Showing papers on "Rapid eye movement sleep published in 1997"

Contributions of the Pedunculopontine Region to Normal and Altered REM Sleep

Abstract: The pedunculopontine (PPN) region of the upper brainstem is recognized as a critical modulator of activated behavioral states such as wakefulness and rapid eye movement (REM) sleep. The expression of REM sleep-related physiology (e.g. thalamocortical arousal, ponto-geniculate-occipital (PGO) waves, and atonia) depends upon a subpopulation of PPN neurons that release acetylcholine (ACh) to act upon muscarinic receptors (mAChRs). Serotonin's potent hyperpolarization of cholinergic PPN neurons is central to present working models of REM sleep control. A growing body of experimental evidence and clinical experience suggests that the responsiveness of the PPN region, and thereby modulation of REM sleep, involves closely adjacent glutamatergic neurons and alternate afferent neurotransmitters. Although many of these afferents are yet to be defined, dopamine-sensitive GABAergic pathways exiting the main output nuclei of the basal ganglia and adjacent forebrain nuclei appear to be the most conspicuous and the most likely to be clinically relevant. These GABAergic pathways are ideally sited to modulate the physiologic hallmarks of REM sleep differentially (e.g. atonia versus cortical activation), because each originates from a functionally unique forebrain circuit and terminates in a unique pattern upon brain stem neurons with unique membrane characteristics. Evidence is reviewed that changes in the quality, timing, and quantity of REM sleep that characterize narcolepsy, REM sleep behavior disorder, and neurodegenerative and affective disorders (depression and schizophrenia) reflect 1) changes in responsiveness of cells in the PPN region governed by these afferents; 2) increase or decrease in PPN cell number; or 3) mAChRs mediating increased responsiveness to ACh derived from the PPN. Auditory evoked potentials and acoustic startle responses provide means independent from recording sleep to assess pathophysiologies affecting the PPN and its connections and thereby complement investigations of their role in affecting daytime functions (e.g. arousal and attention).

Plasma Epinephrine and Norepinephrine Concentrations of Healthy Humans Associated With Nighttime Sleep and Morning Arousal

Abstract: We assessed the activity of the sympathetic nervous system during undisturbed nocturnal sleep and periods of wakefulness directly before and after sleep in healthy young men. Changes induced by periods of rapid eye movement and by morning awakening, both periods reported to demonstrate an enhanced risk for the onset of cardiovascular diseases, were of particular interest. In 13 healthy men (age, 18 to 35 years), blood for determination of epinephrine and norepinephrine was drawn every 7 minutes between 9:30 PM and 8:30 AM with the subjects resting in a strictly horizontal position. Lights were switched off at 11 PM until awakening at 7 AM. At 8:30 AM, subjects stood up and a final blood sample was drawn. Sleep was monitored somnopolygraphically, and heart rate and blood pressure were continuously measured. Average epinephrine but not norepinephrine concentrations were significantly lower during nocturnal sleep than during wakefulness before and after sleep. In parallel, heart rate and blood pressure declined significantly during sleep. During rapid eye movement sleep, both epinephrine and norepinephrine concentrations were significantly lower than during sleep stages 1 and 2 and slow-wave sleep. Whereas epinephrine concentrations gradually began to increase after morning awakening, norepinephrine levels were not significantly enhanced. However, standing up at the end of the experiment sharply increased norepinephrine concentrations by 180%, whereas epinephrine levels were less enhanced (46%) by the change of body position. This study suggests that the decrease in the activity of the sympathoadrenal branch of the sympathetic nervous system is probably due to an entrainment to the sleep-wake cycle, whereas the low activity of the noradrenergic branches depends mainly on horizontal body position during nocturnal sleep. The activities of the sympathoadrenal and noradrenergic branches of the sympathetic nervous system seem to be downregulated during rapid eye movement sleep. Awakening itself selectively enhances epinephrine levels. Subsequent orthostasis activates both the sympathoadrenal and, most prominently, the noradrenergic branches of the sympathetic nervous system.

GABA release in the dorsal raphe nucleus: role in the control of REM sleep.

