health risk.

Objective/Background To compare sleep and circadian variability in adults with delayed sleep–wake phase disorder (DSWPD) to healthy controls. Patients/Methods Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break. Results and conclusions Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD. Clinical trial Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252 , NCT01487252 .

Introduction Light avoidance is a common coping behavior of individuals with migraine headaches. It is not known whether timing of light exposure is different in individuals with chronic migraine (CM) compared to those without migraine and how this may relate to headache frequency and severity. We tested this by examining timing of the brightest and darkest light and headaches in women with chronic migraines and healthy controls. Methods Sixteen women with CM (mean age = 33.07) and 18 female healthy controls (HC; mean age = 32.22) completed daily ratings of headache severity (0-10, severity > 2 classified as headache) concurrent with light exposure measured by wrist actigraphy for approximately one month (M=28.00 days, range=21-36). Start time of each day’s 10-hour periods of maximum light (M10) and 5-hour periods of lowest light (L5) were calculated and averaged for each participant. T-tests and Cohen’s d effect sizes were used to compare groups. Pearson correlation coefficients were calculated to examine associations between M10/L5 timing and headache frequency and severity. Results M10 was earlier in the CM group compared to the HC group (07:42±00:47 vs. 08:50±00:58, t(32)=3.69, p=0.0008, d=1.08). The CM group exhibited non-significant trend towards earlier L5 compared to the HC group (12:26±00:48 vs. 01:07±01:03, t(32)=1.89, p=0.0723, d=0.62). Among individuals with CM, later M10 timing was associated with more severe average daily headache (r=0.60, p=0.0136) and more frequent headaches (r=0.55, p=0.0257). Later L5 timing was significantly associated with more severe average daily headache (r=0.66, p=0.0052) and showed a non-significant trend toward association with more frequent headaches (r=0.47, p=0.0686). Conclusion Timing of the greatest light exposure period was earlier in CM compared to HC. Within the CM group, those who had earlier light and dark periods reported lower headache severity and fewer days with headaches. These findings suggest the possibility of a role for the circadian system in chronic migraine. Support This study was supported by grant R21NS081088 from the National Institutes of Health.

This article reviews delayed and advanced sleep-wake phase disorders. Diagnostic procedures include a clinical interview to verify the misalignment of the major nocturnal sleep episode relative to the desired and social-normed timing of sleep, a 3-month or greater duration of the sleep-wake disturbance, and at least a week of sleep diary data consistent with the sleep timing complaint. Treatment options include gradual, daily shifting of the sleep schedule (chronotherapy); shifting circadian phase with properly timed light exposure (phototherapy); or melatonin administration. Future directions are discussed to conclude the article.

Chronic insomnia disorder is a prevalent condition and a significant proportion of these individuals also have obstructive sleep apnea (OSA). These two sleep disorders have distinct pathophysiology and are managed with different treatment approaches. High comorbidity rates have been a catalyst for emerging studies examining multidisciplinary treatment for OSA comorbid with insomnia disorder. In this article, we describe a randomized clinical trial of Cognitive Behavioral Treatment for insomnia (CBT-I) and Positive Airway Pressure (PAP) for OSA. Participants are randomized to receive one of three treatment combinations. Individuals randomized to treatment Arm A receive sequential treatment beginning with CBT-I followed by PAP, in treatment Arm B CBT-I and PAP are administered concurrently. These treatment arms are compared to a control condition, treatment Arm C, where individuals receive PAP alone. Adopting an incomplete factorial study design will allow us to evaluate the efficacy of multidisciplinary treatment (Arms A & B) versus standard treatment alone (Arm C). In addition, the random allocation of individuals to the two different combined treatment sequences (Arm A and Arm B) will allow us to understand the benefits of the sequential administration of CBT-I and PAP relative to concurrent treatment of PAP and CBT-I. These findings will provide evidence of the clinical benefits of treating insomnia disorder in the context of OSA.

