Sleep Disturbance in Tourette's Disorder: Potential Underlying Mechanisms.

Purpose of review: Sleep disturbance is common in TD. However, our understanding of the pathophysiological mechanisms involved is preliminary. This review summarizes findings from neuroimaging, genetic, and animal studies to elucidate potential underlying mechanisms of sleep disruption in TD. Recent findings: Preliminary neuroimaging research indicates increased activity in the premotor cortex, and decreased activity in the prefrontal cortex is associated with NREM sleep in TD. Striatal dopamine exhibits a circadian rhythm; and is influenced by the suprachiasmatic nucleus via multiple molecular mechanisms. Conversely, dopamine receptors regulate circadian function and striatal expression of circadian genes. The association of TD with restless legs syndrome and periodic limb movements indicates shared pathophysiology, including iron deficiency, and variants in the BTDB9 gene. A mutations in the L-Histidine Decarboxylase gene in TD, suggests the involvement of the histaminergic system, implicated in arousal, in TD. Summary: These biological markers have implications for application of novel, targeted interventions, including noninvasive neuromodulation, iron supplementation, histamine receptor antagonists, and circadian-based therapies for tic symptoms and/or sleep and circadian rhythms in TD.

Effects of forehead cooling and supportive care on menopause-related sleep difficulties, hot flashes and menopausal symptoms: a pilot study.

OBJECTIVE/BACKGROUND: This pilot study explored the efficacy of a novel forehead cooling device for perceived sleep difficulties and hot flashes in menopausal-age women. PARTICIPANTS: 20 women (55.1 ± 4.2 years; 19 post-menopausal) with insomnia symptoms and self-reported two or more hot flashes per day. METHODS: Participants completed daily assessments of sleep and hot flashes (via diaries) across 1 baseline week and 4 weeks of open-label, in-home, nightly treatment with a forehead cooling device (15-18°C) along with sleep hygiene instructions. They also completed ratings of insomnia and menopausal symptoms using standardized questionnaires. RESULTS: Women reported reductions in sleep onset latency (SOL), wakefulness after sleep onset (WASO), and nocturnal hot flash severity during the first week of treatment (SOL: 25.7 ± 18.4 min; WASO: 36.3 ± 27.3 min; hot flash severity: 3.0 ± 2.8) compared with baseline (SOL: 38 ± 26.3 min; WASO: 52.2 ± 35.6 min; hot flash severity: 6.8 ± 3.7), with further improvements after 2-4 weeks of use (p < .001). There were also clinically meaningful reductions in insomnia severity and hot flash-related daily interference and lower psychological and physical symptom scores on the Greene climacteric scale after treatment (all p's<0.001). CONCLUSIONS: This exploratory, naturalistic, pilot study shows that nightly use of a forehead cooling device produces improvements in self-reported sleep and reductions in insomnia, hot flash, and other menopausal, symptoms. Controlled studies are warranted to determine the role of this therapy in the management of sleep difficulties and menopausal symptoms in women. Further mechanistic studies are needed to understand the physiological impact of forehead cooling on sleep and menopausal symptoms.

Effects of a forehead cooling device in veterans with chronic insomnia disorder and co-morbid medical and psychiatric conditions: a pilot study.

PURPOSE: While forehead cooling has been studied in patients with insomnia in the absence of comorbid medical/psychiatric disorders, it has never been evaluated in patients with insomnia in the presence of co-morbid medical/psychiatric disorders. METHODS: Veterans with chronic insomnia disorder and co-morbid medical and psychiatric conditions received 4-week open-label, in-home, nightly treatment with a forehead cooling device (14-16 °C) along with personalized sleep hygiene following baseline assessments. Pre- and post-treatment, participants completed the Insomnia Severity Index (ISI), the Generalized Anxiety Disorder 7-item scale (GAD-7), and the Patient Health Questionnaire 9-item scale (PHQ-9). Participants recorded daily sleep and anxiety/arousal symptoms. RESULTS: Of 24 veterans (20 men, 42.2 ± 9.5 years), 17 (71%) had marked insomnia severity improvement (a decrease of > 8 on the ISI) and 10 (42%) participants scored 7 or below on the ISI at post-treatment reflecting remission. Participants reported reductions in sleep onset latency (SOL) (F = 12.9, p < 0.001), and wakefulness after sleep onset (WASO) (F = 8.4, p < 0.001) across treatment. They also had significant reductions in insomnia severity (t = 10.04, p < 0.001), anxiety (t = 3.59, p = 0.002), and depression (t = 7.75, p < 0.001) from pre- to post-treatment. CONCLUSION: This pilot study shows that 4-week nightly use of a forehead cooling device produces improvements in insomnia, anxiety, and depressive symptoms in veterans with chronic insomnia disorder and co-morbid medical and psychiatric conditions. Controlled studies are warranted to determine the role of this therapy in the management of insomnia in veterans. TRIAL REGISTRATION: Not required as a small sample size feasibility study.

