Showing papers on "Rapid eye movement sleep published in 2018"

The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder

Abstract: Background Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. Objectives To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. Methods Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. Results Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. Conclusion Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Rapid Eye Movement Sleep, Sleep Continuity and Slow Wave Sleep as Predictors of Cognition, Mood, and Subjective Sleep Quality in Healthy Men and Women, Aged 20-84 Years.

Abstract: Sleep and its sub-states are assumed to be important for brain function across the lifespan but which aspects of sleep associate with various aspects of cognition, mood and self-reported sleep quality has not yet been established in detail. Sleep was quantified by polysomnography, quantitative Electroencephalogram (EEG) analysis and self-report in 206 healthy men and women, aged 20–84 years, without sleep complaints. Waking brain function was quantified by five assessments scheduled across the day covering objectively assessed performance across cognitive domains including sustained attention and arousal, decision and response time, motor and sequence control, working memory, and executive function as well as self-reports of alertness, mood and affect. Controlled for age and sex, self-reported sleep quality was negatively associated with number of awakenings and positively associated with the duration of Rapid Eye Movement (REM) sleep, but no significant associations with Slow Wave Sleep (SWS) measures were observed. Controlling only for age showed that associations between objective and subjective sleep quality were much stronger in women than in men. Analysis of 51 performance measures demonstrated that, after controlling for age and sex, fewer awakenings and more REM sleep were associated significantly with better performance on the Goal Neglect task, which is a test of executive function. Factor analysis of the individual performance measures identified four latent variables labeled Mood/Arousal, Response Time, Accuracy, and Visual Perceptual Sensitivity. Whereas Mood/Arousal improved with age, Response Times became slower, while Accuracy and Visual perceptual sensitivity showed little change with age. After controlling for sex and age, nominally significant association between sleep and factor scores were observed such that Response Times were faster with more SWS, and Accuracy was reduced where individuals woke more often or had less REM sleep. These data identify a positive contribution of SWS to processing speed and in particular highlight the importance of sleep continuity and REM sleep for subjective sleep quality and performance accuracy across the adult lifespan. These findings warrant further investigation of the contribution of sleep continuity and REM sleep to brain function.

Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep

Abstract: Rapid eye movement sleep (REMS) is a peculiar brain state combining the behavioral components of sleep and the electrophysiological profiles of wake. After decades of research our understanding of REMS still is precluded by the difficulty to observe its spontaneous dynamics and the lack of multimodal recording approaches to build comprehensive datasets. We used functional ultrasound (fUS) imaging concurrently with extracellular recordings of local field potentials (LFP) to reveal brain-wide spatiotemporal hemodynamics of single REMS episodes. We demonstrate for the first time the close association between global hyperemic events – largely outmatching wake levels in most brain regions – and local hippocampal theta (6–10 Hz) and fast gamma (80–110 Hz) events in the CA1 region. In particular, the power of fast gamma oscillations strongly correlated with the amplitude of subsequent vascular events. Our findings challenge our current understanding of neurovascular coupling and question the evolutionary benefit of such energy-demanding patterns in REMS function.

Cardiovascular autonomic dysfunction in insomnia patients with objective short sleep duration

