Showing papers on "Rapid eye movement sleep published in 2003"
TL;DR: Sleep deprivation from 0-5 h after training for this task impaired memory consolidation for contextual fear conditioning whereas sleep deprivation from 5-10H after training had no effect, suggesting that sleep deprivation may act by modifying these molecular mechanisms of memory storage.
Abstract: Many behavioral and electrophysiological studies in animals and humans have suggested that sleep and circadian rhythms influence memory consolidation. In rodents, hippocampus-dependent memory may be particularly sensitive to sleep deprivation after training, as spatial memory in the Morris water maze is impaired by rapid eye movement sleep deprivation following training. Spatial learning in the Morris water maze, however, requires multiple training trials and performance, as measured by time to reach the hidden platform is influenced by not only spatial learning but also procedural learning. To determine if sleep is important for the consolidation of a single-trial, hippocampus-dependent task, we sleep deprived animals for 0–5 and 5–10 h after training for contextual and cued fear conditioning. We found that sleep deprivation from 0–5 h after training for this task impaired memory consolidation for contextual fear conditioning whereas sleep deprivation from 5–10 h after training had no effect. Sleep deprivation at either time point had no effect on cued fear conditioning, a hippocampus-independent task. Previous studies have determined that memory consolidation for fear conditioning is impaired when protein kinase A and protein synthesis inhibitors are administered at the same time as when sleep deprivation is effective, suggesting that sleep deprivation may act by modifying these molecular mechanisms of memory storage.
436 citations
TL;DR: Helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans, and both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine.
Abstract: Depression is a multifactorial illness and genetic factors play a role in its etiology. The understanding of its physiopathology relies on the availability of experimental models potentially mimicking the disease. Here we describe a model built up by selective breeding of mice with strikingly different responses in the tail suspension test, a stress paradigm aimed at screening potential antidepressants. Indeed, “helpless” mice are essentially immobile in the tail suspension test, as well as the Porsolt forced-swim test, and they show reduced consumption of a palatable 2% sucrose solution. In addition, helpless mice exhibit sleep–wakefulness alterations resembling those classically observed in depressed patients, notably a lighter and more fragmented sleep, with an increased pressure of rapid eye movement sleep. Compared with “nonhelpless” mice, they display higher basal seric corticosterone levels and lower serotonin metabolism index in the hippocampus. Remarkably, serotonin1A autoreceptor stimulation induces larger hypothermia and inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis in helpless than in nonhelpless mice. Thus, helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans. Finally, both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine. The helpless line of mice may provide an opportunity to approach genes influencing susceptibility to depression and to investigate neurophysiological and neurochemical substrates underlying antidepressant effects.
252 citations
TL;DR: Recent advances provide compelling evidence that narcolepsy may be a neurodegenerative or autoimmune disorder resulting in a loss of hypothalamic neurons containing the neuropeptide orexin (also known as hypocretin).
Abstract: Narcolepsy is a common cause of chronic sleepiness distinguished by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy and hallucinations. Recent advances provide compelling evidence that narcolepsy may be a neurodegenerative or autoimmune disorder resulting in a loss of hypothalamic neurons containing the neuropeptide orexin (also known as hypocretin). Because orexin promotes wakefulness and inhibits rapid eye movement sleep, its absence may permit inappropriate transitions between wakefulness and sleep. These discoveries have considerably improved our understanding of the neurobiology of sleep and should foster the development of rational treatments for a variety of sleep disorders.
234 citations
TL;DR: In healthy adults, age-related alterations in nocturnal wake time and daytime sleepiness are associated with elevations of both plasma IL-6 and cortisol concentrations, but REM sleep decline with age is primarily associated with cortisol increases.