Introduction This study examines the effects of treatment sequences using cognitive-behavioral therapy for insomnia (CBT-I) and continuous positive airway pressure (CPAP) therapy on daytime functioning in people with comorbid insomnia and sleep apnea (COMISA). Methods 118 participants with COMISA (Age=49.99±13.12; 53.4% female) were randomized to one of the three study arms: Arm A- CBT-I followed by CPAP, Arm B- CBT-I concurrent with CPAP, and Arm C- CPAP only. Participants were assessed at four time points [baseline/ start of phase 1 (A1), CPAP titration/ start of phase 2 (A2), 30 days (A3) and 90 days (A4) after CPAP initiation]. This study examined secondary outcome measures of daytime functioning, including the Functional Outcomes of Sleep Questionnaire (FOSQ), Epworth Sleepiness Scale, and Flinders Fatigue Scale (FFS). Results Linear mixed model analyses showed a main effect of time on improving functional outcomes in all measurements, with all p< 0.001. There were also arm by time interactions on FOSQ [F(6, 105.36)=4.21, p=0.001] and FFS scores [F(6, 106.95)=3.10, p=0.008]. Pairwise comparisons with Bonferroni adjustment showed improved FOSQ scores in Arm A from A1 to A2 (p=0.011) and A2 to A3 (p=0.005), Arm B from A2 to A3 (p< 0.001), and Arm C from A2 to A3 (p=0.006). For FFS scores, improvements were shown in Arm A from A1 to A2 (p=0.003), and Arm B from A2 to A3 (p < 0.001). Conclusion The results show daytime functioning improvements in patients with COMISA following CPAP and CBT-I. In addition, CBT-I appears to facilitate improvement in sleepiness-related functional status and daytime fatigue. The findings suggest that the combination of CBT-I and CPAP may have a beneficial effect on daytime functioning in patients with COMISA. Support This study was supported by the National Institutes of Health (R01HL114529).

Objective To determine whether an intervention to reduce eveningness chronotype improves sleep, circadian, and health (emotional, cognitive, behavioral, social, physical) outcomes. Method Youth aged 10 to 18 years with an evening chronotype and who were “at risk” in 1 of 5 health domains were randomized to: (a) Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C; n = 89) or (b) Psychoeducation (PE; n = 87) at a university-based clinic. Treatments were 6 individual, weekly 50-minute sessions during the school year. TranS-C addresses sleep and circadian problems experienced by youth by integrating evidence-based treatments derived from basic research. PE provides education on the interrelationship between sleep, stress, diet, and health. Results Relative to PE, TranS-C was not associated with greater pre−post change for total sleep time (TST) or bed time (BT) on weeknights but was associated with greater reduction in evening circadian preference (pre−post increase of 3.89 points, 95% CI = 2.94−4.85, for TranS-C, and 2.01 points, 95% CI = 1.05−2.97 for PE, p = 0.006), earlier endogenous circadian phase, less weeknight−weekend discrepancy in TST and wakeup time, less daytime sleepiness, and better self-reported sleep via youth and parent report. In terms of functioning in the five health domains, relative to PE, TranS-C was not associated with greater pre−post change on the primary outcome. However, there were significant interactions favoring TranS-C on the Parent-Reported Composite Risk Scores for cognitive health. Conclusion For at-risk youth, the evidence supports the use of TranS-C over PE for improving sleep and circadian functioning, and improving health on selected outcomes. Clinical trial registration information: Triple Vulnerability? Circadian Tendency, Sleep Deprivation and Adolescence. https://clinicaltrials.gov ; NCT01828320 .

Study Objectives: This study examined empirically derived symptom cluster profiles among patients who present with insomnia using clinical data and polysomnography. Methods: Latent profile analysis was used to identify symptom cluster profiles of 175 individuals (63% female) with insomnia disorder based on total scores on validated self-report instruments of daytime and nighttime symptoms (Insomnia Severity Index, Glasgow Sleep Effort Scale, Fatigue Severity Scale, Beliefs and Attitudes about Sleep, Epworth Sleepiness Scale, Pre-Sleep Arousal Scale), mean values from a 7-day sleep diary (sleep onset latency, wake after sleep onset, and sleep efficiency), and total sleep time derived from an in-laboratory PSG. Results: The best-fitting model had three symptom cluster profiles: "High Subjective Wakefulness" (HSW), "Mild Insomnia" (MI) and "Insomnia-Related Distress" (IRD). The HSW symptom cluster profile (26.3% of the sample) reported high wake after sleep onset, high sleep onset latency, and low sleep efficiency. Despite relatively comparable PSG-derived total sleep time, they reported greater levels of daytime sleepiness. The MI symptom cluster profile (45.1%) reported the least disturbance in the sleep diary and questionnaires and had the highest sleep efficiency. The IRD symptom cluster profile (28.6%) reported the highest mean scores on the insomnia-related distress measures (eg, sleep effort and arousal) and waking correlates (fatigue). Covariates associated with symptom cluster membership were older age for the HSW profile, greater obstructive sleep apnea severity for the MI profile, and, when adjusting for obstructive sleep apnea severity, being overweight/obese for the IRD profile. Conclusions: The heterogeneous nature of insomnia disorder is captured by this data-driven approach to identify symptom cluster profiles. The adaptation of a symptom cluster-based approach could guide tailored patient-centered management of patients presenting with insomnia, and enhance patient care.

