Barbato, Giuseppe; Barker, Charles; Bender, Charles; Wehr, Thomas A
There is no agreement in the literature as to whether sleep interruption causes rapid eye movement (REM) pressure to increase, and if so, whether this increase is expressed as shortened REM latency, increased REM density, or increased duration of REM sleep. The purpose of the present study was to examine the effect of different durations of spontaneous sleep interruptions on the regulation of REM sleep that occurs after return to sleep. The occurrence of spontaneous periods of wakefulness and their effects on subsequent REM sleep periods were analysed in a total sample of 1189 sleep interruptions which occurred across 364 extended nights in 13 normal subjects. Compared with sleep interruptions that last less than 10 min, sleep interruptions that last longer than 10 min occur preferentially out of REM sleep. In both the short and long types of sleep interruptions, the duration of REM periods that ended in wakefulness were shorter than the duration of those that were not interrupted by wakefulness. REM densities of the REM periods that terminated in periods of wakefulness were higher than those of uninterrupted REM periods. The proportion of episodes of wakefulness following REM sleep that were long-lasting progressively increased over the course of the extended night period. The sleep episodes that followed the periods of wakefulness were characterised by a short REM latency. REM duration was increased in episodes that followed long sleep interruptions compared to those that followed short sleep interruptions. REM density did not appear to change significantly in the episodes that followed sleep interruption. REM sleep mechanisms appear to be the main force controlling sleep after a spontaneous sleep interruption, presumably because during the second half of the night, where more sleep interruptions occur, the pressure for non-rapid eye movement sleep is reduced and the circadian rhythm in REM sleep propensity reaches its peak. Processes promoting REM sleep at the
Peever, John; Fuller, Patrick M.
Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy. PMID:26766231
Grozinger, M; Beersma, DGM; Fell, J; Roschke, J
In selective REM sleep deprivation (SRSD), the occurrence of stage REM is repeatedly interrupted by short awakenings. Typically, the interventions aggregate in clusters resembling the REM episodes in undisturbed sleep. This salient phenomenon can easily be explained if the nonREM-REM sleep process
Crick, F; Mitchison, G
The broad features of rapid eye movement (REM) sleep are reviewed. Memory storage in the brain is probably quite unlike that in a digital computer, being distributed, superimposed and robust. Such memory systems are easily overloaded. If the stored memories share common features, random stimulation often produces mixed outputs. Simulations show that such overloading can be reduced by a process we call 'reverse learning'. We propose that this process is what is happening in REM sleep and that it explains in an unforced manner the condensation commonly found in dreams. Evidence for and against the proposed theory is discussed and several alternative theories are briefly described. The absence of REM sleep in the Enchidna and in two species of dolphins (that have relatively large brains) suggests that REM may allow the brain to be smaller than if REM were lacking.
McNamara, Patrick; Johnson, Patricia; McLaren, Deirdre; Harris, Erica; Beauharnais, Catherine; Auerbach, Sanford
We review the literature on the neurobiology of rapid eye movement (REM) and non-rapid eye movement (NREM) sleep states and associated dreams. REM is associated with enhanced activation of limbic and amygdalar networks and decreased activation in dorsal prefrontal regions while stage II NREM is associated with greater cortical activation than REM. Not surprisingly, these disparate brain activation patterns tend to be associated with dramatically different dream phenomenologies and dream content. We present two recent studies which content-analyzed hundreds of dream reports from REM and NREM sleep states. These studies demonstrated that dreamer-initiated aggressive social interactions were more characteristic of REM than NREM, and dreamer-initiated friendliness was more characteristic of NREM than REM reports. Both REM and NREM dreams therefore may function to simulate opposing types of social interactions, with the REM state specializing in simulation of aggressive interactions and the NREM state specializing in simulation of friendly interactions. We close our review with a summary of evidence that dream content variables significantly predict daytime mood and social interactions. Copyright © 2010 Elsevier Inc. All rights reserved.
Benington, J H; Heller, H C
We have hypothesized that REM sleep is functionally and homeostatically related to NREM sleep rather than to waking. In other words, REM sleep rather than to waking. In other words, REM sleep occurs in response to NREM-sleep expression and compensates for some process that takes place during NREM sleep. Under normal conditions, the need for REM sleep does not accrue during waking. The primary basis for this hypothesis is the fact that REM-sleep expression is a function of prior NREM-sleep expression. That is, REM sleep follows NREM sleep within sleep periods, REM-sleep episodes occur at intervals determined by the amount of NREM-sleep time elapsed, and total time spent in REM sleep is consistently about 1/4 of prior NREM-sleep time, regardless of how much time is spent in NREM sleep. Our experimental tests of the hypothesis support it. (1) REM-sleep propensity accumulates quite rapidly during a 2-hr interval spent predominantly in NREM sleep. (2) The timing of individual REM-sleep episodes is controlled homeostatically, by accumulation within NREM sleep of a propensity for REM sleep. The NREM sleep-related model of REM-sleep regulation (Fig. 1) explains a number of phenomena of REM-sleep expression, including the frequent and periodic occurrence of REM-sleep episodes throughout sleep periods, that have been accommodated by the waking-related model but are not functionally accounted for by it. In our opinion, the NREM sleep-related model of REM-sleep regulation recommends itself partly by its simplicity. According to the waking-related model, two independent and competing sleep propensities accumulate during waking and are discharged in two distinct sleep states that perform different waking-related recovery processes. One behaviour, sleep, is thought to perform two independent and competing functions that alternate at regular intervals. In the NREM sleep-related model of REM-sleep regulation, sleep debt simply reflects a need for NREM sleep. That is, the cerebrally
Grözinger, Michael; Beersma, Domien G.M.; Fell, Jürgen; Röschke, Joachim
In selective REM sleep deprivation (SRSD), the occurrence of stage REM is repeatedly interrupted by short awakenings. Typically, the interventions aggregate in clusters resembling the REM episodes in undisturbed sleep. This salient phenomenon can easily be explained if the nonREM–REM sleep process
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Ocampo-Garcés, Adrián; Hernández, Felipe; Palacios, Adrian G.