Abstract: Two phenotypes have been proposed: insomnia with objective near-normal sleep duration, related to increased psychological symptoms, and insomnia with objective short sleep duration, associated with cardiometabolic morbidity. Reduced heart rate variability has also been implicated in the pathophysiology of cardiometabolic disease; however, there are little data on whether cardiovascular function differs between patients with objective short sleep duration and near-normal sleep duration. Participants (Mage = 49.9 ± 11.3 years; 62.8% female) were 180 adults with chronic insomnia (Mduration = 15.7 ± 13.6). Objective sleep duration was based on total sleep time averaged across two consecutive nights of polysomnography and subjective sleep duration was based on 2-week sleep diaries. The sample was divided into two groups, with sleep duration shorter (polysomnography-total sleep time: n = 46; sleep diary: n = 95) or equal/longer (polysomnography-total sleep time: n = 134; sleep diary: n = 85) than 6 hr. Electrocardiogram data derived from polysomnography were used to obtain heart rate and heart rate variability during stage 2 (N2) and rapid eye movement sleep. Heart rate variability measures included absolute and normalized high-frequency component, an index of parasympathetic activation, and the ratio of low- to high-frequency (LF/HF ratio), an index of sympathovagal balance. After controlling for covariates (e.g., co-morbidity), patients with objective short sleep duration had reduced high-frequency (p < .05) and elevated low-frequency/high-frequency ratio (p = .036) and heart rate (p = .051) compared with patients with near-normal sleep duration. No differences were observed between phenotypes when subjective sleep duration was used. Insomnia patients with objective short sleep duration showed significantly dampened parasympathetic activation and increased sympathovagal imbalance relative to their counterparts with near-normal sleep duration. These findings highlight the importance of treating insomnia, as treatment may reduce the risk of cardiovascular disease.

Body temperature and sleep.

Abstract: Sleep in mammals is accompanied by a decrease in core body temperature (CBT). The circadian clock in the hypothalamic suprachiasmatic nucleus regulates daily rhythms in both CBT and arousal states, and these rhythms are normally coupled. Reductions in metabolic heat production resulting from behavioral quiescence and reduced muscle tone along with changes in autonomic nervous system activity and thermoeffector activity contribute to the sleep-related fall in CBT. Reductions in sympathetic tone to the peripheral vasculature resulting in heat loss through the skin are reflected in a sleep-related increase in distal skin temperature that is a prominent feature of sleep onset in humans. Within a sleep episode, patterns of autonomic nervous system and thermoeffector activity and the ability to defend against heat and cold exposure differ during nonrapid eye movement (NREM) and rapid eye movement sleep. Anatomic and functional integration of the control of arousal states and thermoregulation occur in the preoptic/anterior hypothalamus. Subsets or warm-sensing neurons in the preoptic/anterior hypothalamus implicated in CBT regulation are spontaneously activated during sleep onset and NREM sleep compared to waking and may underlie sleep-related changes in autonomic nervous system and thermoeffector activity.

Autonomic regulation during sleep and wakefulness: a review with implications for defining the pathophysiology of neurological disorders.

Abstract: Cardiovascular and respiratory parameters change during sleep and wakefulness This observation underscores an important, albeit incompletely understood, role for the central nervous system in the differential regulation of autonomic functions Understanding sleep/wake-dependent sympathetic modulations provides insights into diseases involving autonomic dysfunction The purpose of this review was to define the central nervous system nuclei regulating sleep and cardiovascular function and to identify reciprocal networks that may underlie autonomic symptoms of disorders such as insomnia, sleep apnea, restless leg syndrome, rapid eye movement sleep behavior disorder, and narcolepsy/cataplexy In this review, we examine the functional and anatomical significance of hypothalamic, pontine, and medullary networks on sleep, cardiovascular function, and breathing

Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein

Abstract: Author(s): McDowell, Kimberly A; Shin, David; Roos, Kenneth P; Chesselet, Marie-Francoise | Abstract: BackgroundSleep disruptions occur early and frequently in Parkinson's disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models.ObjectiveThe objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model.MethodsAt 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype.ResultsThy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness.ConclusionsAlpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD.

Sleep disorders and the risk of stroke.

Abstract: Introduction: Stroke is a major cause of disability and death in the United States and across the world, and the incidence and prevalence of stroke are expected to rise significantly due to an aging population. Obstructive sleep apnea, an established independent risk factor for stroke, is a highly prevalent disease that is estimated to double the risk of stroke. It remains uncertain whether non-apnea sleep disorders increase the risk of stroke.Areas covered: This paper reviews the literature describing the association between incident stroke and sleep apnea, rapid eye movement sleep behavior disorder, restless legs syndrome, periodic limb movements of sleep, insomnia, and shift work.Expert commentary: Trials of continuous positive airway pressure for stroke prevention in sleep apnea patients have been largely disappointing, but additional trials that target populations not yet optimally studied are needed. Self-reported short and long sleep duration may be associated with incident stroke. However,...