Impact of acute sleep restriction on cerebral glucose metabolism during recovery non-rapid eye movement sleep among individuals with primary insomnia and good sleeper controls.

BACKGROUND: Restricting time in bed improves insomnia symptoms, but the neural mechanisms for this effect are unknown. Total and partial acute sleep restriction may be useful paradigms for elucidating these effects. We examined the impact of acute sleep restriction on cerebral glucose metabolism during non-rapid eye movement (NREM) sleep in individuals with primary insomnia (n = 17) and good sleep (n = 19). METHODS: Participants underwent [18F]fluorodeoxyglucose positron emission tomography scans during baseline and recovery NREM sleep following one night of partial or total sleep restriction. We compared group differences in baseline-recovery changes, as well as main effects of group and condition (baseline vs. recovery NREM sleep), for relative regional cerebral metabolic rate for glucose (rCMRglc), whole-brain glucose metabolism, and sleep quality. RESULTS: Relative rCMRglc was significantly lower during recovery NREM sleep compared to baseline in the left frontoparietal cortex, medial frontal cortex, posterior cingulate cortex, and thalamus, with no significant group differences. Good sleepers, but not insomnia patients, had lower whole-brain glucose metabolism during recovery NREM sleep compared to baseline. Acute sleep restriction improved sleep quality in individual with insomnia. Subgroup analyses including only participants who underwent partial sleep restriction yielded the same pattern of findings. CONCLUSION: Individuals with insomnia and good sleepers showed similar relative rCMRglc responses to acute sleep restriction. Brain regions showing the greatest baseline-recovery changes in both groups included regions previously shown to have smaller sleep-wake differences in patients with primary insomnia. Acute sleep restriction, and by extension sleep restriction therapy, may impact regional metabolic alterations that characterize insomnia.

Subjective-Objective Sleep Discrepancy Is Associated With Alterations in Regional Glucose Metabolism in Patients With Insomnia and Good Sleeper Controls.

Objectives: Sleep discrepancies are common in primary insomnia (PI) and include reports of longer sleep onset latency (SOL) than measured by polysomnography (PSG) or "negative SOL discrepancy." We hypothesized that negative SOL discrepancy in PI would be associated with higher relative glucose metabolism during nonrapid eye movement (NREM) sleep in brain networks involved in conscious awareness, including the salience, left executive control, and default mode networks. Methods: PI (n = 32) and good sleeper controls (GS; n = 30) completed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans during NREM sleep, and relative regional cerebral metabolic rate for glucose (rCMRglc) was measured. Sleep discrepancy was calculated by subtracting PSG-measured SOL on the PET night from corresponding self-report values the following morning. We tested for interactions between group (PI vs. GS) and SOL discrepancy for rCMRglc during NREM sleep using both a region of interest mask and exploratory whole-brain analyses. Results: Significant group by SOL discrepancy interactions for rCMRglc were observed in several brain regions (pcorrected < .05 for all clusters). In the PI group, more negative SOL discrepancy (self-reported > PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula and middle/posterior cingulate during NREM sleep. In GS, more positive SOL discrepancy (self-reported < PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula, left anterior cingulate cortex, and middle/posterior cingulate cortex. Conclusions: Although preliminary, these findings suggest regions of the brain previously shown to be involved in conscious awareness, and the perception of PSG-defined states may also be involved in the phenomena of SOL discrepancy.

Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers.

STUDY OBJECTIVES: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). METHODS: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21-60), sex, and race. We conducted [18F]fluoro-2-deoxy-D-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. RESULTS: Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected < 0.05. CONCLUSIONS: Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness.

