Increase In Rapid Eye Movement Sleep Research Articles

A potentiation of REM sleep-active neurons in the lateral habenula may be responsible for the sleep disturbance in depression

Psychiatric disorders with dysfunction of the lateral habenula (LHb) show sleep disturbance, especially a disinhibition of rapid eye movement (REM) sleep in major depression. However, the role of LHb in physiological sleep control and how LHb contributes to sleep disturbance in major depression remain elusive. Here, we found that functional manipulations of LHb glutamatergic neurons bidirectionally modulated both non-REM (NREM) sleep and REM sleep. Activity recording revealed heterogeneous activity patterns of LHb neurons across sleep/wakefulness cycles, but LHb neurons were preferentially active during REM sleep. Using an activity-dependent tagging method, we selectively labeled a population of REM sleep-active LHb neurons and demonstrated that these neurons specifically promoted REM sleep. Neural circuit studies showed that LHb neurons regulated REM sleep via projections to the ventral tegmental area but not to the rostromedial tegmental nucleus. Furthermore, we found that the increased REM sleep in a depression mouse model was associated with a potentiation of REM sleep-active LHb neurons, including an increased proportion, elevated spike firing, and altered activity mode. Importantly, inhibition of REM sleep-active LHb neurons not only attenuated the increased REM sleep but also alleviated depressive-like behaviors in a depression mouse model. Thus, our results demonstrated that REM sleep-active LHb neurons selectively promoted REM sleep, and a potentiation of these neurons contributed to depression-associated sleep disturbance.

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.

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.

Effect of prolonged sedation with dexmedetomidine, midazolam, propofol, and sevoflurane on sleep homeostasis in rats

BackgroundSleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative–hypnotics on sleep homeostasis is not clear. MethodsWe conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague–Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. ResultsDexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01). ConclusionsIn contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis.

Regulation of REM sleep in mice: The role of dopamine and serotonin function in the basolateral amygdala

Animals have a sleep cycle that involves the repetitive occurrence of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. In a previous study, we discovered that a transient increase in dopamine (DA) levels in the basolateral amygdala (BLA) during NREM sleep terminates NREM sleep and initiates REM sleep by acting on Drd2-positive neurons (Hasegawa et al., 2022). In this study, we identified the neurons activated by the transient increase of DA in the BLA and found that chemogenetic excitation of these neurons increased REM sleep. Additionally, we demonstrated that acute inhibition of serotonin (5HT) in the BLA elicited a transient increase in DA in the BLA, which triggered REM sleep.

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.

TRANSVENOUS PHRENIC NERVE STIMULATION EFFECTIVELY TREATS CENTRAL SLEEP APNEA DURING BOTH RAPID AND NONRAPID EYE MOVEMENT SLEEP

TRANSVENOUS PHRENIC NERVE STIMULATION EFFECTIVELY TREATS CENTRAL SLEEP APNEA DURING BOTH RAPID AND NONRAPID EYE MOVEMENT SLEEP

Roles of Neuropeptides in Sleep-Wake Regulation.

Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including neuropeptides. Neuropeptides are a group of peptides produced by neurons and neuroendocrine cells of the central nervous system. Like traditional neurotransmitters, neuropeptides can bind to specific surface receptors and subsequently regulate neuronal activities. For example, orexin is a crucial component for the maintenance of wakefulness and the suppression of rapid eye movement (REM) sleep. In addition to orexin, melanin-concentrating hormone, and galanin may promote REM sleep. These results suggest that neuropeptides play an important role in sleep–wake regulation. These neuropeptides can be divided into three categories according to their effects on sleep–wake behaviors in rodents and humans. (i) Galanin, melanin-concentrating hormone, and vasoactive intestinal polypeptide are sleep-promoting peptides. It is also noticeable that vasoactive intestinal polypeptide particularly increases REM sleep. (ii) Orexin and neuropeptide S have been shown to induce wakefulness. (iii) Neuropeptide Y and substance P may have a bidirectional function as they can produce both arousal and sleep-inducing effects. This review will introduce the distribution of various neuropeptides in the brain and summarize the roles of different neuropeptides in sleep–wake regulation. We aim to lay the foundation for future studies to uncover the mechanisms that underlie the initiation, maintenance, and end of sleep–wake states.

