Rapid Eye Movement Sleep Time Research Articles

Involvement of the Hippocampal Alpha2A-Adrenoceptors in Anxiety-Related Behaviors Elicited by Intermittent REM Sleep Deprivation-Induced Stress in Mice.

Attention deficit/hyperactivity disorder (AD/HD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. In patients with AD/HD, a decrease in the total and rapid eye movement (REM) sleep times has been observed. We have previously reported that mice with REM sleep deprivation-induced stress (REMSD) may show the hyperactivity- and inattention-like symptoms of AD/HD. However, in this model, impulsivity has not yet been investigated. Impulsivity and anxiety-related behaviors are evaluated by the elevated plus maze test (EPM). In this study, we investigated whether REMSD causes changes in the EPM and expression of alpha2A-adrenoceptors in the hippocampus and frontal cortex in a mouse model. Mice were deprived of REM sleep intermittently using the small-platform method (20 h/d) for 3 d. The time spent in the open arm and the expression levels of alpha2A-adrenoceptor in the hippocampus were significantly increased and decreased, respectively, by the REMSD. The time spent in the open arm was significantly limited by oxymetazoline (an alpha2A-adrenoceptor agonist), methylphenidate, and atomoxetine, which are clinically used to treat AD/HD. Moreover, the positive effects of oxymetazoline were attenuated by yohimbine and BRL44408, which are selective alpha2- and alpha2A-adrenoceptor antagonists, respectively. These results suggest that the increase in the time spent in the open arm induced by REMSD may serve as a model of impulsivity in AD/HD. Furthermore, the REMSD eliciting impulsivity-like behavior and the low-levels of anxiety may be linked to alpha2A-adrenoceptor signaling, as indicated by a decrease in alpha2A-adrenoceptor signaling, particularly in the mouse hippocampus.

Clinical efficacy of proton pump inhibitor combined with ranitidine in the treatment of throat reflux

Objective:To investigate the clinical effect of proton pump inhibitor combined with ranitidine on patients with laryngopharyngeal reflux. Method:Seventy patients with laryngopharyngeal reflux diagnosed in our hospital were randomly divided into group A and group B according to admission time. The difference of B symptom index, reflux symptom scale, sleep breathing test, quality of life and well-being score between the two groups were detected. Result:Before treatment, the RSI index, RFS similarity and QOLS and MUNSH scores were similar （P>0.05）. After four weeks of treatment, the group B score was 3.3±1.2, the group A score was 8.2±3.5, and the group B score was significantly lower. The RFS score of group A （6.2±2.3） was higher than that of group B （2.1±1.9, P<0.05）. The scores of QOLS and MUNSH in group B were （67.57±7.26） and （23.99±3.44）, respectively. The scores of QOLS and MUNSH in group A （50.13±10.19） and （12.21±1.47）, respectively. The results of the two groups were significantly different （P<0.05）. After treatment, the RSI index, RFS score, QOLS and MUNSH scores of the two groups were lower than those before treatment. （P<0.05）. As for the sleep respiration monitoring （PSG） results, after 4-week treatment, compared with the group A, the total sleep time of the group B was significantly increased （P<0.05）, and the number of wakefulness and wakefulness was significantly decreased. The duration of Ⅲ+Ⅳ sleep was also significantly increased, and the proportion of REM sleep time and AHI was significantly reduced （P<0.05）. Conclusion:Proton pump inhibitor combined with ranitidine is more effective and safer than single drug treatment, and can significantly improve the throat reflux symptoms.

REM sleep is associated with white matter integrity in cognitively healthy, older adults.