Abstract: IL-6 and TNF alpha secretion is increased by sleep loss or restriction. IL-6 secretion progressively increases with age, yet its association with decreased quality and quantity of sleep in old adults is unknown. This study examined the alteration of 24-h secretory pattern of IL-6, TNF alpha, and cortisol in 15 young and 13 old normal sleepers who were recorded in the sleep laboratory for four consecutive nights. Serial 24-h plasma measures of IL-6, TNF alpha, and cortisol were obtained during the fourth day, and daytime sleepiness was assessed with the multiple sleep latency test. Old adults, compared with young subjects, slept poorly at night (wake time and percentage stage 1 sleep were increased, whereas their percentage slow wave sleep and percentage sleep time were decreased, P < 0.05). Accordingly, their daytime sleep latency was longer than in young adults (P < 0.05). The mean 24-h IL-6 and cortisol levels were significantly higher in old than young adults (P < 0.05). In both groups, IL-6 and cortisol plasma concentrations were positively associated with total wake time, with a stronger association of IL-6 and cortisol with total wake time in the older individuals (P < 0.05); their combined effect was additive. IL-6 had a negative association with rapid eye movement (REM) sleep only in the young (P < 0.05), but cortisol was associated negatively with REM sleep both in the young and old, with a stronger effect in the young. We conclude that in healthy adults, age-related alterations in nocturnal wake time and daytime sleepiness are associated with elevations of both plasma IL-6 and cortisol concentrations, but REM sleep decline with age is primarily associated with cortisol increases.
231 citations
TL;DR: It is suggested that there is a continuum of reduced striatal dopamine transporters involved in the pathophysiologic mechanisms causing increased muscle activity during REM sleep in patients with subclinical RBD.
Abstract: STUDY OBJECTIVES Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by complex behavior during REM sleep. The etiology of this disorder is still unknown, but a recent study showed that RBD precedes symptoms of Parkinson disease (PD) by several years, and in a previous study, we found reduced striatal dopamine transporters in idiopathic clinically manifest RBD. DESIGN Hypothesizing that subclinical RBD shows a less severe reduction of striatal dopamine transporters than clinically manifest RBD, we studied striatal postsynaptic dopamine D2-receptors with (S)-2hydroxy-3iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide labeled with iodine 123 (IBZM) and the striatal presynaptic dopamine transporters with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane labeled with iodine 123 (IPT) using single-photon emission computed tomography (SPECT) in the following groups: 8 patients with idiopathic subclinical RBD, 8 patients with idiopathic clinically manifest RBD, 11 controls, and 8 patients with PD stage Hoehn & Yahr I. RESULTS The IPT uptake was highest in controls. There was a significant decrease in IPT uptake from controls to patients with subclinical RBD, from patients with subclinical RBD to clinically manifest RBD, and from patients with clinically manifest RBD to patients with PD (controls: right = 4.07 +/- 0.29, left = 4.07 +/- 0.30; subclinical RBD: right = 3.56 +/- 0.21, left = 3.55 +/- 0.25; clinically manifest RBD: right = 3.18 +/- 0.43, left = 3.2 +/- 0.43; PD: ipsilateral to the clinically affected body side = 3.25 +/- 0.35, contralateral to the clinically affected body side = 2.51 +/- 0.28). Muscle activity during REM sleep lasting persistently longer than 0.5 seconds was independently associated with reduction of striatal dopamine transporters (P = 0.001). The IBZM uptake was not significantly different between the groups. CONCLUSIONS This study suggests that there is a continuum of reduced striatal dopamine transporters involved in the pathophysiologic mechanisms causing increased muscle activity during REM sleep in patients with subclinical RBD.
217 citations
TL;DR: Polysomnography shows respiratory disturbances occur predominantly during non-rapid eye movement sleep and are characterized by ataxic breathing, central apneas, sustained hypoxemia, and unusually prolonged obstructive "hypopneas" secondary to delayed arousal responses.
206 citations
TL;DR: This study shows for the first time an impaired cortical activation during both wakefulness and REM sleep in idiopathic RBD, despite an absence of changes on sleep architecture compared with controls.
Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by a loss of atonia and an increase in phasic muscle activity during REM sleep, leading to complex nocturnal motor behaviors. Brainstem structures responsible for the pathogenesis of RBD are also implicated in cortical activation. To verify the hypothesis that electroencephalogram (EEG) activation will be impaired in RBD, we performed quantitative analyses of waking and REM sleep EEG in 15 idiopathic RBD patients and 15 age- and gender-matched healthy subjects. During wakefulness, RBD patients showed a considerably higher theta power in frontal, temporal, and occipital regions with a lower beta power in the occipital region. The dominant occipital frequency was significantly lower in RBD. During REM sleep, beta power in the occipital region was lower in RBD. This study shows for the first time an impaired cortical activation during both wakefulness and REM sleep in idiopathic RBD, despite an absence of changes on sleep architecture compared with controls. EEG slowing in these patients may represent an early sign of central nervous system dysfunction, perhaps paralleled by subclinical cognitive deficits. The topographical distribution of EEG slowing and possible pathophysiological mechanisms are discussed in light of the known association between RBD and neurodegenerative disorders.
