Showing papers on "Rapid eye movement sleep published in 2009"
TL;DR: A rapid eye movement (REM) sleep hypothesis of emotional-memory processing is proposed, the implications of which may provide brain-based insights into the association between sleep abnormalities and the initiation and maintenance of mood disturbances.
Abstract: Cognitive neuroscience continues to build meaningful connections between affective behavior and human brain function. Within the biological sciences, a similar renaissance has taken place, focusing on the role of sleep in various neurocognitive processes and, most recently, on the interaction between sleep and emotional regulation. This review surveys an array of diverse findings across basic and clinical research domains, resulting in a convergent view of sleep-dependent emotional brain processing. On the basis of the unique neurobiology of sleep, the authors outline a model describing the overnight modulation of affective neural systems and the (re)processing of recent emotional experiences, both of which appear to redress the appropriate next-day reactivity of limbic and associated autonomic networks. Furthermore, a rapid eye movement (REM) sleep hypothesis of emotional-memory processing is proposed, the implications of which may provide brain-based insights into the association between sleep abnormalities and the initiation and maintenance of mood disturbances.
817 citations
TL;DR: It is hypothesize that access to sleep-dependent consolidation requires memories to be encoded under control of prefrontal-hippocampal circuitry, with the same circuitry controlling subsequent consolidation during sleep.
467 citations
TL;DR: Autonomic dysfunction and colour vision appear to be more linked to rapid eye movement sleep behaviour disorder status than Parkinson's disease, suggesting a unique pathophysiology of these abnormalities.
Abstract: Idiopathic rapid eye movement sleep behaviour disorder is an important risk factor in the development of Parkinson's disease. Numerous potential predictive markers of Parkinson's disease may present before motor symptoms emerge, but testing of these markers in rapid eye movement sleep behaviour disorder has been performed only in small studies. There has been no comparison of markers between patients with idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease, and between men and women. We evaluated an array of potential Parkinson's disease predictive markers in 159 patients; including 68 with idiopathic rapid eye movement sleep behaviour disorder, 36 controls, 34 Parkinson's patients with rapid eye movement sleep behaviour disorder and 21 Parkinson's patients without rapid eye movement sleep behaviour disorder. Compared with controls, patients with idiopathic rapid eye movement sleep behaviour disorder demonstrated substantial olfactory loss (P < 0.001). Olfaction was more impaired in Parkinson's disease than idiopathic rapid eye movement sleep behaviour disorder and did not differ between Parkinson's patients with, or without, rapid eye movement sleep behaviour disorder. Numerous measures of motor function including the Unified Parkinson Disease Rating Scale alternate tap, Purdue Peg Board and Timed 'Up and Go' were impaired in idiopathic rapid eye movement sleep behaviour disorder compared with controls (P < 0.01). All of these motor measures were worse with Parkinson's disease than with idiopathic rapid eye movement sleep behaviour disorder, regardless of rapid eye movement sleep behaviour disorder status. Autonomic symptoms and systolic blood pressure drop were impaired in patients with idiopathic rapid eye movement sleep behaviour disorder compared with controls (P = 0.003). Orthostatic abnormalities in Parkinson's disease were found in the group with rapid eye movement sleep behaviour disorder (P < 0.001). However, Parkinson's patients without rapid eye movement sleep behaviour disorder were not different than controls and had less impairment than those with idiopathic rapid eye movement sleep behaviour disorder (P = 0.004) and Parkinson's patients with rapid eye movement sleep behaviour disorder (P < 0.001). Colour vision was impaired in idiopathic rapid eye movement sleep behaviour disorder compared with controls (P < 0.001). However, only Parkinson's patients with rapid eye movement sleep behaviour disorder had abnormalities significantly different than controls (P < 0.001), and there were significant differences between Parkinson's patients with or without rapid eye movement sleep behaviour disorder (P < 0.04). Idiopathic rapid eye movement sleep behaviour disorder patients had slightly increased harm avoidance scores on personality testing (P = 0.04). Other than slightly better performances among women in the Purdue Peg Board, there was no difference in any measure between men and women, suggesting similar pathogenic processes underlying rapid eye movement sleep behaviour disorder. Patients with idiopathic rapid eye movement sleep behaviour disorder demonstrate abnormalities in numerous potential markers of neurodegenerative disease--these markers are heterogeneous, generally correlate with each other and occur equally in men and women. Although these abnormalities are usually intermediate between control values and Parkinson's patients, autonomic dysfunction and colour vision appear to be more linked to rapid eye movement sleep behaviour disorder status than Parkinson's disease, suggesting a unique pathophysiology of these abnormalities.