There is increasing awareness that self-reported sleep abnormalities are negatively associated with brain structure and function in older adults. Less is known, however, about how objectively measured sleep associates with brain structure. We objectively measured at-home sleep to investigate how sleep architecture and sleep quality related to white matter microstructure in older adults. 43 cognitively normal, older adults underwent diffusion tensor imaging (DTI) and a sleep assessment within a six-month period. Participants completed the PSQI, a subjective measure of sleep quality, and used an at-home sleep recorder (Zeo, Inc.) to measure total sleep time (TST), sleep efficiency (SE), and percent time in light sleep (LS), deep sleep (DS), and REM sleep (RS). Multiple regressions predicted fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum as a function of total PSQI score, TST, SE, and percent of time spent in each sleep stage, controlling for age and sex. Greater percent time spent in RS was significantly associated with higher FA (β = 0.41, p = 0.007) and lower MD (β = -0.30, p = 0.03). Total PSQI score, TST, SE, and time spent in LS or DS were not significantly associated with FA or MD (p>0.13). Percent time spent in REM sleep, but not quantity of light and deep sleep or subjective/objective measures of sleep quality, positively predicted white matter microstructure integrity. Our results highlight an important link between REM sleep and brain health that has the potential to improve sleep interventions in the elderly.

Putative role of GPR139 on sleep modulation using pharmacological and genetic rodent models

GPR139 is a G-protein coupled receptor expressed in circumventricular regions of the habenula and septum. Amino acids L-tryptophan and L-phenylalanine have been shown to activate GPR139 at physiologically relevant concentrations. The aim of the present study was to investigate the role of GPR139 on sleep modulation using pharmacological and genetic (GPR139 knockout mice, KO) rodent models. To evaluate the effects of GPR139 pharmacological activation on sleep, rats were orally dosed with the selective GPR139 agonist JNJ-63533054 (3–30 mg/kg). When acutely administered at the beginning of the light phase, the GPR139 agonist dose-dependently reduced non-rapid eye movement (NREM) latency and increased NREM sleep duration without altering rapid eye movement (REM) sleep. This effect progressively dissipated upon 7-day repeated dosing, suggesting functional desensitization. Under baseline conditions, GPR139 KO mice spent less time in REM sleep compared to their wild type littermates during the dark phase, whereas NREM sleep was not altered. Under conditions of pharmacologically enhanced monoamine endogenous tone, GPR139 KO mice showed a blunted response to citalopram or fluoxetine induced REM sleep suppression and an attenuated response to the wake promoting effect of amphetamine. These findings indicate an emerging role of GPR139 in the modulation of sleep states.

A study on sleep apnea in patients with abnormal sewda type of depression

Objective: To preliminarily investigate the clinical features and PSG in abnormal sewda-type depressive insomnia. Methods: A total of 127 abnormal sewda-type depressive insomnia patients were evaluated with overnight PSG, and 32 normal participants were compared. Results: Patients with abnormal sewda-type depressive insomnia were compared with the control group; the sleep symptoms showed a long incubation period of sleep, low sleep maintenance rate, low sleep efficiency and poor sleep quality as well as daytime dysfunction. At process and continuity of sleep: Total sleep time, sleep efficiency, sleep maintenance rate in abnormal sewda-type depressive insomnia group were shorter than the control group. Wake after sleep onset, and sleep latency were longer than the control group. At sleep structure: N1 ratio and N2 ratio in depressive insomnia group were longer than the control group, N3 ratio and REM sleep ratio shorter than the control group. At REM index: REM latency, REM cycles, and REM sleep time were shorter than the control group. Conclusion: Insomnia symptoms in abnormal sewda-type depression comorbid insomnia patients were similar to the ordinary insomnia patients. The PSG characteristics had significant changes in sleep process, sleep structure and REM indicators. The severity of the abnormal sewda-type depression was closely related to REM indicators. Change of REM sleep characteristics may be the specificity, and these could be taken as reference in diagnosis and identification of abnormal sewda-type depressive insomnia.

0141 A Novel, Orally Available Orexin 2 Receptor-Selective Agonist, TAK-994, Shows Wake-Promoting Effects Following Chronic Dosing in an Orexin-Deficient Narcolepsy Mouse Model