The purpose of this study was to introduce a novel statistical technique called the location-scale mixed model that can be used to analyze the mean level and intra-individual variability (IIV) using longitudinal sleep data.We applied the location-scale mixed model to examine changes from baseline in sleep efficiency on data collected from 54 participants with chronic insomnia who were randomized to an 8-week Mindfulness-Based Stress Reduction (MBSR; n = 19), an 8-week Mindfulness-Based Therapy for Insomnia (MBTI; n = 19), or an 8-week self-monitoring control (SM; n = 16). Sleep efficiency was derived from daily sleep diaries collected at baseline (days 1-7), early treatment (days 8-21), late treatment (days 22-63), and post week (days 64-70). The behavioral components (sleep restriction, stimulus control) were delivered during late treatment in MBTI.For MBSR and MBTI, the pre-to-post change in mean levels of sleep efficiency were significantly larger than the change in mean levels for the SM control, but the change in IIV was not significantly different. During early and late treatment, MBSR showed a larger increase in mean levels of sleep efficiency and a larger decrease in IIV relative to the SM control. At late treatment, MBTI had a larger increase in the mean level of sleep efficiency compared to SM, but the IIV was not significantly different.The location-scale mixed model provides a two-dimensional analysis on the mean and IIV using longitudinal sleep diary data with the potential to reveal insights into treatment mechanisms and outcomes.

Background: we previously demonstrated that patients with mild Alzheimer’s disease and parkinsonian features (AD + PF) are at a higher risk of having daytime sleepiness than mild AD patients without PF (AD −PF). Objective: to determine whether AD + PF patients demonstrate a known a consequence of daytime sleepiness, reduced performance-based sustained attention, compared with AD −PF patients. Methods: a nocturnal polysomnogram and a next-day multiple sleep latency test (MSLT) were performed. Between MSLT nap opportunities, a 10-min psychomotor vigilance test (PVT) was administered and analysed for reciprocal mean response times (IMEAN), number of lapses (LAPSE) and reciprocal mean slowest 10% (ISLOW). Results: a total of 35 patients met criteria (AD + PF, n= 16; AD −PF, n= 19). Comparatively, the AD + PF group had slower IMEAN results [F(1,28) = 6.64, P< 0.05] and higher LAPSE rates [F(1,27)= 7.57, P< 0.05]. ISLOW measures were not different between groups. When accounting for MSLT results, IMEAN and LAPSE results were no longer significantly different between groups during morning tests, but remained significantly different on afternoon tests. Conclusion: PFs in mild AD are associated with decreased sustained attention as measured by the PVT. Sleepiness did not fully account for the impairment in sustained attention, suggesting that the presence of PFs has an independent negative association with sustained attention in mild AD.

The purpose of this study was to examine the process of care in an interdisciplinary sleep clinic for patients with obstructive sleep apnea (OSA) and comorbid insomnia. A mixed-methods approach was used to examine clinical and patient-centered measures for 34 patients who received positive-airway pressure for OSA or cognitive-behavior therapy for insomnia. The results revealed baseline-to-follow-up improvements on several self-reported sleep parameters and measures of daytime functioning. Qualitative analyses from patient interviews revealed three themes: conceptual distinctions about each sleep disorder, importance of treating both sleep disorders, and preferences with regard to the sequence of treatment. These findings indicate that patients with OSA and comorbid insomnia encounter unique challenges. A dimensional approach to assessment and treatment is proposed for future research.

This article begins with a review of the major central nervous system functional systems that allow for optimal alertness during the waking day, and the rapid initiation and good maintenance of sleep at night. Subsequent sections discuss each of the 6 primary circadian rhythm sleep disorders. Attention is paid to known or suspected pathophysiology, diagnostic criteria and assessment methodology, and treatment options. The article concludes with a discussion of challenges that must be met to improve the recognition and treatment of these quite impactful sleep disorders.

