Stage N2 Sleep Research Articles

Sleep, cardiovascular risk factors, and kidney function: The Multi-Ethnic Study of Atherosclerosis (MESA)

ObjectivesExamine the associations of sleep measures with kidney function changes over time among individuals from a community-based study. MethodsThe sample includes 1657 participants (287 with chronic kidney disease [CKD]) in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (mean age: 57.7 years, male: 46.0%). We examined associations between a large set of sleep variables (polysomnography, actigraphy, and questionnaires) and cardiovascular disease risk factors and changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio over approximately 5 years using high-dimensional regression. We investigated the modifying effect of sleep on the associations between cardiovascular disease risk factors and kidney function. ResultsSleep metrics predicted kidney function decline only among individuals with baseline CKD. Among this group, eGFR decline was associated with decreased stage N3 sleep (0.32 mL/min/1.73 m2/y per 10% decrease in N3, p < .001); increased actigraphy napping frequency (beta: -0.20 [-0.30, -0.07]); and actigraphy sleep midpoint trajectory in early morning (ref: midnight, beta: -0.84 [-1.19, -0.50]). Urinary albumin-to-creatinine ratio increase was associated with high wake bouts trajectory (ref: low, beta: 0.97 [0.28, 1.67]) and increased sleep-related hypoxemia (oxygen saturation %time<90 [≥5%], beta: 2.17 [1.26, 3.08]). Sleep metrics--N3 sleep, naps, and midpoint trajectory--significantly modified associations between hemoglobin A1C and eGFR decline. ConclusionsReduced deep sleep, daytime napping, increased wake bouts, delayed sleep rhythms, and overnight hypoxemia are associated with longitudinal kidney function decline, with effects most apparent in individuals with CKD. Deep sleep, napping, and sleep timing modified the association between hemoglobin A1C and kidney function.

Sleep in multiple sclerosis: a systematic review and meta-analysis of polysomnographic findings.

This study aims to explore the polysomnographically measured sleep differences between patients with multiple sclerosis (MS) and healthy control patients. An electronic literature search was conducted in EMBASE, MEDLINE, all EBM databases, CINAHL, and PsycINFO from inception to March 2022. A random-effects model was applied to explore the pooled effect sizes of polysomnographic differences between patients with MS and control patients. Thirteen studies were identified for meta-analysis. The meta-analyses revealed significant reductions in stage N2 sleep and sleep efficiency and increases in wake time after sleep onset, the periodic limb movement index, and the periodic limb movement arousal index in patients with MS compared with control patients. Meta-regression analyses showed that some of the heterogeneity was explained by age and daytime sleepiness of patients with MS. Our study showed that polysomnographic abnormalities are present in MS. Our findings also underscore the need for a comprehensive polysomnographic assessment of sleep changes in patients with MS. Furthermore, the effects of age and daytime sleepiness in patients with MS on sleep changes should also be carefully considered and closely monitored in the management of MS. Zhang Y, Ren R, Yang L, etal. Sleep in multiple sclerosis: a systematic review and meta-analysis of polysomnographic findings. J Clin Sleep Med. 2023;19(2):253-265.

Bidirectional associations between physical activity and sleep in older adults: a multilevel analysis using polysomnography

Although recent studies have examined the bidirectional associations between physical activity and sleep parameters, few have focused on older adults utilizing objective assessments, such as polysomnography. This micro-longitudinal observational study included 92 Japanese older adults (aged 65–86 years) who underwent objective evaluations of sleep quality using polysomnography and completed subjective sleep-related questionnaires. Activity levels were assessed using an accelerometer. Polysomnography, subjective sleep-related questionnaires, and accelerometer were administered for 7 consecutive days. Multilevel models (participant-, day-level) were used to examine the temporal associations of objective and subjective sleep parameters with sedentary behavior and physical activity. In the day-level analysis, higher levels of sedentary behavior during daytime were associated with longer rapid eye movement (REM) sleep, shorter REM latency, lower levels of non-REM sleep (stage N3), and reduced delta power during daytime. Higher levels of low-intensity physical activity during daytime were associated with lower levels of REM sleep, longer REM latency, and increased stage N3 sleep in the day-level analysis. Higher levels of moderate-to-vigorous physical activity were associated with increased REM latency. Longer subjective sleep time was associated with increased next-day moderate-to-vigorous physical activity. Thus, low-intensity physical activity may provide objective benefits related to deep sleep parameters in older adults.