Regulation of Lateral Hypothalamic Orexin Activity by Local GABAergic Neurons.

Abstract: Orexin (also known as hypocretin) neurons are considered a key component of the ascending arousal system. They are active during wakefulness, at which time they drive and maintain arousal, and are silent during sleep. Their activity is controlled by long-range inputs from many sources, as well as by more short-range inputs, including from presumptive GABAergic neurons in the lateral hypothalamus/perifornical region (LH/PF). To characterize local GABAergic input to orexin neurons, we used channelrhodopsin-2-assisted circuit mapping in brain slices. We expressed channelrhodopsin-2 in GABAergic neurons (Vgat+) in the LH/PF and recorded from genetically identified surrounding orexin neurons (LH/PFVgat → Orx). We performed all experiments in mice of either sex. Photostimulation of LH/PF GABAergic neurons inhibited the firing of orexin neurons through the release of GABA, evoking GABAA-mediated IPSCs in orexin neurons. These photo-evoked IPSCs were maintained in the presence of TTX, indicating direct connectivity. Carbachol inhibited LH/PFVgat → Orx input through muscarinic receptors. By contrast, application of orexin was without effect on LH/PFVgat → Orx input, whereas dynorphin, another peptide produced by orexin neurons, inhibited LH/PFVgat → Orx input through κ-opioid receptors. Our results demonstrate that orexin neurons are under inhibitory control by local GABAergic neurons and that this input is depressed by cholinergic signaling, unaffected by orexin and inhibited by dynorphin. We propose that local release of dynorphin may, via collaterals, provides a positive feedback to orexin neurons and that, during wakefulness, orexin neurons may be disinhibited by acetylcholine and by their own release of dynorphin.SIGNIFICANCE STATEMENT The lateral hypothalamus contains important wake-promoting cell populations, including orexin-producing neurons. Intermingled with the orexin neurons, there are other cell populations that selectively discharge during nonrapid eye movement or rapid eye movement sleep. Some of these sleep-active neurons release GABA and are thought to inhibit wake-active neurons during rapid eye movement and nonrapid eye movement sleep. However, this hypothesis had not been tested. Here we show that orexin neurons are inhibited by a local GABAergic input. We propose that this local GABAergic input inhibits orexin neurons during sleep but that, during wakefulness, this input is depressed, possibly through cholinergically mediated disinhibition and/or by release of dynorphin from orexin neurons themselves.

Serum brain-derived neurotrophic factor (BDNF) in sleep-disordered patients: relation to sleep stage N3 and rapid eye movement (REM) sleep across diagnostic entities.

Abstract: Experimental and clinical evidence suggests an association between neuroplasticity, brain-derived neurotrophic factor and sleep. We aimed at testing the hypotheses that brain-derived neurotrophic factor is associated with specific aspects of sleep architecture or sleep stages in patients with sleep disorders. We included 35 patients with primary insomnia, 31 patients with restless legs syndrome, 17 patients with idiopathic hypersomnia, 10 patients with narcolepsy and 37 healthy controls. Morning serum brain-derived neurotrophic factor concentrations were measured in patients and controls. In patients, blood sampling was followed by polysomnographic sleep investigation. Low brain-derived neurotrophic factor levels were associated with a low percentage of sleep stage N3 and rapid eye movement sleep across diagnostic entities. However, there was no difference in brain-derived neurotrophic factor levels between diagnostic groups. Our data indicate that serum levels of brain-derived neurotrophic factor, independent of a specific sleep disorder, are related to the proportion of sleep stage N3 and REM sleep. This preliminary observation is in accordance with the assumption that sleep stage N3 is involved in the regulation of neuroplasticity.

Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women

Abstract: Study Objectives: Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, ...

Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder.

Abstract: BACKGROUND: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. OBJECTIVE: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. METHODS: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT-associated variants and the entire coding sequence of MAPT were analyzed. Age-, sex-, and ethnicity-adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder. RESULTS: MAPT-H2 variants were associated with PD (odds ratios: 0.62-0.65; P = 0.010-0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12-2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48-0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. CONCLUSIONS: Our results confirm the protective effect of the MAPT-H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society.

Human Rapid Eye Movement Sleep Shows Local Increases in Low-Frequency Oscillations and Global Decreases in High-Frequency Oscillations Compared to Resting Wakefulness.

Abstract: It is often assumed that during rapid eye movement (REM) sleep the cerebral cortex homogenously shows electroencephalogram (EEG) activity highly similar to wakefulness. However, to date no studies have compared neural oscillatory activity in human REM sleep to resting wakefulness with high spatial sampling. In the current study, we evaluated high-resolution topographical changes in neural oscillatory power between both early and late naturalistic REM sleep and resting wakefulness in adult humans. All-night recordings with 256-channel high-density EEG (hd-EEG) were collected in healthy volunteers (N = 12). Topographic analysis revealed that, compared to wake, both the first and last cycle of REM sleep were associated with increased low-frequency oscillations in local central and occipital regions. In contrast, high-frequency activity in both α and β bands (8-20 Hz) was globally decreased during both early and late REM sleep cycles compared to wakefulness. No significant differences in topographic power in any frequency band were observed between REM sleep cycles occurring early and late in the night. We replicated these findings in an independent dataset (N = 33). Together, our findings show that human REM sleep shows consistent topographical changes in oscillatory power across both early and late sleep cycles compared to resting wakefulness.

Circadian and Homeostatic Modulation of Multi-Unit Activity in Midbrain Dopaminergic Structures.

Abstract: Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase. Combining neural activity recordings with electroencephalogram (EEG) recordings revealed a strong vigilance state dependent modulation of neuronal activity with increased activity during wakefulness and rapid eye movement sleep relative to non-rapid eye movement sleep in both SN and VTA. Six-hours of sleep deprivation induced a significant depression of neuronal activity in both areas. Surprisingly, these alterations lasted for up to 48 hours and persisted even after the normalization of cortical EEG waves. Our results show that sleep and sleep disturbances significantly affect neuronal activity in midbrain DA structures. We propose that these changes in neuronal activity underlie the well-known relationship between sleep alterations and several disorders involving dysfunction of the DA circuitry such as addiction and depression.

Nocturnal REM Sleep Without Atonia Is a Diagnostic Biomarker of Pediatric Narcolepsy.

Abstract: Study Objectives:Compare nocturnal REM sleep without atonia (nRWA) and REM sleep behavior disorder (RBD) between pediatric patients with and without narcolepsy and determine if the nRWA index is a ...

The low-down on sleeping down low: pigeons shift to lighter forms of sleep when sleeping near the ground.

Abstract: Sleep in birds is composed of two distinct sub-states, remarkably similar to mammalian slow-wave sleep (SWS) and rapid eye movement (REM) sleep. However, it is unclear whether all aspects of mammalian sleep are present in birds. We examined whether birds suppress REM sleep in response to changes in sleeping conditions that presumably evoke an increase in perceived predation risk, as observed previously in rodents. Although pigeons sometimes sleep on the ground, they prefer to sleep on elevated perches at night, probably to avoid nocturnal mammalian ground predators. Few studies to date have investigated how roosting sites affect sleep architecture. We compared sleep in captive pigeons on days with and without access to high perches. On the first (baseline) day, low and high perches were available; on the second day, the high perches were removed; and on the third (recovery) day, the high perches were returned. The total time spent sleeping did not vary significantly between conditions; however, the time spent in REM sleep declined on the low-perch night and increased above baseline when the pigeons slept on the high perch during the recovery night. Although the amount of SWS did not vary significantly between conditions, SWS intensity was lower on the low-perch night, particularly early in the night. The similarity of these responses between birds and mammals suggests that REM sleep is influenced by at least some ecological factors in a similar manner in both groups of animals.

