Rapid Eye Movement Sleep Duration Research Articles

Spindles in WAG/Rij Rats with Absence Epilepsy and Comorbid Depression

WAG/Rij rats are a valid model of absence epilepsy and comorbid depression. We have previously shown that WAG/Rij rats have disturbances in the sleep-wake cycle and changes in the characteristics of sleep spindles. A negative correlation was also found between the number of spike-wave discharges (SWD) and the duration of rapid eye movement (REM) sleep. Clinical evidence suggests that the traditional antidepressants imipramine and fluoxetine are effective in suppressing symptoms of depression, but may have a negative impact on the sleep-wake cycle and comorbid epilepsy in patients. Our previous studies in WAG/Rij rats showed that imipramine, when administered chronically, increases the number of SWDs, while fluoxetine at the same dose reduces their number, although both antidepressants have a pronounced antidepressant effect. Comparison of the effects of the antidepressants imipramine and fluoxetine on the sleep-wake cycle and sleep spindles in WAG/Rij rats remains unstudied. The purpose of this work is to find out: 1) what effects do imipramine and fluoxetine have on the sleep-wake cycle and the characteristics of sleep spindles in WAG/Rij rats and 2) whether there are differences in their effects. To achieve this goal, the characteristics of the sleep-wake cycle and sleep spindles were compared in WAG/Rij rats after chronic administration of antidepressants and saline and in non-epileptic Wistar rats. Administration of imipramine led to a significant decrease in the duration of REM sleep. The administration of imipramine, compared with fluoxetine, also increased the latency of the transition to sleep and the transition to REM sleep. Sleep spindle amplitude was significantly increased by both antidepressants. However, the spectral power density of “slow” and “medium” spindles, which predominate in WAG/Rij rats compared to Wistar rats, was significantly higher after administration of imipramine than fluoxetine. The results suggest that imipramine causes greater negative changes in the sleep-wake cycle and sleep spindles than fluoxetine. Studies in the WAG/Rij rat model indicate that fluoxetine is more preferable antidepressant for the treatment of depressive disorders comorbid with absence epilepsy, since it does not cause a significant deterioration in sleep quality. These results are consistent with clinical data.

A REM-active basal ganglia circuit that regulates anxiety

Rapid eye movement (REM) sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som) neurons in the entopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is both necessary and sufficient for maintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP → LHb → VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.

The Effect of Type-2 Diabetes Mellitus on Sleep Architecture and Sleep Apnea Severity in Patients With Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) is a severe condition that is characterized by recurrent partial or complete breathing interruptions during sleep, leading to insulin resistance, microvascular complications, and cardiovascular complications. It is of great importance to know the impact of type 2 diabetes mellitus (DM), which is prevalent in the world and in our country, Turkey, leads to significant mortality and morbidity, significantly affects the quality of life, and requires continuous follow-up, on sleep in patients with OSAS and to raise awareness on this issue. In this study, we aimed to determine the effects of diabetes on sleep duration and sleep architecture in patients with OSAS and to investigate the relationship between OSAS severity and DM control. Fifty diabeticand 42 non-diabetic patientsdiagnosed with OSAS at the Sleep Disorders Center ofSüreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey, between October 2022 and March 2023 were included in the study. Polysomnographic and biochemical parameters of the two groups were compared. The effect of OSAS severity and sleep architecture on diabetes control was investigated. No significant difference was found between diabetic and non-diabetic patients in terms of total sleep duration, sleep efficiency, and sleep latency, whereas REM (rapid eye movement) latency was prolonged and REM sleep duration and percentage were significantly lower in diabetic patients. The severity of OSAS was found to be greater in diabetic patients and they spent significantly more time below 90% saturation during sleep. No correlation was found between the groups in the glycated hemoglobin (HbA1c) parameter, which we examined in terms of diabetes control, sleep architecture, and OSAS severity. The presence of diabetes aggravates the severity of OSAS, prolongs the transition to REM sleep, and leads to a decrease in REM duration. Sleep is essential for both mental and physical well-being. In this regard, it is of utmost importance to examine diabetic patients for OSAS and to perform polysomnography in appropriate patients.

Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT1 Receptors Located in the Locus Ceruleus Norepinephrine Neurons.

Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid eye movement sleep (REMS) are lacking. This polysomnographic study in male rats showed that the first-in-class selective melatonin MT1 receptor partial agonist UCM871 increases the duration of REMS without affecting that of NREMS. The REMS-promoting effects of UCM871 occurred by inhibiting, in a dose-response manner, the firing activity of the locus ceruleus (LC) norepinephrine (NE) neurons, which express MT1 receptors. The increase of REMS duration and the inhibition of LC-NE neuronal activity by UCM871 were abolished by MT1 pharmacological antagonism and by an adeno-associated viral (AAV) vector, which selectively knocked down MT1 receptors in the LC-NE neurons. In conclusion, MT1 receptor agonism inhibits LC-NE neurons and triggers REMS, thus representing a novel mechanism and target for REMS disorders and/or psychiatric disorders associated with REMS impairments.

Reduced rapid eye movement sleep in late middle-aged and older apolipoprotein E ɛ4 allele carriers.

Apolipoprotein E ɛ4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD). In addition, APOE4 carriers may exhibit sleep disturbances, but conflicting results have been reported, such that there is no clear consensus regarding which aspects of sleep are impacted. Our objective was to compare objective sleep architecture between APOE4 carriers and non-carriers, and to investigate the modulating impact of age, sex, cognitive status, and obstructive sleep apnea (OSA). A total of 198 dementia-free participants aged >55 years old (mean age: 68.7 ± 8.08 years old, 40.91% women, 41 APOE4 carriers) were recruited in this cross-sectional study. They underwent polysomnography, APOE4 genotyping, and a neuropsychological evaluation. ANCOVAs assessed the effect of APOE4 status on sleep architecture, controlling for age, sex, cognitive status, and the apnea-hypopnea index. Interaction terms were added between APOE4 status and covariates. Rapid eye movement (REM) sleep percentage (F = 9.95, p = .002, ηp2 = 0.049) and duration (F = 9.23, p = .003, ηp2 = 0.047) were lower in APOE4 carriers. The results were replicated in a subsample of 112 participants without moderate-to-severe OSA. There were no significant interactions between APOE4 status and age, sex, cognitive status, and OSA in the whole sample. Our results show that APOE4 carriers exhibit lower REM sleep duration, including in cognitively unimpaired individuals, possibly resulting from early neurodegenerative processes in regions involved in REM sleep generation and maintenance.

Relationships between rumination and different types of rapid eye movement sleep in patients with chronic insomnia disorder

Background and objectiveRumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. MethodsThis study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. ResultsThe CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher β power during REM sleep, higher β and σ power during phasic REM sleep, and higher β, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with β power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. ConclusionThe CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (β) wave power in REM sleep.

Abstract P540: Sleep Duration, Rapid Eye Movement Sleep, and Subclinical Myocardial Damage

Introduction: Sleep is strongly linked to clinical cardiovascular disease and was added in 2022 to the AHA’s Life’s Essential 8. Optimizing sleep duration and quality may reduce the risk of cardiovascular disease. Few studies have examined self-reported sleep duration and percent time in rapid eye movement (REM) sleep measured by single night in-home polysomnography with high sensitivity cardiac troponin T (hs-troponin T), a biomarker of subclinical cardiovascular disease. Methods: We conducted a cross-sectional study of adults without a history of cardiovascular disease who participated in both the Atherosclerosis Risk in Communities (ARIC) Study and the Sleep Heart Health Study (SHHS) in 1995-1998. We used linear regression with sleep duration and percentage time of REM sleep modeled as predictors with restricted cubic splines and examined associations with the outcome, hs-troponin T. We adjusted for age, sex, body mass index, waist-to-hip ratio, alcohol intake, smoking status, systolic blood pressure, hypertension medication use, diabetes, HDL- and LDL-cholesterol, and cholesterol-lowering medication use. Results: Among 1,587 participants (mean age 63, 54% female), the mean sleep duration was 7.3 hours, and mean % REM time was 20.7. Sleep duration was not associated with hs-troponin T ( Figure, Panel A ). However, percentage REM sleep was negatively associated with hs-troponin T, but with a threshold effect; there was a negative linear association of hs-troponin T with % REM sleep but only at values <15% ( Figure, Panel B ). Conclusion: While self-reported sleep duration was not associated with TnT levels, there was evidence that low % REM sleep, a specific neurophysiological sleep state, was associated with subclinical cardiovascular disease. These findings suggest that multiple sleep dimensions should be considered in efforts to optimize cardiovascular health.

