Showing papers on "Rapid eye movement sleep published in 2010"

The memory function of sleep

Abstract: Sleep improves the consolidation of both declarative and non-declarative memories. Diekelmann and Born discuss the potential mechanisms through which slow wave sleep and rapid eye movement sleep support system and synaptic consolidation. Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory, depending on the specific conditions of learning and the timing of sleep. Consolidation during sleep promotes both quantitative and qualitative changes of memory representations. Through specific patterns of neuromodulatory activity and electric field potential oscillations, slow-wave sleep (SWS) and rapid eye movement (REM) sleep support system consolidation and synaptic consolidation, respectively. During SWS, slow oscillations, spindles and ripples — at minimum cholinergic activity — coordinate the re-activation and redistribution of hippocampus-dependent memories to neocortical sites, whereas during REM sleep, local increases in plasticity-related immediate-early gene activity — at high cholinergic and theta activity — might favour the subsequent synaptic consolidation of memories in the cortex.

Polysomnographic diagnosis of idiopathic REM sleep behavior disorder.

Abstract: The presence of either excessive tonic chin EMG activity during REM sleep, or excessive phasic submental or limb EMG twitching is required to diagnose REM sleep behavior disorder (RBD). The aim was to identify cut-off values and to assess the sensitivity and specificity of these values taken separately or combined to diagnose idiopathic RBD patients. Eighty patients presenting with a clinical diagnosis of idiopathic RBD and 80 age- and gender-matched normal controls were studied in the sleep laboratory. Receiver operating characteristic curves were drawn to find optimal cut-off values for three REM sleep EMG parameters. Tonic and phasic EMG activity were measured in the chin, but not in the limbs. Videos were examined during the recording but were not systematically reviewed by the authors. Total correct classification of 81.9% was found for tonic chin EMG density ≥30%; 83.8% for phasic chin EMG density ≥15% and 75.6% for ≥24 leg movements per hour of REM sleep. Five patients did not fulfill any of these three polysomnographic (PSG) criteria. Conversely, one subject of the control group met the PSG criteria for RBD. This study estimates the diagnostic value of a visual scoring method for the diagnosis of idiopathic RBD and establishes cut-off values to be used in clinical and research set-ups. For the five RBD patients who did not show chin EMG abnormalities, it cannot be excluded that they had increased phasic EMG activity in the upper limbs and presented visible motor activity.

Severity of REM atonia loss in idiopathic REM sleep behavior disorder predicts Parkinson disease

Abstract: Background: Over 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinson disease (PD) or dementia. At present, there is no way to predict who will develop disease. Since polysomnography is performed in all patients with idiopathic RBD at diagnosis, there is an opportunity to analyze if baseline sleep variables predict eventual neurodegenerative disease. Methods: In a longitudinally studied cohort of patients with idiopathic RBD, we identified those who had developed neurodegenerative disease. These patients were matched by age, sex, and follow-up duration to patients with RBD who remained disease-free and to controls. Polysomnographic variables at baseline (i.e., before development of neurodegenerative disease) were compared between groups. Results: Twenty-six patients who developed neurodegenerative disease were included (PD 12, multiple system atrophy 1, dementia 13). The interval between polysomnogram and disease onset was 6.7 years, mean age was 69.5, and 81% were male. There were no differences between groups in sleep latency, sleep time, % stages 2–4, % REM sleep, or sleep efficiency. However, patients with idiopathic RBD who developed neurodegenerative disease had increased tonic chin EMG activity during REM sleep at baseline compared to those who remained disease-free (62.7 ± 6.0% vs 41.0 ± 6.0%, p = 0.020). This effect was seen only in patients who developed PD (72.9 ± 6.0% vs 41.0 ± 6.0%, p = 0.002), and not in those who developed dementia (54.3 ± 10.3, p = 0.28). There was no difference in phasic submental REM EMG activity between groups. Conclusions: In patients with REM sleep behavior disorder initially free of neurodegenerative disease, the severity of REM atonia loss on baseline polysomnogram predicts the development of Parkinson disease.

GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep

Abstract: The lateral hypothalamus (LH), where wake-active orexin (Orx)-containing neurons are located, has been considered a waking center. Yet, melanin-concentrating hormone (MCH)-containing neurons are codistributed therein with Orx neurons and, in contrast to them, are active during sleep, not waking. In the present study employing juxtacellular recording and labeling of neurons with Neurobiotin (Nb) in naturally sleeping-waking head-fixed rats, we identified another population of intermingled sleep-active cells, which do not contain MCH (or Orx), but utilize gamma-aminobutyric acid (GABA) as a neurotransmitter. The 'sleep-max' active neurons represented 53% of Nb-labeled MCH-(and Orx) immunonegative (-) cells recorded in the LH. For identification of their neurotransmitter, Nb-labeled varicosities of the Nb-labeled/MCH- neurons were sought within sections adjacent to the Nb-labeled soma and immunostained for the vesicular transporter for GABA (VGAT) or for glutamate. A small proportion of sleep-max Nb+/MCH- neurons (19%) discharged maximally during slow-wave sleep (called 'S-max') in positive correlation with delta electroencephalogram activity, and from VGAT staining of Nb-labeled varicosities appeared to be GABAergic. The vast proportion of sleep-max Nb+/MCH- neurons (81%) discharged maximally during paradoxical sleep (PS, called 'P-max') in negative correlation with electromyogram amplitude, and from Nb-labeled varicosities also appeared to be predominantly GABAergic. Given their discharge profiles across the sleep-wake cycle, P-max together with S-max GABAergic neurons could thus serve to inhibit other neurons of the arousal systems, including local Orx neurons in the LH. They could accordingly dampen arousal with muscle tone and promote sleep, including PS with muscle atonia.

Rapid eye movement sleep percentage in children with autism compared with children with developmental delay and typical development.

Abstract: Objective To compare objective polysomnographic parameters between 3 cohorts: children with autism, typical development, and developmental delay without autism. Design Overnight polysomnographic recordings were scored for sleep architecture according to American Academy of Sleep Medicine criteria by a board-certified sleep medicine specialist blind to diagnosis for studies collected between July 2006 and September 2009. Setting Subjects were evaluated in the pediatric ward in the Clinical Research Center of the National Institutes of Health. Participants First 60 consecutive children with autism, 15 with typical development, and 13 with developmental delay matched for nonverbal IQ to the autism group, ranging in age from 2 to 13 years, selected without regard to the presence or absence of sleep problem behavior. Main Outcome Measures Total sleep time, latencies to non–rapid eye movement (REM) and REM sleep, and percentages of total sleep time for stages 1 and 2 sleep, slow-wave sleep, and REM sleep. Results There were no differences between the typical vs developmental delay groups. Comparison of children with autism vs typical children revealed shorter total sleep time ( P = .004), greater slow-wave sleep percentage ( P = .001), and much smaller REM sleep percentage (14.5% vs 22.6%; P P = .001), greater stage 1 sleep percentage ( P P P Conclusion A relative deficiency of REM sleep may indicate an abnormality in neural organization in young children with autism that is not directly associated with or related to inherent intellectual disability but may serve as a window into understanding core neurotransmitter abnormalities unique to this disorder.

Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

Abstract: Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy. Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without cataplexy. Main outcome measures were: rapid eye movement sleep behaviour disorder symptoms; short and long muscle activations per hour rapid eye movement and non-rapid eye movement sleep; and periodic and non-periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep. Outcome variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin deficiency independently predicted rapid eye movement sleep behaviour disorder symptoms (relative risk = 3.69, P = 0.03), long muscle activations per hour rapid eye movement sleep (ln-coefficient = 0.81, P < 0.01), and short muscle activations per hour rapid eye movement sleep (ln-coefficient = 1.01, P < 0.01). Likewise, periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep were only associated with hypocretin deficiency (P < 0.01). A significant association between hypocretin deficiency and cataplexy was confirmed (P < 0.01). In a sub-analysis, hypocretin deficiency suggested the association of periodic limb movements and rapid eye movement sleep behaviour disorder outcomes (symptoms, non-periodic short and long muscle activity) in rapid eye movement sleep. Our results support the hypothesis that hypocretin deficiency is independently associated with rapid eye movement sleep behaviour disorder in narcolepsy. Thus, hypocretin deficiency is linked to the two major disturbances of rapid eye movement sleep motor regulation in narcolepsy: rapid eye movement sleep behaviour disorder and cataplexy. Hypocretin deficiency is also significantly associated with periodic limb movements in rapid eye movement and non-rapid eye movement sleep, and provides a possible pathophysiological link between rapid eye movement sleep behaviour disorder and periodic limb movements in narcolepsy. The study supports the hypothesis that an impaired hypocretin system causes a general instability of motor regulation during wakefulness, rapid eye movement and non-rapid eye movement sleep in human narcolepsy.

Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model

Abstract: Rapid eye movements and complex visual dreams are salient features of human rapid eye movement sleep. However, it remains to be elucidated whether the eyes scan dream images, despite studies that have retrospectively compared the direction of rapid eye movements to the dream recall recorded after having awakened the sleeper. We used the model of rapid eye movement sleep behaviour disorder (when patients enact their dreams by persistence of muscle tone) to determine directly whether the eyes move in the same directions as the head and limbs. In 56 patients with rapid eye movement sleep behaviour disorder and 17 healthy matched controls, the eye movements were monitored by electrooculography in four (right, left, up and down) directions, calibrated with a target and synchronized with video and sleep monitoring. The rapid eye movement sleep behaviour disorder-associated behaviours occurred 2.1 times more frequently during rapid eye movement sleep with than without rapid eye movements, and more often during or after rapid eye movements than before. Rapid eye movement density, index and complexity were similar in patients with rapid eye movement sleep behaviour disorder and controls. When rapid eye movements accompanied goal-oriented motor behaviour during rapid eye movement sleep behaviour disorder (e.g. grabbing a fictive object, hand greetings, climbing a ladder), which happened in 19 sequences, 82% were directed towards the action of the patient (same plane and direction). When restricted to the determinant rapid eye movements, the concordance increased to 90%. Rapid eye movements were absent in 38–42% of behaviours. This directional coherence between limbs, head and eye movements during rapid eye movement sleep behaviour disorder suggests that, when present, rapid eye movements imitate the scanning of the dream scene. Since the rapid eye movements are similar in subjects with and without rapid eye movement sleep behaviour disorder, this concordance can be extended to normal rapid eye movement sleep.

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep.

Abstract: Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.

Sleep induced by stimulation in the human pedunculopontine nucleus area

Abstract: The pedunculopontine nucleus is part of the reticular ascending arousal system and is involved in locomotion and sleep. Two patients with Parkinson disease received electrodes that stimulated the pedunculopontine nucleus area to alleviate their severe gait impairment. Instead, we found that low-frequency stimulation of the pedunculopontine nucleus area increased alertness, whereas high-frequency stimulation induced non-rapid eye movement sleep. In addition, the sudden withdrawal of the low-frequency stimulation was consistently followed by rapid eye movement sleep episodes in 1 patient. These data have the potential to benefit patients who suffer from sleep disorders.

Differential effects of controllable and uncontrollable footshock stress on sleep in mice

Abstract: STRESS CAN HAVE A SIGNIFICANT, LONG-LASTING NEGATIVE IMPACT ON HEALTH INCLUDING CHANGES IN BEHAVIOR AND SLEEP. HOWEVER, STRESSORS are often encountered without producing permanent or pathological changes. The difference between successful and unsuccessful coping with stress may involve the resilience of the organism1 as well as characteristics of the stressor. Stressor controllability, along with intensity and predictability, have been found to be important factors in the effects of stress.2 For example, lack of stressor controllability has been suggested to be a factor in the development of posttraumatic stress disorder (PTSD).3,4 Conditioned fear training is conducted with a fear-inducing stressor (usually inescapable shock, [IS])5,6 presented in an experimental paradigm in which the animal receiving training has no control over the stressor. Through association to IS, initially neutral environmental cues and contexts acquire the capacity to elicit behavioral and physiological responses indicative of fear and anxiety, including behavioral freezing,7–9 autonomic responses,10–12 and fear-potentiated startle.5,6 Disturbances in sleep often follow a stressful or traumatic event,13 and we and others have demonstrated that IS and IS-associated fearful cues and contexts produce similar alterations in sleep, including a prominent reduction in rapid eye movement sleep (REM).14,15 By comparison, training with avoidable, signaled shock (a controllable stressor) in a shuttlebox is followed by significant increases in REM,15–18 even though the same stressor (footshock) is initially experienced before the avoidance response is acquired. The results of these studies have typically been focused on demonstrating a correlation between REM and acquisition of the avoidance response.15–18 It is possible to train animals with escapable shock (ES) as a controllable stressor using a shuttlebox paradigm. In this paradigm, the stressor is always experienced but can be terminated by the animal's action. The effects of ES and IS have not been directly compared with respect to post-stress alterations in sleep. Therefore, in this study, we used a yoked design to examine the effects of ES and IS training and of contextual reminders of ES and IS on sleep in BALB/cJ mice, a “behaviorally reactive” strain that shows greater post-stress reductions in REM and alterations in sleep in response to IS compared to C57BL/6J mice.19–21 We also compared mice in the ES and IS conditions for potential differences in gross motor activity and we examined freezing, a common behavioral index of fear,7,22,23 during exposure to the fearful context. Examining freezing enabled us to compare immediate emotional reactivity across conditions and to determine the relationship of initial emotionality to subsequent changes in arousal and sleep.