The type and severity of daytime symptoms reported by insomnia sufferers may vary markedly. Whether distinctive daytime symptom profiles are related to different insomnia diagnoses has not been studied previously. Using profile analysis via multidimensional scaling, we investigated the concurrent validity of ICSD-2 insomnia diagnoses by analysing the relationship of prototypical profiles of daytime symptoms with a subset of ICSD-2 diagnoses, such as insomnia associated to a mental disorder, psychophisiological insomnia, paradoxical insomnia, inadequate sleep hygiene, idiopathic insomnia, obstructive sleep apnea and restless legs syndrome. In a sample of 332 individuals meeting research diagnostic criteria for insomnia (221 women, M(age) =46 years.), the profile analysis identified four prototypical patterns of daytime features. Pearson correlation coefficients indicated that the diagnoses of insomnia associated to a mental disorder and idiopathic insomnia were associated with a daytime profile characterized by mood disturbance and low sleepiness; whereas the diagnoses of psychophysiological insomnia and inadequate sleep hygiene were related to a profile marked by poor sleep hygiene, daytime tension and low fatigue. Furthermore, whereas paradoxical insomnia was consistently associated to lower daytime impairment, insomnia associated to a mental disorder appeared as the most severe daytime form of insomnia. This classification of insomnia sufferers along multiple defining dimensions provides initial validation for two basic insomnia subtypes, with a presumably distinct aetiology: insomnia characterized mainly by an 'internal' component, and a 'learned' insomnia. Research to determine which dimensions are critical for inclusion or differential weighting for defining a general typological system for insomnia sufferers is warranted.

Study Objectives: To determine if vestibular stimulation is an effective therapy for transient insomnia in a sleep phase advance model.

Summary The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18–52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P

Study objectives There is a need for the accurate assessment of circadian phase outside of the clinic/laboratory, particularly with the gold standard dim light melatonin onset (DLMO). We tested a novel kit designed to assist in saliva sampling at home for later determination of the DLMO. The home kit includes objective measures of compliance to the requirements for dim light and half-hourly saliva sampling. Design Participants were randomized to one of two 10-day protocols. Each protocol consisted of two back-to-back home and laboratory phase assessments in counterbalanced order, separated by a 5-day break. Setting Laboratory or participants' homes. Participants Thirty-five healthy adults, age 21-62 y. Interventions N/A. Measurements and results Most participants received at least one 30-sec epoch of light > 50 lux during the home phase assessments (average light intensity 4.5 lux), but on average for 50 lux or sampling errors. There was no significant difference between the home and laboratory DLMOs (P > 0.05); on average the home DLMOs occurred 9.6 min before the laboratory DLMOs. The home DLMOs were highly correlated with the laboratory DLMOs (r = 0.91, P Conclusions Participants were reasonably compliant to the home phase assessment procedures. The good agreement between the home and laboratory dim light melatonin onsets (DLMOs) demonstrates that including objective measures of light exposure and sample timing during home saliva sampling can lead to accurate home DLMOs. Clinical trial registration Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.

Study objectives To investigate the effects of a physiologic and a pharmacologic dose of exogenous melatonin on sleep latency and sleep efficiency in sleep episodes initiated across a full range of circadian phases. Design Double-blind placebo-controlled parallel-group design in a 27-day forced desynchrony paradigm with a 20-hour scheduled sleep-wake cycle. Setting Private suite of a general clinical research center, in the absence of time-of-day information. Subjects Thirty-six healthy, 18- to 30-year-old, men (n = 21) and women (n = 15). Interventions Oral melatonin (0.3 mg or 5.0 mg) or identical-appearing placebo was administered 30 minutes prior to each 6.67-hour sleep episode during forced desynchrony. Measurements and results Both doses of melatonin improved polysomnographically determined sleep efficiency from 77% in the placebo group to 83% for sleep episodes occurring during circadian phases when endogenous melatonin was absent. However, this remained below the average sleep efficiency of 88% observed during sleep episodes scheduled during the circadian night, when endogenous melatonin was present. Melatonin did not significantly affect sleep initiation or core body temperature. Melatonin appeared to maintain efficacy across the study and did not significantly affect percentages of slow-wave sleep or rapid eye movement sleep. Conclusions Exogenous melatonin administration possesses circadian-phase-dependent hypnotic properties, allowing for improved consolidation of sleep that occurs out of phase with endogenous melatonin secretion during the circadian night. The results support the hypothesis that both exogenous and endogenous melatonin attenuate the wake-promoting drive from the circadian system.

