Showing papers on "Rapid eye movement sleep published in 2013"
TL;DR: Optogenetic tools suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.
Abstract: Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes In contrast, their acute silencing (eNpHR30, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain
362 citations
TL;DR: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.
306 citations
TL;DR: The results confirmed that this complex is affected in Parkinson’s disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapidEye movement sleep behaviour disorder.
Abstract: In Parkinson’s disease, rapid eye movement sleep behaviour disorder is an early non-dopaminergic syndrome with nocturnal violence and increased muscle tone during rapid eye movement sleep that can precede Parkinsonism by several years. The neuronal origin of rapid eye movement sleep behaviour disorder in Parkinson’s disease is not precisely known; however, the locus subcoeruleus in the brainstem has been implicated as this structure blocks muscle tone during normal rapid eye movement sleep in animal models and can be damaged in Parkinson’s disease. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex in patients with Parkinson’s disease using combined neuromelanin-sensitive, structural and diffusion magnetic resonance imaging approaches. We compared 24 patients with Parkinson’s disease and rapid eye movement sleep behaviour disorder, 12 patients without rapid eye movement sleep behaviour disorder and 19 age- and gender-matched healthy volunteers. All subjects underwent clinical examination and characterization of rapid eye movement sleep using video-polysomnography and multimodal imaging at 3 T. Using neuromelanin-sensitive imaging, reduced signal intensity was evident in the locus coeruleus/subcoeruleus area in patients with Parkinson’s disease that was more marked in patients with than those without rapid eye movement sleep behaviour disorder. Reduced signal intensity correlated with the percentage of abnormally increased muscle tone during rapid eye movement sleep. The results confirmed that this complex is affected in Parkinson’s disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapid eye movement sleep behaviour disorder. In longitudinal studies, the technique may also provide early markers of non-dopaminergic Parkinson’s disease pathology to predict the occurrence of Parkinson’s disease.
242 citations
TL;DR: Exposure to blue‐enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first non‐rapid eye movement episode.
Abstract: SUMMARY Light in the short wavelength range (blue light: 446–483 nm) elicits direct effects on human melatonin secretion, alertness and cognitive performance via non-image-forming photoreceptors. However, the impact of blue-enriched polychromatic light on human sleep architecture and sleep electroencephalographic activity remains fairly unknown. In this study we investigated sleep structure and sleep electroencephalographic characteristics of 30 healthy young participants (16 men, 14 women; age range 20–31 years) following 2 h of evening light exposure to polychromatic light at 6500 K, 2500 K and 3000 K. Sleep structure across the first three non-rapid eye movement non-rapid eye movement – rapid eye movement sleep cycles did not differ significantly with respect to the light conditions. All-night non-rapid eye movement sleep electroencephalographic power density indicated that exposure to light at 6500 K resulted in a tendency for less frontal non-rapid eye movement electroencephalographic power density, compared to light at 2500 K and 3000 K. The dynamics of non-rapid eye movement electroencephalographic slow wave activity (2.0–4.0 Hz), a functional index of homeostatic sleep pressure, were such that slow wave activity was reduced significantly during the first sleep cycle after light at 6500 K compared to light at 2500 K and 3000 K, particularly in the frontal derivation. Our data suggest that exposure to blue-enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first nonrapid eye movement episode.
210 citations
TL;DR: It is demonstrated that the thalamus finely tunes the frequency of slow waves during non-REM sleep and anesthesia, and thus provides the first conclusive evidence that a dynamic interplay of the neocortical and thalamic oscillators ofSlow waves is required for the full expression of this key physiological EEG rhythm.