Exploration of Insomnia With Excessive Daytime Sleepiness From Clinical and Polysomnographic Perspectives

Objectives: Insomnia is a disorder that involves poor sleep quality at nighttime and various symptoms in the daytime. Although it is known to increase cardiovascular risk as well as psychiatric comorbidities such as depression and anxiety, less attention has been paid to daytime sleepiness in patients with insomnia. This study aimed to investigate clinical and polysomnographic characteristics and identify factors influencing excessive daytime sleepiness in patients with insomnia.Methods: Between 2014 and 2022, 1,241 patients with insomnia as the primary symptom who underwent polysomnography were included in the study. Patients with an Epworth sleepiness scale ≥10 were classified as having insomnia accompanied by daytime sleepiness, and sleep-related questionnaire responses and polysomnography findings were utilized for analysis.Results: A total of 327 patients (26.3%) had daytime sleepiness, and a higher prevalence was observed in younger and male individuals. Poor sleep quality, severe depression, and insomnia were identified through the questionnaire. Polysomnography showed longer total sleep times, a higher proportion of stage N3 sleep, and higher sleep efficiency. The variables related to the Epworth sleepiness scale identified in multiple regression analysis were age, the Korean Beck Depression Inventory-II, sleep latency, and the apnea-hypopnea index on polysomnography.Conclusions: Insomnia with excessive daytime sleepiness was more affected by depression than indicated by polysomnography findings. The pathophysiology is presumed to be related to sleep misperception, and further studies are needed to elucidate the discrepancy between excessive daytime sleepiness and polysomnography findings.

Effects of exercise on sleep spindles in Parkinson's disease.

BackgroundIn a randomized, controlled trial, we showed that high-intensity rehabilitation, combining resistance training and body-weight interval training, improves sleep efficiency in Parkinson's disease (PD). Quantitative sleep EEG (sleep qEEG) features, including sleep spindles, are altered in aging and in neurodegenerative disease.ObjectiveThe objective of this post-hoc analysis was to determine the effects of exercise, in comparison to a sleep hygiene, no-exercise control group, on the quantitative characteristics of sleep spindle morphology in PD.MethodsWe conducted an exploratory post-hoc analysis of 24 PD participants who were randomized to exercise (supervised 3 times/week for 16 weeks) versus 26 PD participants who were assigned to a sleep hygiene, no-exercise control group. At baseline and post-intervention, all participants completed memory testing and underwent polysomnography (PSG). PSG-derived sleep EEG central leads (C3 and C4) were manually inspected, with rejection of movement and electrical artifacts. Sleep spindle events were detected based on the following parameters: (1) frequency filter = 11–16 Hz, (2) event duration = 0.5–3 s, and (3) amplitude threshold 75% percentile. We then calculated spindle morphological features, including density and amplitude. These characteristics were computed and averaged over non-rapid eye movement (NREM) sleep stages N2 and N3 for the full night and separately for the first and second halves of the recording. Intervention effects on these features were analyzed using general linear models with group x time interaction. Significant interaction effects were evaluated for correlations with changes in performance in the memory domain.ResultsA significant group x time interaction effect was observed for changes in sleep spindle density due to exercise compared to sleep hygiene control during N2 and N3 during the first half of the night, with a moderate effect size. This change in spindle density was positively correlated with changes in performance on memory testing in the exercise group.ConclusionsThis study is the first to demonstrate that high-intensity exercise rehabilitation has a potential role in improving sleep spindle density in PD and leading to better cognitive performance in the memory domain. These findings represent a promising advance in the search for non-pharmacological treatments for this common and debilitating non-motor symptom.

Polysomnographic features of idiopathic restless legs syndrome: a systematic review and meta-analysis of 13 sleep parameters and 23 leg movement parameters.

This study aims to explore the polysomnographically measured sleep and leg movement differences between idiopathic restless legs syndrome (RLS) patients and healthy controls. An electronic literature search was conducted in EMBASE, MEDLINE, all EBM databases, CINAHL, and PsycINFO. Only observational case-control studies were included in the meta-analysis. The differences in 13 sleep parameters and 23 leg movement parameters between RLS patients and healthy controls were explored. Thirty-eight studies were identified for systematic review, 31 of which were used for meta-analysis. Meta-analyses revealed significant reductions in total sleep time, sleep efficiency, stage N2 and rapid eye movement (REM) sleep percentages, and increases in wake time after sleep onset, stage shifts per hour, stage N1 percentage, REM latency, arousal index, and apnea-hypopnea index. Some leg movement parameters, such as periodic limb movement during sleep (PLMS) index, PLMS sequence duration, number of PLMS sequence, and periodicity index, were higher in RLS patients compared with healthy controls. Further, our meta-analysis revealed a higher PLMS index during non-REM sleep compared with that during REM sleep. RLS patients manifest a lightening of sleep, increased sleep fragmentation, and greater sleep-related breathing disruption and limb movements during sleep relative to healthy normal individuals. The distributions of PLMS during a night's sleep may provide more information to clarify the specific characteristics of leg movements in RLS. PLMS in RLS are concentrated in non-REM sleep. The periodicity index may be a more sensitive and specific marker of RLS than the PLMS index. Zhang H, Zhang Y, Ren R, etal. Polysomnographic features of idiopathic restless legs syndrome: a systematic review and meta-analysis of 13 sleep parameters and 23 leg movement parameters. J Clin Sleep Med. 2022;18(11):2561-2575.