Lonicerae Japonicae Flos Extract Promotes Sleep in Sleep-Deprived and Lipopolysaccharide-Challenged Mice.

Lonicerae Japonicae Flos (LJF) is commonly used in Chinese herbal medicines and exhibits anti-viral, anti-oxidative, and anti-inflammatory properties. The reciprocal relationship between sleep, the immune system and the central nervous system is well-established in the animal models. In this study, we used the mouse model to analyze the beneficial effects of the LJF on the dysregulated sleep-wakefulness cycle in response to acute sleep deprivation and lipopolysaccharide (LPS)-induced inflammation and the potential underlying mechanisms. Polysomnography data showed that LJF increased the time spent in non-rapid eye movement (NREM) sleep during the day under basal conditions. Furthermore, latency to sleep was reduced and the time spent in rapid eye movement (REM) sleep was increased during recovery from acute sleep deprivation. Furthermore, LJF-treated mice showed increased REM sleep and altered electroencephalogram (EEG) power spectrum in response to intra-peritoneal injection of LPS. LJF significantly reduced the levels of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in the blood serum as well as hippocampus, and medial prefrontal cortex (mPFC) tissues in the LPS-challenged mice by inhibiting microglial activation. Moreover, LJF increased the time spent in REM sleep in the LPS-challenged mice compared to the control mice. These results suggested that LJF stimulated the sleep drive in response to acute sleep deprivation and LPS-induced inflammation, thereby increasing REM sleep for recovery and neuroprotection. In conclusion, our findings demonstrate that the clinical potential of LJF in treating sleep disorders related to sleep deprivation and neuro-inflammation.

Associations of Habitual Sleep Duration and Sleep Stages With Speech-in-Noise Performance

Speech-in-noise performance involves central auditory and cortical processing and is fundamental to communication. We investigated cross-temporal associations of habitual sleep duration and stages (1996-1998) with speech-in-noise performance (2016-2017) in a subset of the Atherosclerosis Risk in Communities Study participated in the Sleep Heart Health Study(N=755, 61±5 years, 53% female). Speech-in-noise performance was measured by Quick Speech-in-Noise Test; range:0-30; lower scores=worse performance. Time spent in each stage (stage 1;2;3/4;rapid eye movement (REM)) was measured by polysomnography. Habitual sleep duration was calculated by self-reported duration on weekdays and weekends. In models adjusting for demographic and disease covariates, every 10-minute increase in REM sleep was associated with better speech-in-noise performance (0.10 points,95% CI:0.00,0.21); every 1-hour increase in habitual sleep duration was associated with worse speech-in-noise performance (-1.28 points,95% CI:-2.49,-0.08) among participants sleep >8 hours. Long sleep duration might be a risk marker of speech-in-noise performance, but REM sleep might be a protective factor.

Abstract 13446: Rapid Eye Movement Sleep is Associated With Ambulatory Blood Pressure in Hypertension

