Granulocyte-macrophage colony-stimulating factor modulates rapid eye movement (REM) sleep and non-REM sleep in rats.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that may affect various functions of the CNS because the molecule and its receptors are expressed in the brain. The present study examines the effects of GM-CSF on sleep using rats and the secretion of three neurotransmitters/hormones that are involved in sleep regulation. When infused intracerebroventricularly at doses as low as 10 pmol for 10 hr during the dark period, GM-CSF promoted predominantly rapid eye movement (REM) sleep and moderate amounts of non-REM sleep without eliciting fever. An injection of GM-CSF (3.0 pmol) into the arcuate nucleus increased the release of nitric oxide (NO) from the hypothalamus but did not alter plasma levels of growth hormone. The release of somatostatin (SRIF) from the medial basal hypothalamus was stimulated by 1 x 10(-)(11) M GM-CSF. These findings indicated that centrally administered GM-CSF stimulates SRIF release through activation of the NO system in the hypothalamus. Because SRIF promotes REM sleep, it may also mediate the effects of GM-CSF on REM sleep. The present study indicates a novel central effect of GM-CSF that modulates sleep, supporting the notion that hematopoietic cytokines also play roles in the CNS.     

Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We 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 wakefulness and RBD/RSWA/phasic motor activity during REM sleep.     

Optogenetic activation of melanin‐concentrating hormone neurons increases non‐rapid eye movement and rapid eye movement sleep during the night in rats

Neurons containing melanin‐concentrating hormone (MCH) are located in the hypothalamus. In mice, optogenetic activation of the MCH neurons induces both non‐rapid eye movement (NREM) and rapid eye movement (REM) sleep at night, the normal wake‐active period for nocturnal rodents [R. R. Konadhode et al. (2013) J. Neurosci., 33, 10257–10263]. Here we selectively activate these neurons in rats to test the validity of the sleep network hypothesis in another species. Channelrhodopsin‐2 (ChR2) driven by the MCH promoter was selectively expressed by MCH neurons after injection of rAAV‐MCHp‐ChR2‐EYFP into the hypothalamus of Long–Evans rats. An in vitro study confirmed that the optogenetic activation of MCH neurons faithfully triggered action potentials. In the second study, in Long–Evans rats, rAAV‐MCH‐ChR2, or the control vector, rAAV‐MCH‐EYFP, were delivered into the hypothalamus. Three weeks later, baseline sleep was recorded for 48 h without optogenetic stimulation (0 Hz). Subsequently, at the start of the lights‐off cycle, the MCH neurons were stimulated at 5, 10, or 30 Hz (1 mW at tip; 1 min on – 4 min off) for 24 h. Sleep was recorded during the 24‐h stimulation period. Optogenetic activation of MCH neurons increased both REM and NREM sleep at night, whereas during the day cycle, only REM sleep was increased. Delta power, an indicator of sleep intensity, was also increased. In control rats without ChR2, optogenetic stimulation did not increase sleep or delta power. These results lend further support to the view that sleep‐active MCH neurons contribute to drive sleep in mammals.     

REM sleep eye movement activity and CSF concentrations of 5-hydroxyindoleacetic acid in psychiatric patients

The relationship between rapid-eye-movement (REM) sleep tonic and phasic activity measures and the pre- and postprobenecid cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) was examined in a sample of 14 unmedicated psychiatric patients. The average duration of an eye movement burst and the average number of eye movements within a burst were found to be inversely related to the probenecid corrected accumulation of 5-HIAA in the CSF. These results are interpreted as indicating an association between REM burst eye movement activity and serotonin turnover in psychiatric subjects.     

Wicket spikes during rapid eye movement sleep.

Wicket spikes correspond to a normal variant activity. They usually occur in adults over 50 years of age during drowsiness and light nonrapid eye movement (NREM) sleep. No data exist in the precise distribution of this activity during all the different sleep stages, particularly during rapid eye movement (REM) sleep. The authors report five observations of persistence of this activity during REM sleep. Only one patient was over 50 years of age. The authors found a predominant expression on one temporal side, but inconsistently on the left side (three on the left side versus two on the right side). Wicket spikes always persist in REM sleep. They have an identical morphology as drowsiness or stage 2 sleep. There were no changes in their location. The authors found no correlation with the tonic or phasic phases of REM sleep.     

Rapid eye movement sleep characteristics during and after mood-disturbing events

Twenty-nine women undergoing divorce were monitored for six nights to explore the relation of mood disturbance and rapid eye movement (REM) sleep. Follow-up evaluations were completed on 13 women one to two years later. The more traditional women were more depressed and had shortened REM latencies. Depression was also related to an irregular eye movement density sequence throughout the night. Although depression and REM latency were both significantly improved at follow-up, the REM latency of those initially most depressed remained at a lower than normal level and the eye movement density sequency remained irregular, suggesting some lag in the sleep response or a traitlike vulnerability to future depression.     