The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson's disease dementia.

Abstract: OBJECTIVE: Two common and characteristic sleep disturbances have been described in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD); excessive daytime sleepiness and REM sleep behaviour disorder (RBD). This study is an analysis of a secondary outcome measure of a larger study already reported, aimed to determine whether memantine has an effect on the sleep disturbances in DLB and PDD patients. METHODS: Patients with DLB or PDD were included in a placebo-controlled, randomised controlled study of memantine (20 mg per day) for 24 weeks. The Stavanger Sleep Questionnaire and the Epworth Sleepiness Scale were used to evaluate the effect on sleep disturbances. RESULTS: Forty two patients started treatment; 20 with memantine and 22 with placebo. The primary analysis was the comparison of change between the two groups during a 24-week period, using the modified ITT population (last observation carried forward). At 24 weeks, patients treated with memantine were less physically active during sleep while patients in the placebo group worsened. Mean difference between the groups (0.5 [0.05-0.90]) was significant (p = 0.006). No significant change was observed in severity of excessive daytime sleepiness. CONCLUSIONS: Memantine decreases probable REM sleep behaviour disorder in patients with DLB and PDD. Both diagnostic groups contributed equally to the outcome. (Less)

Sleep in psychiatric disorders: where are we now?

Abstract: Although the precise function of sleep is unknown, decades of research strongly implicate that sleep has a vital role in central nervous system (CNS) restoration, memory consolidation, and affect regulation. Slow-wave sleep (SWS) and rapid eye movement (REM) sleep have been of significant interest to psychiatrists; SWS because of its putative role in CNS energy recuperation and cognitive function, and REM sleep because of its suggested involvement in memory, mood regulation, and possible emotional adaptation. With the advent of the polysomnogram, researchers are now beginning to understand some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. The same neurochemistry that controls the sleep-wake cycle has also been implicated in the pathophysiology of numerous psychiatric disorders. Thus it is no surprise that several psychiatric disorders have prominent sleep symptoms. This review will summarize normal sleep architecture, and then examine sleep abnormalities and comorbid sleep disorders seen in schizophrenia, as well as anxiety, cognitive, and substance abuse disorders.

Changes in cardiac variability after REM sleep deprivation in recurrent nightmares.

Abstract: STUDY OBJECTIVES To assess whether dysfunctional autonomic regulation during REM sleep as indexed by heart rate variability (HRV) is a pathophysiological factor in frequent nightmares (NMs). DESIGN Monitoring with polysomnography (PSG) and electrocardiography (ECG) for 3 consecutive nights: Night 1 (N1), adaptation night; N2, administration of partial REM sleep deprivation; N3, recovery night. Differences between NM and control (CTL) groups assessed for ECG measures drawn from wakefulness, REM sleep, and Stage 2 sleep on both N1 and N3. SETTING Hospital-based sleep laboratory. PARTICIPANTS Sixteen subjects with frequent NMs (> or = 1 NM/week; mean age = 26.1 +/- 8.7 years) but no other medical or psychiatric disorders and 11 healthy comparison subjects ( < 1 NM/month; mean age = 27.1+/- 5.6 years). RESULTS NM and CTL groups differed on 2 REM sleep measures only on N1; the NM group had longer REM latencies and REM/NREM cycle durations than did the CTL group. No differences were found on time domain and absolute frequency domain ECG measures for either N1 or N3. However, altered HRV for the NM group was suggested by significantly higher LFnu, lower HFnu, and higher LF/HF ratio than for the CTL group. CONCLUSIONS Results are consistent with a higher than normal sympathetic drive among NM subjects which is unmasked by high REM sleep propensity. Results also support a growing literature linking anxiety disorders of several types (panic disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder) to altered HR variability.