Shorter total sleep time is associated with lower CD4+/CD8+ T cell ratios in virally suppressed men with HIV.

Although poor sleep quality is associated with lower CD4+ T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+ and CD8+ T cell counts and the CD4+/CD8+ T cell ratio. Overall, 289 men with mean (±SD) age 55.3 ± 11.3 years and mean CD4+ T cell count 730 ± 308 cells/mm3 were evaluated. Total sleep time (TST) was significantly associated with CD8+ but not CD4+ T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+ T cells/mm3 (p = 0.05) and a 5.6% (p = 0.0007) decline in CD4+/CD8+ T cell ratio. In adjusted models, every hour of shorter rapid eye movement (REM) sleep was associated with an additional 113 CD8+ T cells/mm3 (p = 0.02) and a 15.1% lower CD4+/CD8+ T cell ratio (p = 0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH.

Anatomical Substrates of Rapid Eye Movement Sleep Rebound in a Rodent Model of Post-sevoflurane Sleep Disruption.

Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing rapid eye movement (REM) sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study, the authors hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane-exposed and REM sleep-deprived animals is largely similar. Adult rats and Targeted Recombination in Active Populations mice were implanted with electroencephalographic electrodes for sleep-wake recording and randomized to sevoflurane, REM deprivation, or control conditions. Conventional c-Fos immunohistochemistry and genetically tagged c-Fos labeling were used to quantify activated neurons in a group of REM-associated nuclei in the midbrain and basal forebrain. REM sleep duration increased during recovery from sevoflurane anesthesia relative to controls (157.0 ± 24.8 min vs. 124.2 ± 27.8 min; P = 0.003) and temporally correlated with increased c-Fos expression in the sublaterodorsal nucleus, a region active during REM sleep (176.0 ± 36.6 cells vs. 58.8 ± 8.7; P = 0.014), and decreased c-Fos expression in the ventrolateral periaqueductal gray, a region that is inactive during REM sleep (34.8 ± 5.3 cells vs. 136.2 ± 19.6; P = 0.001). Fos changes similar to those seen in sevoflurane-exposed mice were observed in REM-deprived animals relative to controls (sublaterodorsal nucleus: 85.0 ± 15.5 cells vs. 23.0 ± 1.2, P = 0.004; ventrolateral periaqueductal gray: 652.8 ± 71.7 cells vs. 889.3 ± 66.8, P = 0.042). In rodents recovering from sevoflurane, REM-on and REM-off neuronal activity maps closely resemble those of REM sleep-deprived animals. These findings provide new evidence in support of the idea that sevoflurane does not substitute for endogenous REM sleep.

Circadian sleep regulation and brain tissue microstructure in cognitively unimpaired older adults