The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults.

Electroencephalographic slow-wave activity (0.5-4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow wave activity was associated with higher prefrontal metabolism during wakefulness and whether this relationship interacted with age. Fifty-two participants aged 25-61 years were enrolled into studies that included polysomnography and a (18) [F]-fluoro-deoxy-glucose positron emission tomography scan during wakefulness. Absolute and relative measures of NREM slow wave activity were assessed. Semiquantitative and relative measures of cerebral metabolism were collected to assess whole brain and regional metabolism, focusing on two regions of interest: the dorsolateral prefrontal cortex and the orbitofrontal cortex. Greater relative slow wave activity was associated with greater dorsolateral prefrontal metabolism. Age and slow wave activity interacted significantly in predicting semiquantitative whole brain metabolism and outside regions of interest in the posterior cingulate, middle temporal gyrus and the medial frontal gyrus, such that greater slow-wave activity was associated with lower metabolism in the younger participants and greater metabolism in the older participants. These results suggest that slow-wave activity is associated with cerebral metabolism during wakefulness across the adult lifespan within regions important for executive function.

Comparing neural correlates of REM sleep in posttraumatic stress disorder and depression: a neuroimaging study.

Rapid eye movement (REM) sleep disturbances predict poor clinical outcomes in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In MDD, REM sleep is characterized by activation of limbic and paralimbic brain regions compared to wakefulness. The neural correlates of PTSD during REM sleep remain scarcely explored, and comparisons of PTSD and MDD have not been conducted. The present study sought to compare brain activity patterns during wakefulness and REM sleep in 13 adults with PTSD and 12 adults with MDD using [¹8F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET). PTSD was associated with greater increase in relative regional cerebral metabolic rate of glucose (rCMRglc) in limbic and paralimbic structures in REM sleep compared to wakefulness. Post-hoc comparisons indicated that MDD was associated with greater limbic and paralimbic rCMRglc during wakefulness but not REM sleep compared to PTSD. Our findings suggest that PTSD is associated with increased REM sleep limbic and paralimbic metabolism, whereas MDD is associated with wake and REM hypermetabolism in these areas. These observations suggest that PTSD and MDD disrupt REM sleep through different neurobiological processes. Optimal sleep treatments between the two disorders may differ: REM-specific therapy may be more effective in PTSD.

Chronotype and diurnal patterns of positive affect and affective neural circuitry in primary insomnia.

While insomnia is a well-established risk factor for the initial onset, recurrence or relapse of affective disorders, the specific characteristics of insomnia that confer risk remain unclear. Patients with insomnia with an evening chronotype may be one particularly high-risk group, perhaps due to alterations in positive affect and its related affective circuitry. We explored this possibility by comparing diurnal patterns of positive affect and the activity of positive affect-related brain regions in morning- and evening-types with insomnia. We assessed diurnal variation in brain activity via the relative regional cerebral metabolic rate of glucose uptake by using [(18) F]fluorodeoxyglucose-positron emission tomography during morning and evening wakefulness. We focused on regions in the medial prefrontal cortex and striatum, which have been consistently linked with positive affect and reward processing. As predicted, chronotypes differed in their daily patterns in both self-reported positive affect and associated brain regions. Evening-types displayed diurnal patterns of positive affect characterized by phase delay and smaller amplitude compared with those of morning-types with insomnia. In parallel, evening-types showed a reduced degree of diurnal variation in the metabolism of both the medial prefrontal cortex and the striatum, as well as lower overall metabolism in these regions across both morning and evening wakefulness. Taken together, these preliminary findings suggest that alterations in the diurnal activity of positive affect-related neural structures may underlie differences in the phase and amplitude of self-reported positive affect between morning and evening chronotypes, and may constitute one mechanism for increased risk of mood disorders among evening-type insomniacs.

Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US Military Veterans.