236 citations
TL;DR: Results indicate that blockade of OX2R is sufficient to initiate and prolong sleep, consistent with the hypothesis of a deactivation of the histaminergic system.
Abstract: Orexins are peptides produced by lateral hypothalamic neurons that exert a prominent role in the maintenance of wakefulness by activating orexin-1 (OX1R) and orexin-2 (OX2R) receptor located in wake-active structures. Pharmacological blockade of both receptors by the dual OX1/2R antagonist (2R)-2-[(1S)-6,7-dimethoxy-1-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydroisoquinolin-2(1H)-yl]-N-methyl-2-phenylethanamide (almorexant) has been shown to promote sleep in animals and humans during their active period. However, the selective distribution of OX1R and OX2R in distinct neuronal circuits may result in a differential impact of these receptors in sleep-wake modulation. The respective role of OX1R and OX2R on sleep in correlation with monoamine release was evaluated in rats treated with selective antagonists alone or in combination. When administered in either phase of the light/dark cycle, the OX2R antagonist 1-(2,4-dibromophenyl)-3-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]urea (JNJ-10397049) decreased the latency for persistent sleep and increased nonrapid eye movement and rapid eye movement sleep time. Almorexant produced less hypnotic activity, whereas the OX1R antagonist 1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea (SB-408124) had no effect. Microdialysis studies showed that either OX2R or OX1/2R antagonism decreased extracellular histamine concentration in the lateral hypothalamus, whereas both OX1R and OX1/2R antagonists increased dopamine release in the prefrontal cortex. Finally, coadministration of the OX1R with the OX2R antagonist greatly attenuated the sleep-promoting effects of the OX2R antagonist. These results indicate that blockade of OX2R is sufficient to initiate and prolong sleep, consistent with the hypothesis of a deactivation of the histaminergic system. In addition, it is suggested that simultaneous inhibition of OX1R attenuates the sleep-promoting effects mediated by selective OX2R blockade, possibly correlated with dopaminergic neurotransmission.
219 citations
TL;DR: The results suggest that the Hcrt system promotes wakefulness throughout the light/dark period by activating multiple downstream targets, which themselves are inhibited with increased sleep pressure.
Abstract: The hypocretins (Hcrts) (also called orexins) are two neuropeptides expressed in the lateral hypothalamus that play a crucial role in the stability of wakefulness. Previously, our laboratory demonstrated that in vivo photostimulation of Hcrt neurons genetically targeted with ChR2, a light-activated cation channel, was sufficient to increase the probability of an awakening event during both slow-wave sleep and rapid eye movement sleep. In the current study, we ask whether Hcrt-mediated sleep-to-wake transitions are affected by light/dark period and sleep pressure. We found that stimulation of Hcrt neurons increased the probability of an awakening event throughout the entire light/dark period but that this effect was diminished with sleep pressure induced by 2 or 4 h of sleep deprivation. Interestingly, photostimulation of Hcrt neurons was still sufficient to increase activity assessed by c-Fos expression in Hcrt neurons after sleep deprivation, although this stimulation did not cause an increase in transitions to wakefulness. In addition, we found that photostimulation of Hcrt neurons increases neural activity assessed by c-Fos expression in the downstream arousal-promoting locus ceruleus and tuberomammilary nucleus but not after 2 h of sleep deprivation. Finally, stimulation of Hcrt neurons was still sufficient to increase the probability of an awakening event in histidine decarboxylase-deficient knock-out animals. Collectively, these results suggest that the Hcrt system promotes wakefulness throughout the light/dark period by activating multiple downstream targets, which themselves are inhibited with increased sleep pressure.
213 citations
TL;DR: A better understanding of the mechanisms and factors that contribute to sleep deprivation and delirium can guide the development of new methods and models for prevention and treatment of these problems and consequently improve patient outcomes.