Sleep and sleep disorders in chronic obstructive pulmonary disease

Abstract: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the US. Numerous studies have demonstrated that sleep disturbances are common in COPD patients, with more prominent complaints in patients with more severe disease and with increasing age. Sleep disturbances may occur due to the effects of breathing abnormalities on sleep and sleep disruption. However, other etiologies may include the medications used to treat COPD, concomitant anxiety and depression, and the presence of comorbid sleep disorders. The respiratory disturbances that occur in these patients during sleep have been evaluated by examining sleep-related oxygen desaturation, reduction in pulmonary function during sleep, and development of hypoventilation during rapid eye movement sleep. Treatment includes use of nocturnal oxygen therapy, noninvasive positive pressure ventilation, and long-acting medications. There has been little study on improving sleep quality beyond treating the respiratory disease, despite the fact that numerous studies show poor sleep quality, a high prevalence of insomnia, and tolerability of newer hypnotic agents in the setting of COPD. This article defines the scope of sleep problems in the setting of COPD, reviews the impact of sleep on ventilation, explores the role of obstructive sleep apnea in the setting of COPD, and reviews therapeutic options.

REM sleep behaviour disorder in older individuals: epidemiology, pathophysiology and management.

Abstract: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a sleep disorder in which patients appear to be enacting their dreams while in REM sleep. The behaviours are typically violent, in association with violent dream content, so serious harm can be done to the patient or the bed partner. The disorder predominantly affects older adults, and has an estimated prevalence in adults of 0.4-0.5%. However, the frequency is much higher in certain neurodegenerative diseases, especially Parkinson's disease, dementia with Lewy bodies and multiple systems atrophy. RBD can occur in the absence of diagnosed neurological diseases (the 'idiopathic' form), although patients with this form of RBD may have subtle neurological abnormalities and often ultimately develop a neurodegenerative disorder. Data from animal models and cases of RBD developing after brainstem (pontine tegmentum, medulla) lesions have led to the understanding that RBD is caused by a lack of normal REM muscle atonia and a lack of normal suppression of locomotor generators during REM sleep. Clonazepam is used as first-line therapy for RBD and melatonin as second-line therapy, although evidence for both of these interventions comes from uncontrolled case series. Because the risk of injury to the patient or the bed partner is high, interventions to improve the safety of the sleep environment are also often necessary. This review describes the epidemiology, pathophysiology and treatment of RBD.

Altered sleep architecture and higher incidence of subsyndromal depression in low endogenous melatonin secretors

Abstract: Melatonin secretion is synchronized to the sleep/wake cycle and has been suggested to have somnogenic properties Sleep/wake cycle disruption and alterations in the secretary pattern of melatonin is present in various psychiatric disorders The objective of this study was to investigate the sleep architecture and the presence of depression in individuals with low endogenous melatonin levels The study included 16 participants (mean age 303 ± 149 years) The first night of testing included psychiatric evaluation followed by melatonin secretion profile evaluation by Dim Light Melatonin Onset test and then standard montage polysomnographic testing On the second night, only polysomnographic testing was carried out with an imposed sleep period of 8 h Low endogenous melatonin secretors (LEMS) showed no discernible peaks in melatonin secretion compared to normal secretors (controls) LEMS demonstrated significant alterations in rapid eye movement sleep but not in non-rapid eye movement sleep along with poor sleep initiation and quality compared to controls 556% of the low melatonin secretors group presented with subsyndromal depression Melatonin has significant bearing on sleep architecture and a lack of melatonin may desynchronize endogenous rhythms allowing subsyndromal depression to manifest

Sleep architecture as correlate and predictor of symptoms and impairment in inter-episode bipolar disorder: taking on the challenge of medication effects.