A study on the effect of mobile phone use on sleep.

Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Association between early stage N2 sleep spindle burst characteristics and vigilance groups: an observational study on patients from a tertiary sleep centre

Objective. Obstructive sleep apnoea (OSA) is associated with impaired vigilance. This paper examines the hypothesis that sleep spindle (Sp) characteristics during nocturnal sleep can be mapped to vigilance deficits measured by the psychomotor vigilance task (PVT) in patients with OSA. Approach. The PVT was performed prior to In-laboratory Polysomnography for 250 patients. PVT outcomes were clustered into three vigilance groups (VGs). Spindles were scored manually for a Training Cohort of 55 patients, (9491 Sps) across different blocks of NREM sleep (SBs) and validated in a Test Cohort (25 patients, 4867 Sps). We proposed a novel set of Sp features including a spindle burst index (SBI), which quantifies the burst characteristics of spindles and constructed models mapping them to VGs. We also explored the performance of conventional Sp features (such as Sp number and density) in our modelling approach. Main results. In the Training Cohort, we observed statistically significant differences in the SBI across VGs and SBs independent of OSA severity (1st stage N2 SBI; p = <0.001 across VGs). In the Test Cohort, a Model based on the proposed SBI predicted VG membership with 88% accuracy. A model based on conventional Sp features mapped to VGs with 80% accuracy, and a model using mixed burst and conventional features reached an accuracy of 88%. Significance. Spindle features measured during diagnostic In-laboratory polysomnography measurements can be mapped to PVT outcomes. The novel SBI proved useful for exploring the relationship between PVT outcomes and sleep. Further studies in larger populations are needed to verify these conclusions.

The Rise and Fall of Slow Wave Tides: Vacillations in Coupled Slow Wave/Spindle Pairing Shift the Composition of Slow Wave Activity in Accordance With Depth of Sleep.

Slow wave activity (SWA) during sleep is associated with synaptic regulation and memory processing functions. Each cycle of non-rapid-eye-movement (NREM) sleep demonstrates a waxing and waning amount of SWA during the transitions between stages N2 and N3 sleep, and the deeper N3 sleep is associated with an increased density of SWA. Further, SWA is an amalgam of different types of slow waves, each identifiable by their temporal coupling to spindle subtypes with distinct physiological features. The objectives of this study were to better understand the neurobiological properties that distinguish different slow wave and spindle subtypes, and to examine the composition of SWA across cycles of NREM sleep. We further sought to explore changes in the composition of NREM cycles that occur among aging adults. To address these goals, we analyzed subsets of data from two well-characterized cohorts of healthy adults: (1) The DREAMS Subjects Database (n = 20), and (2) The Cleveland Family Study (n = 60). Our analyses indicate that slow wave/spindle coupled events can be characterized as frontal vs. central in their relative distribution between electroencephalography (EEG) channels. The frontal predominant slow waves are identifiable by their coupling to late-fast spindles and occur more frequently during stage N3 sleep. Conversely, the central-associated slow waves are identified by coupling to early-fast spindles and favor occurrence during stage N2 sleep. Together, both types of slow wave/spindle coupled events form the composite of SWA, and their relative contribution to the SWA rises and falls across cycles of NREM sleep in accordance with depth of sleep. Exploratory analyses indicated that older adults produce a different composition of SWA, with a shift toward the N3, frontal subtype, which becomes increasingly predominant during cycles of NREM sleep. Overall, these data demonstrate that subtypes of slow wave/spindle events have distinct cortical propagation patterns and differ in their distribution across lighter vs. deeper NREM sleep. Future efforts to understand how slow wave sleep and slow wave/spindle coupling impact memory performance and neurological disease may benefit from examining the composition of SWA to avoid potential confounds that may occur when comparing dissimilar neurophysiological events.