Abstract: The cessation of firing of serotonergic dorsal raphe neurons is a key controlling event of rapid eye movement (REM) sleep. We tested the hypothesis that this cessation of activity is due to gamma-aminobutyric acid (GABA) release using the in vivo microdialysis technique. We found that REM sleep is accompanied by a selective increase in GABA release, but not by a change in glutamate or glycine release in the dorsal raphe nucleus. Microinjection of the GABA agonist muscimol into the dorsal raphe increased REM sleep, although microperfusion of the GABA antagonist picrotoxin blocked REM sleep. These results implicate GABA release as a critical element in the production of the REM sleep state and in the control of discharge in serotonergic neurons across the sleep/wake cycle.

Sleep-promoting and hypothermic effects of daytime melatonin administration in humans.

Abstract: Sleep-promoting and hypothermic effects of orally administered melatonin during the daytime were assessed using a placebo-controlled, double-blind, cross-over design. Following a 7-hour nighttime sleep opportunity, healthy young male subjects (n = 8) were given either a placebo or one of three doses of melatonin (1 mg, 10 mg, and 40 mg) at 1000 hours. Sleep was polygraphically assessed in a 4-hour sleep opportunity from 1200 to 1600 hours. All doses of melatonin significantly shortened the latency to sleep onset. Melatonin also significantly increased total sleep time and decreased wake after sleep onset (WASO). Sleep following melatonin administration contained significantly more stage 2 and less stage 3-4, while stage 1 and rapid eye movement (REM) sleep were unaffected. In addition to the sleep-promoting effects, melatonin completely suppressed the normal diurnal rise of core body temperature. These data suggest that melatonin may be an effective method of promoting sleep for individuals attempting to sleep during their subjective day, such as shiftworkers and individuals rapidly traveling across multiple time zones.

Mice Lacking the TNF 55 kDa Receptor Fail to Sleep More After TNFα Treatment

Abstract: Tumor necrosis factor (TNF) is a well characterized sleep-regulatory substance. To study receptor mechanisms for the sleep-promoting effects of TNF, sleep patterns were determined in control and TNF 55 kDa receptor knock-out (TNFR-KO) mice with a B6 × 129 background after intraperitoneal injections of saline or murine TNFα. The TNFR-KO mice had significantly less baseline sleep than the controls. TNFα dose-dependently increased non-rapid eye movement sleep (NREMS) in the controls but did not influence sleep in TNFR-KO mice. Although TNFR-KO mice failed to respond to TNFα, they had an increase in NREMS and a decrease in rapid eye movement sleep after interleukin-1β treatment. These results indicate that TNFα affects sleep via the 55 kDa receptor and provide further evidence that TNFα is involved in physiological sleep regulation. Current results also extend the list of species to mice in which TNFα and interleukin-1β are somnogenic.

Pontine Nitric Oxide Modulates Acetylcholine Release, Rapid Eye Movement Sleep Generation, and Respiratory Rate

Abstract: Pontine cholinergic neurotransmission is known to play a key role in the regulation of rapid eye movement (REM) sleep and to contribute to state-dependent respiratory depression. Nitric oxide (NO) has been shown to alter the release of acetylcholine (ACh) in a number of brain regions, and previous studies indicate that NO may participate in the modulation of sleep/wake states. The present investigation tested the hypothesis that inhibition of NO synthase (NOS) within the medial pontine reticular formation (mPRF) of the unanesthetized cat would decrease ACh release, inhibit REM sleep, and prevent cholinergically mediated respiratory depression. Local NOS inhibition by microdialysis delivery of N(G)-nitro-L-arginine (NLA) significantly reduced ACh release in the cholinergic cell body region of the pedunculopontine tegmental nucleus and in the cholinoceptive mPRF. A second series of experiments demonstrated that mPRF microinjection of NLA significantly reduced the amount of REM sleep and the REM sleep-like state caused by mPRF injection of the acetylcholinesterase inhibitor neostigmine. Duration but not frequency of REM sleep epochs was significantly decreased by mPRF NLA administration. Injection of NLA into the mPRF before neostigmine injection also blocked the ability of neostigmine to decrease respiratory rate during the REM sleep-like state. Taken together, these findings suggest that mPRF NO contributes to the modulation of ACh release, REM sleep, and breathing.