Abstract Introduction The use of an orexin 2 receptor (OX2R) agonist may be a promising approach for the treatment of narcolepsy type 1. TAK-994 is a novel, orally available OX2R-selective agonist with &amp;gt;700-fold selectivity against orexin 1 receptor. Single administration of TAK-994 ameliorates narcolepsy-like symptoms such as fragmentation of wakefulness and cataplexy-like episodes in orexin/ataxin-3 mice, a narcolepsy mouse model with orexin deficiency. In this study, we evaluated the effect of chronic dosing with TAK-994 on sleep/wakefulness states in orexin/ataxin-3 mice. Methods Orexin/ataxin-3 mice were grouped into two cohorts: a control group and a 14-day treatment group. In the control group, vehicle was administered orally to mice three times a day: zeitgeber time 12 (ZT12), ZT15 and ZT18, for 14 days. In the 14-day treatment group, TAK-994 was administered orally to mice at ZT12, ZT15 and ZT18 for 14 days. Electroencephalogram/electromyogram analysis was performed on day 1 and day 14 (ZT12-ZT21), and the subsequent sleep phase (ZT0-ZT10). Results On day 1, TAK-994 significantly increased wakefulness time, accompanied by a decrease in non-rapid eye movement (NREM) sleep time and rapid eye movement (REM) sleep time, in orexin/ataxin-3 mice compared with the control group. On day 14, TAK-994 also significantly increased wakefulness time, and decreased NREM sleep time and REM sleep time in orexin/ataxin-3 mice. There were no changes in the time spent in wakefulness, NREM sleep and REM sleep during the subsequent sleep phase after chronic dosing with TAK-994. Conclusion Wake-promoting effects of TAK-994 were observed following chronic dosing for up to 14 days in orexin/ataxin-3 mice with no rebound of sleep. Overall, there was no clear difference in efficacy between the single and repeated administration of TAK-994 in orexin/ataxin-3 mice. Support This work was conducted by Takeda Pharmaceutical Company Limited.

0880 A Pilot Study Evaluating the Effect of Head Elevation During Sleep on Obstructive Sleep Apnea in Pre-Pubertal Children with Down Syndrome

Abstract Introduction Children with down syndrome are at high risk for developing obstructive sleep apnea when compared to typically developing children. Treatment of obstructive sleep apnea is complicated as these children often struggle with traditional therapies such as positive airway pressure. In adult populations it has been shown that head elevation is successful in reducing the severity of OSA (AHI). The hypothesis of this study is that head elevation (30°) would improve OSA in a cohort of pre-pubertal children with down syndrome. Methods Children with down syndrome, aged 4-13, presenting to the sleep clinic at Texas Children’s Hospital were screened for enrollment into the study (n=21; 11 male). Subjects were randomized to begin a diagnostic polysomnogram with either the head of the bed flat (0°) or elevated (30°). Head position was alternated every 2 hours during the study. Studies were performed in an AASM pediatric sleep center by a registered PSG technologist. Studies were scored using AASM pediatric scoring rules. Data was analyzed using paired student t-tests. Each subject served as their own control. Results There was no significant difference in AHI (p=0.71), RDI (p=0.7), O2 nadir (p=0.17), total sleep time (p=0.34), sleep efficiency (p=0.28), time in REM sleep (p=0.94) or arousal index (p=0.14) when the head of the bed was flat (0°) versus elevated (30°). The study shows that head elevation is not successful in significantly reducing obstructive sleep apnea in a pre-pubertal pediatric population of children with down syndrome. Conclusion In children with down syndrome, aged 4-13, referred for a diagnostic sleep study, there is no improvement in OSA due to head elevation (30°) when compared to sleeping flat (0°). These findings were independent of if the subject started with the head of the bed flat or elevated. Other cofounders were eliminated as each subject served as their own control. Support No external funding was utilized for this study.