Introduction: Growing evidence suggests that aberrant sleep architecture is linked to heightened risk of cardiovascular disease independently of sleep apnea. Rapid Eye Movement (REM) sleep is characterized by increased sympathetic activity and blood pressure (BP) compared to non-REM sleep stages. However, whether REM sleep is associated with BP across the 24 hours has not been investigated. Hypothesis: We hypothesized that increased REM sleep would be associated with higher ambulatory BP. Methods: We recruited 137 individuals (58% men, aged 39±14 years, office systolic/diastolic BP [SBP/DBP] 125±14/77±11 mmHg) who completed overnight polysomnography followed by 24-h ambulatory BP monitoring. Sleep was scored according to standard criteria. 24-h, daytime, and nighttime averages were calculated for SBP, DBP and heart rate. REM sleep duration was computed as percentage of total sleep time and used to group participants into tertiles as follows: T1 (REM% ≤18.8), T2 (REM% 18.9-24), and T3 (REM% ≥24.1). Results: Sex ratio, body mass index, and apnea-hypopnea index were similar across REM tertiles, but age increased with increasing tertiles (p=0.029). 24-h SBP (T1 vs T2 vs T3: 121±12 vs 117±7 vs 124±12 mmHg, p=0.015) and DBP (72±7 vs 70±6 vs 76±8 mmHg, p&lt;0.001) differed across REM sleep tertiles, with significantly higher values in those in the highest tertile. Results were consistent when considering daytime SBP (T1 vs T2 vs T3: 126±12 vs 122±8 vs 132±14 mmHg, p&lt;0.001) and DBP (77±7 vs 76±6 vs 83±9 mmHg, p&lt;0.001), and nighttime DBP (65±9 vs 61±7 vs 65±8 mmHg, p=0.047). No differences were noted on nighttime SBP or any heart rate measures. A significant interaction was found between hypertension status and REM sleep in multiple regression analysis, with the observed associations being significant only among hypertensives (n=69). In those with hypertension, REM sleep duration was associated with 24-h mean BP independently of age, sex, body mass index, apnea-hypopnea index and antihypertensive medications (standardized beta 0.22, p=0.041). Conclusions: Longer REM sleep duration is independently associated with elevated ambulatory BP in individuals with hypertension. REM sleep may be a novel cardiovascular risk indicator in this population.

Proton Pump Inhibitor "Lansoprazole" Inhibits Locus Coeruleus's Neuronal Activity and Increases Rapid Eye Movement Sleep.

Alteration of the bodily CO2 concentration and proton pump activity affects the sleep architecture. The brainstem locus coeruleus (LC) area plays an essential role in rapid eye movement (REM) sleep generation and chemoregulation. Previously, we reported that lansoprazole injections (intraperitoneal) increased REM sleep in the rats. However, it is not known if proton pumps in the LC influence REM sleep. Here, we studied the effects of lansoprazole in the LC on the neuronal activity and REM sleep expression. Male Wistar rats (250-300 g) were surgically prepared for sleep recording and drug microinjections into the LC. We determined the localization of proton pumps and expression levels of cFOS in the LC neurons immunohistochemically. Sleep-wake was recorded before and after the microinjections of drugs/vehicles. Our results demonstrate (i) the presence of proton pumps in the LC neurons, (ii) that the microinjection of lansoprazole into the LC reduced the number of cFOS+ve-TH+ve double-labeled neurons in the LC by 52.6% (p < 0.001) compared to the vehicle and (iii) that low and high doses of lansoprazole significantly increased REM sleep by 32% (p < 0.001) and 60% (p < 0.001), respectively, compared to the vehicle. Our results suggest that the proton pumps modulate the LC's noradrenergic (NE-ergic) neuronal activity and REM sleep. The increased amount of REM sleep can be attributed to the inhibition of the LC NE-ergic activity. Further, the REM sleep amount increased after the lansoprazole microinjections into the LC with a significant increase in the REM sleep episode numbers. Overall, our results suggest that proton pumps in the LC may be involved in REM sleep generation.

The Defensive Activation Theory: REM Sleep as a Mechanism to Prevent Takeover of the Visual Cortex.

Regions of the brain maintain their territory with continuous activity: if activity slows or stops (e.g., because of blindness), the territory tends to be taken over by its neighbors. A surprise in recent years has been the speed of takeover, which is measurable within an hour. These findings lead us to a new hypothesis on the origin of REM sleep. We hypothesize that the circuitry underlying REM sleep serves to amplify the visual system’s activity periodically throughout the night, allowing it to defend its territory against takeover from other senses. We find that measures of plasticity across 25 species of primates correlate positively with the proportion of rapid eye movement (REM) sleep. We further find that plasticity and REM sleep increase in lockstep with evolutionary recency to humans. Finally, our hypothesis is consistent with the decrease in REM sleep and parallel decrease in neuroplasticity with aging.