Study Objectives: To determine rapid eye movement (REM) sleep phase preference in a crepuscular mammal (Octodon degus) by challenging the specific REM sleep homeostatic response during the diurnal and nocturnal anticrepuscular rest phases. Design: We have investigated REM sleep rebound, recovery, and documented REM sleep propensity measures during and after diurnal and nocturnal selective REM sleep deprivations. Subjects: Nine male wild-captured O. degus prepared for polysomnographic recordings Interventions: Animals were recorded during four consecutive baseline and two separate diurnal or nocturnal deprivation days, under a 12:12 light-dark schedule. Three-h selective REM sleep deprivations were performed, starting at midday (zeitgeber time 6) or midnight (zeitgeber time 18). Measurements and Results: Diurnal and nocturnal REM sleep deprivations provoked equivalent amounts of REM sleep debt, but a consistent REM sleep rebound was found only after nocturnal deprivation. The nocturnal rebound was characterized by a complete recovery of REM sleep associated with an augment in REM/total sleep time ratio and enhancement in REM sleep episode consolidation. Conclusions: Our results support the notion that the circadian system actively promotes REM sleep. We propose that the sleep-wake cycle of O. degus is modulated by a chorus of circadian oscillators with a bimodal crepuscular modulation of arousal and a unimodal promotion of nocturnal REM sleep. Citation: Ocampo-Garcés A; Hernández F; Palacios AG. REM sleep phase preference in the crepuscular Octodon degus assessed by selective REM sleep deprivation. SLEEP 2013;36(8):1247-1256. PMID:23904685
McCarthy, Andrew; Wafford, Keith; Shanks, Elaine; Ligocki, Marcin; Edgar, Dale M; Dijk, Derk-Jan
Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 h of REM-sleep specific restriction through EEG-triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by paroxetine and citalopram were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
BEERSMA, DGM; VANDENHOOFDAKKER, RH
Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects
Beersma, Domien G.M.; Hoofdakker, Rutger H. van den
Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects
Brain activation patterns and mental, electrophysiological, and neurobiological features of rapid eye movement (REM) sleep suggest more functions than only elaborative encoding. Hence, the periodic occurrence of REM sleep episodes and dreaming may be regarded as a recurrent adaptive interference, which incorporates recent memories into a broader vital context comprising emotions, basic needs and individual genetic traits.
Kempfner, J; Sørensen, Gertrud Laura; Sorensen, H B D
Rapid eye movement sleep Behavior Disorder (RBD) is a strong early marker of later development of Parkinsonism. Currently there are no objective methods to identify and discriminate abnormal from normal motor activity during REM sleep. Therefore, a REM sleep detection without the use of chin...... electromyography (EMG) is useful. This is addressed by analyzing the classification performance when implementing two automatic REM sleep detectors. The first detector uses the electroencephalography (EEG), electrooculography (EOG) and EMG to detect REM sleep, while the second detector only uses the EEG and EOG....
Chung, Gih Sung; Choi, Byung Hoon; Lee, Jeong Su; Lee, Jin-Seong; Jeong, Do-Un; Park, Kwang Suk
Polysomnography (PSG) is currently considered the gold standard for assessing sleep quality. However, the numerous sensors that must be attached to the subject can disturb sleep and limit monitoring to within hospitals and sleep clinics. If data could be obtained without such constraints, sleep monitoring would be more convenient and could be extended to ordinary homes. During rapid-eye-movement (REM) sleep, respiration rate and variability are known to be greater than in other sleep stages. Hence, we calculated the average rate and variability of respiration in an epoch (30 s) by applying appropriate smoothing algorithms. Increased and irregular respiratory patterns during REM sleep were extracted using adaptive and linear thresholds. When both parameters simultaneously showed higher values than the thresholds, the epochs were assumed to belong to REM sleep. Thermocouples and piezoelectric-type belts were used to acquire respiratory signals. Thirteen healthy adults and nine obstructive sleep apnea (OSA) patients participated in this study. Kappa statistics showed a substantial agreement (κ > 0.60) between the standard and respiration-based methods. One-way ANOVA analysis showed no significant difference between the techniques for total REM sleep. This approach can also be applied to the non-intrusive measurement of respiration signals, making it possible to automatically detect REM sleep without disturbing the subject
Tilley, Andrew J.
Subjects, awaked, presented with a word list, and tested with arousal measures, were reawaked during REM or non-REM sleep and retested. Recall was facilitated by REM sleep. It was hypothesized that the high arousal level associated with REM sleep incidentally maintained the memory trace in a more retrievable form. (Author/SJL)
Batterink, Laura J; Westerberg, Carmen E; Paller, Ken A
Memory reactivation during slow-wave sleep (SWS) influences the consolidation of recently acquired knowledge. This reactivation occurs spontaneously during sleep but can also be triggered by presenting learning-related cues, a technique known as targeted memory reactivation (TMR). Here we examined whether TMR can improve vocabulary learning. Participants learned the meanings of 60 novel words. Auditory cues for half the words were subsequently presented during SWS in an afternoon nap. Memory performance for cued versus uncued words did not differ at the group level but was systematically influenced by REM sleep duration. Participants who obtained relatively greater amounts of REM showed a significant benefit for cued relative to uncued words, whereas participants who obtained little or no REM demonstrated a significant effect in the opposite direction. We propose that REM after SWS may be critical for the consolidation of highly integrative memories, such as new vocabulary. Reactivation during SWS may allow newly encoded memories to be associated with other information, but this association can include disruptive linkages with pre-existing memories. Subsequent REM sleep may then be particularly beneficial for integrating new memories into appropriate pre-existing memory networks. These findings support the general proposition that memory storage benefits optimally from a cyclic succession of SWS and REM. Copyright © 2017 Elsevier Inc. All rights reserved.