1139 Sleep Disturbances In Chronic Stroke Patients: Emotional And Cognitive Impact

Abstract Introduction The objective was to investigate the impact of sleep-wake disturbances (SWD) on cognition and quality of life in the post-acute phase of stroke. Methods Adult stroke (n=92) patients were assessed for SWD via overnight polysomnography. The mean age was 52 ± 1 years and mean latency from injury was 117 ± 10 days. Sleep measures included total sleep time (TST), sleep and REM latency, percent time in sleep stages, apnea/hypopnea index (AHI), wake after sleep onset (WASO), and arousal index. The primary cognitive/outcome measures were: Montreal Cognitive Assessment (MoCA), California Verbal Learning Test (CVLT-II), Neuro-QoL and Mayo Portland Adaptability Inventory (MPAI). Results Women had lower AHI (F(1,88)=9.360, p&amp;lt;.01), fewer arousals (F(1,90)=4.53, p&amp;lt;.05), and spent significantly more time in SWS (F(1,90)=11.525, p&amp;lt;.001) than men; however, SWS was reduced in both sexes. SWS made up &amp;lt; 3% of TST in 60% of patients and was not correlated with higher AHI. SWDs negatively impacted subjective quality of life (NeuroQOL). Longer latencies to sleep were associated with increased depression (p&amp;lt;.05) and decreased positive affect (p&amp;lt;.01). Increased sleep efficiency led to improved positive affect (p&amp;lt;.05) and decreases in emotional/behavioral dyscontrol (p&amp;lt;.05). Increased time in REM sleep decreased emotional/behavioral dyscontrol (p&amp;lt;.05), while increasing satisfaction with social roles and activities(p&amp;lt;.01). SWDs also negatively impacted cognitive/outcome scores. Increased TST and sleep efficiency led to higher scores on CVLT-II list B and long delay free recall (p&amp;lt;.05), while higher AHI led to poorer performance on long delay and forced choice recognition trials (p&amp;lt;.01). Additionally, non-REM AHI negatively impacted MPAI adjustment scores (F(1,69)=4.036, p&amp;lt;.05). Conclusion Male stroke patients displayed significantly more arousals and spent less time in SWS than females. For both sexes, better sleep indicated improved quality of life. Sleep measures were correlated with cognitive/outcome measures. Non-REM AHI significantly predicted outcome at discharge from rehabilitation facility. Support

1129 Sex Dependent Effects on Sleep Architecture After Traumatic Brain Injury: Impact on Outcome

Abstract Introduction Traumatic Brain Injury (TBI) is frequently associated with problems with sleep and diurnal somnolence. After determining if subjective somnolence was associated with sleep disturbances, we investigated if alterations in sleep architecture were associated with cognitive, social and emotional health in a sex dependent manner. For patients receiving positive airway pressure (PAP) treatment, we determined if lack of compliance contributed to cognitive and quality of life issues. Methods Adult TBI subjects (n=57) were assessed via overnight polysomnography. Mean age was 41 years and mean TBI chronicity was 2.5 years. Overall level of disability was determined by the Mayo Portland Inventory II. Sleep measures included slow wave sleep (SWS), REM latency, percent time in all sleep stages, apnea/hypopnea index, wake after sleep onset (WASO), and arousal index. Outcome measures were the California Verbal Learning Test (CVLT), Montreal Cognitive Assessment (MoCA), Trails A and B, Beck Depression Inventory, and Neuro-QoL. Results No sex effects for reporting somnolence were found. Besides being associated with increased subjective anxiety and stigma, somnolence was associated with increased arousals, decreases in SWS and higher incidence of REM AHI. WASO and number of arousals had a negative impact on the amount of SWS and sleep efficiency. Men spent significantly more time in REM sleep, which was correlated with higher scores on the MoCA and CVLT. Women showed more disability. Longer latencies to SWS were associated with increased CVLT performance. AHI was associated with increases in emotional/behavioral dyscontrol, fatigue and self-reported sleep disturbance. All effects were statistically significant. Conclusion Female TBI patients show significant impairments in REM sleep, which may impact learning and memory. Sleep disturbances were associated with poorer cognitive performance and may ultimately affect outcome, as indicated by lower scores on quality of life measures. Support Centre for Neuro Skills

A comparison of automated and manual sleep staging and respiratory event recognition in a portable sleep diagnostic device with in-lab sleep study.