This paper presents a comprehensive review of delayed sleep phase syndrome (DSPS), a circadian-rhythm sleep disorder thought to result from the endogenous circadian pacemaker being "stuck" at a later-than-normal phase, relative to the desired sleep-wake schedule. A full understanding of this disorder is best appreciated from the context of shared modulation of sleep and wakefulness via sleep homeostatic and circadian systems. Typically emerging during adolescence, DSPS comes to clinical attention much less often than prevalence estimates would suggest, perhaps due to underrecognition by clinicians and misattribution of symptoms. Several treatment modalities have been suggested, including phototherapy, chronotherapy, and exogenous melatonin administration. However, caution is raised for the reason that more than 20 years after its initial description in the literature, the basic pathophysiology of DSPS remains poorly understood, as observed in the 2003 National Sleep Disorders Research Plan. Challenges for future research include elucidating the exact sleep homeostatic and circadian contributions to the disorder, improving the objective verification of this diagnosis instead of relying only on self-report information, and conducting treatment research aimed at determining efficacy, effectiveness, and mechanism or mechanisms of action.

The separate contribution of circadian rhythmicity and elapsed time awake on electroencephalographic (EEG) activity during wakefulness was assessed. Seven men lived in an environmental scheduling facility for 4 weeks and completed fourteen 42.85-h 'days', each consisting of an extended (28.57-h) wake episode and a 14.28-h sleep opportunity. The circadian rhythm of plasma melatonin desynchronized from the 42.85-h day. This allowed quantification of the separate contribution of circadian phase and elapsed time awake to variation in EEG power spectra (1-32 Hz). EEG activity during standardized behavioral conditions was markedly affected by both circadian phase and elapsed time awake in an EEG frequency- and derivation-specific manner. The nadir of the circadian rhythm in alpha (8-12 Hz) activity in both fronto-central and occipito-parietal derivations occurred during the biological night, close to the crest of the melatonin rhythm. The nadir of the circadian rhythm of theta (4.5-8 Hz) and beta (20-32 Hz) activity in the fronto-central derivation was located close to the onset of melatonin secretion, i.e. during the wake maintenance zone. As time awake progressed, delta frequency (1-4.5 Hz) and beta (20-32 Hz) activity rose monotonically in frontal derivations. The interaction between the circadian and wake-dependent increase in frontal delta was such that the intrusion of delta was minimal when sustained wakefulness coincided with the biological day, but pronounced during the biological night. Our data imply that the circadian pacemaker facilitates frontal EEG activation during the wake maintenance zone, by generating an arousal signal that prevents the intrusion of low-frequency EEG components, the propensity for which increases progressively during wakefulness.

STUDY OBJECTIVES To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. DESIGN Three-arm, single-site, randomized controlled trial. SETTING Academic medical center. PARTICIPANTS Fifty-four adults with chronic insomnia. INTERVENTIONS Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. MEASUREMENTS AND RESULTS Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. CONCLUSIONS Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. TRIAL REGISTRATION Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781.

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20–35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0–79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only ∼6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.

The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15–24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

A number of paradoxes are apparent in the assessment and treatment of psychophysiological insomnia and sleep state misperception. Three of these paradoxes exist as discrepancies between polysomnographic (PSG) measures and the subjective impressions regarding sleep quality and quantity. The remaining incongruity exists largely within the objective domain. In the case of subjective-objective discrepancies, patients with insomnia: (1) frequently identify themselves as having been awake when awakened from PSG defined sleep; (2) tend to overestimate sleep latency and underestimate total sleep time as compared with PSG measures; (3) appear to derive more benefit from pharmacotherapy that can be explained by objective gains. The remaining paradox pertains to the observation that hypnotic medications, by and large, do not normalize sleep architecture or produce a more 'sleep-like' EEG. In this paper, we review possible explanations for these various paradoxes, introduce a new perspective and suggest possible research avenues. The model introduced is based on the observation that beta and/or gamma activity (which have been found to be associated with cognitive processes) is enhanced in insomnia at or around sleep onset. We propose that this kind of high frequency EEG activity may interfere with the normal establishment of sleep onset-related mesograde amnesia. As a result, the patient with insomnia maintains a level of information and/or memory processing that blurs the phenomenological distinction between sleep and wakefulness and influences retrospective judgments about sleep initiation and duration.

Previous research has suggested an association between the subjective report of illness from environmental chemical odors and poorer cognitive task performance in persons with industrial levels of xenobiotic exposures. The present study investigated baseline morning performance on a computerized divided attention task in active retired adults without occupational exposures or clinical disorders who nonetheless rated themselves currently high versus low in episodic illness from the odor of certain environmental chemicals. The chemically intolerant group showed slower reaction times in registering both centrally and peripherally placed stimuli, but no difference in making target tracking errors. Measures of negative affect did not account for these findings. Taken together with evidence for heightened neurobehavioral sensitization in this population, the data suggest disturbances in allocation of attention and related cognitive functions.