Changes in Brain-Derived Neurotrophic Factor Expression Influence Sleep-Wake Activity and Homeostatic Regulation of Rapid Eye Movement Sleep.

Abstract: Study objectives Brain-derived neurotrophic factor (BDNF) expression and homeostatic regulation of rapid eye movement (REM) sleep are critical for neurogenesis and behavioral plasticity. Accumulating clinical and experimental evidence suggests that decreased BDNF expression is causally linked with the development of REM sleep-associated neuropsychiatric disorders. Therefore, we hypothesize that BDNF plays a role in sleep-wake (S-W) activity and homeostatic regulation of REM sleep. Methods Male and female wild-type (WT; BDNF +/+) and heterozygous BDNF (KD; BDNF +/-) rats were chronically implanted with S-W recording electrodes to quantify baseline S-W activity and REM sleep homeostatic regulatory processes during the light phase. Results Molecular analyses revealed that KD BDNF rats had a 50% decrease in BDNF protein levels. During baseline S-W activity, KD rats exhibited fewer REM sleep episodes that were shorter in duration and took longer to initiate. Also, the baseline S-W activity did not reveal any sex difference. During the 3-hour selective REM sleep deprivation, KD rats failed to exhibit a homeostatic drive for REM sleep and did not exhibit rebound REM sleep during the recovery S-W period. Conclusion Interestingly, both genotypes did not reveal any sex difference in the quality and/or quantity of REM sleep. Collectively, these results, for the first time, unequivocally demonstrate that an intact BDNF system in both sexes is a critical modulator for baseline and homeostatic regulation of REM sleep. This study further suggests that heterozygous BDNF knockdown rats are a useful animal model for the study of the cellular and molecular mechanisms of sleep regulation and cognitive functions of sleep.

Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson's Disease Patients

Abstract: Background: Rapid eye movement (REM) sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) are the most common sleep disorders in Parkinson’s disease (PD). The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment. Methods: From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography (PSG). We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression. Results: We grouped participants as follows: PD only (n = 53), PD + OSA (n = 29), PD + RBD (n = 61), and PD + RBD + OSA (n = 31). Minimum oxygen saturation (SaO2) during whole sleep and in REM sleep was higher in PD + RBD + OSA patients than that in PD + OSA patients. PD + RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) scores than those in the PD group (P < 0.001), especially in visuospatial/executive, attention, and memory functions. The PD + OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA (β = −0.736, P = 0.043) and RBD (β = −2.575, P < 0.001). The severity of RBD (tonic/phasic electromyography activity) and OSA (apnea-hypopnea index/oxygen desaturation index/minimum SaO2) were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA. Conclusions: We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD. Key words: Cognitive Dysfunction; Sleep Apnea, Obstructive; Parkinson’s Disease; Rapid Eye Movement Sleep Behavior Disorder

Arousal responses to respiratory events during sleep: the role of pulse wave amplitude