206 citations
TL;DR: Surprisingly, a decrease in the percentage of time spent with REM sleep muscle atonia was observed with treatment, and the treatment did not modify the indexes of periodic leg movements.
Abstract: The authors evaluated the effects of pramipexole, a dopaminergic D2-D3 receptor agonist, on eight patients with idiopathic REM sleep behavior disorder. Five patients reported a sustained reduction in the frequency or intensity of sleep motor behaviors, which was confirmed by video recording, although no change was observed for the percentage of phasic EMG activity during REM sleep. Surprisingly, a decrease in the percentage of time spent with REM sleep muscle atonia was observed with treatment. The treatment did not modify the indexes of periodic leg movements.
201 citations
TL;DR: A growing body of evidence indicates that the duration of unmodulated parental care and noncircadian environmental conditions may be detrimental for the establishment of these basic rhythmicities.
147 citations
TL;DR: It is reached the tentative conclusion that the sleep‐promoting actions of IL‐1 and GHRH are mediated via anterior hypothalamic neurons that are receptive to these substances, and it seems likely that TNF‐α and CRH also influence these neurons.
Abstract: In the last twenty years we have realized that the immune system synthesizes a class of peptides, termed cytokines, that play a central role in alerting the brain to ongoing inflammation in peripheral tissues. Among the brain's responses to proinflammatory cytokines, or agents that induce these cytokines, are certain alterations in sleep profiles. Characteristically there is an increase in non-rapid eye movement sleep (NREMS), and NREMS intensity is often accompanied by a decrease in rapid eye movement sleep (REMS). Cytokines appear to play a role in normal sleep regulation; during pathology, higher levels of cytokines amplify the physiological cytokine sleep mechanisms. In this review we summarize the extensive literature on the roles of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in sleep regulation, and their interactions with the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH). We reach the tentative conclusion that the sleep-promoting actions of IL-1 and GHRH are mediated via anterior hypothalamic neurons that are receptive to these substances. It also seems likely that TNF-alpha and CRH also influence these neurons. In addition, we discuss an array of research issues raised by these studies that remain to be resolved.
146 citations
TL;DR: It is confirmed that the duration of stage 4 and REM sleep latency are reduced in first episode and neuroleptic-naive patients with schizophrenia and the fact that measures of REM sleep correlate with clinical scales of schizophrenia suggests that REM sleep physiology shares common substrates with symptoms of this disease.
TL;DR: It is concluded that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep and that rapid eye movement sleep (REM sleep) nor non‐REM sleep (NREMS) amounts differed significantly between the groups.
Abstract: Summary
Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.
TL;DR: Cutting down on nigrostriatal dopaminergic projections may contribute to RBD in MSA, and striatal [11C]DTBZ binding was inversely correlated with the severity of REM atonia loss, while thalamic [123I]IBVM binding was not correlated.
Abstract: Objective: To explore the neurochemical basis of REM sleep behavior disorder (RBD) in multiple-system atrophy (MSA). Methods: In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of REM atonia loss by the percentage of REM sleep with tonically increased electromyographic (EMG) activity and the percentage of REM sleep with phasic EMG bursts. PET with (+)-[ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ) was employed to measure the density of striatal monoaminergic terminals and SPECT with (−)-5-[ 123 I]iodobenzovesamicol ([ 123 I]IBVM) to measure the density of thalamic cholinergic terminals. Data in the patient group were compared with data from 15 normal control subjects scanned with [ 11 C]DTBZ and 12 with [ 123 I]IBVM. Results: Age and gender distributions were similar in patient and normal control groups. The MSA subjects showed decreased mean [ 11 C]DTBZ binding in the striatum ( p 123 I]IBVM binding in the thalamus ( p 11 C]DTBZ binding was inversely correlated with the severity of REM atonia loss ( p = 0.003). Thalamic [ 123 I]IBVM binding, however, was not correlated to the severity of REM atonia loss. Conclusion: Decreased nigrostriatal dopaminergic projections may contribute to RBD in MSA.