An Automated Wavelet-Based Sleep Scoring Model Using EEG, EMG, and EOG Signals with More Than 8000 Subjects.

Human life necessitates high-quality sleep. However, humans suffer from a lower quality of life because of sleep disorders. The identification of sleep stages is necessary to predict the quality of sleep. Manual sleep-stage scoring is frequently conducted through sleep experts’ visually evaluations of a patient’s neurophysiological data, gathered in sleep laboratories. Manually scoring sleep is a tough, time-intensive, tiresome, and highly subjective activity. Hence, the need of creating automatic sleep-stage classification has risen due to the limitations imposed by manual sleep-stage scoring methods. In this study, a novel machine learning model is developed using dual-channel unipolar electroencephalogram (EEG), chin electromyogram (EMG), and dual-channel electrooculgram (EOG) signals. Using an optimum orthogonal filter bank, sub-bands are obtained by decomposing 30 s epochs of signals. Tsallis entropies are then calculated from the coefficients of these sub-bands. Then, these features are fed an ensemble bagged tree (EBT) classifier for automated sleep classification. We developed our automated sleep classification model using the Sleep Heart Health Study (SHHS) database, which contains two parts, SHHS-1 and SHHS-2, containing more than 8455 subjects with more than 75,000 h of recordings. The proposed model separated three classes if sleep: rapid eye movement (REM), non-REM, and wake, with a classification accuracy of 90.70% and 91.80% using the SHHS-1 and SHHS-2 datasets, respectively. For the five-class problem, the model produces a classification accuracy of 84.3% and 86.3%, corresponding to the SHHS-1 and SHHS-2 databases, respectively, to classify wake, N1, N2, N3, and REM sleep stages. The model acquired Cohen’s kappa () coefficients as 0.838 with SHHS-1 and 0.86 with SHHS-2 for the three-class classification problem. Similarly, the model achieved Cohen’s of 0.7746 for SHHS-1 and 0.8007 for SHHS-2 in five-class classification tasks. The model proposed in this study has achieved better performance than the best existing methods. Moreover, the model that has been proposed has been developed to classify sleep stages for both good sleepers as well as patients suffering from sleep disorders. Thus, the proposed wavelet Tsallis entropy-based model is robust and accurate and may help clinicians to comprehend and interpret sleep stages efficiently.

Enhanced dehydroepiandrosterone levels are positively correlated with N3 sleep stage in long-term mindfulness meditation practitioners.

ObjectivesMeditation practices positively influence the neural, hormonal and autonomic systems. We have demonstrated that long-term practice of mindfulness meditation increases N3 and rapid eye movement (REM) sleep stages and bring efficient autonomic modulation during sleep. In the present study, the probable humoral correlation that could bring about these changes is evaluated.Material and MethodsLong-term Vipassana meditators (n=41) and controls (n=24) (males, 30-60 years of age) underwent a two-day consecutive whole night polysomnography recording. During the second day, with exposure to 100Lux brightness, blood was sampled from the antecubital vein between 8-9 PM and in subsequent early morning. Sleep stage was scored as per American Society of Sleep Medicine (ASSM) guidelines for the second-day recording. Sleep-related hormones were estimated - melatonin by radioimmunoassay; dehydroepiandrosterone (DHEA), cortisol, growth hormone (GH) and prolactin with enzyme-linked immunosorbent assay (ELISA); DHEA/cortisol ratio was calculated. Percentage of sleep stages and hormonal levels were compared between both groups using independent ‘t’ test and Pearson’s correlation was estimated between sleep stages and hormonal levels.ResultsMeditators showed increased N3, REM sleep stages. Though evening cortisol was comparable between the two groups; early morning cortisol, diurnal DHEA and melatonin were significantly higher in meditators. Diurnal DHEA correlated significantly with the N3 sleep stage in meditators.DiscussionHigher diurnal DHEA despite variations in corresponding cortisol in meditators demonstrates that long-term Vipassana meditation practice modulates the hypothalamicpituitary-adrenal (HPA) axis and thereby influences sleep. Thus, the study provides evidence to explore the mechanism most likely involved with mindfulness meditation intervention in insomnia.