The objectives were to develop and validate an algorithm for editing WatchPAT scoring and assess the accuracy in an unselected clinical population as well as age and sex substrata. Two hundred sixty-two participants were enrolled to undergo WatchPAT simultaneously with in-lab polysomnography (PSG) recordings for developing (n = 30), optimizing (n = 62), and validating (n = 170) an algorithm to review and edit respiratory events and sleep architecture of WatchPAT recordings, which was based on visual inspection of WatchPAT signals. Apnea-hypopnea index (AHI) and sleep indices were compared with PSG-derived and automated WatchPAT indices. Although estimation of total sleep time (TST) was comparable between automated and manual algorithm, estimation of rapid eye movement (REM) sleep time was markedly improved with manual editing from 0.48, 23.0 min (-43.9 to 89.8) to 0.64, 18.3 min (-32.6 to 69.1) (correlation with PSG, mean difference [reference range] from PSG, respectively). Manual scoring also improved correlation and agreement with PSG AHI from 0.65, 2.5 events/h (-24.0 to 28.9) to 0.81, -4.5 events/h (-22.5 to 13.6) as well as concordance for categorical agreement of sleep-disordered breathing severity and concordance for detecting severe REM-related sleep-disordered breathing. Interscorer reliabilities were excellent for TST and AHI, while good for REM sleep time. The automated algorithm performed better in younger than in older patients, while performed similarly between men and women with respect to concordance statistics. The manual algorithm markedly improved concordances more in older patients and women than in their counterparts. Our manual editing algorithm improves correlation and agreement with PSG-derived sleep and breathing indices. Sex and age influence the accuracy of automated analysis and the performance of manual editing on AHI concordance.

Abstract P417: Relationship Between Blood Pressure Variability and Sleep Architecture

Introduction: Blood pressure (BP) variability (BPV) is a novel marker for cardiovascular disease (CVD) independent of high BP. Sleep architecture represents the structured pattern of sleep stages consisting of rapid eye movement (REM) and non-rapid eye movement (NREM), and it is an important element in the homeostatic regulation of sleep. Currently, little is known regarding whether BPV is linked to sleep stages. Our study aimed to examine the relationship between sleep architecture and BPV. Methods: We analyzed in-lab polysomnographic studies collected from individuals who underwent diagnostic sleep studies at a university hospital from 2010 to 2017. BP measures obtained during one year prior to the sleep studies were included. BPV was computed using the coefficient of variation for all individuals who had three or more systolic and diastolic BP data. We conducted linear regression analysis to assess the relationship of systolic BPV (SBPV) and diastolic BPV (DBPV) with the sleep stage distribution (REM and NREM sleep time), respectively. Covariates that can potentially confound the relationships were adjusted in the models, including age, sex, race/ethnicity, body mass index, total sleep time, apnea-hypopnea index, mean BP, and history of medication use (antipsychotics, antidepressants, and antihypertensives) during the past two years before the sleep studies. Results: Our sample (N=3,565; male = 1,353) was racially and ethnically diverse, with a mean age 54 ± 15 years and a mean BP of 131/76 ± 13.9/8.4 mmHg. Among the sleep architecture measures examined, SBPV showed an inverse relationship with REM sleep time after controlling for all covariates ( p = .033). We subsequently categorized SBPV into four quartiles and found that the 3 rd quartile (mean SBP SD = 14.9 ± 2.1 mmHg) had 3.3 fewer minutes in REM sleep compared to the 1 st quartile ( p = .02). However, we did not observe any relationship between DBPV and sleep architecture. Conclusion: Greater SBPV was associated with lower REM sleep time. This finding suggests a possible interplay between BPV and sleep architecture. Future investigation is warranted to clarify the directionality, mechanism, and therapeutic implications.

Different Patterns of Sleep-Dependent Procedural Memory Consolidation in Vipassana Meditation Practitioners and Non-meditating Controls.

AimRapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep, and sleep spindles are all implicated in the consolidation of procedural memories. Relative contributions of sleep stages and sleep spindles were previously shown to depend on individual differences in task processing. However, no studies to our knowledge have focused on individual differences in experience with Vipassana meditation as related to sleep. Vipassana meditation is a form of mental training that enhances proprioceptive and somatic awareness and alters attentional style. The goal of this study was to examine a potential role for Vipassana meditation experience in sleep-dependent procedural memory consolidation.MethodsGroups of Vipassana meditation practitioners (N = 22) and matched meditation-naïve controls (N = 20) slept for a daytime nap in the laboratory. Before and after the nap they completed a procedural task on the Wii Fit balance platform.ResultsMeditators performed slightly better on the task before the nap, but the two groups improved similarly after sleep. The groups showed different patterns of sleep-dependent procedural memory consolidation: in meditators, task learning was positively correlated with density of slow occipital spindles, while in controls task improvement was positively associated with time in REM sleep. Sleep efficiency and sleep architecture did not differ between groups. Meditation practitioners, however, had a lower density of occipital slow sleep spindles than controls.ConclusionResults suggest that neuroplastic changes associated with meditation practice may alter overall sleep microarchitecture and reorganize sleep-dependent patterns of memory consolidation. The lower density of occipital spindles in meditators may mean that meditation practice compensates for some of the memory functions of sleep.

Accuracy of WatchPAT for the Diagnosis of Obstructive Sleep Apnea in Patients with Chronic Obstructive Pulmonary Disease

The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), termed the overlap syndrome (OVS), is associated with adverse outcomes that may be reversed with treatment. However, diagnosis is limited by the apparent need for in-laboratory polysomnography (PSG). WatchPAT is a portable diagnostic device that is validated for the diagnosis of OSA that might represent an attractive tool for the diagnosis of OVS.Subjects with established COPD were recruited from a general population. Subjects underwent PSG and simultaneous recording with WatchPAT. Pulmonary function testing and questionnaires were also performed.A total of 36 subjects were recruited and valid data was obtained on 33 (age 63 ± 7, BMI 28 ± 7, 61% male, FEV1 56 ± 20% predicted). There was no significant difference in the apnea–hypopnea index (AHI) between PSG and WatchPAT (19 ± 20 versus 20 ± 15 events/h; mean difference 2(–2, 5) events/h; p = 0.381). The AHI was not significantly different in rapid eye movement (REM) and non-rapid eye movement (NREM) determined by PSG versus REM and NREM determined by WatchPAT. WatchPAT slightly overestimated total and REM sleep time, and sleep efficiency. The sensitivity of WatchPAT at an AHI cut-off of ≥5, ≥15, and ≥30 events/h for corresponding PSG AHI cut-offs was 95.8, 92.3, and 88.9, respectively; specificity was 55, 65.0, and 95.8, respectively.WatchPAT is able to determine OSA reliably in patients with COPD. The availability of this additional diagnostic modality may lead to improved detection of OVS, which may in turn lead to improved outcomes for a group of COPD patients at high risk of poor outcomes.

Time as a dimension of consciousness. Subjective passage of time during wakefulness, REM, and NREM sleep

In this paper, the authors review experimental data on the ability to perceive the passage of time during wakefulness and sleep. The evolutionary significance of the sense of time and its role in cognitive functions is discussed. Recent findings on neural mechanisms underlying perception and estimation of time as well as temporal order judgments are described. Similarities and differences of the awareness of time in wakefulness, REM, and NREM sleep are analyzed.

Finger Twitches are More Frequent in REM Sleep Than in Non-REM Sleep.

IntroductionAbnormal rapid eye movement (REM) sleep is often symptomatic of chronic disorders, however polysomnography, the gold standard method to measure REM sleep, is expensive and often impractical. Attempts to develop cost-effective ambulatory systems to measure REM sleep have had limited success. As elevated twitching is often observed during REM sleep in some distal muscles, the aim of this study was to assess the potential for a finger-mounted device to measure finger twitches, and thereby differentiate periods of REM and non-REM (NREM) sleep.MethodsOne night of sleep data was collected by polysomnography from each of 18 (3f, 15m) healthy adults aged 23.2 ± 3.3 (mean ± SD) years. Finger movement was detected using a piezo-electric limb sensor taped to the index finger of each participant. Finger twitch densities were calculated for each stage of sleep.ResultsFinger twitch density was greater in REM than in NREM sleep (p < 0.001). Each sleep stage had a unique finger twitch density, except for REM and stage N1 sleep which were similar. Finger twitch density was greater in late REM than in early REM sleep (p = 0.005), and there was a time–state interaction: the difference between finger twitch densities in REM and NREM sleep was greater in late sleep than in early sleep (p = 0.007).ConclusionFinger twitching is more frequent in REM sleep than in NREM sleep and becomes more distinguishable as sleep progresses. Finger twitches appear to be too infrequent to make definitive 30-second epoch determinations of sleep stage. However, an algorithm informed by measures of finger twitch density has the potential to detect periods of REM sleep and provide estimates of total REM sleep time and percentage.