Preoperative REM sleep is associated with complication development after colorectal surgery.

While total sleep duration and rapid eye movement (REM) sleep duration have been associated with long-term mortality in non-surgical cohorts, the impact of preoperative sleep on postoperative outcomes has not been well studied. In this secondary analysis of a prospective observational cohort study, patients who recorded at least 1 sleep episode using a consumer wearable device in the 7 days before elective colorectal surgery were included. 30-day postoperative outcomes among those who did and did not receive at least 6 h of total sleep, as well as those who did and did not receive at least 1 h of rapid eye movement (REM) sleep, were compared. 34 out of 95 (35.8%) patients averaged at least 6 h of sleep per night, while 44 out of 82 (53.7%) averaged 1 h or more of REM sleep. Patients who slept less than 6 h had similar postoperative outcomes compared to those who slept 6 h or more. Patients who averaged less than 1 h of REM sleep, compared to those who achieved 1 h or more of REM sleep, had significantly higher rates of complication development (29.0% vs. 9.1%, P = 0.02), and return to the OR (10.5% vs. 0%, P = 0.04). After adjustment for confounding factors, increased REM sleep duration remained significantly associated with decreased complication development (increase in REM sleep from 50 to 60 min: OR 0.72, P = 0.009; REM sleep ≥ 1 h: OR 0.22, P = 0.03). In this cohort of patients undergoing elective colorectal surgery, those who developed a complication within 30 days were less likely to average at least 1 h of REM sleep in the week before surgery than those who did not develop a complication. Preoperative REM sleep duration may represent a risk factor for surgical complications; however additional research is necessary to confirm this relationship.

Couple Relationships Are Associated With Increased REM Sleep-A Proof-of-Concept Analysis of a Large Dataset Using Ambulatory Polysomnography.

Background/Objectives: Rapid Eye Movement (REM) sleep is associated with memory consolidation and several health effects including stress response, mental health, and longevity. Recently, it has been shown that regularly co-sleeping couples have increased and stabilized REM sleep when co-sleeping as compared to sleeping individually. However, it remained unclear whether this is due to a specific effect of altering the usual sleeping environment by partner deprivation or due to a generalizable REM-sleep promoting effect of couple relationships. The present study aims to clarify this ambiguity.Methods: Married or never married individuals were taken from the Sleep Heart Health Study (n = 5,804) and matched regarding sociodemographic and health parameters. Matching was done using propensity score matching (1:1, nearest neighbor) and resulted in two groups of n = 69 each (married vs. never married). After confirmation of successful matching, samples were compared regarding REM sleep and other polysomnographic parameters (paired Students t-tests or Wilcoxon signed-rank tests).Results: Married individuals showed significantly higher levels of total and relative REM sleep as compared to never married individuals (all p's ≤ 0.003). Neither other sleep stages nor REM-sleep fragmentation differed between groups (all p's ≥ 0.29). Results regarding number of sleep cycles were ambiguous.Conclusion: This is the first between-subjects study to show that couple relationships are associated with increased REM sleep. This finding represents a necessary (but not sufficient) condition for the previously hypothesized self-enhancing feedback loop of REM sleep and sociality as well as for REM-sleep promotion as a mechanism through which couple relationships prevent mental illness.

Manipulation of rapid eye movement sleep via orexin and GABAA receptor modulators differentially affects fear extinction in mice: effect of stable versus disrupted circadian rhythm.