Abstract: Sleep deprivation and delirium are conditions commonly encountered in intensive care unit patients. Sleep in these patients is characterized by sleep fragmentation, an increase in light sleep, and a decrease of both slow wave sleep and rapid eye movement sleep. The most common types of delirium in this population are hypoactive and mixed-type. Knowledge about the mechanisms of sleep and delirium has evolved over time, but these phenomena are not yet well understood. What is known, however, is that different areas in the brainstem transmit information to the thalamus and cortex necessary for sleep-wake regulation. Delirium is related to an imbalance in the synthesis, release, and inactivation of some neurotransmitters, particularly acetylcholine and dopamine. The relationship between sleep deprivation and delirium has been studied for many years and has been viewed as reciprocal. The link between them may be ascribed to shared mechanisms. An imbalance in neurotransmitters as well as alteration of melatonin production may contribute to the pathogenesis of both phenomena. A better understanding of the mechanisms and factors that contribute to sleep deprivation and delirium can guide the development of new methods and models for prevention and treatment of these problems and consequently improve patient outcomes.
211 citations
TL;DR: The objective of this article is to review frequently encountered medical conditions and examine their impact on sleep, and to review frequent sleep-related problems associated with these common medical conditions.
197 citations
TL;DR: Long-term continuous electroencephalographic monitoring of vigilance states in unrestrained rhesus monkeys using an implanted miniaturized telemetry device highlights the suitability of the MPTP model of PD as a tool to model the sleep/wake disturbances of the human disease.
128 citations
TL;DR: It is proposed that the convergent evolution of homeostatically regulated SWS in mammals and birds was directly linked to the convergence evolution of large, heavily interconnected brains capable of performing complex cognitive processes in each group.
117 citations
TL;DR: When RUA and blood gas disturbances are minimized by CPAP, genioglossal activity is reduced in a stepwise manner from stable NREM, to tonic REM to phasic REM sleep to a similar extent in OSA and healthy individuals of both genders.
116 citations
TL;DR: This represents the first demonstration that DBS can selectively modulate human sleep, and it supports an important role for the pedunculopontine nucleus region in modulating human REM sleep.
Abstract: Animal studies suggest that rapid eye movement (REM) sleep is governed by the interaction of REM-promoting and REM-inhibiting nuclei in the pontomesencephalic tegmentum. The pedunculopontine nucleus is proposed to be REM promoting. Using polysomnography, we studied sleep in five parkinsonian patients undergoing unilateral pedunculopontine nucleus deep brain stimulation (DBS). We demonstrated a near doubling of nocturnal REM sleep between the DBS "off" and DBS "on" states, without significant changes in other sleep states. This represents the first demonstration that DBS can selectively modulate human sleep, and it supports an important role for the pedunculopontine nucleus region in modulating human REM sleep. Ann Neurol 2009;66:110-114.
TL;DR: A restricted region within the ventromedial medulla, termed here the “supraolivary medulla” (SOM), is revealed, which contains glutamatergic neurons that project to the spinal ventral horn that comprise key elements of the medullary circuitry mediating REM atonia.
Abstract: Considerable data support a role for glycinergic ventromedial medulla neurons in the mediation of the postsynaptic inhibition of spinal motoneurons necessary for the motor atonia of rapid-eye movement (REM) sleep in cats. These data are, however, difficult to reconcile with the fact that large lesions of the rostral ventral medulla do not result in loss of REM atonia in rats. In the present study, we sought to clarify which medullary networks in rodents are responsible for REM motor atonia by retrogradely tracing inputs to the spinal ventral horn from the medulla, ablating these medullary sources to determine their effects on REM atonia and using transgenic mice to identify the neurotransmitter(s) involved. Our results reveal a restricted region within the ventromedial medulla, termed here the "supraolivary medulla" (SOM), which contains glutamatergic neurons that project to the spinal ventral horn. Cell-body specific lesions of the SOM resulted in an intermittent loss of muscle atonia, taking the form of exaggerated phasic muscle twitches, during REM sleep. A concomitant reduction in REM sleep time was observed in the SOM-lesioned animals. We next used mice with lox-P modified alleles of either the glutamate or GABA/glycine vesicular transporters to selectively eliminate glutamate or GABA/glycine neurotransmission from SOM neurons. Loss of SOM glutamate release, but not SOM GABA/glycine release, resulted in exaggerated muscle twitches during REM sleep that were similar to those observed after SOM lesions in rats. These findings, together, demonstrate that SOM glutamatergic neurons comprise key elements of the medullary circuitry mediating REM atonia.
TL;DR: The hypothalamic MCHergic system, via its action in the DR, plays an important role in the generation and/or maintenance of the states of sleep.
TL;DR: Excessive tonic and phasic EMG activity during REM sleep increases over time in subjects with idiopathic RBD, suggesting that there is an underlying progressive pathologic process damaging the brainstem structures that modulate REM sleep.