AbstractBackgroundCircadian dysfunction increases with age, leading to changes in the circadian regulation of physiological and biological rhythms, including sleep. Actigraphy studies demonstrated that altered 24‐h rest‐activity patterns, an estimate of circadian sleep‐wake regulation, is related to cognitive decline and tightly linked to Alzheimer’s disease progression. Here, we assessed whether circadian sleep regulation, measured during a multiple naps protocol, is related to brain microstructural integrity in a group of cognitively unimpaired older adults.MethodEighty‐six retired older individuals (mean age [SD] = 69.9 ± 5.2 y.o., 32 females, Table 1) with no major sleep disorders or medical condition, underwent an in‐lab 40‐h multiple naps protocol and brain structural magnetic resonance imaging. As rapid eye movement (REM) sleep is under strong circadian control, circadian REM sleep amplitude was computed by fitting a Gaussian curve on REM sleep duration (% of total sleep time) measured for each nap opportunity. The multiparametric mapping protocol was used to derive indices of brain tissue microstructure using magnetization transfer saturation (MTsat), R1 and R2* maps (hMRI toolbox v0.2.2). Statistical models were adjusted for age, sex, education, and for additional covariates related to sleep architecture and its circadian modulation, including mean REM% and sleep efficiency (SE), the accumulation of REM sleep and sleep need (slope of a fitted first‐order polynomial curve), and circadian SE amplitude.ResultsWhole‐brain voxel‐based quantification analysis revealed that low circadian REM amplitude was related to low MTsat, R1 and R2* values in several white matter regions mostly located around the lateral ventricles (Figure 1A). In addition, a significant association was observed between low circadian REM amplitude and low R1 values in two grey matter clusters encompassing the hippocampus, entorhinal cortex, thalamus and hypothalamus (Figure 1B).ConclusionOur findings provide first evidence that changes in circadian sleep regulation is associated with microstructural changes in key brain regions sensitive to the aging process and involved in sleep‐wake regulation. These results further emphasize the relevance of monitoring circadian sleep regulation for the early detection of individuals at risk for neurodegeneration and cognitive decline.

Circadian adaptation to night shift work is associated with higher REM sleep duration

ObjectiveTo investigate the influence of the degree of circadian adaptation to night work on sleep architecture following night shift. MethodsThirty four night workers (11 females; 33.8 ± 10.1years) completed a simulated night shift following 2-7 typical night shifts. Participants completed a laboratory-based simulated night shift (21:00-07:00 hours), followed by a recovery sleep opportunity (∼09:00-17:00 hours), recorded using polysomnography. Urinary 6-sulphatoxymelatonin (aMT6s) rhythm acrophase was used as a marker of circadian phase. Sleep duration and architecture were compared between individuals with aMT6s acrophase before (unadapted group, n = 22) or after (partially adapted group, n = 12) bedtime. ResultsBedtime occurred on average 2.16 hours before aMT6s acrophase in the partially adapted group and 3.91 hours after acrophase in the unadapted group. The partially adapted group had more sleep during the week before the simulated night than the unadapted group (6.47 ± 1.02 vs. 5.26 ± 1.48 hours, p = .02). After the simulated night shift, both groups had similar total sleep time (partially adapted: 6.68 ± 0.80 hours, unadapted: 6.63 ± 0.88 hours, p > .05). The partially adapted group had longer total rapid eye movement sleep duration than the unadapted group (106.79 ± 32.05 minutes vs. 77.90 ± 28.86 minutes, p = .01). After 5-hours, rapid eye movement sleep accumulation was higher in the partially adapted compared to the unadapted group (p = .02). Sleep latency and other stages were not affected by circadian adaptation. DiscussionPartial circadian adaptation to night shift was associated with longer rapid eye movement sleep duration during daytime sleep, highlighting the influence of entrainment between the sleep-wake cycle and the circadian pacemaker in night workers. The findings have important implications for sleep and subsequent alertness associated with shift work.

Neural substrates underlying REM sleep duration in patients with major depressive disorder: A longitudinal study combining multimodal MRI data

IntroductionPrior studies have discussed rapid eye movement (REM) sleep disturbance as a potential endophenotype of major depressive disorder (MDD). However, the neural substrates underlying the percentage of REM sleep duration (REM%) and its association with disease progression in MDD remain unclear. MethodsOne hundred and fourteen MDD patients and 74 healthy controls (HCs) underwent resting-state functional and perfusion magnetic resonance imaging (MRI) scans as well as overnight polysomnography examination to assess brain function and REM%, with 48 patients completing follow-up visits. Correlation and mediation analyses were conducted to investigate the associations among baseline REM%, multimodal brain imaging measures, and the improvement of depressive symptoms at follow-up in MDD. ResultsWe found voxel-wise correlations between baseline REM% and multimodal brain imaging metrics in many brain regions involved in sensorimotor, visual processing, emotion, and cognition in patients with MDD. Moreover, the baseline REM% was correlated with the improvement of depressive symptoms from acute to remitted status in patients through regulating brain activity in the left inferior temporal gyrus and cerebral blood flow in the bilateral paracentral lobule. ConclusionOur findings help to identify the neural underpinnings of REM% in depression and highlight REM% as a potential prognostic biomarker to predict disease progression. These may inform future novel interventions of MDD from the perspective of regulating REM sleep.