Sleep disruption, and especially rapid eye movement (REM) sleep disruption, is associated with fear inhibition impairment in animals and humans. The REM sleep-fear inhibition relationship raises concern for individuals with posttraumatic stress disorder (PTSD), whose sleep disturbance is commonly treated with hypnotics that disrupt and/or decrease REM sleep, such as benzodiazepines or "Z-drugs." Here, we examined the effects of the Z-drug zolpidem, a gamma-aminobutyric acidA (GABAA) receptor positive allosteric modulator, as well as suvorexant, an orexin receptor antagonist (hypnotics which decrease and increase REM sleep, respectively) in the context of circadian disruption in murine models of fear inhibition-related processes (i.e. fear extinction and safety learning). Adult male C57Bl/6J mice completed fear and safety conditioning before undergoing shifts in the light-dark (LD) cycle or maintaining a consistent LD schedule. Fear extinction and recall of conditioned safety were thereafter tested daily. Immediately prior to the onset of the light phase between testing sessions, mice were treated with zolpidem, suvorexant, or vehicle (methylcellulose). Polysomnographic analyses showed the temporal distribution of REM sleep was misaligned during LD cycle-shifts, while REM sleep duration was preserved. Suvorexant increased REM sleep and improved fear extinction rate, relative to zolpidem, which decreased REM sleep. Survival analysis demonstrated LD shifted mice treated with suvorexant were faster to achieve complete extinction than vehicle and zolpidem-treated mice in the LD shifted condition. By contrast, retention of conditioned safety memory was not influenced by either treatment. This study thus provides preclinical evidence for the potential clinical utility of hypnotics which increase REM sleep for fear extinction after PTSD-relevant sleep disturbance.

Cocaine-induced neural adaptations in the lateral hypothalamic melanin-concentrating hormone neurons and the role in regulating rapid eye movement sleep after withdrawal.

Sleep abnormalities are often a prominent contributor to withdrawal symptoms following chronic drug use. Notably, rapid eye movement (REM) sleep regulates emotional memory, and persistent REM sleep impairment after cocaine withdrawal negatively impacts relapse-like behaviors in rats. However, it is not understood how cocaine experience may alter REM sleep regulatory machinery, and what may serve to improve REM sleep after withdrawal. Here, we focus on the melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH), which regulate REM sleep initiation and maintenance. Using adult male Sprague Dawley rats trained to self-administer intravenous cocaine, we did transcriptome profiling of LH MCH neurons after long-term withdrawal using RNA-sequencing, and performed functional assessment using slice electrophysiology. We found that three weeks after withdrawal from cocaine, LH MCH neurons exhibit a wide range of gene expression changes tapping into cell membrane signaling, intracellular signaling, and transcriptional regulations. Functionally, they show reduced membrane excitability and decreased glutamatergic receptor activity, consistent with increased expression of voltage-gated potassium channel gene Kcna1 and decreased expression of metabotropic glutamate receptor gene Grm5. Finally, chemogenetic or optogenetic stimulations of LH MCH neural activity increase REM sleep after long-term withdrawal with important differences. Whereas chemogenetic stimulation promotes both wakefulness and REM sleep, optogenetic stimulation of these neurons in sleep selectively promotes REM sleep. In summary, cocaine exposure persistently alters gene expression profiles and electrophysiological properties of LH MCH neurons. Counteracting cocaine-induced hypoactivity of these neurons selectively in sleep enhances REM sleep quality and quantity after long-term withdrawal.

Improvements in quality of life in female obstructive sleep apnea patients using a gender specific positive airway pressure device