Idiopathic rapid eye movement sleep behaviour disorder

Neurological Sciences - Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by elaborate behaviours during REM sleep usually associated with action-filled dreams....     

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord.     

Minute eye movement during sleep.

The minute eye movements of 4 sleeping subjects were studied with a piezo-electric strain-gauge transducer. The frequency and amplitude of ocular microtremor activity diminished during sleep. Activity increased after auditory stimulation and with the appearance of a K complex in the EEG. The ocular microtremor activity also increased with the onset of rapid eye movement (REM). Low amplitude 'micronystagmoid' movements were observed at intervals throughout sleep. In contrast to the changes observed during sleep, ocular microtremor activity did not diminish during hypnosis. The transducer was far more sensitive than the conventional EOG recording system.     

Genetics of rapid eye movement sleep in humans

The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ) and dizygotic (DZ) twins examining the heritability of REM sleep EEG. We studied the architecture, spectral composition and phasic parameters of REM sleep and identified genetic effects on whole investigated EEG frequency spectrum as well as phasic REM parameters (REM density, REM activity and organization of REMs in bursts). In addition, cluster analysis based on the morphology of the EEG frequency spectrum revealed that the similarity among MZ twins is close to intra-individual stability. The observed strong genetic effects on REM sleep characteristics establish REM sleep as an important source of endophenotypes for psychiatric and neurological diseases.     

Characterization of the mu rhythm during rapid eye movement sleep.

OBJECTIVE: The rolandic mu rhythm, a resting activity of somatosensory cortex, is a striking feature of the waking human electroencephalogram. This study will demonstrate that activity with identical features occurs during rapid eye movement (REM) sleep. METHODS: Eye and chin leads were added during prolonged closed circuit television (video) electroencephalographic (EEG) recording with scalp (12 patients) or subdural electrodes including 64 contract grids over the frontoparietal cortices (5 patients). Sleep staging was performed by reformatting into standard polysomnography montages (using two EEG channels, and eye and chin channels) and applying standard scoring criteria. The recordings were then reviewed using all EEG channels to assess rhythmic EEG activity by a reader blinded to the sleep staging. RESULTS: During scalp recordings, 7-10 Hz central rhythms were seen during wakefulness in 7 patients, with 6 of these also having similar rhythms during REM sleep. Similar activity was seen over somatosensory cortex during wakefulness and REM in all invasively recorded patients. This activity was blocked by contralateral body movement or contralateral somatosensory stimuli, even during REM sleep. It was absent in other sleep stages. CONCLUSIONS: This REM sleep activity recapitulates all the characteristics of the waking rolandic mu rhythm. This demonstrates functional similarity between the states of wakefulness and REM sleep.     

Seizure susceptibility decreases with enhancement of rapid eye movement sleep

The study examined the effect of enhanced rapid eye movement (REM) sleep duration on the seizure threshold determined by electrical stimulation of the amygdala in rats. The duration of REM sleep was specifically increased by the microinjection of a cholinergic agonist, carbachol, into the pontine reticular formation. This was accompanied by a significant increase in the threshold current required to elicit an afterdischarge in the amygdala. The results suggest that an increase in REM sleep decreases the likelihood of cortical seizure activity, an effect that is manifest even in other stages of the sleep-wakefulness cycle and not only in the REM state, per se.     

Rhythmic movement disorder (head banging) in an adult during rapid eye movement sleep.

Sleep-related rhythmic movements (head banging or body rocking) are extremely common in normal infants and young children, but less than 5% of children over the age of 5 years old exhibit these stereotyped motor behaviors. They characteristically occur during drowsiness or sleep onset rather than in deep sleep or rapid eye movement (REM) sleep. We present a 27-year-old man with typical rhythmic movement disorder that had persisted into adult life and was restricted to REM sleep. This man is the oldest subject with this presentation reported to date and highlights the importance of recognizing this nocturnal movement disorder when it does occur in adults.     

Rapid eye movement sleep,non-rapid eye movement sleep,dreams, and hallucinations

After the discovery of rapid eye movement (REM) sleep in 1953, oneiric activity was long thought to be associated uniquely with REM sleep. Subsequent evaluation of sleep in humans combining neurophysiologic, psychophysiologic, and, more recently, functional neuroimaging investigations, has instead shown that dreaming also occurs during non-REM (NREM) sleep. It has been documented that hallucinatory activity during sleep is a normal phenomenon that is not constant throughout the night but increases toward morning when it tends to become present to the same extent in REM and NREM sleep. The role of sleep mechanisms in the generation of visual hallucinations is well-recognized in narcolepsy in the case of hypnagogic hallucinations, which are thought to derive from a REM-dissociation state in which dream imagery intrudes into wakefulness. Similar mechanisms have been hypothesized to play a role in the physiopathogenesis of visual hallucinations in various neuropsychiatric disorders. Furthermore, a growing body of evidence indicates that not only REM but also NREM processes, such as arousal-related processes, may play a role in the physiopathogenesis of hallucinations in the aforementioned disorders. The role of these processes has been most extensively documented in visual hallucinations occurring in the context of delirium tremens and Parkinson’s disease.     