Abstract: RAPID EYE MOVEMENT (REM) SLEEP BEHAVIOR DISORDER (RBD) IS CHARACTERIZED BY UNPLEASANT DREAMS, DREAM-ENACTING BEHAVIOURS, and increased tonic and phasic electromyographic (EMG) activity during REM sleep. It is thought that excessive EMG activity in RBD reflects dysfunction of the brainstem structures responsible for muscle atonia during REM sleep.1 In animals, experimental lesions in the brainstem produce increased tonic and phasic EMG activity and abnormal behaviors during REM sleep.2–5 In humans, RBD can be idiopathic or associated with neurodegenerative diseases.6 Follow-up of patients with idiopathic RBD shows an increased risk for developing neurodegenerative diseases such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy.7–11 Idiopathic RBD patients with longer follow-up are more likely to be found to have these neurodegenerative diseases,9 suggesting that a progressive pathologic process takes place in these patients. It has never been determined, however, if the excessive EMG activity during REM sleep of patients with idiopathic RBD increases with time, a finding that would likely reflect a progressive impairment of the brainstem structures that regulate REM sleep atonia. We assessed, in this study, whether the amount of excessive tonic and phasic EMG activity during REM sleep increases over time in subjects with idiopathic RBD after several years of clinical follow-up.
TL;DR: A correlation between the emotional intensities of the morning dream and the morning picture ratings supports a possible emotional carry‐over effect and suggests REM sleep may enhance morning reactivity to negative emotional stimuli.
Abstract: Rapid eye movement (REM) sleep and dreaming may be implicated in cross-night adaptation to emotionally negative events. To evaluate the impact of REM sleep deprivation (REMD) and the presence of dream emotions on a possible emotional adaptation (EA) function, 35 healthy subjects randomly assigned to REMD (n = 17; mean age 26.4 +/- 4.3 years) and control (n = 18; mean age 23.7 +/- 4.4 years) groups underwent a partial REMD and control nights in the laboratory, respectively. In the evening preceding and morning following REMD, subjects rated neutral and negative pictures on scales of valence and arousal and EA scores were calculated. Subjects also rated dream emotions using the same scales and a 10-item emotions list. REMD was relatively successful in decreasing REM% on the experimental night, although a mean split procedure was applied to better differentiate subjects high and low in REM%. High and low groups differed - but in a direction contrary to expectations. Subjects high in REMD% showed greater adaptation to negative pictures on arousal ratings than did those low in REMD% (P < 0.05), even after statistically controlling sleep efficiency and awakening times. Subjects above the median on EA(valence) had less intense overall dream negativity (P < 0.005) and dream sadness (P < 0.004) than subjects below the median. A correlation between the emotional intensities of the morning dream and the morning picture ratings supports a possible emotional carry-over effect. REM sleep may enhance morning reactivity to negative emotional stimuli. Further, REM sleep and dreaming may be implicated in different dimensions of cross-night adaptation to negative emotions.
TL;DR: The findings indicate that information processing of olfactory stimuli is present in sleep and that the emotional tone of dreams can be influenced significantly depending upon the hedonic characteristic of the stimulus used.
Abstract: Research has shown that external stimuli presented during sleep can affect dream content, thus reflecting information processing of the sleeping brain. Olfactory stimuli should have a stronger effect on dream emotions because their processing is linked directly to the limbic system. Because selective olfactory stimulation does not increase arousal activity, intense olfactory stimulation is therefore a prime paradigm for studying information processing during sleep. Fifteen healthy, normosmic volunteers were studied by intranasal chemosensory stimulation during rapid eye movement sleep based on air-dilution olfactometry. For olfactory stimulation, hydrogen sulphide (smell of rotten eggs) and phenyl ethyl alcohol (smell of roses) was used and compared with a control condition without stimulation. The olfactory stimuli affected significantly the emotional content of dreams: the positively toned stimulus yielded more positively toned dreams, whereas the negative stimulus was followed by more negatively toned dreams. Direct incorporations, i.e. the dreamer is smelling something, were not found. The findings indicate that information processing of olfactory stimuli is present in sleep and that the emotional tone of dreams can be influenced significantly depending upon the hedonic characteristic of the stimulus used. It would be interesting to conduct learning experiments (associating specific odours with declarative material) to study whether this declarative material is incorporated into subsequent dreams if the corresponding odour cue is presented during sleep. It would also be interesting to study the effect of positively toned olfactory stimuli on nightmares.