Sleep restriction causes impaired cognitive performance that can result in adverse consequences in many occupational settings. Individuals may rely on self-perceived alertness to decide if they are able to adequately perform a task. It is therefore important to determine the relationship between an individual's self-assessed alertness and their objective performance, and how this relationship depends on circadian phase, hours since awakening, and cumulative lost hours of sleep. Healthy young adults (aged 18-34) completed an inpatient schedule that included forced desynchrony of sleep/wake and circadian rhythms with twelve 42.85-hour "days" and either a 1:2 (n = 8) or 1:3.3 (n = 9) ratio of sleep-opportunity:enforced-wakefulness. We investigated whether subjective alertness (visual analog scale), circadian phase (melatonin), hours since awakening, and cumulative sleep loss could predict objective performance on the Psychomotor Vigilance Task (PVT), an Addition/Calculation Test (ADD) and the Digit Symbol Substitution Test (DSST). Mathematical models that allowed nonlinear interactions between explanatory variables were evaluated using the Akaike Information Criterion (AIC). Subjective alertness was the single best predictor of PVT, ADD, and DSST performance. Subjective alertness alone, however, was not an accurate predictor of PVT performance. The best AIC scores for PVT and DSST were achieved when all explanatory variables were included in the model. The best AIC score for ADD was achieved with circadian phase and subjective alertness variables. We conclude that subjective alertness alone is a weak predictor of objective vigilant or cognitive performance. Predictions can, however, be improved by knowing an individual's circadian phase, current wake duration, and cumulative sleep loss.

The purpose of the present study was to examine explicit and implicit memory for auditory events presented immediately prior to sleep onset. The results of the present study suggest subjects allowed 10 minutes of sleep demonstrate deficient explicit memory for auditory stimuli presented immediately prior to sleep onset. Subjects showed severe free recall deficits for word pairs presented 3 minutes prior to sleep onset and recognition deficits for stimuli from 1 minute prior to sleep onset. Implicit memory for word pairs presented prior to sleep onset seemed intact, and no recency effect was observed. In contrast to the 10-minute condition, subjects allowed 30 seconds of sleep demonstrated no equivalent explicit memory deficits. Memory performance in both delay conditions, however, appeared globally impaired relative to control data from subjects who remained awake. The results are interpreted in terms of elaboration of stimulus encoding, interruption of consolidation and retrograde versus anterograde amnesia.

The relation between cognitive processing and sleep is examined in three areas: the effect of sleep in producing deficits in memory for events that take place immediately before sleep, the effect of naps on performance following sleep, and the capacity of individuals to process information presented while asleep. A review of the literature and discussion of practical implications lead to the conclusions that sleep does produce a form of amnesia for events taking place immediately before sleep and that sleep inertia can produce detrimental effect. on subsequent performance, particularly if individuals have been sleep deprived. Nevertheless, naps have been found to improve subsequent performance during critical work periods if time for recovery from sleep inertia is provided. In the area of cognitive processing during sleep, con- siderable evidence exists for some forms of cognitive processing. However, elaborated processing of semantic information during sleep has rarely been demonstrated in the absence of...

Nearly 20% of the labor force worldwide, work shifts that include work hours outside 07:00 h to 18:00 h. Shift work is common in many occupations that directly affect the health and safety of others (e.g., protective services, transportation, healthcare), whereas quality of life, health, and safety during shift work and the commute home can affect workers in any field. Increasing evidence indicates that shift-work schedules negatively influence worker physiology, health, and safety. Shift work disrupts circadian sleep and alerting cycles, resulting in disturbed daytime sleep and excessive sleepiness during the work shift. Moreover, shift workers are at risk for shift work disorder (SWD). This review focuses on shift work and the assessment and management of sleepiness and sleep disruption associated with shift work schedules and SWD. Management strategies include approaches to promote sleep, wakefulness, and adaptation of the circadian clock to the imposed work schedule. Additional studies are needed to further our understanding of the mechanisms underlying the health risks of shift work, understanding which shift workers are at most risk of SWD, to investigate treatment options that address the health and safety burdens associated with shift work and SWD, and to further develop and assess the comparative effectiveness of countermeasures and treatment options.

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18–74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.