OBJECTIVE: Pharmacological and cognitive-behavioral treatments targeting insomnia and nightmares have been shown to be effective in the treatment of military veterans with sleep complaints comorbid with symptoms of stress-related disorders, including Post-Traumatic Stress Disorder (PTSD), but the two approaches have not been directly compared. This randomized controlled trial compared the effects of prazosin vs. a behavioral sleep intervention (BSI), targeting nightmares and insomnia against a placebo pill control condition on sleep and daytime symptoms. METHODS: Fifty United States military veterans (mean age 40.9years, SD=13.2years) with chronic sleep disturbances were randomized to prazosin (n=18), BSI (n=17), or placebo (n=15). Each intervention lasted 8weeks. Participants completed self-report measures of insomnia severity, sleep quality, and sleep disturbances. All kept a sleep diary throughout the intervention period. Polysomnographic studies were conducted pre- and post-intervention. RESULTS: Both active treatment groups showed greater reductions in insomnia severity and daytime PTSD symptom severity. Sleep improvements were found in 61.9% of those who completed the active treatments and 25% of those randomized to placebo. CONCLUSION: BSI and prazosin were both associated with significant sleep improvements and reductions in daytime PTSD symptoms in this sample of military veterans. Sleep-focused treatments may enhance the benefits of first-line PTSD treatments.

A Neurobiological Model of Insomnia.

Insomnia is a common clinical condition resulting in significant costs and morbidity. Previous models of insomnia focusing on psychological and behavioral processes are useful clinically, but lack neurobiological specificity. We propose an insomnia model based on basic and clinical neuroscience findings, and hypothesize that insomnia results from persistent activity in wake-promoting neural structures during NREM sleep. The simultaneous occurrence of sleeping and waking neural activity helps to explain clinical phenomenology and treatment effects in insomnia.

Protecting sleep, promoting health in later life: a randomized clinical trial.

OBJECTIVES: To determine in healthy people aged > or = 75 years 1) if restricting time in bed and education in health sleep practices are superior to an attention-only control condition (i.e., education in healthy dietary practices) for maintaining or enhancing sleep continuity and depth over 2.5 years; and 2) if maintenance or enhancement of sleep continuity and depth promotes the maintenance or enhancement of health-related quality of life. METHODS: Single-blind, randomized, clinical trial in a university-based sleep center, enrolling 64 adults (n = 30 women, 34 men; mean age = 79 years) without sleep/wake complaints (e.g., insomnia or daytime sleepiness), followed by randomized assignment to either: 1) restriction of time in bed by delaying bedtime 30 minutes nightly for 18 months, together with education in healthy sleep practices (SLEEP); or 2) attention-only control condition with education in health dietary practices (NUTRITION). RESULTS: SLEEP did not enhance sleep continuity or depth; however, compared with NUTRITION, SLEEP was associated with decreased time spent asleep (about 30 minutes nightly over 18 months). Contrary to hypothesis, participants in SLEEP reported a decrement in physical health-related quality of life and an increase in medical burden (cardiovascular illness), relative to NUTRITION. Neither markers of inflammation, body mass index, or exercise explained treatment-related changes in medical burden. CONCLUSIONS: Although we cannot exclude a positive effect of education in healthy nutrition, for healthy elderly >75 years of age without sleep complaints, reducing sleep time may be detrimental, whereas allowing more time to sleep (about 7.5 hours nightly) is associated with better maintenance of physical health-related quality of life and stability of medical illness burden over 30 months.

Memory before and after sleep in patients with moderate obstructive sleep apnea.

OBJECTIVE: The aim of this study was to investigate the effects of obstructive sleep apnea (OSA) on procedural and declarative memory encoding in the evening prior to sleep, on memory consolidation during subsequent sleep, and on retrieval in the morning after sleep. METHODS: Memory performance (procedural mirror-tracing task, declarative visual and verbal memory task) and general neuropsychological performance were assessed before and after one night of polysomnographic monitoring in 15 patients with moderate OSA and 20 age-, sex-, and IQ-matched healthy subjects. RESULTS: Encoding levels prior to sleep were similar across groups for all tasks. Conventional analyses of averaged mirror tracing performance suggested a significantly reduced overnight improvement in OSA patients. Single trial analyses, however, revealed that this effect was due to significantly flattened learning curves in the evening and morning session in OSA patients. OSA patients showed a significantly lower verbal retention rate and a non-significantly reduced visual retention rate after sleep compared to healthy subjects. Polysomnography revealed a significantly reduced REM density, increased frequency of micro-arousals, elevated apnea-hypopnea index, and subjectively disturbed sleep quality in OSA patients compared to healthy subjects. CONCLUSIONS: The results suggest that moderate OSA is associated with a significant impairment of procedural and verbal declarative memory. Future work is needed to further determine the contribution of structural or functional alterations in brain circuits relevant for memory, and to test whether OSA treatment improves or normalizes the observed deficits in learning.