Influence of sex hormone use on sleep architecture in a transgender cohort.

Sex differences in sleep architecture are well-documented, with females experiencing longer total sleep time, more slow wave sleep (SWS), and shorter Rapid Eye Movement (REM) sleep duration than males. Although studies imply that sex hormones could affect sleep, research on exogenous sex hormones on sleep architecture is still inconclusive. This study examined sleep architecture changes in transgender individuals after 3 months of gender-affirming hormone therapy (GAHT). We assessed sleep architecture in 73 transgender individuals: 38 transmasculine participants who started using testosterone and 35 transfeminine participants who started using estrogens and antiandrogens. Sleep architecture was measured before GAHT and after 3 months of GAHT for 7 nights using an ambulatory single-electrode sleep EEG device. Changes in sleep architecture were analyzed using linear mixed models, and non-normally distributed outcomes were log-transformed and reported as percentages. In transmasculine participants, SWS decreased by 7 minutes (95% CI: -12; -3) and 1.7% (95% CI: -3%; -0.5%), REM sleep latency decreased by 39% (95% CI: -52%; -22%) and REM sleep duration increased by 17 minutes (95% CI: 7; 26) after 3 months of GAHT. In transfeminine participants, sleep architecture showed no significant changes after 3 months of GAHT. Sleep architecture changes after 3 months of masculinizing GAHT in line with sleep in cisgender males, while it shows no changes after feminizing GAHT. The sex-specific nature of these changes raises new questions about sex hormones and sleep. Future research should focus on studying possible underlying neural mechanisms and clinical consequences of these changes.

Reducing brain kynurenic acid synthesis precludes kynurenine-induced sleep disturbances.

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg-1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF-04859989 (30 mg kg-1; s.c.); or (iv) PF-04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non-rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non-rapid eye movement sleep delta power and sleep spindles. PF-04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non-rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics.

The REM microarousal and REM duration as the potential indicator in paradoxical insomnia

ObjectiveAlthough paradoxical insomnia is a prevalent subtype of chronic insomnia, the etiology of it is unclear. Contrary to complaints of little or no sleep, polysomnography (PSG) findings show that paradoxical insomnia patients have near normal sleep macrostructure. The purpose of this study is to determine the changes of microstructure and explore the etiology of paradoxical insomnia. MethodsThe PSG findings of 89 paradoxical insomnia patients were compared with those of 41 gender balanced healthy controls without sleep complaints. All subjects underwent nocturnal PSG recordings. Conventional PSG measures and microarousals were quantified and statistically analyzed. Receiver operating characteristic curve and correlation analysis were used to evaluate the potential of REM sleep microarousals and REM duration as indicators of paradoxical insomnia. ResultsCompared with the controls, paradoxical insomnia patients had no significant differences in sleep macrostructures. Statistical analysis showed that non-rapid eye movement (NREM) microarousals revealed no significant differences between paradoxical insomnia patients and controls. Noticeably, more spontaneous microarousals appeared in rapid eye movement (REM) stage for paradoxical insomnia patients. Based on receiver operating characteristic curve (ROC), the optimal cutoff value of REM sleep microarousals could predict paradoxical insomnia. Furthermore, a positive correlation between microarousals in REM sleep and the duration of REM sleep was presented in paradoxical insomnia patients. ConclusionsThe frequency of REM microarousals and the duration of REM sleep could reflect the real sleep state of paradoxical insomnia patients. That suggested PSG investigation extended to microarousal could be helpful to understand the etiology in paradoxical insomnia.