Cellular basis of pontine ponto-geniculo-occipital wave generation and modulation

Abstract: 1. Pontogeniculooccipital (PGO) waves are recorded during rapid eye movement (REM) sleep from the pontine reticular formation. 2. PGO wave-like field potentials can also be recorded in many other parts of the brain in addition to the pontine reticular formation, but their distribution is different in different species. Species differences are due to variation in species-specific postsynaptic target sites of the pontine PGO generator. 3. The triggering neurons of the pontine PGO wave generator are located within the caudolateral peribrachial and the locus subceruleus areas. 4. The transferring neurons of the pontine PGO generator are located within the cholinergic neurons of the laterodorsal tegmentum and the pedunculopontine tegmentum. 5. The triggering and transferring neurons of the pontine PGO wave generator are modulated by aminergic, cholinergic, nitroxergic, GABA-ergic, and glycinergic cells of the brainstem. The PGO system is also modulated by suprachiasmatic, amygdaloid, vestibular, and brainstem auditory cell groups.

A polysomnographic comparison of veterans with combat-related PTSD, depressed men, and non-ill controls

Abstract: Post-traumatic stress disorder (PTSD) overlaps major depression (MD) clinically, but differs with respect to treatment response and some biological markers. Sleep disturbances represent core features of PTSD and are also common in MD. Rapid eye movement sleep (REM) has been postulated to be involved in the pathophysiology of PTSD, and REM abnormalities occur in MD. Twenty-five patients with combat-related PTSD, 16 men with a principal diagnosis of MD, and 10 asymptomatic male controls were compared by polysomnography (PSG) under medication and substance-free conditions. Data were obtained from recordings made after an accommodation night. One subject from each group was excluded for significant apnea or limb movements. Sleep efficiency was decreased in the PTSD group compared to the MD and control groups. REM density was comparably increased in PTSD and MD groups, while the amount of REM sleep was reduced in PTSD compared to MD groups. These sleep measures were not significantly associated with co-morbid depression, substance-use disorder histories, or subclinical sleep apnea or limb movements within the PTSD group. These findings support sleep maintenance being impaired in chronic PTSD patients. Increased REM density in PTSD patients was replicated and was comparable to increases in the MD group. Divergence of REM time between these clinical groups suggests the possibility of different underlying mechanisms.

Sleep-Disordered Breathing in Patients With Acute Supra- and Infratentorial Strokes: A Prospective Study of 39 Patients

Abstract: Background and Purpose Although recent studies suggest a high prevalence of obstructive sleep apnea (OSA) in patients with acute stroke, a systematic characterization of sleep-disordered breathing based on the severity and topography of stroke has not been performed. Methods We prospectively studied 39 noncomatose adult subjects (15 women, 24 men; mean age, 57 years) with a first acute stroke. Sleep history, cardiovascular risk factors, stroke severity as estimated by the Scandinavian Stroke Scale, and extent of stroke demonstrated on a computed tomographic or magnetic resonance imaging scan of the brain were assessed. Polysomnography was performed a mean of 10 days (range, 1 to 49 days) after stroke onset. Monitoring of breathing during wakefulness, non–rapid eye movement sleep, and rapid eye movement sleep included measurements of nasal/oral airflow, respiratory effort, and oxygen saturation. Results Breathing was abnormal during wakefulness in 7 (18%) subjects and during sleep in 26 (67%). Obstructive ...

Sleep ontogenesis revisited: a longitudinal 24-hour home polygraphic study on 15 normal infants during the first two years of life.