Reward does not facilitate visual perceptual learning until sleep occurs

A growing body of evidence indicates that visual perceptual learning (VPL) is enhanced by reward provided during training. Another line of studies has shown that sleep following training also plays a role in facilitating VPL, an effect known as the offline performance gain of VPL. However, whether the effects of reward and sleep interact on VPL remains unclear. Here, we show that reward interacts with sleep to facilitate offline performance gains of VPL. First, we demonstrated a significantly larger offline performance gain over a 12-h interval including sleep in a reward group than that in a no-reward group. However, the offline performance gains over the 12-h interval without sleep were not significantly different with or without reward during training, indicating a crucial interaction between reward and sleep in VPL. Next, we tested whether neural activations during posttraining sleep were modulated after reward was provided during training. Reward provided during training enhanced rapid eye movement (REM) sleep time, increased oscillatory activities for reward processing in the prefrontal region during REM sleep, and inhibited neural activation in the untrained region in early visual areas in non-rapid eye movement (NREM) and REM sleep. The offline performance gains were significantly correlated with oscillatory activities of visual processing during NREM sleep and reward processing during REM sleep in the reward group but not in the no-reward group. These results suggest that reward provided during training becomes effective during sleep, with excited reward processing sending inhibitory signals to suppress noise in visual processing, resulting in larger offline performance gains over sleep.

P.225 Effect of MP-III-022, positive modulator of alpha 5 containing GABAA receptors, on learning and memory

Sleep-disordered breathing may precipitate angina pectoris (AP) in rapid eye movement (REM) sleep. The purpose of this study was to investigate whether REM sleep is associated with the incidence of AP in different categories of apnea–hypopnea index (AHI).A total of 2710 participants from Sleep Heart Health Study (59.3% women; mean age 61.7 years), who had 6−8 h of sleep; experienced an almost 11-year follow-up period. Complete polysomnography data and medical records were available for all participants. Percentage of REM sleep time (REM%) was classified into grade 1 (<20%), grade 2 (20–25%) and grade 3 (>25%). Logistic regression analysis was used to characterize the independent association between REM sleep and prevalent AP in this multi-center community-based cohort study.Patients with REM% of grade 3 had a higher incidence of AP than those with grade 1 and grade 2 (50.3% vs 42.4% vs 42.1%, respectively; p = 0.003). After adjusting for age, gender, race, AHI, marital status, education level, body mass index, sleep duration, arousal index, diabetes, hypertension and smoking status, multivariate logistic regression analysis revealed that REM% >25% was independently associated with the occurrence of AP (odds ratio = 1.500; 95% confidence interval = 1.188–1.894; p = 0.001).The percentage of REM sleep time may affect the incidence of AP irrespective of AHI level. Therefore, the relationship between sleep structure and cardiovascular disease merits further exploration.

Differences in sleep architecture according to body mass index in children with type 1 diabetes.

Slow wave sleep (SWS), or deep sleep, is thought to be the most restorative stage of sleep and may be of a particular interest in the pathophysiology of obesity. The aim of this study was to investigate differences in sleep architecture based on body mass index (BMI) among a pediatric population with type 1 diabetes mellitus (T1DM). We hypothesized that children with T1DM who are obese would have less SWS than those who are not obese. Of 105 children with T1DM (mean age 13.54 years, 49.5% females) in this study, 19% were obese, 22% were overweight, and 59% had a normal BMI (81% non-obese). The overall SWS% among the participants was 13.2%. In contrast to our hypothesis, there was no significant difference in SWS% between obese and non-obese participants. However, the percent of time spent in rapid eye movement (REM) sleep among obese participants was significantly lower than those who were not obese (P = .022), which remained after adjusting the result for multiple covariates. While we found no significant association between the SWS time and BMI, obese adolescents with T1DM spent less time in REM sleep than those who were not obese. This study adds to the growing body of evidence supporting the importance of addressing sleep in clinical care of youth with T1DM.