Abstract: This study was designed to clarify the association between inter-episode bipolar disorder (BD) and sleep architecture. Participants completed a baseline symptom and sleep assessment and, 3 months later, an assessment of symptoms and impairment. The effects of psychiatric medications on sleep architecture were also considered. Participants included 22 adults with BD I or II (inter-episode) and 22 non-psychiatric controls. The sleep assessment was conducted at the Sleep and Psychological Disorders Laboratory at the University of California, Berkeley. Follow-up assessments 3 months later were conducted over the phone. Results indicate that, at the sleep assessment, BD participants exhibited greater rapid eye movement sleep (REM) density than control participants with no other group differences in sleep architecture. Sleep architecture was not correlated with concurrent mood symptoms in either group. In the BD group, duration of the first REM period and slow-wave sleep (SWS) amount were positively correlated with manic symptoms and impairment at 3 months, while REM density was positively correlated with depressive symptoms and impairment at 3 months. The amount of Stage 2 sleep was negatively correlated with manic symptoms and impairment at 3 months. In contrast, for the control group, REM density was negatively correlated with impairment at 3 months. SWS and Stage 2 sleep were not correlated with symptoms or impairment. Study findings suggest that inter-episode REM sleep, SWS and Stage 2 sleep are correlated with future manic and depressive symptoms and impairment in BD. This is consistent with the proposition that sleep architecture may be a mechanism of illness maintenance in BD.

REM sleep behavior disorder in psychiatric populations.

Abstract: To the Editor: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a loss of REMrelated muscle atonia and abnormal motor activities during REM sleep with consequent sleep-related injuries.1,2 It has been increasingly reported among psychiatric populations and has a potential association with use of psychotropics, particularly selective serotonin reuptake inhibitor (SSRI), tricyclic, and serotonin and noradrenergic reuptake inhibitor (SNRI) antidepressants.3–8 A previous case report5 found that cessation of SSRI treatment did not result in complete resolution of clinical RBD symptoms and polysomnographic (PSG) abnormalities. Our recent clinical epidemiologic study8 found that 3.8% of psychiatric outpatients might have RBD features over the past year. The prevalence is 10 times more common than that of the typical RBD in the elderly general population.9 In addition, the RBD features could result in sleep-related injuries and violence, with potential medicolegal repercussions.8,10 In the current study, we conducted a comprehensive evaluation of clinical and PSG features as well as follow-up response to an open intervention of antidepressant regimen modification.

Isoflurane Anesthesia Does Not Satisfy the Homeostatic Need for Rapid Eye Movement Sleep

Abstract: General anesthesia and sleep are states of consciousness that share numerous traits, including hypnosis, amnesia, and immobility1 Accordingly, the investigation of anesthetic mechanisms and sleep mechanisms has converged2 This convergence, however, has focused largely on non–rapid eye movement (NREM) sleep rather than rapid eye movement (REM) sleep In animal models, REM sleep can be characterized electrophysiologically by (1) low amplitude, desynchronized cortical waveforms, (2) synchronized hippocampal θ activity, and (3) muscle atonia3 The IV drug urethane is the only general anesthetic that has been suggested to mimic sleep cycles with periods of NREM- and REM-like activity assessed by electroencephalography (EEG), as well as by cholinergic and monoaminergic neuropharmacology4 Because urethane is carcinogenic, it is used only in animal models and thus has no direct relationship to clinical anesthesiology5 However, clinically relevant IV anesthetics such as propofol do seem to satisfy the brain’s homeostatically regulated need for REM sleep, because there is no observed REM rebound after prolonged propofol infusion6 Furthermore, there are no differences in recovery from sleep deprivation between propofol anesthesia and ad libitum sleep7 Collectively, these data suggest a neurophysiologic or neurochemical trait that is common to or functionally equivalent during both IV anesthesia and REM sleep No underlying mechanisms of REM sleep satiation during anesthesia have been elucidated, in part because there are a number of impediments to studying REM sleep–like traits expressed during general anesthesia First, there is no obvious neocortical EEG correlate to REM sleep in the anesthetized state Second, mobility is suppressed during general anesthesia by spinal mechanisms8 that would mask the periodic supraspinal atonia mechanisms associated with REM sleep9,10 Finally, other physiologic perturbations observed during REM sleep, such as heart rate, arterial blood pressure, or respiratory variability,11 may also be confounded by general anesthetic effects What is also unclear is whether inhaled drugs such as isoflurane are capable of repaying REM sleep debt as has been suggested for propofol It has been demonstrated that isoflurane anesthesia induces transient alterations in sleep architecture in humans12 and that total sleep deprivation before isoflurane induction is associated with reduced anesthetic requirement in animals13 However, there have been no studies of recovery from sleep deprivation during inhaled anesthesia Tung et al7 discussed 3 possibilities for the relationship of anesthesia and sleep requirements First, general anesthesia could be permissive for normal sleep processes to occur, which would allow repayment of sleep debt during general anesthesia Second, general anesthesia could, similar to the waking state, allow for the further accumulation of sleep debt Third, general anesthesia could be a distinct state in which sleep debt is neither accumulated nor repaid The findings of Tung et al7 suggest that the effects of propofol are closest to the first condition, ie, a state conducive to sleep recovery Assessing whether inhaled anesthetics such as isoflurane have a similar sleep recovery profile is clinically important As one example, critical care patients experience sleep deprivation or fragmentation14 and frequently present for surgical interventions In patients with disorders such as obstructive sleep apnea, determining which anesthetics best satisfy the need for sleep may potentially attenuate postoperative apnea and hypoxemia associated with sleep rebound phenomena15 This is especially true in patients receiving analgesia from epidural catheters or peripheral nerve blocks, because there may be less postoperative suppression of REM sleep with the decreased use of IV opiates16 Beyond the immediate perioperative period, REM sleep rebound has been found to occur in the second or third night after surgery, with potential for adverse sequelae17,18 The objectives for this investigation were (1) to test the hypothesis that isoflurane anesthesia facilitates recovery from sleep deprivation as well as natural sleep and (2) to study neurophysiologic features that may be common to both states REM sleep was the focus of this investigation because (1) it shares many traits with general anesthesia,1 (2) it is a state of cortical activation3 and its relationship to general anesthesia is therefore less clear, (3) unlike NREM sleep, it can be more selectively restricted,19 and (4) rebound after deprivation may be associated with physiologic complications and is therefore of clinical importance15,17,18