Abstract: Slow waves represent one of the prominent EEG signatures of non-rapid eye movement (non-REM) sleep and are thought to play an important role in the cellular and network plasticity that occurs during this behavioral state. These slow waves of natural sleep are currently considered to be exclusively generated by intrinsic and synaptic mechanisms within neocortical territories, although a role for the thalamus in this key physiological rhythm has been suggested but never demonstrated. Combining neuronal ensemble recordings, microdialysis, and optogenetics, here we show that the block of the thalamic output to the neocortex markedly (up to 50%) decreases the frequency of slow waves recorded during non-REM sleep in freely moving, naturally sleeping-waking rats. A smaller volume of thalamic inactivation than during sleep is required for observing similar effects on EEG slow waves recorded during anesthesia, a condition in which both bursts and single action potentials of thalamocortical neurons are almost exclusively dependent on T-type calcium channels. Thalamic inactivation more strongly reduces spindles than slow waves during both anesthesia and natural sleep. Moreover, selective excitation of thalamocortical neurons strongly entrains EEG slow waves in a narrow frequency band (0.75–1.5 Hz) only when thalamic T-type calcium channels are functionally active. These results demonstrate that the thalamus finely tunes the frequency of slow waves during non-REM sleep and anesthesia, and thus provide the first conclusive evidence that a dynamic interplay of the neocortical and thalamic oscillators of slow waves is required for the full expression of this key physiological EEG rhythm.
190 citations
TL;DR: Evidence is provided that prolonged video‐gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video‐ gaming is initiated at normal bedtime, and physiological arousal may not necessarily be the mechanism by which technology use affects sleep.
Abstract: Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep. Language: en
135 citations
TL;DR: A single night of fragmented sleep, resulting in reduced REM sleep, induced a shift in insulin concentrations, from being lower in the morning and higher in the afternoon, while GLP-1 concentrations and fullness scores were decreased, which may lead to increased food intake and snacking, thus contributing to a positive energy balance.
Abstract: In addition to short sleep duration, reduced sleep quality is also associated with appetite control. The present study examined the effect of sleep fragmentation, independent of sleep duration, on appetite profiles and 24Â h profiles of hormones involved in energy balance regulation. A total of twelve healthy male subjects (age 23 (sd 4) years, BMI 24·4 (sd 1·9)Â kg/m2) completed a 24Â h randomised crossover study in which sleep (23.30-07.30 hours) was either fragmented or non-fragmented. Polysomnography was used to determine rapid-eye movement (REM) sleep, slow-wave sleep (SWS) and total sleep time (TST). Blood samples were taken at baseline and continued hourly for the 24Â h period to measure glucose, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1) and melatonin concentrations. In addition, salivary cortisol levels were measured. Visual analogue scales were used to score appetite-related feelings. Sleep fragmentation resulted in reduced REM sleep (69·4Â min compared with 83·5Â min; P<Â 0·05) and preservation of SWS without changes in TST. In fragmented v. non-fragmented sleep, glucose concentrations did not change, while insulin secretion was decreased in the morning, and increased in the afternoon (P<Â 0·05), and GLP-1 concentrations and fullness scores were lower (P<Â 0·05). After dinner, desire-to-eat ratings were higher after fragmented sleep (P<Â 0·05). A single night of fragmented sleep, resulting in reduced REM sleep, induced a shift in insulin concentrations, from being lower in the morning and higher in the afternoon, while GLP-1 concentrations and fullness scores were decreased. These results may lead to increased food intake and snacking, thus contributing to a positive energy balance.
135 citations
TL;DR: REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes and had an additional protective effect compared to wakefulness.
Abstract: Since the formal characterization of sleep stages, there have been reports that seizures may preferentially occur in certain phases of sleep. Through ascending cholinergic connections from the brainstem, rapid eye movement (REM) sleep is physiologically characterized by low voltage fast activity on the electroencephalogram, REMs, and muscle atonia. Multiple independent studies confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1% or less). We review a total of 42 distinct conventional and intracranial studies in the literature which comprised a net of 1458 patients. Indexed to duration, we found that REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes. REM sleep had an additional protective effect compared to wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer generalized seizures, and 1.11 times fewer focal interictal discharges. In further studies REM sleep has also demonstrated utility in localizing epileptogenic foci with potential translation into postsurgical seizure freedom. Based on emerging connectivity data in sleep, we hypothesize that the influence of REM sleep on seizures is due to a desynchronized EEG pattern which reflects important connectivity differences unique to this sleep stage.