TL;DR: REM‐associated activation of these areas, especially non‐visual primary sensory cortices, TRN and claustrum, parallels findings from waking studies on the interactions between multiple sensory data, and their ‘binding’ into a unified percept, suggesting that these mechanisms are also shared in waking and dreaming and that the sharing goes beyond the expected visual scanning mechanisms.
Abstract: We studied the neural correlates of rapid eye movement during sleep (REM) by timing REMs from video recording and using rapid event-related functional MRI. Consistent with the hypothesis that REMs share the brain systems and mechanisms with waking eye movements and are visually-targeted saccades, we found REM-locked activation in the primary visual cortex, thalamic reticular nucleus (TRN), 'visual claustrum', retrosplenial cortex (RSC, only on the right hemisphere), fusiform gyrus, anterior cingulate cortex, and the oculomotor circuit that controls awake saccadic eye movements (and subserves awake visuospatial attention). Unexpectedly, robust activation also occurred in non-visual sensory cortices, motor cortex, language areas, and the ascending reticular activating system, including basal forebrain, the major source of cholinergic input to the entire cortex. REM-associated activation of these areas, especially non-visual primary sensory cortices, TRN and claustrum, parallels findings from waking studies on the interactions between multiple sensory data, and their 'binding' into a unified percept, suggesting that these mechanisms are also shared in waking and dreaming and that the sharing goes beyond the expected visual scanning mechanisms. Surprisingly, REMs were associated with a decrease in signal in specific periventricular subregions, matching the distribution of the serotonergic supraependymal plexus. REMs might serve as a useful task-free probe into major brain systems for functional brain imaging.
TL;DR: It is suggested that word-pair learning relies on stage 2 sleep spindles and requires little SWS, andSleep-dependent motor and declarative memory consolidation is not affected by SWS deprivation.
Abstract: Study Objectives:
The effects of REM sleep and slow wave sleep (SWS) deprivation on sleep-dependent motor and declarative memory consolidation.
TL;DR: REM sleep and NREM sleep seem to share some homeostatic mechanisms in response to sleep deprivation, as indicated mainly by the similar direction and topography of changes in low‐frequency activity.
Abstract: Studies on homeostatic aspects of sleep regulation have been focussed upon non-rapid eye movement (NREM) sleep, and direct comparisons with regional changes in rapid eye movement (REM) sleep are sparse. To this end, evaluation of electroencephalogram (EEG) changes in recovery sleep after extended waking is the classical approach for increasing homeostatic need. Here, we studied a large sample of 40 healthy subjects, considering a full-scalp EEG topography during baseline (BSL) and recovery sleep following 40 h of wakefulness (REC). In NREM sleep, the statistical maps of REC versus BSL differences revealed significant fronto-central increases of power from 0.5 to 11 Hz and decreases from 13 to 15 Hz. In REM sleep, REC versus BSL differences pointed to significant fronto-central increases in the 0.5-7 Hz and decreases in the 8-11 Hz bands. Moreover, the 12-15 Hz band showed a fronto-parietal increase and that at 22-24 Hz exhibited a fronto-central decrease. Hence, the 1-7 Hz range showed significant increases in both NREM sleep and REM sleep, with similar topography. The parallel change of NREM sleep and REM sleep EEG power is related, as confirmed by a correlational analysis, indicating that the increase in frequency of 2-7 Hz possibly subtends a state-aspecific homeostatic response. On the contrary, sleep deprivation has opposite effects on alpha and sigma activity in both states. In particular, this analysis points to the presence of state-specific homeostatic mechanisms for NREM sleep, limited to <2 Hz frequencies. In conclusion, REM sleep and NREM sleep seem to share some homeostatic mechanisms in response to sleep deprivation, as indicated mainly by the similar direction and topography of changes in low-frequency activity.
TL;DR: An oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus is demonstrated, strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia.
Abstract: Depth recordings in patients with Parkinson's disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of approximately 70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at approximately 70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep-wake cycle, being suppressed during slow wave sleep and re-emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle-eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at approximately 70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at approximately 70 Hz may be involved in movement and arousal.
TL;DR: Results indicate that the orexin neurons are necessary for the circadian suppression of REM sleep and suggest that other signaling molecules such as dynorphin or glutamate may act in concert with orexins to suppress REM sleep during the active period.