0151 Subjective sleep onset latency is influenced by the sleep structure and body heat loss in human subjects

Abstract Introduction Humans can estimate the time that has elapsed during sleep (time estimation ability; TEA). Although research on the TEA during sleep has advanced in the field of sleep research, few studies have focused on the relationship between the subjective sleep onset latency (SOL), which is an indicator of TEA, and objective sleep structures, body heat loss, and body temperature. This paper investigates the association of the subjective SOL with sleep structures such as the objective SOL, duration of each sleep stage, subjective sleep parameters, and body heat loss in healthy young participants. Methods Twenty six participants (7 men and 19 women, mean age of 21.5 ± 0.5 years) having no sleep problems participated in a 1-hour polysomnographic recording that obtained objective sleep parameters during the daytime while temperatures of the skin (i.e., dorsum of the hand and foot, forehead, and subclavian) and eardrum were recorded at intervals of 1 min. The distal–proximal skin temperature gradient (DPG), which is a good predictor of body heat loss and sleepiness, was calculated. Subjective parameters, such as the subjective SOL, sleep time, sleep depth, sleepiness, and mood, were evaluated before and after sleep. We examined the association of the subjective SOL with objective sleep parameters, DPG, and other subjective parameters. Results Most participants estimated their sleep latency to be longer than their actual SOL (mean objective SOL of 7.6 min vs. subjective SOL of 13.7 min). The objective SOL was significantly correlated with each sleep stage parameter whereas the subjective SOL was negatively correlated with the stage N2 sleep duration (Rho = −0.454, p = 0.020) and correlated with the stage N2 sleep latency (Rho = 0.402, p = 0.051). Participants who estimated a shorter subjective SOL had a higher DPG before sleep periods than that after sleep onset (Rho = −0.692, p &amp;lt; 0.001). Additionally, the subjective SOL was correlated with the subjective sleep depth, subjective wake after sleep onset, and restorative sleep. Conclusion The subjective sleep onset latency in the healthy young participants was affected by the degree of body heat loss before sleep onset and stable shallow nonrapid-eye-movement sleep. Support (If Any)

0152 A functional role for global slow oscillations in major depressive disorder with hypersomnia

Abstract Introduction Sleep slow oscillations (SOs, 0.5-1.5Hz) during stages N2 and N3 sleep facilitate cortical communication and are important to the restorative properties of sleep. Spatiotemporal clustering analysis of SOs on the electrode manifold has identified 3 topographically distinct patterns of SOs: Frontal, Local, and Global. Global SOs are spatially widespread cortical events implicated in anterior-posterior long-range communication. However, their precise functional significance is not fully understood. Patients experiencing Major Depressive Disorder (MDD) with comorbid hypersomnia show local deficits in parieto-central slow wave activity, suggesting that frontally-initiated SOs are not propagating to parietal-central regions. Hypersomnolence in MDD may therefore be connected to insufficiently restorative sleep. Here, we retrospectively examine associations between Global SOs in N2 and N3 sleep and hypersomnia severity in healthy controls and MDD patients. Methods MDD patients with (n=22) and without (n=22) hypersomnia, and age-gender balanced healthy controls (n=22) underwent overnight polysomnography studies with 256-channel hdEEG. After detection of SOs, our previously developed classification method was applied retrospectively to all SOs in this dataset, including leveraging a k-means clustering algorithm naïve to the MDD/Hypersomnia label. Fractions of global SOs during stages N2 and N3 were compared across healthy controls and MDD patients. Finally, the fraction of global SOs occurring during the night was correlated against all subjects’ individual scores on the Hypersomnia Severity Index (HSI). Results Analysis of EEG data revealed pronounced, but not statistically significant deficits in global SOs during N3 sleep in MDD patients with comorbid hypersomnia. These deficits were significantly correlated with HSI when examining MDD patients together (Pearson’s r = -0.397, p&amp;lt;0.01). Conclusion Our findings suggest that MDD patients with higher hypersomnia severity experience more pronounced deficits in Global SOs. Given the importance of SOs for the restorative properties of sleep, it is possible that MDD patients with hypersomnia might incur an enhanced sleep need driven by the homeostatic cost of a deficit in Global SOs.. Future studies are necessary to investigate causal mechanisms underlying these findings. Support (If Any) American Sleep Medicine Foundation (76-JF-12), Brain and Behavior Research Foundation (19193), and NIMH (K23MH099234) to DTP.