Functional neuroimaging of sleep disorders.

Functional neuroimaging methods provide a means to understand brain function in patients with sleep disorders. This paper summarizes functional neuroimaging findings in sleep disorders patients, and studies addressing the pharmacology of sleep and sleep disorders. Areas in which functional neuroimaging methods may be helpful in sleep medicine, and in which future development is advised, include: 1) clarification of pathophysiology; 2) aid in differential diagnosis; 3) assessment of treatment response; 4) guiding new drug development; and 5) monitoring treatment response.

EEG spectral analysis in primary insomnia: NREM period effects and sex differences.

STUDY OBJECTIVES: To compare NREM EEG power in primary insomnia (PI) and good sleeper controls (GSC), examining both sex and NREM period effects; to examine relationships between EEG power, clinical characteristics, and self-reports of sleep. DESIGN: Overnight polysomnographic study. SETTING: Sleep laboratory. PARTICIPANTS: PI (n=48; 29 women) and GSC (n=25; 15 women). INTERVENTIONS: None. MEASUREMENTS: EEG power from 1-50 Hz was computed for artifact-free sleep epochs across four NREM periods. Repeated measures mixed effect models contrasted differences between groups, EEG frequency bands, and NREM periods. EEG power-frequency curves were modeled using regressions with fixed knot splines. RESULTS: Mixed models showed no significant group (PI vs. GSC) differences; marginal sex differences (delta and theta bands); significant differences across NREM periods; and group*sex and group*NREM period interactions, particularly in beta and gamma bands. Modeled power-frequency curves showed no group difference in whole-night NREM, but PI had higher power than GSC from 18-40 Hz in the first NREM period. Among women, PI had higher 16 to 44-Hz power than GSC in the first 3 NREM periods, and higher 3 to 5-Hz power across all NREM periods. PI and GSC men showed no consistent differences in EEG power. High-frequency EEG power was not related to clinical or subjective sleep ratings in PI. CONCLUSIONS: Women with PI, but not men, showed increased high-frequency and low-frequency EEG activity during NREM sleep compared to GSC, particularly in early NREM periods. Sex and NREM period may moderate quantitative EEG differences between PI and GSC.

Sleeping well, aging well: a descriptive and cross-sectional study of sleep in "successful agers" 75 and older.

OBJECTIVES: To examine diary-based, laboratory-based, and actigraphic measures of sleep in a group of healthy older women and men (> or =75 years of age) without sleep/wake complaints and to describe sleep characteristics which may be correlates of health-related quality of life in old age. DESIGN: Cross-sectional, descriptive study. SETTING: University-based sleep and chronobiology program. INTERVENTION: None. PARTICIPANTS: Sixty-four older adults (30 women, 34 men; mean age 79). MEASUREMENTS: We used diary-, actigraphic-, and laboratory-based measures of sleep, health-related quality of life, mental health, social support, and coping strategies. We used two-group t-tests to compare baseline demographic and clinical measures between men and women, followed by ANOVA on selected EEG measures to examine first-night effects as evidence of physiological adaptability. Finally, we examined correlations between measure of sleep and health-related quality of life. RESULTS: We observed that healthy men and women aged 75 and older can experience satisfactory nocturnal sleep quality and daytime alertness, especially as reflected in self-report and diary-based measures. Polysomnography (psg) suggested the presence of a first-night effect, especially in men, consistent with continued normal adaptability in this cohort of healthy older adults. Continuity and depth of sleep in older women were superior to that of men. Diary-based measures of sleep quality (but not psg measures) correlated positively (small to moderate effect sizes) with physical and mental health-related quality of life. CONCLUSIONS: Sleep quality and daytime alertness in late life may be more important aspects of successful aging than previously appreciated. Good sleep may be a marker of good functioning across a variety of domains in old age. Our observations suggest the need to study interventions which protect sleep quality in older adults to determine if doing so fosters continued successful aging.