Eisensehr, I; Noachtar, S; Strupp, M; v, L; Brandt, T; Buttner, U
Saccades, including fast phases of nystagmus, disappear during drowsiness and non-rapid eye movement (NREM) sleep, but are present during the alert state and REM sleep. The purpose of this study was to determine whether spontaneous nystagmus is present in patients with vestibular neuritis during REM sleep. Eight patients with spontaneous nystagmus due to vestibular neuritis and eight control patients without any nystagmus underwent at least one night of polysomnography. Fa...
McDevitt, Elizabeth A; Duggan, Katherine A; Mednick, Sara C
Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. Copyright © 2014 Elsevier Inc. All rights reserved.
Beersma, D.G.M.; Dijk, D.J.; Blok, Guus; Everhardus, I.
Nine healthy male subjects were deprived of REM sleep during the first 5 h after sleep onset. Afterwards recovery sleep was undisturbed. During the deprivation period the non-REM EEG power spectrum was reduced when compared to baseline for the frequencies up to 7 Hz, despite the fact that non-REM
Kempfner, Jacob; Sørensen, Gertrud Laura; Sørensen, Helge Bjarup Dissing
Rapid eye movement sleep Behavior Disorder (RBD) is a strong early marker of later development of Parkinsonism. Currently there are no objective methods to identify and discriminate abnormal from normal motor activity during REM sleep. Therefore, a REM sleep detection without the use of chin...... electromyography (EMG) is useful. This is addressed by analyzing the classification performance when implementing two automatic REM sleep detectors. The first detector uses the electroencephalography (EEG), electrooculography (EOG) and EMG to detect REM sleep, while the second detector only uses the EEG and EOG....... Method: Ten normal controls and ten age matched patients diagnosed with RBD were enrolled. All subjects underwent one polysomnographic (PSG) recording, which was manual scored according to the new sleep-scoring standard from the American Academy of Sleep Medicine. Based on the manual scoring...
Murphy, P J; Rogers, N L; Campbell, S S
The stage from which the spontaneous ending of sleep occurred was investigated in 138 sleep episodes obtained from 14 younger (19-28 years) and 11 older (60-82 years) individuals. The possible influences of circadian phase and quality of the preceding sleep period, as well as the impact of aging on characteristics of sleep termination were examined. Under experimental conditions in which subjects were isolated from time cues, and behavioral options to sleep were limited, no age-associated differences in the duration of sleep periods, or in the number or duration of REM episodes were observed. Despite similar percentages of NREM (stages 2-4) and REM sleep across age groups, younger subjects awakened preferentially from REM while older subjects did not. Of the sleep episodes obtained from older subjects, those with sleep efficiencies higher than the median were more likely to terminate from REM than those with lower sleep efficiencies. For all subjects, the REM episodes from which sleep termination occurred were truncated relative to those that did not end the sleep period. In addition, nonterminating REM episodes that were interrupted by a stage shift were most often interrupted by brief arousals to stage 0. Such arousals within nonterminating REM episodes occurred, on average, after a similar duration as the terminating point of sleep-ending REM episodes. The results from this study demonstrate that there are age-related differences in the sleep stage from which spontaneous awakenings occur, and that these differences may be due in part to the quality of the sleep period preceding termination. Findings regarding the characteristics of both terminating and nonterminating REM episodes are consistent with the notion that the neural and biochemical context of REM sleep may facilitate a smooth transition to wakefulness. It is speculated that age-associated changes in sleep continuity may render unnecessary the putative role of REM sleep in providing a 'gate' to
Nader, Rebecca S.; Smith, Carlyle T.; Nixon, Margaret R.
Posttraining rapid eye movement (REM) sleep has been reported to be important for efficient memory consolidation. The present results demonstrate increases in the intensity of REM sleep during the night of sleep following cognitive procedural/implicit task acquisition. These REM increases manifest as increases in total number of rapid eye…
Kimura, M; Okano, S; Inoué, S
The aim of the present study was to determine the pattern of sleep disturbances and the effects on sleep of aniracetam, a cognitive enhancer, in stroke-prone spontaneously hypertensive rats (SHRSP). Compared with normotensive control rats, SHRSP exhibited an impaired sleep pattern characterized by suppressed diurnal rapid eye movement (REM) sleep and excessive nocturnal non-REM sleep. At a dose of 30 mg/kg per day p.o., aniracetam increased REM sleep in the light period after administration for 5 consecutive days. Consequently, suppressed REM sleep in SHRSP was restored by repeated treatment with aniracetam. Aniracetam could be useful in improving REM sleep impairment associated with vascular dementia.