TL;DR: A reduction in dream-like quality of the REM content reports between the first and second halves of the night was found to be associated with suicidal tendency, which may indicate that depressed subjects fail to self-regulate mood and integrate affect into long-term memory networks during sleep.
Abstract: To examine the relationship between the emotional quality of dreams, REM sleep variables and suicidal tendency in depressed individuals, 26 depressed volunteers (10 males and 16 females) were assessed with the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS), and underwent 3 nights of polysomnography There was a significant negative correlation between suicidality scores and REM latency and a positive correlation between suicidality and REM percent Suicidal subjects had a significantly shorter mean REM latency and a higher mean REM percentage than the non-suicidal subjects As expected in normal subjects, 20 subjects had an increase in dream-like quality (DLQ) of REM reports between the first and second halves of the night The six subjects with a negative DLQ difference also scored as suicidal A reduction in dream-like quality of the REM content reports between the first and second halves of the night was found to be associated with suicidal tendency The findings may indicate that these subjects fail to self-regulate mood and integrate affect into long-term memory networks during sleep Theoretical and clinical implications of these findings in depression are discussed
TL;DR: The experimental evidence shows that the interaction between thermoregulatory and sleep processes occurs at the level of the preoptic-hypothalamic thermostat.
Abstract: This review describes the systemic physiological phenomena characterizing the interaction between thermoregulatory and sleep processes in the adult mammal. Homeostatic thermoregulation is preserved across the behavioral states of quiet wakefulness and non-rapid eye movement sleep notwithstanding state-dependent differences in threshold and gain of effector responses to thermal loads. In many mammalian species rapid eye movement sleep is characterized by the suppression or depression of thermoregulatory responses to thermal loads. In human adults, however, rapid eye movement sleep is not as thermally altered as in other mammals. The experimental evidence shows that the interaction between thermoregulatory and sleep processes occurs at the level of the preoptic-hypothalamic thermostat. A main open question concerns the nature of the over-riding demand imposing on the central nervous system the temporary suspension of homeostatic integrative regulation in rapid eye movement sleep.
TL;DR: A delay in maximal induction, and the degradation of the maintenance phase of LTP, may represent sleep deprivation-induced impairment of the underlying neurochemical mechanisms normally responsible for memory acquisition.
TL;DR: Shortly after initiation of mirtazapine treatment in four patients with parkinsonism, the authors observed the appearance of REM sleep behavior disorder (RBD), which was accompanied by hallucinations and confusion in two patients with severe motor symptoms.
Abstract: Shortly after initiation of mirtazapine (a noradrenergic and serotonergic antidepressant) treatment in four patients with parkinsonism, the authors observed the appearance of REM sleep behavior disorder (RBD). In the two patients with severe motor symptoms, RBD was accompanied by hallucinations and confusion. These disturbances resolved with drug discontinuation, and remained resolved by 12- to 24-month follow-up, suggesting that RBD can be triggered by a drug lacking anticholinergic activity.
TL;DR: The extent of hypocretin neuronal loss together with an accompanying loss of cells in the lateral hypothalamus may explain the differences in severity of symptoms seen in human narcolepsy.
TL;DR: Steiger A (Max Planck Institute of Psychiatry, Munich, Germany).
Abstract: .
Steiger A (Max Planck Institute of Psychiatry, Munich, Germany). Sleep and endocrinology (Minisymposium). J Intern Med 2003; 254: 13–22.