134 citations
TL;DR: Supporting the view that the functional integrity of the default mode network (DMN) reflects “level of consciousness,” functional uncoupling of the DMN during deep sleep and recoupling during REM sleep is observed, suggesting a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.
Abstract: Rapid eye movement (REM) sleep constitutes a distinct “third state” of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects “level of consciousness,” we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.
115 citations
TL;DR: It is found that increasing sleep spindle density increases memory discrimination for highly arousing and negative stimuli without altering measures of bias, indicating a broader role for sleep in the processing of emotional stimuli with differing effects based on arousal and valence.
Abstract: Sleep affects declarative memory for emotional stimuli differently than it affects declarative memory for nonemotional stimuli. However, the interaction between specific sleep characteristics and emotional memory is not well understood. Recent studies on how sleep affects emotional memory have focused on rapid eye movement sleep REM but have not addressed non-REM sleep, particularly sleep spindles. This is despite the fact that sleep spindles are implicated in declarative memory as well as neural models of memory consolidation e.g., hippocampal neural replay. Additionally, many studies examine a limited range of emotional stimuli and fail to disentangle differences in memory performance because of variance in valence and arousal. Here, we experimentally increase non-REM sleep features, sleep spindle density, and SWS, with pharmacological interventions using zolpidem Ambien and sodium oxybate Xyrem during daytime naps. We use a full spread of emotional stimuli to test all levels of valence and arousal. We find that increasing sleep spindle density increases memory discrimination da for highly arousing and negative stimuli without altering measures of bias ca. These results indicate a broader role for sleep in the processing of emotional stimuli with differing effects based on arousal and valence, and they raise the possibility that sleep spindles causally facilitate emotional memory consolidation. These findings are discussed in terms of the known use of hypnotics in individuals with emotional mood disorders.
114 citations
TL;DR: The relative recovery of motor function during REM sleep in some of the cases of PD with RBD emphasizes the complexity of motor pathway control during wakefulness and REM sleep.
TL;DR: Circadian misalignment and sleep disruption is evident in patients with MCI, and is consistent with changes observed in Alzheimer's disease, and could be a marker for disease trajectory and may even be implicated in disease pathogenesis.
Abstract: Background While it is evident that Alzheimer's disease is associated with disturbed sleep and circadian rhythms, the extent to which such changes are evident in older people 'at risk' of developing dementia is unknown. Objective In this study, we aimed to determine whether patients with mild cognitive impairment (MCI) demonstrated significant alterations in the timing of melatonin secretion onset and amount, as well as sleep architecture. Methods Thirty patients with MCI and 28 age-matched controls underwent psychiatric, medical, and neuropsychological assessment, followed by overnight polysomnography and dim light melatonin onset assessment. Participants also performed an episodic memory task while in the laboratory. Dim light melatonin onset was computed using a standardized algorithm, and area under the curve was computed for melatonin secretion. Sleep architecture measures including wake after sleep onset and latency to rapid eye movement sleep were derived. Results Patients with MCI had advanced timing of their melatonin secretion onset relative to controls, but the levels of melatonin secreted did not differ between groups. The MCI group also had greater wake after sleep onset and increased rapid eye movement sleep latency. There were differential associations between dim light melatonin onset and cognition between the two groups, with earlier dim light melatonin onset being associated with poorer memory performance in MCI patients. Conclusion Circadian misalignment and sleep disruption is evident in patients with MCI, and is consistent with changes observed in Alzheimer's disease. Such findings could be a marker for disease trajectory, and may even be implicated in disease pathogenesis.
TL;DR: Observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger catapLexy by inhibiting brainstem regions that suppress muscle atonia.
Abstract: Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal gray, lateral pontine tegmentum, locus ceruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy. These lesions did not alter basic sleep-wake behavior but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia.
TL;DR: Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRα locus and weaker associations within TNFSF4, Cathepsin H and the P2RY11-DNMT1 loci, suggesting an autoimmune basis.