0831 Identifying Sleep-Related Breathing Disorders in Underserved Demographics Using Commercial Portable Monitoring Devices: A Case Report

Abstract Introduction An estimated twenty-five percent of American women are at high risk of having obstructive sleep apnea (OSA). However, male sex is the predominantly reported risk factor. Women are less likely to report “classic” symptoms such as snoring that prompt referral for sleep evaluation. This dichotomy potentially represents a disparity in clinical evaluation and treatment of OSA in women. Consumer digital health devices are frequently used to monitor sleep in people with and without sleep disturbances. They are generally highly sensitive yet have lower specificity when compared with formal actigraphy or polysomnography. They may be used in conjunction with physician evaluation to guide decision-making. Report of Cases: A 33 year-old female with a pertinent past medical history of obesity (BMI 37.83 kg/m ), depression, chronic pain, and anxiety was referred to our sleep center with a multi-year history of excessive daytime fatigue and non-restorative sleep that persisted despite healthy habits counseling and unremarkable lab evaluation. She ultimately presented her primary care physician with biometric data collected by her Garmin watch and Oura ring. This data, which included a reported low SpO of 83%, motivated a referral to Sleep Medicine. Her presentation Epworth Sleepiness Scale (ESS) score and Insomnia Severity Index (ISI) were 14 and 17, respectively. Polysomnography revealed an AHI of 32.6/hr, oxygen nadir of 79%, ODI of 28.7/hr, and a 97.2% sleep efficiency. PLMS index was 23.2/hour but did not contribute to sleep fragmentation and there was increased proportion of stage N3 sleep (28.2%). Severe OSA was treated with APAP. The two month follow-up ESS and ISS improved to 9 and 4, respectively. Device data revealed greater than 6 hours of consistent nightly use with a residual AHI of 3.1/hr. She subjectively stated APAP “has been a life changer” personally and professionally, as well as spousal report of resolution of snoring. Her consumer devices similarly reported improved sleep measures. Conclusion Minorities and women may be underserved in evaluation, diagnosis, and treatment of OSA. Portable monitoring using readily available consumer biometric devices may be a viable strategy for patients to further identify high risk features and prompt referral by primary care. Support (If Any) This work was supported by the Defense Health Agency, Defense Medical Research and Development Program, Clinical Research Intramural Initiative for Military Women’s Health (DM170708; Mysliwiec) and the Air Force Research Laboratory, Wright Patterson Air Force Base, Ohio (FA8650-18-2-6953; Peterson).

0687 The circadian misalignment is associated with reduced slow-wave sleep in individuals with autism spectrum disorder

Abstract Introduction Sleep disturbances are one of the key features among individuals with autism spectrum disorder (ASD). Many studies have uncovered critical developmental links between cognition, behavior, and sleep. It is suggested that the circadian system desynchronization plays a vital role in the development of ASD. While research on sleep disruption and circadian disturbance has accumulated, only a few studies have investigated a relationship between sleep architecture and circadian rhythm of individuals with ASD to date. We aim to elucidate the relation using the methods of dim light melatonin onset (DLMO) and ambulatory PSG. Methods Eleven individuals with autism (3 females, age: 13.07 ± 4.76 years; age range: 8-23 years) were recruited. After a week of systematic desensitization, an ambulatory overnight PSG was conducted in the participant’s home. Participants collected saliva samples independently at home on two consecutive days. The first evening sample took place 3 hours before the average sleep onset time and continued each 30-minute interval afterward for a total of 5 evening samples. The DLMO was calculated for each day by plotting melatonin levels against the time of saliva sampling. Linear regression was used to determine the best-fit line equation for each plot to calculate when melatonin levels first reached 4 pg/mL and continued to rise. Results The percentage of Stage N3 sleep across the night was significantly negatively associated with phase angle (time between DLMO and sleep onset), revealing that Stage N3 percentage decreases as the phase angle increases. The Phase angle showed a significant positive association with REM percentage across the night. Additionally, a significant difference was found between the mean phase angle for the ASD subjects in this study and the mean phase angle expected from a group of age-matched, typically developing (TD) individuals. Conclusion Our data revealed that circadian misalignment in individuals with ASD is associated with sleep architecture characterized by reduced slow-wave sleep and increased REM sleep. Given the importance of slow-wave sleep for memory and cognitive functions, this finding may contribute to understanding the relationship between sleep alterations and brain development in ASD. Support (If Any)