Abstract: MANY RESEARCHERS HAVE HYPOTHESIZED THAT THE POORLY CONSOLIDATED WAKE AND INAPPROPRIATELY TIMED RAPID EYE MOVEMENT (REM) SLEEP of narcolepsy could be caused by disruption of the circadian rhythms of sleep and wakefulness.1–4 The suprachiasmatic nucleus (SCN) is essential for the timing and consolidation of sleep and wakefulness;5 and squirrel monkeys with SCN lesions lose the circadian rhythms of sleep and wakefulness and are unable to produce long bouts of wakefulness.6 Similarly, people with narcolepsy have difficulty maintaining wakefulness, and their naps often include bouts of REM sleep, regardless of the time of day.1 Most likely, this is not caused by a primary defect in the generation of circadian rhythms because the daily rhythms of body temperature and cortisol are essentially normal.7 Instead, people with narcolepsy may have a specific defect in the circadian control of sleep and wakefulness.
Considerable basic research supports this hypothesis. Narcolepsy with cataplexy is caused by a loss of the orexin/hypocretin-producing neurons.8–10 Since the orexin neurons receive both direct and indirect signals from the SCN and send projections to many state-regulatory brain regions, they are anatomically well positioned to mediate the circadian timing of sleep and wakefulness.11–17 Extracellular levels of orexin vary in a circadian pattern, with high levels during the waking period, and lesions of the SCN abolish this rhythm.18–20 Furthermore, nonspecific lesions of the orexin field or of the pathways between the SCN and the orexin neurons disrupt the timing of sleep/wake behavior.12,13,21 We therefore hypothesized that the orexin neurons are an essential relay for the circadian signals that time and consolidate sleep and wake.
To determine whether the orexin neurons are necessary for the circadian control of sleep and wakefulness, we examined free-running circadian rhythms in 2 different strains of orexin deficient mice: orexin/ataxin-3 (Atx) mice with an acquired, selective loss of the orexin/hypocretin neurons and orexin peptide knockout (KO) mice.22,23
TL;DR: Many parasomnias can be recognized by history alone, but some require nocturnal polysomnography for appropriate diagnosis and management and a scheme to distinguish non-rapid eye movement sleep parasomal seizures is provided.
TL;DR: The ability of IL‐6 to enhance sleep‐associated emotional memory consolidation highlights an example of a functional interaction between the central nervous and immune system.
Abstract: The cytokine IL-6 has been considered to exert neuromodulating influences on the brain, with promoting influences on sleep. Sleep enhances the consolidation of memories, and, in particular, late nocturnal sleep also represents a period of enhanced IL-6 signaling, due to a distinctly enhanced availability of soluble IL-6 receptors during this period, enabling trans-signaling of IL-6 to neurons. Thus, a contribution of IL-6 to sleep-dependent memory consolidation is hypothesized. To test this hypothesis, we compared effects of intranasally administered IL-6 (vs. placebo) on sleep-dependent consolidation of declarative (neutral and emotional texts, 2-dimensional object location) and procedural (finger sequence tapping) memories in 17 healthy young men. IL-6 distinctly improved the sleep-related consolidation of emotional text material (P<0.03), which benefits mostly from sleep in the second night-half, in which rapid eye movement sleep (REM) dominates the non-REM-REM sleep cycle. During this second night-half, the amount of electroencephalogram slow-wave activity (0.5-4 Hz) distinctly increased after IL-6 (P<0.01). Other types of memory were not affected. The ability of IL-6 to enhance sleep-associated emotional memory consolidation highlights an example of a functional interaction between the central nervous and immune system.
TL;DR: It is suggested that methylphenidate reduces sleep quantity but does not alter sleep architecture in children diagnosed with ADHD, suggesting an adequate amount of sleep is integral to good daytime functioning, thus the sleep side effects of methylphenidates may affect adversely the daytime symptoms the drug is targeted to control.
Abstract: In the present study, we assessed the effects of regular use of methylphenidate medication in children diagnosed with attention deficit hyperactivity disorder (ADHD) on sleep timing, duration and sleep architecture Twenty-seven children aged 6-12 years meeting diagnostic criteria for Diagnostic and Statistical Manual version IV ADHD and 27 control children matched for age (+/-3 months) and gender Two nights of standard polysomnographic (PSG) recordings were conducted ADHD children were allocated randomly to an on- or 48 h off-methylphenidate protocol for first or second recordings Control children's recordings were matched for night, but no medication was used Mixed modelling was employed in the analyses so that the full data set was used to determine the degree of medication effects Methylphenidate in ADHD children prolonged sleep onset by an average of 29 min [confidence interval (CI) 116, 467], reduced sleep efficiency by 65% (CI 26, 103) and shortened sleep by 12 h (CI 065, 19) Arousal indices were preserved Relative amounts of stages 1, 2 and slow wave sleep were unchanged by medication Rapid eye movement sleep was reduced (-24%) on the medication night, an effect that became non-significant when control data were incorporated in the analyses PSG data from ADHD children off-medication were similar to control data Our findings suggest that methylphenidate reduces sleep quantity but does not alter sleep architecture in children diagnosed with ADHD An adequate amount of sleep is integral to good daytime functioning, thus the sleep side effects of methylphenidate may affect adversely the daytime symptoms the drug is targeted to control
TL;DR: There was a significant interaction whereby on the happy mood induction night the bipolar group exhibited significantly longer SOL than did the control group, while there was no difference on the baseline nights.