TL;DR: Different threat simulations and modes of defense seem to play a role during dream-enacted behaviors (e.g., fleeing a disaster during SW/ST, counterattacking a human or animal assault during RBD), paralleling and exacerbating the differences observed between normal dreaming in nonrapid eye movement (NREM) vs rapidEye movement (REM) sleep.
TL;DR: The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment.
Abstract: Study Objectives: Rapid eye movement sleep behavior disorder (RBD) is a condition closely associated with Parkinson disease (PD). RBD is a sleep disturbance that frequently manifests early in the development of PD, likely reflecting disruption in normal functioning of anatomical areas affected by neurodegenerative processes. Although specific neuropathological aspects shared by RBD and PD have yet to be fully documented, further characterization is critical to discovering reliable biomarkers that predict PD onset. In the current study, we tested the hypothesis of altered functional connections of the substantia nigra (SN) in patients in whom RBD was diagnosed. Design: Between-groups, single time point imaging. Setting: UTHSC-H 3 telsa MRI center. Participants: Ten patients with RBD, 11 patients with PD, and 10 age-matched controls. Interventions: NA. Measurements and Results: We measured correlations of SN time series using resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD, patients in whom PD was diagnosed, and age- matched controls. Using voxelwise analysis of variance, different correlations (P < 0.01, whole-brain corrected) between left SN and left putamen were found in patients with RBD compared with controls and patients with PD. SN correlations with right cuneus/precuneus and superior occipital gyrus were significantly different for patients with RBD compared with both controls and patients with PD. Conclusions: The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and
TL;DR: It is proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocRETin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakeful and RBD/RSWA/phasic motor activity during REM sleep.
TL;DR: It is concluded that specifically SWS reduction is critically involved in the impairment of glucose tolerance associated with disturbed sleep and glucose metabolism in subjects predisposed to reduced SWS should be thoroughly monitored.
TL;DR: The sensitivity of quantitative electroencephalographic analysis to identify early pathophysiological alterations in the R6/2 mouse model of Huntington's disease is demonstrated and longitudinal studies in other preclinical Huntington’s disease models are needed to determine the generality of these observations as a potential adjunct in therapeutic development.
Abstract: Deficits in sleep and circadian organization have been identified as common early features in patients with Huntington's disease that correlate with symptom severity and may be instrumental in disease progression. Studies in Huntington's disease gene carriers suggest that alterations in the electroencephalogram may reflect underlying neuronal dysfunction that is present in the premanifest stage. We conducted a longitudinal characterization of sleep/wake and electroencephalographic activity in the R6/2 mouse model of Huntington's disease to determine whether analogous electroencephalographic 'signatures' could be identified early in disease progression. R6/2 and wild-type mice were implanted for electroencephalographic recordings along with telemetry for the continuous recording of activity and body temperature. Diurnal patterns of activity and core body temperature were progressively disrupted in R6/2 mice, with a large reduction in the amplitude of these rhythms apparent by 13 weeks of age. The diurnal variation in sleep/wake states was gradually attenuated as sleep became more fragmented and total sleep time was reduced relative to wild-type mice. These genotypic differences were augmented at 17 weeks and evident across the entire 24-h period. Quantitative electroencephalogram analysis revealed anomalous increases in high beta and gamma activity (25-60 Hz) in all sleep/wake states in R6/2 mice, along with increases in theta activity during both non-rapid eye movement and rapid eye movement sleep and a reduction of delta power in non-rapid eye movement sleep. These dramatic alterations in quantitative electroencephalographic measures were apparent from our earliest recording (9 weeks), before any major differences in diurnal physiology or sleep/wake behaviour occurred. In addition, the homeostatic response to sleep deprivation was greatly attenuated with disease progression. These findings demonstrate the sensitivity of quantitative electroencephalographic analysis to identify early pathophysiological alterations in the R6/2 model of Huntington's disease and suggest longitudinal studies in other preclinical Huntington's disease models are needed to determine the generality of these observations as a potential adjunct in therapeutic development.