Abstract: The sleep organization of 15 normal infants (seven boys, eight girls) was studied at their homes during six 24-hour periods, i.e. at 3, 6, 9, 12, 18, and 24 months of age, using the Oxford Medical System. Sleep states and stages were scored visually at 30-second intervals, according to Rechtschaffen and Kales' criteria, adapted for children by Guilleminault. All sleep parameters were analyzed for the entire 24-hour period, i.e. during both the nocturnal and the diurnal part of the nycthemere. The results showed a continuous decrease in total sleep time, rapid eye movement (REM) sleep, and indeterminate sleep, and also an increase in waking time, quiet sleep, and stages 1 and 2 sleep. Except for slow-wave sleep, which remained very stable for the different ages, analysis of variance applied to the data showed clear age and day-night effects on sleep ontogenesis. Modifications with age were more precocious and more pronounced for the diurnal part of the nycthemere, especially as regards REM sleep. For the nocturnal part, there was a significant increase in sleep efficiency and in the length of the REM period after 12 months of age, while total sleep duration and number of awakenings decreased. In addition to normative data for clinical use, this study provides three new interesting results related to the maturation of sleep mechanisms and functions: 1) the high stability of the percentage of slow-wave sleep along these 2 years, 2) the presence (from 12 months of age) of a stage 2/REM sleep ratio equal to one, and a sleep change occuring earlier, during the diurnal rather than the nocturnal part of the nycthemere. The first two points could be regarded as indexes of sleep maturation reflecting developmental and neurophysiological changes in central nervous system structures. The third point underlines the importance of the circadian rhythm and the concept of "experience" in the maturation of sleep.

Development of REM and slow wave sleep in the rat

Abstract: Active sleep (AS) in the neonate has been considered to be an immature form of rapid eye movement (REM) sleep. Quiet sleep (QS) has been thought to represent an immature form of slow wave sleep (SWS). To determine the relationship between the behaviorally determined states of AS and QS and electrographically determined REM sleep and SWS, we examined sleep ontogeny in the developing rat using an experimental routine that permitted long-term recordings and minimized the effects of maternal separation. Under these conditions, a transient state that included electroencephalographic slow wave activity and phasic motor activity was eventually replaced with the mature SWS pattern. Our work suggests that neonatal QS is not an immature form of SWS and that AS is best considered as an undifferentiated behavioral state from which both SWS and REM sleep develop.

Generalized anxiety and sleep architecture: A polysomnographic investigation.

Abstract: The sleep of 15 adult subjects who reported heightened generalized anxiety in the absence of other psychiatric syndromes and a 15-adult contrast group were studied by means of nocturnal polysomnography. Analysis of polysomnography variables revealed a significant discriminant function that accounted for 79% of the variance between groups, indicating that high-anxiety/worry subjects took longer to fall asleep, had a smaller percentage of deep (slow-wave) sleep, and more frequent transitions into light sleep [stage 1 nonrapid eye movement (NREM)]. Additional analyses indicated that high-anxiety/worry subjects had a greater percentage of light sleep, more early microarousals, a lower rapid eye movement (REM) density relative to low-anxiety subjects. These subjects also showed more electrodermal storming when slow-wave sleep and REM sleep variables were covaried. Results indicated disrupted sleep depth and continuity similar to that documented in clinical anxiety disorder patients and distinct from that of depressed patients. These results indicate that generalized anxiety and worry in otherwise healthy individuals may act to produce a clinically significant sleep disturbance in the absence of other psychiatric symptoms.

Selective and total sleep deprivation: effect on the sleep EEG in the rat

Abstract: Although sleep deprivation is known to exert an antidepressant effect in depressed patients, the involvement of sleep regulation is still unknown. Selective sleep deprivation experiments were performed in the rat to investigate the interactions between non-REM sleep (NREMS) and REM sleep (REMS) in an animal model. A12-h total sleep deprivation (TD) period ending at lights on was followed by one of the following protocols: (1) recovery sleep (TD12); (2) 4-h total sleep deprivation (TD16); (3) 4-h slow-wave deprivation (SWD); (4) 4-h REMS deprivation (RD). In the SWD protocol, the reduction of EEG slow-wave activity (SWA; power density in the 0.75-4.0 Hz band) was obtained by curtailing NREMS episodes to 20 s. During RD the number of interventions required to prevent REMS increased during the first 2 h and then remained constant. While RD caused only a minor reduction of NREMS, it increasingly suppressed SWA in NREMS. The rebound of SWA occurred later and was less prominent after RD than after SWD. Whereas an REMS rebound occurred after all three 4-h sleep deprivation protocols, a persistent increase in the dark period was present only after TD16. It is concluded that (a) SWA in NREMS is inhibited by an increased level of REMS propensity; (b) the hypothesis that REMS propensity increases only during NREMS is not supported; and (c) the results are compatible with the hypothesis that the suppression of NREMS intensity is the common denominator of different antidepressive sleep manipulations in depressive patients.