A bidirectional interaction between sleep electroencephalogram and endocrine activity is well established in various species including humans. Various hormones (peptides and steroids) participate in sleep regulation. A keyrole was shown for the reciprocal interaction between sleep-promoting growth hormone-releasing hormone (GHRH) and sleep-impairing corticotropin-releasing hormone (CRH). Changes in the GHRH : CRH ratio result in changes of sleep-endocrine activity. It is thought that the change of this ratio in favour of CRH contributes to aberrances of sleep during ageing and depression (shallow sleep, blunted GH and elevated cortisol). Besides GHRH, ghrelin and galanin enhance slow wave sleep. Somatostatin is another sleep-impairing factor. Neuropeptide Y acts as a CRH antagonist and induces sleep onset. There are hints that CRH promotes rapid eye movement sleep (REMS). In animals prolactin enhances REMS. In humans vasocactive intestinal polypeptide (VIP) appears to play a role in the temporal organization of sleep as, after VIP, the non-REMS–REMS cycle decelerated. Cortisol appears to enhance REMS. Finally, gonadal hormones participate in sleep regulation. Oestrogen replacement therapy and CRH-1 receptor antagonism in depression are beneficial clinical applications of sleep-endocrine research.
TL;DR: It is demonstrated that stimuli associated with an aversive event can alter sleep and suppress REM in much the same way as exposure to the event itself.
Abstract: Fear conditioning is thought to model anticipatory anxiety. Inbred mouse strains exhibit different levels of reactivity to aversive environmental stimuli, which may reflect anxiety. We examined the effects of fear conditioning on sleep in mouse strains that differ on behavioral measures of anxiety. Mice (BALB/cJ [C], C57BL/6J [B6], CB6F1/J [CB6], n = 7-10 per strain) were implanted with transmitters for recording sleep by telemetry. Baseline sleep was recorded, and the mice were trained to associate a cue (tone) with footshock (15 cue-shock pairings on 4 consecutive days). Sleep was recorded after shock training and again 4 to 5 days later after presentation of the cue alone. Shock training produced a relatively selective suppression of rapid eye movement sleep (REM) that was greater in the C strain compared to the B6 and CB6 mice. Post-training exposure to the cue alone suppressed REM in all strains. The C strain exhibited a relatively greater immediate suppression of REM, and the CB6 hybrid mice showed the greatest overall suppression of REM. These data demonstrate that stimuli associated with an aversive event can alter sleep and suppress REM in much the same way as exposure to the event itself. Fear conditioning may provide a model for examining genetic and neural mechanisms underlying the influence of anxiety on sleep.
TL;DR: The findings suggest that lysozomal storage abnormalities in Niemann-Pick disease patients may impact the hypothalamus and, more specifically, hypocretin-containing cells, which might be partially responsible for sleep abnormalities and cataplexy in patients with NiemANN- pick disease.
Abstract: Design and patients Subjects with Niemann-Pick disease, type C have been reported to display narcolepsylike symptoms, including cataplexy. In this study, 5 patients with juvenile Niemann-Pick disease were evaluted for sleep abnormalities using nocturnal polysomnography, clinical evaluation, and the Multiple Sleep Latency Test. HLA typing and cerebrospinal fluid hypocretin levels were also evaluated in 4 patients. Niemann-Pick disease diagnosis was confirmed in all cases biochemically and by the presence of foam cells in the bone marrow. Results Deterioration of intellectual function; the presence of pyramidal, dystonic and cerebellar features; and splenomegaly were observed in all cases. Cataplexy was reported in 1 patient. Nocturnal polysomnography revealed disrupted sleep in all patients. Total sleep time, sleep efficiency, rapid eye movement sleep, and delta sleep amounts were decreased when compared to age-matched controls. Altered sleep patterns included sudden increases in muscle tone during delta sleep, electroencephalographic sigma activity connected with rapid eye movements and muscle atonia, atypical K-complexes and spindle activity, and the presence of alpha-delta sleep. All Niemann-Pick disease cases exhibited fragmentary myoclonus. Shortened mean sleep latencies were observed in 3 patients during the Multiple Sleep Latency Test, but sleep-onset rapid eye movement periods were observed only in the case with cataplexy. This patient was HLA DQB1*0602 positive, while the other subjects were HLA negative. Cerebrospinal fluid hypocretin-1 levels were reduced in 2 patients (1 with cataplexy) while in the 2 other patients, the levels were at the lower range of the normal values. Hypocretin levels in the Niemann-Pick disease group (204.8 +/- 39.3 pg/mL) were significantly reduced when compared to controls (265.8 +/- 48.8 pg/mL). Conclusions The findings suggest that lysozomal storage abnormalities in Niemann-Pick disease patients may impact the hypothalamus and, more specifically, hypocretin-containing cells. These changes might be partially responsible for sleep abnormalities and cataplexy in patients with Niemann-Pick disease.