Abstract: Summary The study aims at assessing the changes in electroencephalography (as measured by the A-phases of cyclic alternating pattern) and autonomic activity (based on pulse wave amplitude) at the recovery of airway patency in patients with obstructive sleep apnea syndrome. Analysis of polysomnographic recordings from 20 male individuals with obstructive sleep apnea syndrome was carried out in total sleep time, non-rapid eye movement and rapid eye movement sleep. Scoring quantified the combined occurrence (time range of 4 s before and 4 s after respiratory recovery) or separate occurrence of A-phases (cortical activation), and pulse wave amplitude drops (below 30%) to apneas, hypopneas or flow limitation events. A dual response (A-phase associated with a pulse wave amplitude drop) was the most frequent response (71.8% in total sleep time) for all types of respiratory events, with a progressive reduction from apneas to hypopneas and flow limitation events. The highly significant correlation in total sleep time (r = 0.9351; P < 0.0001) between respiratory events combined with A-phases and respiratory events combined with pulse wave amplitude drops was confirmed both in non-rapid eye movement (r = 0.9622; P < 0.0001) and rapid eye movement sleep (r = 0.7162; P < 0.0006). In conclusion, a dual cortical and autonomic activation is the most common manifestation at the recovery of airway patency. The significant correlation between A-phases and relevant pulse wave amplitude drops suggests a possible role of pulse wave amplitude as a marker of cerebral response to respiratory events.

The inappropriate occurrence of rapid eye movement sleep in narcolepsy is not due to a defect in homeostatic regulation of rapid eye movement sleep.

Abstract: Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. The later three symptoms together with a short rapid eye movement (REM) sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates. We first performed 48 hr of REM sleep deprivation using the classic small-platforms-over-water method. We found that narcoleptic mice are similarly REM sleep deprived to WT mice. Although they had shorter sleep latency, Orex-KO mice recovered similarly to WT during the following 10 hr of recovery. Interestingly, Orex-KO mice also had cataplexy episodes immediately after REM sleep deprivation, anticipating REM sleep rebound, at a time of day when cataplexy does not occur in baseline condition. We then evaluated REM sleep propensity using our new automated method of deprivation that performs a specific and efficient REM sleep deprivation. We showed that REM sleep propensity is similar during light phase in Orex-KO and WT mice. However, during the dark phase, REM sleep propensity was not suppressed in Orex-KO mice when hypocretin/orexin neuropeptides are normally released. Altogether our data suggest that in addition to the well-known wake-promoting role of hypocretin/orexin, these neuropeptides would also suppress REM sleep. Therefore, hypocretin/orexin deficiency would facilitate the occurrence of REM sleep at any time of day in an opportunistic manner as seen in human narcolepsy.

Relationships between sleep paralysis and sleep quality: current insights.

Abstract: Sleep paralysis is the unusual experience of waking up in the night without the ability to move. Currently little is known about the experience, despite the fact that the vast majority of episodes are associated with extreme fear and in a minority of cases can lead to clinically significant levels of distress. The aim of this work was to review the existing literature pertaining to the relationship sleep paralysis has to sleep more generally, measured both with subjective questionnaires and objective laboratory recordings. In terms of subjective sleep variables, worse sleep quality has been found in multiple studies to be associated with increased odds of sleep paralysis occurrence. In addition, insomnia symptoms (but not a diagnosed insomnia disorder) have also been found to predict sleep paralysis. Associations between sleep paralysis and other unusual and/or threatening sleep experiences such as nightmares, exploding head syndrome, and lucid dreaming have been reported. In terms of objective measurements, the limited literature to date shows sleep paralysis to be a "mixed" state of consciousness, combining elements of rapid eye movement sleep with elements of wakefulness. Future research needs to focus on longitudinal designs to disentangle the direction of effects and more typically employ a broader assessment of sleep paralysis that better captures associated features such as hallucinations, fear, and distress.

REM Sleep Behavior Disorder.