Financial strain is a significant correlate of sleep continuity disturbances in late-life.

Although psychological stress has been associated with disturbed sleep in younger populations, little is known about the stress-sleep relationship in late-life. In the present study, we evaluated relationships among a chronic stressor, ongoing financial strain, and sleep in a heterogenous sample (n=75) of community-dwelling elders (mean age=74.0 years). Self-report measures included ongoing financial strain, mental health, physical health and subjective sleep quality. Sleep duration, continuity, and architecture were measured by polysomnography (PSG). Analysis of variance and regression were used to test the hypothesis that ongoing financial strain is a significant correlate of disturbed sleep in the elderly. Covariates included age, sex, mental health and physical health. Analyses revealed that ongoing financial strain is a significant correlate of PSG-assessed sleep latency, wakefulness after sleep onset, and sleep efficiency. After adjusting for the effects of age, sex, mental health, and physical health on sleep, ongoing financial strain was associated with lower sleep efficiency (p<.01). Our results show that chronic stress, as measured by ongoing financial strain, is a significant correlate of sleep disturbances in the elderly, even after adjusting for factors known to impact sleep in late-life.

Daytime symptoms in primary insomnia: a prospective analysis using ecological momentary assessment.

OBJECTIVES: To prospectively characterize and compare daytime symptoms in primary insomnia (PI) and good sleeper control (GSC) subjects using ecological momentary assessment; to examine relationships between daytime symptom factors, retrospective psychological and sleep reports, and concurrent sleep diary reports. METHODS: Subjects included 47 PI and 18 GSC. Retrospective self-reports of daytime and sleep symptoms were collected. Daytime symptoms and sleep diary information were then collected for 1 week on hand-held computers. The Daytime Insomnia Symptom Scale (DISS) consisted of 19 visual analog scales completed four times per day. Factors for the DISS were derived using functional principal components analysis. Nonparametric tests were used to contrast DISS, retrospective symptom ratings, and sleep diary results in PI and GSC subjects, and to examine relationships among them. RESULTS: Four principal components were identified for the DISS: Alert Cognition, Negative Mood, Positive Mood, and Sleepiness/Fatigue. PI scored significantly worse than GSC on all four factors (p<0.0003 for each). Among PI subjects DISS scales and retrospective psychological symptoms were related to each other in plausible ways. DISS factors were also related to self-report measures of sleep, whereas retrospective psychological symptom measures were not. CONCLUSIONS: Daytime symptom factors of alertness, positive and negative mood, and sleepiness/fatigue, collected with ecological momentary assessment, showed impairment in PI versus GSC. DISS factors showed stronger relationships to retrospective sleep symptoms and concurrent sleep diary reports than retrospective psychological symptoms. The diurnal pattern of symptoms may inform studies of the pathophysiology and treatment outcome of insomnia.

Diurnal variation in regional brain glucose metabolism in depression.

BACKGROUND: This study compared diurnal variation in mood and regional cerebral metabolic rate of glucose (rCMRglc) in depressed and healthy subjects. METHODS: Depressed and healthy subjects were investigated using [18F]-fluoro-deoxyglucose positron emission tomography scans during morning and evening wakefulness. All subjects completed subjective mood ratings at both times of day. Statistical parametric mapping was used to compare rCMRglc between the two groups across time of day. RESULTS: Depressed patients showed evening mood improvements compared with healthy subjects. Compared with healthy subjects, depressed patients showed smaller increases in rCMRglc during evening relative to morning wakefulness in lingual and fusiform cortices, midbrain reticular formation, and locus coeruleus and greater increases in rCMRglc in parietal and temporal cortices. Depressed patients had hypermetabolism in limbic-paralimbic regions and hypometabolism in frontal and parietal cortex at both times of day compared with healthy subjects. CONCLUSIONS: Variation in rCMRglc differs across times of day in depressed and healthy subjects. In depressed patients, evening mood improvements were associated with increased metabolic activity in ventral limbic-paralimbic, parietal, temporal, and frontal regions and in the cerebellum. This increased metabolic pattern during evening wakefulness may reflect partial normalization of primary and compensatory neural systems involved in affect production and regulation.

M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.