Abstract: The present study investigates whether interepisode mood regulation impairment contributes to disturbances in sleep onset latency (SOL) and rapid eye movement (REM) sleep. Individuals with interepisode bipolar disorder (n = 28) and healthy controls (n = 28) slept in the laboratory for 2 baseline nights, a happy mood induction night, and a sad mood induction night. There was a significant interaction whereby on the happy mood induction night the bipolar group exhibited significantly longer SOL than did the control group, while there was no difference on the baseline nights. In addition, control participants exhibited shorter SOL on the happy mood induction night compared to the baseline nights, a finding that was not observed in the bipolar group. On the sad mood induction night, participants in both groups had shorter SOL and increased REM density when compared to the baseline nights. Bipolar participants exhibited heightened REM density compared to control participants on both nights. These results raise the possibility that regulation of positive stimuli may be a contributor to difficulties with SOL, while hyperactivity may be characteristic of REM sleep.
TL;DR: Evidence for the possible utility of GABA(B) receptor agonists for the treatment of subjective and objective sleep abnormalities related to schizophrenia and their effects on sleep architecture, cognition and negative symptoms in patients with schizophrenia is presented.
Abstract: Evidence for an intrinsic relationship between sleep, cognition and the symptomatic manifestations of schizophrenia is accumulating. This review presents evidence for the possible utility of GABA(B) receptor agonists for the treatment of subjective and objective sleep abnormalities related to schizophrenia. At the phenotypic level, sleep disturbance occurs in 16-30% of patients with schizophrenia and is related to reduced quality of life and poor coping skills. On the neurophysiological level, studies suggest that sleep deficits reflect a core component of schizophrenia. Specifically, slow-wave sleep deficits, which are inversely correlated with cognition scores, are seen. Moreover, sleep plays an increasingly well documented role in memory consolidation in schizophrenia. Correlations of slow-wave sleep deficits with impaired reaction time and declarative memory have also been reported. Thus, both behavioural insomnia and sleep architecture are critical therapeutic targets in patients with schizophrenia. However, long-term treatment with antipsychotics often results in residual sleep dysfunction and does not improve slow-wave sleep, and adjunctive GABA(A) receptor modulators, such as benzodiazepines and zolpidem, can impair sleep architecture and cognition in schizophrenia. GABA(B) receptor agonists have therapeutic potential in schizophrenia. These agents have minimal effect on rapid eye movement sleep while increasing slow-wave sleep. Preclinical associations with increased expression of genes related to slow-wave sleep production and circadian rhythm function have also been reported. GABA(B) receptor deficits result in a sustained hyperdopaminergic state and can be reversed by a GABA(B) receptor agonist. Genetic, postmortem and electrophysiological studies also associate GABA(B) receptors with schizophrenia. While studies thus far have not shown significant effects, prior focus on the use of GABA(B) receptor agonists has been on the positive symptoms of schizophrenia, with minimal investigation of GABA(B) receptor agonists such as baclofen or gamma-hydroxybutyric acid and their effects on sleep architecture, cognition and negative symptoms in patients with schizophrenia. Further study is needed.
TL;DR: Results from comparative analyses suggest that animals are particularly vulnerable to predation during REM sleep, a finding that lends further support to the notion that REM sleep must serve an important function.
TL;DR: It is hypothesized that cerebral SNA increases during phasic REM sleep, constricting cerebral vessels as a protective mechanism against cerebral hyperperfusion during the large arterial pressure surges that characterize this sleep state.
Abstract: Sympathetic nerve activity (SNA) in neurons projecting to skeletal muscle blood vessels increases during rapid-eye-movement (REM) sleep, substantially exceeding SNA of non-REM (NREM) sleep and quie
TL;DR: The results indicate that effects of ovarian hormones on recovery sleep differ from those on spontaneous sleep, and the hormonal modulation of recovery sleep architecture may affect recovery of sleep related functions after sleep loss.