Effects of lithium on dopamine behavioural supersensitivity induced by rapid eye movement sleep deprivation

The effects of lithium on the potentiation of d-amphetamine-induced hyperlocomotion were evaluated in rapid eye movement (REM) sleep deprived rats. Under control conditions, pretreatment with lithium during 7 days did not modify the hyperlocomotion produced by d-amphetamine. REM sleep deprivation induced a pronounced potentiation of the locomotor response to d-amphetamine. In a stress control group this potentiation also occurred, but to a lesser degree than in the REM sleep deprived group. Lithium pretreatment prevented the increased response to d-amphetamine in both REM sleep deprived and stress control animals. The effects of lithium in REM sleep deprived rats are in accordance with reports that lithium is able to prevent the development of dopamine receptor supersensitivity. However, it cannot be excluded that in both REM sleep deprived and stress control groups the increased response to d-amphetamine is related to noradrenergic changes and/or noradrenergic-dopaminergic interactions. REM sleep deprivation seems to be an interesting model to study the underlying mechanisms of manic-depressive illness.     

Activation of the motor cortex during phasic rapid eye movement sleep

When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder. Ann Neurol 2016;79:326–330     

Effects of auditory stimulation during rapid eye movement sleep in healthy volunteers and depressed patients.

Auditory and somesthesic forms of stimulation have substantially increased rapid eye movement (REM) sleep in cats. We investigated whether auditory stimulation, applied during REM sleep or outside REM sleep, would have similar effects in normal volunteers. We also administered auditory stimulation to depressed patients during REM sleep. Subjects were studied during 1 acclimatization night, 2 baseline nights, 4 consecutive nights with auditory stimulation, and 1 followup night without auditory stimulation. Normal volunteers were randomly divided into Group R, which received auditory stimulation during each REM sleep episode, and Group NR, which received auditory stimulation at the end of each REM sleep episode. Depressed patients (Group D) received auditory stimulation during each REM sleep period. Only Group R showed increased REM sleep time during the nights of auditory stimulation and throughout the followup night. This group also increased their sleep efficiency. Group NR showed reduced sleep efficiency due to an increase in both the duration and frequency of awakenings. Group D did not show increased REM sleep time, but did show shortened REM sleep episodes, increased REM sleep frequency, and increased duration of awakenings. Group D did not show clinical changes.     

Intracranial pressure and rapid eye movement sleep in hydrocephalus.

Intracranial pressure (ICP) was monitored for 24 h in 30 hydrocephalic patients (21 infants, 9 children) representing borderline cases. The need for surgery was uncertain because their hydrocephalus seemed to be more or less arrested. In 13 cases an electroencephalogram, an electro-oculogram, an electromyogram and an actogram were simultaneously recorded. During sleep related to a period of rapid eye movement (REM) fairly regular steep-rising waves of raised ICP recurred every 50-75 min, decreasing slowly to previous levels in 25-40 min. No concomitant clinical symptoms were exhibited. The cerebral pulse wave amplitude increase during REM sleep, but might vary during one period of REM sleep. The relationship between these raised ICP waves and an increase in cerebral blood flow occurring during REM sleep is studied.     

Rapid eye movement sleep alterations in myasthenia gravis.

The nocturnal sleep patterns of 10 patients with myasthenia gravis and five controls were recorded in the conventional manner for 7 hours on two consecutive nights. One patient was retested 4 weeks after institution of prednisone therapy. All the myasthenics had a significant disturbance in rapid eye movement (REM) sleep cycles. In the patient who was retested after clinically successful prednisone therapy, the REM sleep pattern had become normal. Since acetylcholine is the putative brain stem transmitter substance involved in the maintenance of REM sleep, our findings suggest a disturbed central mechanism of acetylcholine in myasthenia gravis.     

Rapid eye movement sleep deprivation as a probe in elderly subjects

The effects of a 2-night rapid eye movement (REM) sleep deprivation (RSD) procedure on electroencephalographic sleep and mood were examined in 15 healthy elderly control subjects, 14 elderly patients with endogenous depression, and 15 patients with primary degenerative dementia. Compared with control subjects, both patient groups maintained a higher amount of REM sleep time and REM activity during RSD. Unexpectedly, depressed patients showed little rebound in visually scored or automated REM sleep measures following RSD, and they showed stability of REM activity temporal distribution from baseline to recovery conditions. This contrasted with the rebound in REM sleep activity seen in control subjects, and the more modest increase in demented patients. The RSD was fairly specific, with some impact on delta sleep during the procedure but not during recovery sleep. Mood ratings were unaffected by RSD. These findings demonstrated a greater plasticity of REM sleep regulation in the healthy elderly control subjects and suggested a higher REM "pressure" with a "ceiling effect" in depressed patients. Patients with dementia appeared to have an impaired capacity to respond to the challenge of RSD.