Central Deficiency of Corticotropin-Releasing Hormone Receptor Type 1 (CRH-R1) Abolishes Effects of CRH on NREM But Not on REM Sleep in Mice

Abstract: SINCE ITS DISCOVERY IN 1981, NUMEROUS INSIGHTS INTO THE ROLE AND FUNCTION OF CORTICOTROPIN-RELEASING HORMONE (CRH) HAVE BEEN accumulated.1 It is commonly regarded as one of the major factors controlling the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and autonomic components in responses to stress.2,3 Secretion of CRH from the paraventricular nucleus (PVN) of the hypothalamus constitutes the initial step in these processes which finally peak in arousal and wakefulness. Additionally, extrahypothalamic actions of CRH indicate that this neuropeptide acts as a neuromodulator in the CNS and thus might be involved in the regulation of spontaneous behaviors (e.g., food intake, locomotor activity, anxiety) even in the absence of stressors.4 Up to now it remains unclear whether the arousal effects of CRH are exerted in consequence of its action in the periphery, through other stress hormones, or centrally, by a direct action of this neuropeptide within the brain. Many studies, however, hypothesize a regulatory influence of CRH on sleep and waking as one of its central effects. Previously, Opp reported that Lewis rats, in which CRH synthesis and its secretion from the hypothalamus are decreased, have reduced amounts of waking and increased non-rapid eye movement sleep (NREMS) in comparison to Fischer 344 and Sprague-Dawley (Sp-D) rats in which the level of the neuropeptide in the brain is normal.5 In another experiment, Chang and Opp demonstrated that intracerebroventricular (i.c.v.) application of an antisense oligonucleotide probe directed against CRH mRNA reduces spontaneous waking in Sp-D rats during their activity phase.6 Further corroborating this hypothesis, a possible involvement of central CRH on sleep reflects the receptor distribution, as found consistently in many brain regions, such as the basal forebrain, the thalamus, hypothalamus, midbrain, pons, and the medulla, which are closely related to waking.7,8 Concerning the degree of involvement and depending on the kind of behavior regulated by the interplay of CRH and its receptor subtypes (CRH receptor type 1 and 2; CRH-R1 and CRH-R2) literature sometimes presents conflicting results. For example, 3 independent laboratories studied 3 differently generated CRH-R2 knockout (CRH-R2 KO) mouse lines with regard to behavioral and endocrine activity. Only 2 groups could show significant increases of anxiety-related behavior9,10; only one of these 2 observed augmentation of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) release in response to stress,9 whereas the third group showed opposite endocrine changes with absence of anxiety-related behavior.11 While the role of CRH-R1 in anxiety seems to be more established, sleep-wake rhythmicity results also diverge. Chang and Opp could show that central application of a CRH-R1 antagonist (α-helical CRH) prior to the onset of the dark period reduced spontaneous waking in rats,12 whereas Gonzalez and colleagues did not find such effects.13 To elucidate more closely whether this neuropeptide and its receptors are involved in the central mechanism of sleep-wake regulation, the central effects of CRH need to be considered separately from those on the HPA system in an experimental approach, where its central (spontaneous) and peripheral (stress-induced) regulatory influences are distinguishable. Along these lines, we have recently demonstrated that central CRH is driving REM sleep in a genetic mouse model of CRH excess. This conditional model overexpresses CRH in either the entire central nervous system, or only in the anterior forebrain without affecting basal HPA-axis activity14; both genetic mutant lines exhibit similarly altered REM sleep.15 Complementing the previously used gain-of-function model, the present study made use of conditional (CNS-specific) CRH-R1 knockout (CKO) mice and their control littermates (CL), in which the impact of central CRH mediated via CRH-R1 on sleep-wake behavior can be separately analyzed with the presence of a functional HPA axis.