0874 REM Sleep deterioration may modulate tinnitus

Abstract Introduction Sleep quality deterioration often acts as aggravating comorbidity in a variety of chronic conditions. Tinnitus is an auditory symptom that often negatively combines with poor sleep quality, and it has been associated with sleep fragmentation and sleep apnea. Tinnitus is known to be heterogeneous and yet the relationship between tinnitus psychoacoustic characteristics and how precisely sleep is impacted has initiated limited explorative studies, notably for a particular subgroup of patients, which describes that their tinnitus perceived loudness is highly modulated by sleep. Methods For this observational prospective study, a sample of 29 tinnitus subjects were recruited. The study group was composed of 15 “on-off tinnitus” subjects who were reporting significant modulations of tinnitus loudness related to night sleep and naps, and a control group composed of 14 subjects that described a constant and permanent tinnitus that was not impacted by sleep. The control group was matched in age, gender and tinnitus impact on quality of life with the study group. All patients underwent a polysomnography (PSG) assessment for one complete night and were asked to fill a screening questionnaire and report tinnitus intensity before and after the PSG. Results The “On-off tinnitus” group subjects had less Stage 3 sleep (p< 0.01), less Rapid-Eye Movement (REM) Sleep (p< 0.05) and more Stage 2 sleep (p< 0.05) in proportion and duration compared to the control group subjects. In addition, in the “On-off tinnitus” sample, a correlation was found between REM sleep duration and tinnitus overnight modulation (p< 0.05) as well as tinnitus impact on quality of life (p< 0.05). These correlations were not present in the control group. Conclusion This study demonstrates that among the tinnitus population, patients presenting a tinnitus whose intensity is highly modulated by sleep have a deteriorated sleep quality, in which REM sleep may play a role in the overnight tinnitus modulation. Potential physiological explanations accounting for this observation are hypothesized and discussed. Support (if any) This study was supported by Felicia and Jean-Jacques Lopez-Loreta Foundation, Robin Guillard EIRL and APHP Hôtel Dieu sleep department.

0130 Reduced Entropy in EEG During Rapid Eye Movement Sleep in Men with Depression

Abstract Introduction Depression is an increasingly prevalent mental health condition. Patients with depression have disrupted rapid eye movement (REM) sleep as characterized by shortened REM latency, increased REM sleep duration, and increased REM density. However, it is unknown whether the dynamic patterns of EEG within REM episodes are altered in these patients. Here we investigated the complexity of EEG during REM sleep using the analysis of irregularity on multiple temporal time scales and compared the difference in such a nonlinear property of EEG between patients with depression and controls. Methods We analyzed the overnight EEG recordings (256 Hz) collected from the left central channel in 19 older men with depression and 19 age-matched otherwise healthy control men in the Osteoporotic Fractures in Men Study (MrOS) obtained from the National Sleep Research Resource (NSRR). To quantify the irregularity/complexity in EEG fluctuations during REM, a Multiscale Entropy (MSE) analysis was performed on each 30-second epoch to calculate the entropy at different time scales between ~0.004 and ~0.078 seconds (i.e., 1/256, 2/256, …, 20/256 seconds). Results As compared to control men, men with depression had significantly lower entropy values at multiple time scales between 0.023-0.031 seconds (time scale =6/256 second: 0.363□0.008 [SE] for depression, 0.408□0.009 for controls; time scale =7/256 second: 0.295□0.009 for depression, 0.342□0.008 for controls; time scale =8/256 second: 0.225□0.009 for depression, 0.269□0.008 for controls; all FDR-adjusted P-values< 0.001), indicating reduced temporal irregularity/complexity in EEG fluctuations. The differences were not statistically significant at smaller or larger time scales. Conclusion EEG complexity/irregularity within REM sleep were altered in patients with depression. Our results indicate the capability of MSE analysis in capturing important complexity features of EEG fluctuations, which might be missed using those entropy algorithms focused on EEG fluctuations at a single time scale. Support (if any) RF1AG059867, RF1AG064312. The National Heart, Lung, and Blood Institute provided funding for the ancillary MrOS Sleep Study, "Outcomes of Sleep Disorders in Older Men," under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. The NSRR was supported by the National Heart, Lung, and Blood Institute (R24 HL114473, 75N92019R002).

Gut Microbiota Composition and Functionality Are Associated With REM Sleep Duration and Continuous Glucose Levels.