Roman, Alexis; Meftah, Soraya; Arthaud, Sébastien; Luppi, Pierre-Hervé; Peyron, Christelle
Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. The three latter symptoms together with a short REM sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates. We first performed 48hrs of REM sleep deprivation using the classic small-platforms-over-water method. We found that narcoleptic mice are similarly REM sleep deprived to WT mice. Although they had shorter sleep latency, Orex-KO mice recovered similarly to WT during the following 10hrs of recovery. Interestingly, Orex-KO mice also had cataplexy episodes immediately after REM sleep deprivation, anticipating REM sleep rebound, at a time of day when cataplexy does not occur in baseline condition. We then evaluated REM sleep propensity using our new automated method of deprivation that performs a specific and efficient REM sleep deprivation. We showed that REM sleep propensity is similar during light phase in Orex-KO and WT mice. However, during the dark phase REM sleep propensity was not suppressed in Orex-KO mice when hypocretin/orexin neuropeptides are normally released. Altogether our data suggest that in addition to the well-known wake-promoting role of hypocretin/orexin, these neuropeptides would also suppress REM sleep. Therefore, hypocretin/orexin deficiency would facilitate the occurrence of REM sleep at any time of day in an opportunistic manner as seen in human narcolepsy.
Weber, Franz; Chung, Shinjae; Beier, Kevin T; Xu, Min; Luo, Liqun; Dan, Yang
Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.
We are at least as dream deprived as we are sleep deprived. Many of the health concerns attributed to sleep loss result from a silent epidemic of REM sleep deprivation. REM/dream loss is an unrecognized public health hazard that silently wreaks havoc with our lives, contributing to illness, depression, and an erosion of consciousness. This paper compiles data about the causes and extent of REM/dream loss associated with commonly used medications, endemic substance use disorders, rampant sleep disorders, and behavioral and lifestyle factors. It examines the consequences of REM/dream loss and concludes with recommendations for restoring healthy REM/dreaming. © 2017 New York Academy of Sciences.
Neikrug, Ariel B; Ancoli-Israel, Sonia
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during REM sleep that results in motor behaviors. Diagnosis of RBD involves a clinical interview in which history of dream enactment behaviors is elicited and a subsequent overnight polysomnography (PSG) evaluation to assess for REM sleep without atonia (RWA) and/or observe motor behaviors during REM sleep. Therefore, the nature of RBD diagnosis involves both subjective and objective measurements that attempt to qualify and quantify the different diagnostic sub-criteria. The primary aim of the current study was to identify and summarize the available clinical measurements that have been used for RBD assessment. Two major online databases (MEDLINE and PsycInfo) were searched for articles developing, validating, or evaluating psychometric properties of the RBD diagnostic criteria or methods used for diagnosis. Studies of adult subjects (18 years or more) that included sufficient psychometric data for validation were included. Fifty-eight studies were found to meet review criteria. The objective measurements for assessment of RBD reviewed included visual electromyographic (EMG) scoring methods, computerized EMG scoring methods, cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy, actigraphy, behavioral classification and video analysis. Subjective measurements of RBD included interviews and questionnaires. Sleep history may be sufficient for diagnosis of RBD in some populations. However, PSG is necessary for a definitive diagnosis. EMG scoring methods vary in definition used and there is no single accepted approach to scoring muscle activity. Additional validation studies are required for establishing cutoff scores for the different methods. Questionnaires were shown to be appropriate screening tools, yet further validation in different populations is necessary. Copyright © 2011 Elsevier Ltd. All rights reserved.
Ferri, Raffaele; Rundo, Francesco; Silvani, Alessandro; Zucconi, Marco; Bruni, Oliviero; Ferini-Strambi, Luigi; Plazzi, Giuseppe; Manconi, Mauro
We aimed to analyze quantitatively rapid eye movement (REM) sleep electroencephalogram (EEG) in controls, drug-naïve idiopathic REM sleep behavior disorder patients (iRBD), and iRBD patients treated with clonazepam. Twenty-nine drug-naïve iRBD patients (mean age 68.2 years), 14 iRBD patients under chronic clonazepam therapy (mean age 66.3 years), and 21 controls (mean age 66.8 years) were recruited. Power spectra were obtained from sleep EEG (central derivation), using a 2-second sliding window, with 1-second steps. The power values of each REM sleep EEG spectral band (one every second) were normalized with respect to the average power value obtained during sleep stage 2 in the same individual. In drug-naïve patients, the normalized power values showed a less pronounced REM-related decrease of power in all bands with frequency sleep EEG structure changes found in this study disclose subtle but significant alterations in the cortical electrophysiology of RBD that might represent the early expression of the supposed neurodegenerative processes already taking place at this stage of the disease and might be the target of better and effective future therapeutic strategies for this condition. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail email@example.com.
Preeti Devnani; Racheal Fernandes
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, ...
Full Text Available A 45-year-old woman with a past medical history of hypertension and chronic headaches was referred to the sleep laboratory for high clinical suspicion for sleep apnea based on a history of snoring, witnessed apnea and excessive daytime sleepiness. An overnight sleep study was performed. Images during N3 Sleep and REM sleep are shown (Figures 1 and 2. Alpha intrusion in delta sleep is seen in patients with fibromyalgia, depression, chronic fatigue syndrome, anxiety disorder, and primary sleep disorders like psychophysiological insomnia, obstructive sleep apnea, circadian disorders and narcolepsy (1. Bursts of alpha waves during REM sleep may be more common during phasic REM than tonic REM. The REM alpha bursts (alpha activity lasting at least 3 seconds without an increase in EMG amplitude may represent microarousals (2. Hypersynchronous theta activity should be differentiated from the spike and waveform activity seen in seizures.
Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J
The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.
Full Text Available The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers. Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1 placebo analgesia improved with REM sleep deprivation; 2 pain relief expectations did not differ between REM sleep deprivation and control groups; and 3 REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.
McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Arndt, Katlyn; Erickson, Maia; Tabatabai, Grace; Boeve, Bradley F; Silber, Michael H
REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Tertiary-care sleep center. Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. N/A. RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD. © 2015 Associated Professional Sleep Societies, LLC.