TL;DR: It is concluded that sleep may inhibit sympathetic and arousal response to hypoglycemia and continuous measurement of glucose levels during sleep may add important features in the treatment of children with DM.
TL;DR: The data suggest that NE is wake promoting during the period of time between a mildly stressful event or a low dose of amphetamine and sleep onset, which is similar to current models of the involvement of NE in the regulation of these 2 states.
Abstract: Study objectives Mice lacking the ability to make norepinephrine (NE) were used to investigate how NE may be involved in regulating sleep and sleep latency under normal conditions and as a response to mild stress or varying doses of amphetamine. Design Sleep latency was measured in NE-deficient and control mice after behavioral interventions and after 3 low doses of amphetamine. Sleep-wake states were measured using electroencephalography and electromyography for the first 6 hours after lights-on under baseline conditions and after an injection of saline. The first 6 hours after lights-off were also measured under baseline conditions. Setting N/A. Patients or participants Mice lacking the dopamine beta-hydroxylase gene (Dbh -/-), which is required for NE synthesis, and their littermate controls were used. Interventions N/A. Measurements and results As measured behaviorally and with electroencephalography, sleep latency was significantly shorter in the NE-deficient mice after cage changing, saline injection, and 3 different doses of amphetamine. There were no differences between the 2 groups in any sleep parameters under baseline conditions or after saline injection during the day or night. Conclusions The NE-deficient mice showed a significantly shorter latency to sleep under many different conditions, measured both behaviorally and with electroencephalography. These data suggest that NE is wake promoting during the period of time between a mildly stressful event or a low dose of amphetamine and sleep onset. The NE-deficient mice did not show deficits in wake or increases in rapid eye movement sleep, as predicted from current models of the involvement of NE in the regulation of these 2 states.
TL;DR: The association between awake levels of the anti-inflammatory/TH2 cytokine IL-10 and subsequent amounts of delta sleep support the notion of a bidirectional interplay between cytokines and sleep in humans.
Abstract: OBJECTIVE Alcoholics who are at risk for infectious disease show profound disturbances of sleep along with decrements of cellular immunity. This study examined the relationships between sleep, nocturnal expression of immunoregulatory cytokines, and natural killer (NK) cell activity in alcoholic patients as compared with control subjects. METHODS Alcoholic patients (N = 24) and comparison control subjects (N = 23) underwent all-night polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 hours. Stimulated expression of T(H)1 (interferon gamma, IFN-gamma), anti-inflammatory/T(H)2 (interleukin 10, IL-10), and proinflammatory cytokines (IL-6) was measured along with NK cell activity across the night. RESULTS Alcoholic patients showed lower levels of IL-6 production, suppression of the IL-6/IL-10 ratio, and a reduction of NK cell activity, coupled with losses of delta sleep and increases of rapid eye movement sleep, as compared with control subjects. In addition, alcoholics showed a persistent low ratio of IFN-gamma/IL-10 and reduced levels of NK cell activity, whereas controls had increases of these two immune measures across the night. IL-6 also differentially changed in the two groups; alcoholics showed increases and controls had decreases of IL-6 from 03:00 hours to 06:30 hours. At 06:30 hours, rapid eye movement sleep predicted increases of IL-6 and decreases of NK cell activity independent of the relative contribution of age and chronic alcohol consumption. At 23:00 hours before sleep onset, levels of IL-10 predicted subsequent amounts of delta sleep. CONCLUSIONS These data further implicate sleep in the regulation of immune function and suggest that disordered sleep contributes to immune alterations in patients with chronic alcoholism. Moreover, the association between awake levels of the anti-inflammatory/T(H)2 cytokine IL-10 and subsequent amounts of delta sleep support the notion of a bidirectional interplay between cytokines and sleep in humans.
TL;DR: Despite the high prevalence of reported sleep disturbance in children with ADHD, stimulant medication appears to have minimal effects on subjective and objective sleep characteristics inChildren with reported ADHD.
TL;DR: The cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications are examined.