Study Objectives: Females with obstructive sleep apnea (OSA) have more flow limitation, lower apnea-hypopnea index (AHI), shorter apneas, and less severe oxygen desaturations than males. A female-specific auto-adjusting continuous positive airway pressure (fAPAP) algorithm has been developed to target these characteristics. This study investigated the effects of fAPAP therapy on quality of life (QoL) in women with OSA. Methods: Female patients with AHI ≥ 15/h were eligible. Participants underwent polygraphy or polysomnography. The primary endpoint was change from baseline in Functional Outcomes of Sleep Questionnaire (FOSQ) score after 3 months’ fAPAP (AutoSet for Her, ResMed). Secondary endpoints included other sleep-related and QoL questionnaires. Results: A total of 122 patients were enrolled in the study (age 53.7 ± 9.5 years, body mass index 32.8 ± 6.2 kg/m2, apnea-hypopnea index [AHI] 39.0 ± 18.2/h); 111/122 completed the study. There was a significant improvement (p<0.0001) in FOSQ score from baseline (15.0 ± 3.3) to 3 months (16.9 ± 3.2). Significant improvements were also seen in the Patient Health Questionnaire-9 score (12.3 ± 6.0 vs. 7.2 ± 5.4), Epworth Sleepiness Scale score (10.8 ± 4.9 vs. 7.3 ± 4.7), EuroQol (EQ)-5D Index score (0.636 ± 0.248 vs. 0.763 ± 0.210), EQ-5D visual analogue scale score (54.4 ± 21.7 vs. 64.5 ± 21.5) (all p<0.0001), and Changes in Sexual Functioning Questionnaire score (38.7 ± 9.5 vs. 42.4 ± 8.5; p=0.001). In patients with PSG data, fAPAP improved other respiratory parameters (AHI, oxygen desaturation index, oxygen saturation; all p<0.0001), and increased time spent in rapid eye movement (REM) sleep (39.7 ± 24.0 vs. 48.1 ± 24.5 min; p=0.022). Average daily fAPAP usage was 4.8 ± 2.0 h/night. Conclusion: Usage of fAPAP significantly improved QoL and increased REM sleep, with good treatment compliance.

Supine Alarm Device can Restore REM Sleep in Patients with Obstructive Sleep Apnea

The obstructive sleep apnea syndrome (OSAS) is a type of sleep-related breathing disorder and a highly prevalent disease. Because of frequent arousals during the night, OSAS leads to a fragmentation of sleep and the loss of its restorative function. Being in the supine position during sleep makes the individual more susceptible to obstructive apneic events. This influence of sleeping position on OSAS is thought to be generally greater in rapid eye movement (REM) sleep than in non-rapid eye movement (NREM) sleep stages. The aim of the present study was to evaluate the effect of a supine alarm device that combines an auditory and vibrational signal to discourage patients with OSAS from lying in the supine position during sleep. Thirteen participants with OSAS spent two nights in the sleep laboratory, one night with the device activated and the other night with it deactivated in randomized order. Full-night polysomnography, evening and morning blood pressure, and subjective sleep quality were assessed. Under treatment with the activated supine alarm device, participants had significantly fewer respiratory events, a higher baseline blood oxygenation level, fewer oxygen desaturations, and a significant increase in REM sleep compared to the control condition. Subjective sleep quality significantly improved, whereas psychosomatic symptoms during sleep decreased. Treatment with the supine alarm device appears to improve the amount of REM sleep and subjective sleep in patients with OSAS. Future research would benefit of evaluating patient acceptance and adherence to treatment in the home setting and long-term outcomes.

Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response.

Sleep/wake behavior is regulated by distinct groups of neurons, such as dopaminergic, noradrenergic, and orexinergic neurons. Although monoaminergic neurons are usually considered to be wake-promoting, the role of serotonergic neurons in sleep/wake behavior remains inconclusive because of the effect of serotonin (5-HT)-deficiency on brain development and the compensation for inborn 5-HT deficiency by other sleep/wake-regulating neurons. Here, we performed selective ablation of central 5-HT neurons in the newly developed Rosa-diphtheria toxin receptor (DTR)-tdTomato mouse line that was crossed with Pet1Cre/+ mice to examine the role of 5-HT neurons in the sleep/wake behavior of adult mice. Intracerebroventricular administration of diphtheria toxin completely ablated tdTomato-positive cells in Pet1Cre/+; Rosa-DTR-tdTomato mice. Electroencephalogram/electromyogram-based sleep/wake analysis demonstrated that central 5-HT neuron ablation in adult mice decreased the time spent in rapid eye movement (REM) sleep, which was associated with fewer transitions from non-REM (NREM) sleep to REM sleep than in control mice. Central 5-HT neuron-ablated mice showed attenuated wake response to a novel environment and increased theta power during wakefulness compared to control mice. The current findings indicated that adult 5-HT neurons work to support wakefulness and regulate REM sleep time through a biased transition from NREM sleep to REM sleep.