Unilateral Cortical Spreading Depression Affects Sleep Need and Induces Molecular and Electrophysiological Signs of Synaptic Potentiation In Vivo

Abstract: Cortical spreading depression (CSD) is an electrophysiological phenomenon first described by Leao in 1944 as a suppression of spontaneous electroencephalographic activity, traveling across the cerebral cortex. In vitro studies suggest that CSD may induce synaptic potentiation. One recent study also found that CSD is followed by a non-rapid eye movement (NREM) sleep duration increase, suggesting an increased need for sleep. Recent experiments in animals and humans show that the occurrence of synaptic potentiation increases subsequent sleep need as measured by larger slow wave activity (SWA) during NREM sleep, prompting the question whether CSD can affect NREM SWA. Here, we find that, in freely moving rats, local CSD induction increases corticocortical evoked responses and strongly induces brain derived neurotrophic factor (BDNF) in the affected cortical hemisphere but not in the contralateral one, consistent with synaptic potentiation in vivo. Moreover, for several hours after CSD, large slow waves occur in the affected hemisphere during rapid eye movement sleep and quiet waking but disappear during active exploration. Finally, we find that CSD increases NREM sleep duration and SWA, the latter specifically in the affected hemisphere. These effects are consistent with an increase in synaptic strength triggered by CSD, although nonphysiological phenomena associated with CSD may also play a role.

Sex differences and the effect of gaboxadol and zolpidem on EEG power spectra in NREM and REM sleep.

Abstract: Hypnotics that interact with the GABA(A) receptor have marked effects on the electroencephalogram (EEG) during sleep. It is not known whether the effects of hypnotics on EEG power spectra differ between the sexes. The effects of 5, 10 and 15 mg of gaboxadol (GBX) and 10 mg of zolpidem (ZOL) on EEG power spectra were assessed in a randomized, double-blind, placebo-controlled, 5-way cross-over design study using a phase-advance model of transient insomnia. Sleep stage specific EEG power spectra were computed in 36 men and 45 women. GBX enhanced power density in delta and theta activity in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and suppressed sleep spindle activity in NREM sleep. The increase of delta and theta activity in NREM and REM sleep was significantly larger for women than for men but the suppression of spindle activity did not differ between the sexes. After ZOL administration, no sex differences were observed in the reduction of delta and theta activity in NREM sleep, but the increase in sleep spindle activity in NREM sleep was greater in women than in men. These sex dependent and differential effects of GBX and ZOL may be related to their differential affinity for GABA(A) receptor subtypes and their modulation by neurosteroids.

Brainstem Circuitry Regulating Phasic Activation of Trigeminal Motoneurons during REM Sleep

Abstract: Background Rapid eye movement sleep (REMS) is characterized by activation of the cortical and hippocampal electroencephalogram (EEG) and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw) phasic activity during REMS. The trigeminal motor nucleus (Mo5), which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt), but also from the adjacent paramedian reticular area (PMnR). On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD) nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.