Morning work: effects of early rising on sleep and alertness.

Abstract: The aim of the present study is to investigate how early morning work affects sleep and alertness. Twenty-two females, employed as airline cabin crew members, participated in the study. The design included two sleep conditions (work day and free day) for an early group and for a control group. The results show that early morning work reduced sleep to 5 hours and 12 minutes and that the reduction of sleep consisted of less stage 2 and rapid eye movement (REM) sleep. However, when the analysis was restricted to the first 5 hours, no differences in sleep stages, arousals, or sleep continuity were obtained between groups or conditions. Analysis of electroencephalogram (EEG) power density for the 0.5-16.5 Hz bands across nonREM periods showed no differences. With respect to the subjective ratings, early morning work was associated with more apprehension of difficulties in awakening and insufficient sleep. Daytime alertness and ease of awakening did not differ between groups, but the early group had significantly more sleepiness and complained more of unrefreshing sleep in connection with the work day compared to the free day. Ratings of insufficient sleep and high daytime sleepiness were mainly predicted (multiple regression analyses) by short total sleep time (TST), whereas apprehension of an unpleasant awakening was predicted by an early wake-up time. It was concluded that early morning work causes a reduction of sleep time and an increase in apprehension stress.

Serotonin at the Laterodorsal Tegmental Nucleus Suppresses Rapid-Eye-Movement Sleep in Freely Behaving Rats

Abstract: Serotonin [5-hydroxytryptamine (5-HT)] is believed to play an important inhibitory role in the regulation of rapid-eye-movement (REM) sleep. 5-HT may exert this effect on neurons of the laterodorsal tegmental (LDT) nuclei that are implicated as important in the generation of REM sleep and phasic REM events such as ponto-geniculo-occipital (PGO) waves and respiratory variability. In rat brainstem in vitro , 5-HT hyperpolarizes and inhibits the bursting properties of LDT neurons assumed to be involved in generating REM sleep and PGO waves. This study tests the hypothesis that in vivo 5-HT at the LDT nuclei suppresses REM sleep and phasic REM events. Ten rats were implanted with bilateral cannulae aimed at the LDT and with electrodes for recording the electroencephalogram, neck electromyogram, PGO waves, and diaphragm electromyogram. During REM sleep, 5-HT (100 nl; 1–1.5 mm), saline, or sham microinjections were performed; repeated microinjections were separated by ∼1 hr. After the first microinjection, REM sleep as a percent of the total sleep time was reduced with 5-HT (mean percent REM, 19.9 ± 2.5% for 5-HT vs 26.8 ± 2.4% for saline; p = 0.02). REM duration was reduced by 37% with 5-HT ( p = 0.01), but REM episode frequency was changed less consistently ( p = 0.21), suggesting that 5-HT mainly disrupted REM sleep maintenance. Per unit time of REM sleep, 5-HT had no effect on the amount or variability of REM PGO activity ( p > 0.740) or on the mean or coefficient of variation of REM respiratory rate ( p > 0.11). With subsequent microinjections, the effects of 5-HT on REM sleep were similar. A dose-dependent REM sleep suppression with 5-HT was observed in five rats tested. These data suggest that in vivo 5-HT at the LDT nuclei suppresses REM sleep expression. Although 5-HT did not disproportionately reduce the occurrence of phasic events within REM, total REM phasic activity was reduced because of less REM sleep after 5-HT.