A novel GABAB receptor positive allosteric modulator, ASP8062, exerts analgesic effects in a rat model of fibromyalgia

The gamma-aminobutyric acid type B (GABAB) receptor agonist, the sodium salt of gamma-hydroxybutyrate (GHB), significantly improved pain, sleep disturbance and fatigue in fibromyalgia (FM) patients. However, the use of GABAB receptor agonists is limited by their undesirable side-effects. To clarify whether GABAB receptor positive allosteric modulator (PAM) approach would achieve analgesia with less side-effects than GABAB receptor agonist in FM, we investigated the potential of a novel GABAB receptor PAM, ASP8062, for FM treatment. We examined the in vitro profiles of ASP8062, the effects of a GABAB receptor PAM and an agonist on pain in a rat model of FM, and the sleep/wake cycle, EEG during sleep stages and motor coordination in rats. ASP8062 showed PAM activity on human and rat GABAB receptors. Oral administration of ASP8062 significantly reversed the decrease in muscle pressure threshold in reserpine-induced myalgia rats. The analgesic effects of ASP8062 were significantly blocked by a GABAB receptor antagonist. ASP8062 had a significant effect on motor coordination at a 1000-fold higher dose than the analgesic dose in rats. ASP8062 significantly decreased total REM sleep time and frequency of sleep interruptions, and increased the power in delta waves frequency during non-REM sleep in rats. ASP8062, a novel GABAB receptor PAM, has therapeutic potential to exert analgesic effects with less side-effects compared to GABAB receptor agonists in patients with FM.

SLEEP AND CARDIAC TACHYARRHYTHMIA: RESULTS FROM THE CROSS-SECTIONAL SLEEP HEART HEALTH STUDY

Despite the well-known relationship between sleep disorders and general cardiovascular risk, few studies have examined sleep quality and quantity at pre-clinical levels in patients with cardiac arrhythmias (CA). Patients with CA are at an elevated risk of stroke, sudden cardiac death, disability, and reduced quality of life. In this study, we sought to elucidate the sleep-related predictors of arrhythmia using both subjective and objective measures of sleep. Baseline, comorbidity, electrocardiogram, and polysomnography data from the Sleep Heart Health Study (age 44-90 y) was available for secondary analysis. ECG data was used to identify participants with cardiac arrhythmias during polysomnography. Exposure variables used included blood oxygen saturation, sleep stages, and tertiles of sleep quality and quantity. Unadjusted and adjusted logistic regression was used to quantify the association between sleep and non-sleep related factors and arrhythmia. Of the 5,804 original SHHS sample, a total of 3,453 participants with complete variables of interest were included in the final analysis (mean age: 68.1 ± 10.6 Years, 54% male, 499 with arrhythmia (Atrial Tachyarrhythmia and Conduction Abnormalities), and 2,954 Controls). At the bivariate level, underweight (BMI < 18.5) (OR: 2.86, 95% CI: 1.1 – 7.2, P < 0.0001), sleep time < 6 hours (OR: 2.58, 1.5-4.3, P < 0.0001), % time in REM sleep ( < 17.6; OR: 1.53, 1.2-1.0, P < 0.0001), sleep efficiency ( < 81; OR: 1.9, 1.5-2.3) and regular afternoon naps (OR:1.8, 1.3-2.4, P < 0.0001) were significantly associated with CA. Once adjusted for age and sex, only % time in REM sleep and minimum oxygen saturation during REM (OR: 0.97, 0.96-0.98, P=0.006, and; OR: 0.97, 0.96-0.98, P=0.001, respectively) were significantly associated with CA. Preliminary analyses suggest differences in sleep stages and oxygen saturation as potential targets for future work in the prevention and early management of CA. Further study is necessary to understand the nature of these relationships using longitudinal data with adjustment for traditional CA markers.