Kempfner, Jacob; Jennum, Poul; Nikolic, Miki
Idiopathic Rapid-Rye-Movement (REM) sleep Behavior Disorder (iRBD) is a strong early marker of Parkinson's Disease and is characterized by REM sleep without atonia (RSWA) and increased phasic muscle activity. Current proposed methods for detecting RSWA assume the presence of a manually scored...
Fraigne, Jimmy J.; Torontali, Zoltan A.; Snow, Matthew B.; Peever, John H.
Rapid eye movement (REM) sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain, and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC) or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC cells activate neurons in the ventral medial medulla, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray and dorsal paragigantocellular reticular nucleus as well as melanin-concentrating hormone neurons in the hypothalamus and cholinergic cells in the laterodorsal and pedunculo-pontine tegmentum in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie narcolepsy/cataplexy and REM sleep behavior disorder (RBD). This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD. PMID:26074874
Full Text Available REM sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC activate neurons in the ventral medial medulla (VMM, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG and dorsal paragigantocellular reticular nucleus (DPGi as well as melanin-concentrating hormone (MCH neurons in the hypothalamus and cholinergic cells in the laterodorsal (LDT and pedunculo-pontine tegmentum (PPT in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie cataplexy/narcolepsy and REM sleep behaviour disorder (RBD. This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD.
Maren Jasmin Cordi
Full Text Available Memory reactivations in hippocampal brain areas are critically involved in memory consolidation processes during sleep. In particular, specific firing patterns of hippocampal place cells observed during learning are replayed during subsequent sleep and rest in rodents. In humans, experimentally inducing hippocampal memory reactivations during slow-wave sleep (but not during wakefulness benefits consolidation and immediately stabilizes declarative memories against future interference. Importantly, spontaneous hippocampal replay activity can also be observed during rapid-eye movement (REM sleep and some authors have suggested that replay during REM sleep is related to processes of memory consolidation. However, the functional role of reactivations during REM sleep for memory stability is still unclear. Here, we reactivated memories during REM sleep and examined its consequences for the stability of declarative memories. After three hours of early, slow-wave sleep (SWS rich sleep, 16 healthy young adults learned a 2-D object location task in the presence of a contextual odor. During subsequent REM sleep, participants were either re-exposed to the odor or to an odorless vehicle, in a counterbalanced within subject design. Reactivation was followed by an interference learning task to probe memory stability after awakening. We show that odor-induced memory reactivation during REM sleep does not stabilize memories against future interference. We propose that the beneficial effect of reactivation during sleep on memory stability might be critically linked to processes characterizing SWS including, e.g., slow oscillatory activity, sleep spindles or low cholinergic tone, which are required for a successful redistribution of memories from medial temporal lobe regions to neocortical long-term stores.
Girard, Todd A; Cheyne, J Allan
The objective of this prospective naturalistic field study was to determine the distribution of naturally occurring sleep-paralysis (SP) episodes over the course of nocturnal sleep and their relation to bedtimes. Regular SP experiencers (N = 348) who had previously filled out a screening assessment for SP as well as a general sleep survey were recruited. Participants reported, online over the World Wide Web, using a standard reporting form, bedtimes and subsequent latencies of spontaneous episodes of SP occurring in their homes shortly after their occurrence. The distribution of SP episodes over nights was skewed to the first 2 h following bedtime. Just over one quarter of SP episodes occurred within 1 h of bedtime, although episodes were reported throughout the night with a minor mode around the time of normal waking. SP latencies following bedtimes were moderately consistent across episodes and independent of bedtimes. Additionally, profiles of SP latencies validated self-reported hypnagogic, hypnomesic, and hypnopompic SP categories, as occurring near the beginning, middle, and end of the night/sleep period respectively. Results are consistent with the hypothesis that SP timing is controlled by mechanisms initiated at or following sleep onset. These results also suggest that SP, rather than uniquely reflecting anomalous sleep-onset rapid eye movement (REM) periods, may result from failure to maintain sleep during REM periods at any point during the sleep period. On this view, SP may sometimes reflect the maintenance of REM consciousness when waking and SP hallucinations the continuation of dream experiences into waking life.
Chica-Urzola, Heydy Luz
This case concerns an elderly man with a REM sleep behavior disorder, who was initially offered a pharmacological treatment with clonazepam, recommended by other articles, but with poor adherence due to its adverse reactions and persistence of symptoms. He was then offered a treatment with Trazodone was offered, achieving a complete remission of symptoms, with no reported side effects. It is clear that Trazodone has no known indication for this type of disorder; nevertheless, it was considered in this case because of its pharmacological profile, obtaining satisfactory results. Further research is needed in order to document thoroughly the mechanisms of action, efficacy and utility of this molecule in cases such as the one presented. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.
Jung, Youngsin; St Louis, Erik K
REM sleep behavior disorder (RBD) is a common parasomnia disorder affecting between 1 and 7 % of community-dwelling adults, most frequently older adults. RBD is characterized by nocturnal complex motor behavior and polysomnographic REM sleep without atonia. RBD is strongly associated with synucleinopathy neurodegeneration. The approach to RBD management is currently twofold: symptomatic treatment to prevent injury and prognostic counseling and longitudinal follow-up surveillance for phenoconversion toward overt neurodegenerative disorders. The focus of this review is symptomatic treatment for injury prevention. Injury occurs in up to 55 % of patients prior to treatment, even when most behaviors seem to be infrequent or minor, so patients with RBD should be treated promptly following diagnosis to prevent injury risk. A sound evidence basis for symptomatic treatment of RBD remains lacking, and randomized controlled treatment trials are needed. Traditional therapeutic mainstays with relatively robust retrospective case series level evidence include melatonin and clonazepam, which appear to be equally effective, although melatonin is more tolerable. Melatonin also has one small randomized controlled crossover trial supporting its use for RBD treatment. Melatonin dosed 3-12 mg at bedtime should be considered as the first-line therapy, followed by clonazepam 0.25-2.0 mg at bedtime if initial melatonin is judged ineffective or intolerable. However, neither agent is likely to completely stop dream enactment behaviors, so choosing a moderate target dosage of melatonin 6 mg or clonazepam 0.5 mg, or the highest tolerable dosage that reduces attack frequency and avoids adverse effects from overtreatment, is currently the most reasonable strategy. Alternative second- and third-line therapies with anecdotal efficacy include temazepam, lorazepam, zolpidem, zopiclone, pramipexole, donepezil, ramelteon, agomelatine, cannabinoids, and sodium oxybate. A novel non
Ahmed, Samreen; Meng, He; Liu, Tiecheng; Sutton, Blair; Opp, Mark R.; Borjigin, Jimo; Wang, Michael M.