0845 Large arachnoid cysts and hypersomnolence: symptomatic or not?

Abstract Introduction Arachnoid cysts are the most common type of brain cyst. They are often congenital, and most of them are stable and do not require treatment. On the other hand, some of them present a symptomatic problem such as headache, nausea and seizures. This rare condition was seen in a female patient who also had hypersomnolence. Report of Cases: A 37-year-old female presented to hospital for evaluation of excessive daytime sleepiness (EDS) for the past 20 years, with repeated attacks several times a day without any REM sleep related symptoms. She also showed irregular wake sleep pattern of sleep extending over 24 hours, disturbing nocturnal sleep after each episode. Her sleep log showed sudden onset hypersomnolence with sleep duration of 30-40 hours every week. Epworth sleep scale was 10/24. PSG demonstrated her sleep architecture of 8 hours duration was unusual with sleep onset REM period (SOREMP) and decreased N3 sleep stage. MSLT showed reduced sleep onset latency (average: 5 minutes) and sleep onset REM on 1 of 4 naps. Brain MRI revealed a large arachnoid cyst on her left cerebral hemisphere. She was diagnosed as narcolepsy type2 and referred to the department of neurosurgery, but due to unclear association between hypersomnolence and the cyst, surgical treatment was not carried out. She was started on Modafinil 50mg which progressively increased to 200mg, but little effect was seen in sudden onset hypersomnolence and caused side effects such as headache and nausea. After Modafinil was discontinued, Melatonin agonist was administered in order to control her irregular sleep-wake rhythm, and since then her sleep-wake cycle has changed relatively stable and regular. At present, the frequency of hypersomnolence is gradually getting low and Epworth is 4/24. Conclusion In the present case, there is no evidence that her symptoms concerning sleep were secondary to any other disorder. Also, to our knowledge, there have been only a few cases reporting coexistence of hypersomnolence and arachnoid cysts. We are carefully following up on this patient and will reconsider to refer her to neurosurgery if any other symptoms appear. Support (If Any)

0304 Characterizing age and sex-related changes in sleep EEG K-complex morphology in 3,909 individuals

Abstract Introduction K-complexes are hallmarks of sleep stage N2 and are thought to be associated with two distinct roles that serve as either or both, a sleep protective mechanism or a cortical arousal response. K-complexes and their morphological features (number, delta surrounding K complexes, etc.) have been implicated in sustained attention as well as in Alzheimer’s disease wherein a decline in the number of K-complexes appeared to discriminate diseased individuals from healthy controls. Yet, age and sex-related changes in K-complex morphology are not well-known. Methods We analyzed data from the Sleep Heart Health Study (SHHS) to understand age- and sex-related changes in K-complex morphology. The SHHS is a cohort study comprised of 5,804 men and women aged 40 and older aimed at investigating the cardiovascular consequences of sleep-disordered breathing. K-complex (on C3/A2) features were quantified using previously published and validated open-source algorithm (DETOKS; Parekh et. al. J. Neurosci Meth. 2015). Three features of K-complexes were studied: number of K-complexes (density), delta (∆SWAK) and alpha (∆alphaK) surrounding K-complexes. Results Of the 5,804 studies available, 3,909 that had at least 6h of usable EEG were analyzed (mean = 62±11 yrs., range [40-90 yrs.], 53%female). With aging, K-complex density and (rho=-0.1, p&amp;lt;0.0001), ∆SWAK (rho=-0.2, p&amp;lt;0.0001) were inversely associated with age, while ∆alphaK (rho=0.1, p&amp;lt;0.01) was significantly positively associated with age. The inverse association of K-complex density with age was greater in men compared to women (rhomen=-0.3, p&amp;lt;0.0001, rhowomen=-0.1, p&amp;lt;0.01). Women had greater K-complex density compared to men (1.8[1.3-2.4] vs. 1.3[0.9-1.8], median[IQR]; std. mean diff =0.4). The changes in K-complex morphology with age remained significant after controlling for OSA severity. Conclusion Age is associated with decline in K-complex morphology such that K-complex density and delta activity surrounding K-complexes declines whereas alpha activity surrounding K-complexes increases. An age-related decline in delta activity surrounding K-complexes and an increase in alpha activity surrounding K-complexes is consistent with the potential role for these features in either sleep-state maintenance or arousal responsiveness. Whether the decline in K-complex morphology seen here with aging, and its interaction with sex-related differences, is accelerated in neurodegenerative disorders such as AD remains to be tested. Support (If Any) Support: NIH K25HL151912, AASMFoundation BS-233-20

Tailored individual Yoga practice improves sleep quality, fatigue, anxiety, and depression in chronic insomnia disorder