Abstract: Rapid eye movement sleep behavior disorder (RBD) is a brain disorder, characterized by the dream enactment during rapid eye movement (REM) sleep due to a lack of physiologic muscle atonia and increased muscle twitching. Schenk was the first to describe this disorder in 1986; however, few authors reported in the 1970-1980s loss of physiological muscle atonia combined with dream enactment in the course of brainstem disorders and as a consequence of alcoholism and antidepressant treatment. RBD affects less than 1% of the adult population, but can be found in up to 25-50% of neurodegenerative disorders including Parkinson's disease, multisystem atrophy, and dementia with Lewy body. In the last decade, many studies provided evidence that RBD precedes parkinsonian motor signs by several years, suggesting that RBD should no longer be considered a complication but a part of the prodromal phase of these diseases. Etiologically, primary (idiopathic RBD) and several secondary forms in addition to neurodegeneration (related to focal brainstem damage, narcolepsy, autoimmune disorders, and drugs) are known. Pathophysiologically, brainstem and supratentorial mechanisms involving glutamatergic, glycinergic, and GABA-ergic neurotransmission have been implicated. Recently, an animal model of RBD has been described. Clinical features consist of characteristic nocturnal behaviors, but also daytime symptoms including excessive sleepiness and cognitive alterations. The diagnosis of RBD is made according to international diagnostic criteria, based on medical history, and video-polysomnographic features. Current treatment strategies include actions which ensure a safe sleep environment, the avoidance of triggering/exacerbating factors and if necessary pharmacological (mainly clonazepam and melatonin) and non-pharmacological (e.g., behavioral measures) interventions. Future research should clarify the exact sleep-wake characteristics of RBD (also beyond REM sleep) and their evolution over time, the contribution of brainstem but also supratentorial mechanisms to its pathophysiology, and the (early?) diagnostic and (causative?) treatment consequences of RBD in the context of neurodegeneration.

Neuroimaging of Sleep Disturbances in Movement Disorders.

Abstract: Sleep dysfunction is recognized as a distinct clinical manifestation in movement disorders, often reported early on in the disease course. Excessive daytime sleepiness, rapid eye movement sleep behavior disorder and restless leg syndrome, amidst several others, are common sleep disturbances that often result in significant morbidity. In this article, we review the spectrum of sleep abnormalities across atypical Parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as well as Parkinson's disease (PD) and Huntington's disease (HD). We also explore the current concepts on the neurobiological underpinnings of sleep disorders, including the role of dopaminergic and non-dopaminergic pathways, by evaluating the molecular, structural and functional neuroimaging evidence based on several novel techniques including magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Based on the current state of research, we suggest that neuroimaging is an invaluable tool for assessing structural and functional correlates of sleep disturbances, harboring the ability to shed light on the sleep problems attached to the limited treatment options available today. As our understanding of the pathophysiology of sleep and wake disruption heightens, novel therapeutic approaches are certain to transpire.

Effects of Withdrawal from Chronic Intermittent Ethanol Exposure on Sleep Characteristics of Female and Male Mice.

Abstract: Background Sleep disruptions are an important consequence of alcohol use disorders. There is a dearth of preclinical studies examining sex differences in sleep patterns associated with ethanol (EtOH) dependence despite documented sex differences in alcohol-related behaviors and withdrawal symptoms. The purpose of this study was to investigate the effects of chronic intermittent EtOH on sleep characteristics in female and male mice. Methods Female and male C57BL6/J mice had access to EtOH/water 2-bottle choice (2BC) 2 h/d for 3 weeks followed by exposure to EtOH vapor (vapor-2BC) or air for 5 cycles of 4 days. An additional group never experienced EtOH (naive). Mice were implanted with electroencephalographic (EEG) electrodes, and vigilance states were recorded across 24 hours on the fourth day of withdrawal. The amounts of wakefulness, slow-wave sleep (SWS), and rapid eye movement sleep were calculated, and spectral analysis was performed by fast Fourier transformation. Results Overall, vapor-2BC mice showed a decrease in the amount of SWS 4 days into withdrawal as well as a decrease in the power density of slow waves, indicating disruptions in both the amount and quality of sleep in EtOH-dependent mice. This was associated with a decrease in duration and an increase in number of SWS episodes in males and an increase in latency to sleep in females. Conclusions Our results revealed overall deficits in sleep regulation in EtOH-dependent mice of both sexes. Female mice appeared to be more affected with regard to the triggering of sleep, while male mice appeared more sensitive to disruptions in the maintenance of sleep.