Sleep disorders are important risk factors for stroke; conversely, stroke patients suffer from sleep disturbances including disruptions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and a decrease in total sleep. This study was performed to characterize the effect of stroke on sleep architecture of rats using continuous electroencephalography (EEG) and activity monitoring. Rats were implanted with transmitters which enabled continuous real time recording of EEG, electrom...
McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Duwell, Ethan J; Timm, Paul C; Boeve, Bradley F; Silber, Michael H
We aimed to determine whether visual and automated rapid eye movement (REM) sleep without atonia (RSWA) methods could accurately diagnose patients with idiopathic REM sleep behavior disorder (iRBD) and comorbid obstructive sleep apnea (OSA). In iRBD patients (n = 15) and matched controls (n = 30) with and without OSA, we visually analyzed RSWA phasic burst durations, phasic, tonic, and "any" muscle activity by 3-s mini-epochs, phasic activity by 30-s (AASM rules) epochs, and automated REM atonia index (RAI). Group RSWA metrics were analyzed with regression models. Receiver operating characteristic (ROC) curves were used to determine the best diagnostic cutoff thresholds for REM sleep behavior disorder (RBD). Both split-night and full-night polysomnographic studies were analyzed. All mean RSWA phasic burst durations and muscle activities were higher in iRBD patients than in controls (p sleep behavior disorder (PD-RBD), consistent with a common mechanism and presumed underlying etiology of synucleinopathy in both groups. Copyright © 2016 Elsevier B.V. All rights reserved.
Frauscher, Birgit; Jennum, Poul; Ju, Yo-El S
OBJECTIVE: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. METHODS: Data of a self-administered questionnaire...
Nielsen, T; O'Reilly, C; Carr, M; Dumel, G; Godin, I; Solomonova, E; Lara-Carrasco, J; Blanchette-Carrière, C; Paquette, T
Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them. Copyright © 2014 Elsevier Inc. All rights reserved.
Tamminen, Jakke; Lambon Ralph, Matthew A; Lewis, Penelope A
Recent memories are spontaneously reactivated during sleep, leading to their gradual strengthening. Whether reactivation also mediates the integration of new memories with existing knowledge is unknown. We used targeted memory reactivation (TMR) during slow-wave sleep (SWS) to selectively cue reactivation of newly learned spoken words. While integration of new words into their phonological neighbourhood was observed in both cued and uncued words after sleep, TMR-triggered integration was predicted by the time spent in rapid eye movement (REM) sleep. These data support complementary roles for SWS and REM in memory consolidation. Copyright © 2016 Elsevier Inc. All rights reserved.
Dr. W. R. eKlemm
Full Text Available Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses REM to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, 1 when first going to sleep, the brain plunges into Stage N3 (formerly called Stage IV, a deep abyss of sleep, and, as the night progresses, the sleep is punctuated by episodes of REM that become longer and more frequent toward morning, 2 conscious-like dreams are a reliable component of the REM state in which the dreamer is an active mental observer or agent in the dream, 3 the last awakening during a night’s sleep usually occurs in a REM episode during or at the end of a dream, 4 both REM and awake consciousness seem to arise out of a similar brainstem ascending arousal system 5 N3 is a functionally perturbed state that eventually must be corrected so that embodied brain can direct adaptive behavior, and 6 corticofugal projections to brainstem arousal areas provide a way to trigger increased cortical activity in REM to progressively raise the sleeping brain to the threshold required for wakefulness. This paper shows how the hypothesis conforms to common experience and has substantial predictive and explanatory power regarding the phenomenology of sleep in terms of ontogeny, aging, phylogeny, abnormal/disease states, cognition, and behavioral physiology. That broad range of consistency is not matched by competing theories, which are summarized herein. Specific ways to test this wake-up hypothesis are suggested. Such research could lead to a better understanding of awake consciousness.
Klemm, W R
Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses rapid eye movement (REM) to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, (1) when first going to sleep, the brain plunges into Stage N3 (formerly called Stage IV), a deep abyss of sleep, and, as the night progresses, the sleep is punctuated by episodes of REM that become longer and more frequent toward morning, (2) conscious-like dreams are a reliable component of the REM state in which the dreamer is an active mental observer or agent in the dream, (3) the last awakening during a night's sleep usually occurs in a REM episode during or at the end of a dream, (4) both REM and awake consciousness seem to arise out of a similar brainstem ascending arousal system (5) N3 is a functionally perturbed state that eventually must be corrected so that embodied brain can direct adaptive behavior, and (6) cortico-fugal projections to brainstem arousal areas provide a way to trigger increased cortical activity in REM to progressively raise the sleeping brain to the threshold required for wakefulness. This paper shows how the hypothesis conforms to common experience and has substantial predictive and explanatory power regarding the phenomenology of sleep in terms of ontogeny, aging, phylogeny, abnormal/disease states, cognition, and behavioral physiology. That broad range of consistency is not matched by competing theories, which are summarized herein. Specific ways to test this wake-up hypothesis are suggested. Such research could lead to a better understanding of awake consciousness.