Abstract: NATURAL CHANGES IN ESTRADIOL AND PROGESTERONE LEVELS ACROSS THE MENSTRUAL CYCLE, AND ESPECIALLY DURING PREGNANCY AND MENOPAUSE, have been associated with sleep disturbances and changes in sleep EEG in women.1,2 Hormone replacement therapy (estradiol, progesterone, or both) can improve sleep quality in postmenopausal women under baseline conditions.3–8 It is unclear, however, whether hormone replacement therapy can reduce cognitive performance deficits resulting from sleep deprivation9,10 or facilitate sleep recovery after sleep deprivation.11 Given the prevalence of chronic, partial sleep deprivation12 and the frequency with which women are given hormone treatments,13–15 it is important to determine whether and how such treatments may influence the ability to recover lost sleep.
Rodents have been used frequently as models to examine the effects of ovarian hormones on sleep. Changes in hormonal levels during the estrous cycle were associated with changes in sleep patterns,16–20 whereas in ovariectomized rats, estradiol treatment reduced sleep, especially rapid eye movement sleep (REMS), under baseline conditions.21–27 The effects of hormonal changes associated with estrous cycles on recovery sleep after sleep deprivation may not, however, parallel those on baseline sleep. Despite baseline differences in sleep, intact rats did not show estrous cycle-related differences in amounts of non-REMS (NREMS) and REMS during recovery, nor in NREMS EEG delta activity (an index of NREMS intensity and drive), after 6 h of sleep deprivation.28 In mice, neither ovariectomy29 nor lack of aromatase (an enzyme that converts testosterone into estradiol)30 affected recovery REMS or NREMS delta activity after 6 h of sleep deprivation. Although these studies suggest that endogenous sex hormones do not influence recovery sleep after 6 h of sleep deprivation in rodents, the stage of the estrous cycle at the beginning of 4 days of REMS deprivation has been reported to affect the pattern of recovery sleep.31 Nonetheless, the clinically more relevant question of whether hormone replacement after loss of ovarian hormones affects the ability to compensate for lost sleep has not been addressed directly using rodent models.
To examine whether and how replacement of estradiol and/or progesterone after ovariectomy modulates the pattern of baseline sleep and recovery sleep after 6 h of sleep deprivation, we implanted estradiol- and/or progesterone-containing capsules subcutaneously in ovariectomized adult rats. These capsules produced relatively stable physiological levels of circulating hormones. The analytic advantage of this approach is that it allows comparisons between baseline sleep and recovery sleep after sleep deprivation under identical hormonal conditions. This is not possible using intact females, because estrous cycles do not include intervals with stable hormonal levels that are long enough to accommodate lengthy baseline and recovery periods, particularly during proestrus and estrus when estradiol and progesterone levels change rapidly.32,33 Gonadally intact and hormonally untreated male rats were studied for comparison.
TL;DR: The data suggest that the STN may play an active role in an ascending activating network implicated in the transmission of PGO waves during REM sleep in humans.
Abstract: Study Objectives: The aim of this study was to examine whether the subthalamic nucleus (STN) plays a role in the transmission of PGO-like waves during REM sleep in humans Design: Simultaneous recordings from deep brain electrodes to record local field potentials (LFPs), and standard polysomnography to ascertain sleep/wake states Setting: Main Hospital, department of clinical neurophysiology sleep laboratory Participants: 12 individuals with Parkinson's disease, with electrodes implanted in the STN; and, as a control for localization purposes, 4 cluster headache patients with electrodes implanted in the posterior hypothalamus Interventions: All subjects underwent functional neurosurgery for implantation of deep brain stimulation electrodes Results: Sharp, polarity-reversed LFPs were recorded within the STN during REM sleep in humans These subthalamic PGO-like waves (2-3 Hz, 80-200 μV, and 300-500 msec) appeared during REM epochs as singlets or in clusters of 3-13 waves During the pre-REM period, subthalamic PGO-like waves were temporally related to drops in the submental electromyogram and/or onset of muscular atonia Clusters of PGO-like waves occurred typically before and during the bursts of rapid eye movements and were associated with an enhancement in fast (15-35 Hz) subthalamic oscillatory activity Conclusion: Subthalamic PGO-like waves can be recorded during pre-REM and REM sleep in humans Our data suggest that the STN may play an active role in an ascending activating network implicated in the transmission of PGO waves during REM sleep in humans