Abstract: Sleep is a natural periodic suspension of consciousness during which processes of rest and restoration occur. The cognitive, reparative and regenerative accompaniments of sleep appear to be essential for maintenance of health and homeostasis. This brief overview will examine the cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications. In the past, sleep was believed to be a passive state. The tableau of sleep as it unfolds is anything but a passive process. The brain's activity is as complex as wakefulness, never "resting" during sleep. Following the demise of the 'passive theory of sleep' (the reticular activating system is fatigued during the waking day and hence becomes inactive), there arose the 'active theory of sleep' (sleep is due to an active general inhibition of the brain) (1). Hess demonstrated the active nature of sleep in cats, inducing "physiological sleep" with electrical stimulation of the diencephalon (2). Classical experiments of transection of the cat brainstem (3) at midpontine level inhibited sleep completely, implying that centers below this level were involved in the induction of sleep (1, 4). For the first time, measurement of sleep depth without awakening the sleeper using the electroencephalogram (EEG) was demonstrated in animals by Caton and in humans, by Berger (1). This was soon followed by discovery of the rapid eye movement sleep periods (REM) by Aserinski and Kleitman (5), demonstration of periodical sleep cycles and their association with REM sleep (6, 7). Multiple studies and steady discoveries (4) made polysomnography, with its ability to perform simultaneous whole night recordings of EEG, electromyogram (EMG), and electrooculogram (EOC), a major diagnostic tool in study of sleep disorders. This facility has been of further critical importance in allowing evaluation of the interaction between sleep and changes in hemodynamics and autonomic cardiovascular control. Consequently the effects of sleep could be objectively differentiated from the effects of rest and recumbency. Furthermore, the specific effects of sleep onset and termination, and the effects of different sleep stages, could be assessed. Technological advances, with consequently enhanced and relatively non-invasive approaches to cardiovascular regulation, have greatly broadened our understanding of the effects of sleep stage on cardiovascular function. Continuous monitoring of simultaneous measures of polysomnographic and cardiovascular variables enables characterization of the effects of dynamic changes and rapid transitions in sleep stage, such as arousals. The capacity for measuring acute and immediate changes in autonomic, EEG and hemodynamic responses to sleep and arousal on a continuous basis has played an important role in enabling us to understand the interplay between changes in EEG and changes in the more peripheral measurements of neural and circulatory variables, such as sympathetic nerve traffic, heart rate (HR) and blood pressure (BP). Measurements of heart rate variability (HRV) (8-10), baroreflex sensitivity (BRS) (11-16), and intraneural measurement of sympathetic nerve traffic to muscle (MSNA) (17-22) and skin (SSNA) (23-24) have further advanced our understanding of mechanisms linking sleep and cardiovascular physiology.
TL;DR: Dementia patients should be evaluated for common primary sleep disorders that may contribute to nighttime behavioral disturbances and impact treatment decisions.
Abstract: Changes in sleep architecture and circadian rhythms, including increased sleep latency and nighttime awakenings, decreased slow-wave sleep, rapid eye movement sleep, and total sleep time, and increased daytime napping are widespread in people with dementia. In addition, cyclic agitation episodes (“sundowning”), nightmares or hallucinations, sleep attacks, and nocturnal behavioral outbursts are associated with specific dementia syndromes. Sleep hygiene recommendations, particularly those aimed at reducing daytime sleep and improving the sleep environment and routine, can offset the circadian disturbances of some dementia patients. However, they can be burdensome for caregivers to implement, and must be targeted to the specific patterns of sleep disturbances patients are experiencing. Pharmacologic treatments may be useful for symptomatic treatment of insomnia and nighttime behavioral disturbances in dementia patients, but there have been few controlled trials demonstrating their efficacy or long-term safety. Clonazepam is highly effective for treating the nighttime behaviors associated with rapid eye movement behavior disorder. For most dementia patients, however, the side effect risks of prolonged use of sedating medications must be weighed against the potential benefits. Dementia patients should be evaluated for common primary sleep disorders that may contribute to nighttime behavioral disturbances and impact treatment decisions. Continuous positive airway pressure, the gold standard for treating obstructive sleep apnea, can be tolerated by mild to moderately demented individuals with support from supervising caregivers. Increased daily light exposure and physical activity may help normalize circadian restactivity rhythms in some dementia patients, although the frequency and dose needed to maintain treatment effects is currently not known.