Oudiette, Delphine; Dodet, Pauline; Ledard, Nahema; Artru, Emilie; Rachidi, Inès; Similowski, Thomas; Arnulf, Isabelle
Breathing is irregular during rapid eye-movement (REM) sleep, whereas it is stable during non-REM sleep. Why this is so remains a mystery. We propose that irregular breathing has a cortical origin and reflects the mental content of dreams, which often accompany REM sleep. We tested 21 patients with narcolepsy who had the exceptional ability to lucid dream in REM sleep, a condition in which one is conscious of dreaming during the dream and can signal lucidity with an ocular code. Sleep and respiration were monitored during multiple naps. Participants were instructed to modify their dream scenario so that it involved vocalizations or an apnoea, -two behaviours that require a cortical control of ventilation when executed during wakefulness. Most participants (86%) were able to signal lucidity in at least one nap. In 50% of the lucid naps, we found a clear congruence between the dream report (e.g., diving under water) and the observed respiratory behaviour (e.g., central apnoea) and, in several cases, a preparatory breath before the respiratory behaviour. This suggests that the cortico-subcortical networks involved in voluntary respiratory movements are preserved during REM sleep and that breathing irregularities during this stage have a cortical/subcortical origin that reflects dream content.
Chen, Lichao; McKenna, James T.; Bolortuya, Yunren; Brown, Ritchie E.
Dysfunction of the orexin/hypocretin neurotransmitter system causes the sleep disorder narcolepsy, characterized by intrusion of rapid-eye-movement (REM) sleep-like events into normal wakefulness. The sites where orexins act to suppress REM sleep are incompletely understood. Previous studies suggested that the lateral pontomesencephalic tegmentum (lPMT) contains an important REM sleep inhibitory area, and proposed that orexins inhibit REM sleep via orexin type 2 receptors (OxR2) in this regio...
Walker, Matthew P; Liston, Conor; Hobson, J Allan; Stickgold, Robert
Flexible or 'fluid' cognitive processes are regarded as fundamental to problem solving and creative ability, requiring a specific neurophysiological milieu. REM-sleep dreaming is associated with creative processes and abstract reasoning with increased strength of weak associations in cognitive networks. REM sleep is also mediated by a distinctive neurophysiological profile, different to that of wake and NREM sleep. This study compared the performance of 16 subjects on a test of cognitive flexibility using anagram word puzzles following REM and NREM awakenings across the night, and waking performances during the day. REM awakenings provided a significant 32% advantage in the number of anagrams solved compared with NREM awakenings and was equal to that of wake time trials. Correlations of individual performance profiles suggest that REM sleep may offer a different mode of problem solving compared with wake and NREM. When early and late REM and NREM awakening data were separated, a dissociation was evident, with NREM task performance becoming more REM-like later in the night, while REM performance remained constant. These data suggest that the neurophysiology of REM sleep represents a brain state more amenable to flexible cognitive processing than NREM and different from that in wake, and may offer insights into the neurocognitive properties of REM-sleep dreaming.
Ng, Marcus C
Interest in orexin receptor antagonism as a novel mechanism of action against seizures and epilepsy has increased in recent years. Loss of orexinergic activity is associated with rapid eye movement (REM) sleep onset, and REM sleep is generally protective against seizures. This paper discusses the dynamic modulation of seizure threshold by orexin through a postulated "orexi-cortical" axis in which the specific type of orexinergic activity exquisitely regulates sleep-wake states to modify ascending subcortical influences on cortical synchronization with profound subsequent consequences on seizure threshold. This paper also explores the current state of research into experimental orexinergic modulation of seizure threshold and suggests possible future research directions to fully understand the promise and peril of orexinergic manipulation in seizures and epilepsy. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail firstname.lastname@example.org.
Full Text Available Scientific BACKGROUND: Rapid eye movement (REM sleep behavior disorder (RBD is a parasomnia characterised by dream-enacting behaviors and loss of normal REM sleep muscle atonia. It could occur idiopathically or accompanying neurodegenerative diseases. “Acting out of dreams” permits violent or injurious behaviors. These behaviors could result in laceration, fractures, subdural haematomas and so on. In developed countries, the legal implications of these behaviors have been discussing and debating in medical and legal literature. But in Turkey, legal aspects of RBD have not discussed yet. CONCLUSION: In this review, the clinic, pathopysiology, therapy and medicolegal aspects of RBD is discussed
The hypocretinergic neurons are active during wakefulness in conjunction with the presence of motor activity that occurs during survival-related behaviors. These neurons decrease their firing rate during non-REM sleep; however there is still controversy upon the activity and role of these neurons during REM sleep. Hence, in the present report we conducted a critical review of the literature of the hypocretinergic system during REM sleep, and hypothesize a possible role of this system in the generation of REM sleep.
Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi
STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown...... that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated...... in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. CONCLUSIONS: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD....
Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi B
STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown...... that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated......-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. CONCLUSIONS: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD....
Justin R Dunmyre
Full Text Available Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on and REM sleep-inhibiting (REM-off neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data
Postuma, R B; Montplaisir, J Y; Pelletier, A
Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors...