TL;DR: The investigation of sleep is a little studied yet simple and informative way to evaluate the integrity of residual brain function in patients with disorders of consciousness with possible clinical diagnostic and prognostic implications.
Abstract: The goal of our study was to investigate different aspects of sleep, namely the sleep-wake cycle and sleep stages, in the vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS). A 24-h polysomnography was performed in 20 patients who were in a UWS (n=10) or in a MCS (n=10) because of brain injury. The data were first tested for the presence of a sleep-wake cycle, and the observed sleep patterns were compared with standard scoring criteria. Sleep spindles, slow wave sleep, and rapid eye movement sleep were quantified and their clinical value was investigated. According to our results, an electrophysiological sleep-wake cycle was identified in five MCS and three VS/UWS patients. Sleep stages did not always match the standard scoring criteria, which therefore needed to be adapted. Sleep spindles were present more in patients who clinically improved within 6 months. Slow wave sleep was present in eight MCS and three VS/UWS patients but never in the ischemic etiology. Rapid eye movement sleep, and therefore dreaming that is a form of consciousness, was present in all MCS and three VS/UWS patients. In conclusion, the presence of alternating periods of eyes-open/eyes-closed cycles does not necessarily imply preserved electrophysiological sleep architecture in the UWS and MCS, contrary to previous definition. The investigation of sleep is a little studied yet simple and informative way to evaluate the integrity of residual brain function in patients with disorders of consciousness with possible clinical diagnostic and prognostic implications.
TL;DR: Some preliminary support for the involvement of the DLPFC in lucid dreaming is indicated, but further research, controlling for indirect effects of stimulation and including other brain regions, is needed.
TL;DR: The encephalitic process, responsible for narcolepsy-cataplexy and hypoc retin deficiency, reflects a CD8+ inflammatory-mediated response against hypocretin neurons.
Abstract: OBSERVATIONS We described a 63-year-old man with clinical criteria for diencephalic encephalitis with sleepiness, cataplexy, hypocretin deficiency, and central hypothyroidism, together with brainstem encephalitis reflected by supranuclear ophtalmoparesis and rapid eye movement sleep behavior disorder with underlying abnormalities on brain magnetic resonance imaging. An autoimmune process was demonstrated by the detection of antibodies against Ma protein. Death occurred 4 months after disease onset without any tumor detected. Neuropathology, immunohistochemistry, and immunoreactivity results were compared with those obtained in idiopathic narcolepsy-cataplexy and with normal control brains. The principal findings revealed almost exclusive inflammation and tissue injury in the hypothalamus. The type of inflammatory reaction suggests cytotoxic CD8 + T lymphocytes being responsible for the induction of tissue injury. Inflammation was associated with complete loss of hypocretinergic neurons. Autoantibodies of the patient predominantly stained neurons in the hypothalamus and could be absorbed with Ma2.
TL;DR: Data on the populations of neurons responsible for the atonia of REM sleep are reviewed and it is proposed that movements of RBD are induced by descending projections of cortical motor neurons before discussing possible modes of action of clonazepam and melatonin.
TL;DR: Gaining a better understanding of sleep and electroencephalogram changes in patients with Huntington's disease should be a priority, since it will enable clinicians to initiate appropriate investigations and to instigate treatments that could dramatically improve patients' quality of life.