Sleep and gastric function in irritable bowel syndrome: Derailing the brain-gut axis

Abstract: Background —Recently, several studies have shown an alteration in bowel function during sleep in patients with irritable bowel syndrome (IBS), and a recent study also suggests a remarkable increase in rapid eye movement (REM) sleep. These studies have suggested that an alteration in CNS function may play an important role in the pathogenesis of IBS. Aims —To confirm the presence of an alteration in REM sleep in patients with IBS and to assess the relation between sleep and a non-invasive measure of gastric functioning, the electrogastrogram (EGG). Patients —Ten patients with IBSand 10 age and sex matched normal volunteers. Methods —All subjects slept one night in the sleep laboratory and underwent polysomnographic monitoring to determine sleep patterns, and recording of the EGG from surface electrodes. Results —The IBS group had a notable and significant increase in the percentage and duration of REM sleep (p Conclusions —Results confirmed the enhancement of REM sleep in patients with IBS and suggested an intrinsic alteration in autonomic and CNS functioning in patients with IBS.

Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis

Abstract: The pineal hormone melatonin has been implicated in the circadian regulation of sleep. In a crossover design, we investigated the effect of acute administration of 5 mg melatonin and a melatonin agonist (S-20098, 5 and 100 mg) in healthy young men when given 5 h before bedtime on sleep structure and electroencephalogram (EEG) power density. Each trial comprised a baseline, a treatment, and a posttreatment sleep episode. Relative to the placebo condition, all treatments phase advanced the core body temperature rhythm [Krauchi, K., C. Cajochen, D. Mori, C. Hetsch, and A. Wirz-Justice. Sleep Res. 24: 526, 1995; and Krauchi, K., C. Cajochen, D. Mori, and A. Wirz-Justice. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol. 41): R1178-1188, 1997]. Rapid eye movement (REM) sleep was increased after both melatonin and S-20098. This increase in REM sleep was most pronounced in the first REM sleep episode. On the posttreatment night after melatonin and S-20098 administration, more wakefulness was present in the latter one-half of the sleep episode. EEG power density between 0.25 and 20 Hz during either non-REM (NREM) or REM sleep did not differ from placebo. Thus a single early evening dose of melatonin or the agonist S-20098 increases REM sleep propensity and advances sleep termination while, at the same time, the EEG in NREM sleep remains unaffected.

REM sleep motor dysfunction in multiple system atrophy: with special emphasis on sleep talk as its early clinical manifestation

Abstract: Various neurodegenerative diseases involving brainstem structures as one of the main pathological lesions are reported to be associated with REM sleep behaviour disorder. Full blown REM sleep behaviour disorder can be diagnosed clinically, but REM sleep motor dysfunction, a pathophysiological basis of REM sleep behaviour disorder, is difficult to detect without all night polysomnography. Twenty one consecutive patients with multiple system atrophy with no complaints of nocturnal abnormal behaviours were clinically evaluated to determine the presence of sleep related symptoms. All night polysomnography with video monitoring was performed to investigate REM sleep characteristics and patients' behaviours. In 85.7% (18 of 21) of the patients' sleep talk started or increased around or after the clinical onset of the primary diseases. REM sleep without atonia occupied more than 15%(16.2%-100%) of the REM sleep time in all but one patient. In 90.5% (19 of 21) of patients, motor events such as sleep talk and various combinations of craniofacial, orofacial, or limb movements occurred at various frequencies mostly during REM sleep without atonia. In patients with multiple system atrophy, REM sleep motor dysfunction is a common polysomnographic finding which is otherwise overlooked, and sleep talk may be its early clinical manifestation.

Melatonin Effects in a Patient with Severe REM Sleep Behavior Disorder: Case Report and Theoretical Considerations

Abstract: REM sleep behavior disorder (RBD) is so far a possibly underestimated yet well-described sleep disorder. Its major impact is the vigorous sleep behavior that often results in injuries to the patient himself or to people sleeping nearby. We treated a 64-year-old male with a clinically and polysomnographically confirmed diagnosis of RBD with 3 mg melatonin, which led to a significant reduction of motor activity during sleep, as measured by actigraphy (p < 0.0001 in all analyzed movement parameters), and a full clinical recovery over a 5-month treatment period. RBD phenomena gradually returned after melatonin administration was stopped. After 2 months' treatment, polysomnography showed no major changes except an increase of REM sleep (13 vs. 17% of sleep period time) and a better preservation of REM-sleep-associated muscle atonia. Our results suggest that melatonin might be able to reinforce REM sleep in RBD patients by enhancing its active inhibition of motor activity.