BackgroundChronic insomnia disorder (CI) is a prevalent sleep disorder that can lead to disturbed daytime functioning and is closely associated with anxiety and depression. First-choice treatment is cognitive behavioral therapy (CBT-I). Other mind–body interventions, such as Tai-chi and Yoga, have demonstrated subjective improvements in sleep quality. The purpose of this study was to assess the efficacy of Yoga for improvement of subjective and objective sleep quality as well as measures of anxiety, depression, sleepiness, and fatigue in patients with CI.MethodsAdults with CI were prospectively included in this single group pre-post study. Baseline assessments included home polysomnography (PSG), 7-day actigraphy, and questionnaires (Pittsburgh Sleep Quality Index questionnaire (PSQI), Hospital Anxiety Depression scale (HADS), Epworth Sleepiness Scale (ESS), Pichot fatigue scale (PS)). Patients practiced Viniyoga, an individualised Yoga practice with daily self-administered exercises, for 14 weeks. Assessments were repeated at the end of Yoga practice.ResultsTwenty-one patients completed the study. Objective sleep measurements revealed no change in PSG parameters after Yoga practice, but a decrease in arousals on actigraphy (p < 0.001). Subjective symptoms improved for all questionnaires (PSQI, p < 0.001; HAD-A, p = 0.020, HAD-D, p = 0.001, ESS, p = 0.041, PS, p = 0.010). In univariate correlations, decrease in PSQI was associated with increase in sleep stage N3 (p < 0.001) on PSG.ConclusionsWe have demonstrated a positive impact of individualized Yoga practice on subjective parameters related to sleep and daytime symptoms in CI, resulting in fewer arousals on actigraphy. Yoga could be proposed as a potentially useful alternative to CBT-I in CI, as it is easy to practice autonomously over the long-term. However, given the design of the present study, future prospective controlled studies should first confirm our results.Trial registrationClinicalTrials.gov identifier: NCT03314441, date of registration: 19/10/2017.

Methamphetamine-Induced Sleep Impairments and Subsequent Slow-Wave and Rapid Eye Movement Sleep Rebound in Male Rhesus Monkeys.

Use of amphetamine-type stimulants is associated with numerous adverse health outcomes, with disturbed sleep being one of the most prominent consequences of methamphetamine use. However, the extent to which methamphetamine alters sleep architecture, and whether methamphetamine-induced sleep impairment is associated with next-day sleep rebound effects, has received relatively little investigation. In the present study, we investigated the effects of acute morning methamphetamine administration on sleep parameters in adult male rhesus monkeys (N = 4) using a fully-implantable telemetry system. Monkeys were prepared with telemetry devices that continuously monitored electroencephalography (EEG), electromyography (EMG) and electrooculography (EOG) throughout the night. We investigated the effects of morning (10h00) administration of methamphetamine (0.01–0.3 mg/kg, i.m.) on sleep during the night of the injection. In addition, we investigated sleep during the subsequent night in order to assess the possible emergence of sleep rebound effects. Methamphetamine administration dose-dependently increased sleep latency and wake time after sleep onset (WASO). Methamphetamine also decreased total sleep time, which was reflected by a decrease in total time spent in N2, slow-wave (N3) and REM sleep stages, while increasing the percentage of total sleep time spent in sleep stage N1. Importantly, methamphetamine decreased time spent in N3 and REM sleep even at doses that did not significantly decrease total sleep time. Sleep rebound effects were observed on the second night after methamphetamine administration, with increased total sleep time reflected by a selective increase in time spent in sleep stages N3 and REM, as well as a decrease in REM sleep latency. Our findings show that methamphetamine administered 8 h prior to the inactive (dark) phase induces marked changes in sleep architecture in rhesus monkeys, even at doses that do not change sleep duration, and that sleep rebound effects are observed the following day for both N3 and REM sleep stages.

Literature Cases Summarized Based on Their Polysomnographic Findings in Rett Syndrome.

Rett syndrome (RTT) is a severe and rare neurodevelopmental disorder affecting mostly girls. In RTT, an impaired sleep pattern is a supportive criterion for the diagnosis, yet little is known regarding the sleep structure and sleep respiratory events. Aiming to delineate sleep by aggregating RTT case (series) data from published polysomnographic studies, seventy-four RTT cases were collected from eleven studies up until 6 February 2022 (PROSPERO: CRD 42020198099). We compared the polysomnographic data within RTT stratifications and to a typically developing population. MECP2 cases demonstrated shortened total sleep time (TST) with increased stage N3 and decreased REM sleep. In cases with CDKL5 mutations, TST was longer and they spent more time in stage N1 but less in stage N3 than those cases affected by MECP2 mutations and a typically developing population. Sleep-disordered breathing was confirmed by the abnormal apnea/hypopnea index of 11.92 ± 23.67/h TST in these aggregated cases. No association of sleep structure with chronological age was found. In RTT, the sleep macrostructure of MECP2 versus CDKL5 cases showed differences, particularly regarding sleep stage N3. A severe REM sleep propensity reduction was found. Aberrant sleep cycling, possibly characterized by a poor REM ‘on switch’ and preponderance in slow and high-voltage sleep, is proposed.