Abstract: Sleep disturbances in Huntington’s disease may be deleterious to the cognitive performance, affective behaviour, and general well-being of patients, but a comprehensive description of the progression of changes in sleep and electroencephalogram in Huntington’s disease has never been conducted. Here we studied sleep and electroencephalogram disturbances in a transgenic mouse model of Huntington’s disease (R6/2 mice). We implanted 10 R6/2 mice and five wild-type littermates with electromyography electrodes, frontofrontal and frontoparietal electroencephalogram electrodes and then recorded sleep/wake behaviour at presymptomatic, symptomatic and late stages of the disease. In addition to sleep–wake scoring, we performed a spectral analysis of the sleep electroencephalogram. We found that sleep and electroencephalogram were already significantly disrupted in R6/2 mice at 9 weeks of age (presymptomatic stage). By the time they were symptomatic, R6/2 mice were unable to maintain long periods of wakefulness and had an increased propensity for rapid eye movement sleep. In addition, the peak frequency of theta rhythm was shifted progressively from 7 Hz to 6 Hz during rapid eye movement sleep, whereas slow wave activity decreased gradually during non-rapid eye movement sleep. Finally, as the disease progressed, an abnormal electroencephalogram gamma activity (30–40 Hz) emerged in R6/2 mice irrespective of sleep states. This is reminiscent of the increased gamma power described in schizophrenic patients during sleep and events of psychosis. Gaining a better understanding of sleep and electroencephalogram changes in patients with Huntington’s disease should be a priority, since it will enable clinicians to initiate appropriate investigations and to instigate treatments that could dramatically improve patients’ quality of life.
TL;DR: Hypermetabolism in brain regions involved in arousal regulation, fear responses, and reward processing persist during REM sleep in combat veterans with PTSD, using positron emission tomography.
Abstract: Relative regional cerebral metabolic rate of glucose in rapid eye movement (REM) sleep and wakefulness was explored in combat veterans with and without posttraumatic stress disorder PTSD, using positron emission tomography. Hypermetabolism in brain regions involved in arousal regulation, fear responses, and reward processing persist during REM sleep in combat veterans with PTSD.
TL;DR: It is reported that studies are largely supportive of the view that DM1-related EDS is primarily caused by a central dysfunction of sleep regulation rather than by sleep-related disordered breathing (SRDB) or sleep fragmentation.
Abstract: Myotonic dystrophy type 1 (DM1) represents the 1 chronic neuromuscular disease with the most prominent sleep disorders, including excessive daytime sleepiness (EDS), sleep apneas, periodic leg movements during sleep, and rapid eye movement sleep dysregulation. The large majority of DM1 patients complain about EDS, which may have a deleterious impact on work, domestic responsibilities, social life, and quality of life. Here, we review the extant literature and report that studies are largely supportive of the view that DM1-related EDS is primarily caused by a central dysfunction of sleep regulation rather than by sleep-related disordered breathing (SRDB) or sleep fragmentation. The pathogenesis of EDS in DM1 still remains unclear but several arguments favor a model in which brain/brainstem nuclear accumulations of toxic expanded DM protein kinase (DMPK) gene are responsible for aberrant genes expression in modifying alternative splicing. Regarding management, early recognition, and treatment of SRDB with nocturnal noninvasive mechanical ventilation is first mandatory. However, despite its appropriate management, EDS often persists and may require a psychostimulant but no consensus has been yet established. Further studies are needed to clarify the discrepancies between daytime sleepiness/fatigue complaints and subjective/objective measurement of daytime sleepiness, the role of cognitive impairment and apathy in this relationship, and its reversibility with appropriate management.
TL;DR: Cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex, demonstrating a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.
Abstract: Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1–4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of <10 Hz. The induction of 1-Hz oscillations, but not 10-Hz oscillations, in the electroencephalogram by optogenetic stimulation of cortical pyramidal cells during wakefulness triggers a decline in lactate concentration. We conclude that cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.
TL;DR: This is the first study to systematically examine neurocognitive functioning in children with eczema and given the finding of significant deficits it merits replication especially given the prevalence of the condition.
TL;DR: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during ‘rebound’ reversed this to control levels, and nesFatin was designated as a potential new factor in sleep regulation.
Abstract: Study Objectives
Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance.
Design
We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long ‘rebound sleep’. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in ‘deprived’ and ‘rebound’ groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline.
Results
REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during ‘rebound’ reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during ‘rebound’. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep.
Conclusions
The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression.
TL;DR: It is concluded that vagal afferents mediate peripheral TNF-α-induced brain T NF-α and IL-1β mRNA expressions to affect sleep and alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.
Abstract: Study objective Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. Design We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Measurements and results Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. Conclusions We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.