Sleep disruption is associated with worse glucose metabolic control and altered gut microbiota in animal models. We aimed to evaluate the possible links among rapid eye movement (REM) sleep duration, continuous glucose levels, and gut microbiota composition. This observational, prospective, real-life, cross-sectional case-control study included 118 (60 with obesity), middle-aged (39.1-54.8 years) healthy volunteers recruited at a tertiary hospital. Glucose variability and REM sleep duration were assessed by 10-day continuous glucose monitoring (CGM) (Dexcom G6) and wrist actigraphy (Fitbit Charge 3), respectively. The coefficient of variation (CV), interquartile range (IQR), and SD of glucose variability was assessed and the percentage of time in range (% TIR), at 126-139 mg/dL (TIR2), and 140-199 mg/dL (TIR3) were calculated. Shotgun metagenomics sequencing was applied to study gut microbiota taxonomy and functionality. Increased glycemic variability (SD, CV, and IQR) was observed among subjects with obesity in parallel to increased % TIR2 and % TIR3. REM sleep duration was independently associated with % TIR3 (β = -.339; P < .001) and glucose variability (SD, β = -.350; P < .001). Microbial taxa from the Christensenellaceae family (Firmicutes phylum) were positively associated with REM sleep and negatively with CGM levels, while bacteria from Enterobacteriacea family and bacterial functions involved in iron metabolism showed opposite associations. Decreased REM sleep duration was independently associated with a worse glucose profile. The associations of species from Christensenellaceae and Enterobacteriaceae families with REM sleep duration and continuous glucose values suggest an integrated picture of metabolic health.

Morning naps architecture and mentation recall complexity.

Mentation reports were collected after spontaneous awakenings from morning naps in 18 healthy participants, and associations between sleep stages duration and complexity of recalled mentation were investigated. Participants were continuously recorded with polysomnography and allowed to sleep for a maximum of 2 hr. Mentation reports were classified according to both their complexity (1-6 scale) and their perceived timing of occurrence (Recent or Previous Mentation with respect to the final awakening). The results showed a good level of mentation recall, including different types of mentation with lab-related stimuli. N1 + N2 duration was positively related to the complexity of Previous Mentation recall, while rapid eye movement sleep duration was negatively related. This suggests that the recall of complex mentation, such as dreaming with a plot, occurring far from awakening may depend on the length of N1 + N2. However, the duration of sleep stages did not predict the complexity of Recent Mentation recall. Nevertheless, 80% of participants who recalled Recent Mentation had a rapid eye movement sleep episode. Half of the participants reported incorporating lab-related stimuli in their mentation, which positively correlated with both N1 + N2 and rapid eye movement duration. In conclusion, nap sleep architecture is informative about the complexity of dreams perceived as having occurred early during the sleep episode, but not about those perceived as recent.

Effect of Emotional Distress on Sleep Physiology in Underserved Pregnant Women [ID: 1381497

INTRODUCTION: Pregnancy is characterized by an altered pattern of emotions and sleep. The aim of this study was to examine the effect of emotional distress on objective sleep parameters in underserved pregnant women during the COVID-19 pandemic. METHODS: Institutional review board approval was obtained for the study. This was a longitudinal observation study in which we administered weekly validated self-reported surveys (Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, COVID-19-related anxiety, and life-related stressors) to consented pregnant women over the course of their second and third trimesters (n=13). The independent variable, subjective emotional distress, was derived from a sum score of these weekly surveys. A wearable device was used to measure objective sleep physiological data, such as the rapid eye movement (REM), deep, and light sleep stages. The dependent variables were obtained from weekly average scores of the sleep data. Multilevel analysis was conducted, controlling for relevant covariates. RESULTS: Adjusting for gestational age, maternal age at enrollment, and prepregnancy body mass index, higher emotional distress was associated with a shorter duration of deep sleep (b=−.65, P&lt;.05) and longer duration of REM sleep (b=.79, P&lt;.01). There was no significant relationship between emotional distress and light sleep. CONCLUSION: Our study appears to be the first to provide preliminary evidence that emotional distress negatively affects sleep in terms of decreased deep sleep and increased REM sleep during pregnancy. Findings suggest that further research is needed to understand the role of sleep in the relationships between emotional distress and adverse maternal and infant health outcomes.