TL;DR: In this group of young adult males (mean age 19 years), there was a better overall adaptation to the early morning sleep, perhaps related to the general tendency in most adolescents to present some phase-delay during late teen-aged years.
TL;DR: The objective of this study was to characterize the sleep problems seen in children with neoplasms of the CNS through a comprehensive clinical and objective sleep evaluation, and found that sleep is a specific, albeit complex, neurologic process that is controlled by specific brain regions.
Abstract: Objective. Sleep is a complex neurologic process that is generated by and primarily benefits the brain. Sleep can be disrupted by a wide range of brain injuries, many of which may occur in children with neoplasms of the central nervous system (CNS). The specific sleep problems that have been associated with brain injuries include sleepiness, apnea, insomnia, and loss of circadian rhythmicity. The objective of this study was to characterize the sleep problems seen in children with neoplasms of the CNS through a comprehensive clinical and objective sleep evaluation. Methods. A retrospective case series review was conducted of all children with neoplasms of the CNS referred to the sleep clinic for a clinical evaluation between 1994 and 2002. The sleep evaluation of the 14 children in this report included a sleep history, a sleep log, and a polysomnogram. In the 12 children with complaints of daytime sleepiness and/or fatigue, a multiple sleep latency test was performed the day after the polysomnogram. Three children also had a 2-week actigraphic study. Results. The most common sleep complaint in this group of children was excessive daytime sleepiness (EDS), present in 9 of the 14 children. In these children, the sleepiness was manifest by 1 or more of the following symptoms: 1) an increase in total sleep time per 24 hours; 2) the resumption of daytime naps that had been previously discontinued at a younger age; 3) an inability to awaken in the morning to begin the days activities; or 4) the inability to remain awake during activities of daily living, such as school. Of the 9 children with daytime sleepiness, 8 had brain tumors requiring neurosurgical procedures at the time of their diagnosis, 6 of whom required ventricular shunting. The children with the most severe sleepiness had evidence of hypothalamic/pituitary injury with deficiencies in both anterior and posterior pituitary hormones. Five of the children with EDS had polysomnographic evidence of symptomatic narcolepsy with rapid eye movement sleep present on 2 or more of the daytime naps. The symptoms of EDS were effectively controlled with modest doses of daytime stimulant medication and/or scheduled naps. Central apnea leading to respiratory insufficiency and requiring mechanical ventilation to correct was present in 2 children with tumors involving the medulla. Although snoring with possible obstructive sleep apnea was the reason for referral to the sleep clinic in 5 children, none of the children in this series had polysomnographic evidence of significant obstructive sleep apnea. The other sleep problems seen in these children were hypoxia in 2 children, fatigue in 3 children, and seizures during sleep in 1 child. The interval between tumor diagnosis and sleep evaluation varied from 0 months to 9 years (mean: 42 months). The treatment of the sleep problems of this group of children took many forms, including stimulants, scheduled naps, mechanical ventilation, supplemental oxygen, and anticonvulsants. Conclusions. Brain injuries, which invariably are present in children with neoplasms of the CNS, may result in a variety of diagnosable and treatable sleep disorders. The sleep symptoms did not appear to be directly related to the specific therapy the child received, nor the presence of residual tumor. Rather, the primary determinant of the sleep symptoms was the area of the brain that was damaged, regardless of how the damage occurred. Children who sustained damage to the hypothalamic/pituitary region developed EDS regardless of whether the damage was the result of the tumor, surgery, hydrocephalus, or radiation to the whole brain or localized to the suprasellar area. The only children who developed respiratory insufficiency had an injury to the medulla. This observation is consistent with the view that sleep is a specific, albeit complex, neurologic process that is controlled by specific brain regions. EDS and respiratory insufficiency were the most commonly diagnosed severe sleep disorders in these children. The sleep problems of children with brain tumors may develop before, but more often soon after, their tumor diagnosis and treatment. However, the sleep symptoms may not be appreciated by medical providers until years after their onset, which may delay the beginning of effective interventions.
TL;DR: It is demonstrated that the OX(1)R also has a role in orexinergic sleep modulation and reduced the amount and increased the latency to onset of PS.