Carr, Michelle; Nielsen, Tore
Study Objectives: The goals of the study were to assess semantic priming to emotion and nonemotion cue words using a novel measure of associational breadth for participants who either took rapid eye movement (REM) or nonrapid eye movement (NREM) naps or who remained awake, and to assess the relation of priming to REM sleep consolidation and REM sleep inertia effects. Design: The associational breadth task was applied in both a priming condition, where cue words were signaled to be memorized prior to sleep (primed), and a nonpriming condition, where cue words were not memorized (nonprimed). Cue words were either emotional (positive, negative) or nonemotional. Participants were randomly assigned to either an awake (WAKE) or a sleep condition, which was subsequently split into NREM or REM groups depending on stage at awakening. Setting: Hospital-based sleep laboratory. Participants: Fifty-eight healthy participants (22 male) ages 18 to 35 y (mean age = 23.3 ± 4.08 y). Measurements and Results: The REM group scored higher than the NREM or WAKE groups on primed, but not nonprimed emotional cue words; the effect was stronger for positive than for negative cue words. However, REM time and percent correlated negatively with degree of emotional priming. Priming occurred for REM awakenings but not for NREM awakenings, even when the latter sleep episodes contained some REM sleep. Conclusions: Associational breadth may be selectively consolidated during REM sleep for stimuli that have been tagged as important for future memory retrieval. That priming decreased with REM time and was higher only for REM sleep awakenings is consistent with two explanatory REM sleep processes: REM sleep consolidation serving emotional downregulation and REM sleep inertia. Citation: Carr M, Nielsen T. Morning REM sleep naps facilitate broad access to emotional semantic networks. SLEEP 2015;38(3):433–443. PMID:25409100
Morgenthaler, Jarste; Wiesner, Christian D.; Hinze, Karoline; Abels, Lena C.; Prehn-Kristensen, Alexander; Göder, Robert
Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N = 29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both ...
Christensen, Julie Anja Engelhard; Jennum, Poul; Koch, Henriette
Objective: Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are at high risk of developing Parkinson's disease (PD). As wake/sleep-regulation is thought to involve neurons located in the brainstem and hypothalamic areas, we hypothesize that the neurodegeneration in i...... with periodic leg movement disorder (PLMD) and 23 controls. Measures were computed based on manual scorings and data-driven labeled sleep staging. Results: Patients with PD showed significantly lower REM stability than controls and patients with PLMD. Patients with iRBD had significantly lower REM stability......RBD/PD is likely to affect wake/sleep and REM/non-REM (NREM) sleep transitions. Methods: We determined the frequency of wake/sleep and REM/NREM sleep transitions and the stability of wake (W), REM and NREM sleep as measured by polysomnography (PSG) in 27 patients with PD, 23 patients with iRBD, 25 patients...
Li, Wei; Ma, Lei; Yang, Guang; Gan, Wen-Biao
The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.
Iranzo, A; Santamaria, J
A 24-year-old man with sporadic hyperkalemic periodic paralysis (HPP) presented with moderate excessive daytime sleepiness and transitory episodes of weakness which occurred during and after sleep. Multiple sleep latency test (MSLT) demonstrated the presence of five sleep onset REM periods (SOREMPs) and a sleep latency of five minutes. Treatment with a diuretic which decreases serum potassium resolved all the clinical symtomps and a new MSLT showed the absence of SOREMPs and a sleep latency of 13.5 minutes. To our knowledge, the patient herein reported is the first case that associates sleep abnormalities and multiple SOREMPs with HPP. Furthermore, the present case suggests that SOREMPs may be explained by an increased extracellular potassium conductance related to HPP.
Brooks, Patricia L; Peever, John
During REM sleep, skeletal muscles are paralyzed in one moment but twitch and jerk in the next. REM sleep twitches are traditionally considered random motor events that result from momentary lapses in REM sleep paralysis [1-3]. However, recent evidence indicates that twitches are not byproducts of REM sleep, but are in fact self-generated events that could function to promote motor learning and development [4-6]. If REM twitches are indeed purposefully generated, then they should be controlled by a coordinated and definable mechanism. Here, we used behavioral, electrophysiological, pharmacological, and neuroanatomical methods to demonstrate that an inhibitory drive onto skeletal motoneurons produces a temporally coordinated pattern of muscle twitches during REM sleep. First, we show that muscle twitches in adult rats are not uniformly distributed during REM sleep, but instead follow a well-defined temporal trajectory. They are largely absent during REM initiation but increase steadily thereafter, peaking toward REM termination. Next, we identify the transmitter mechanism that controls the temporal nature of twitch activity. Specifically, we show that a GABA and glycine drive onto motoneurons prevents twitch activity during REM initiation, but progressive weakening of this drive functions to promote twitch activity during REM termination. These results demonstrate that REM twitches are not random byproducts of REM sleep, but are instead rather coherently generated events controlled by a temporally variable inhibitory drive. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kevin P Grace
Full Text Available Rapid eye movement (REM sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of rapid eye movement (REM sleep generation posited that induction of the state required activation of the ‘pontine REM sleep generator’ by cholinergic inputs. Here we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii loss-of-function studies show that endogenous cholinergic input to the PFT is not required for REM sleep generation, and (iv Cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.
Casey, Sarah J; Solomons, Luke C; Steier, Joerg; Kabra, Neeraj; Burnside, Anna; Pengo, Martino F; Moxham, John; Goldstein, Laura H; Kopelman, Michael D
It has been debated whether different stages in the human sleep cycle preferentially mediate the consolidation of explicit and implicit memories, or whether all of the stages in succession are necessary for optimal consolidation. Here we investigated whether the selective deprivation of slow wave sleep (SWS) or rapid eye movement (REM) sleep over an entire night would have a specific effect on consolidation in explicit and implicit memory tasks. Participants completed a set of explicit and implicit memory tasks at night, prior to sleep. They had 1 control night of undisturbed sleep and 2 experimental nights, during which either SWS or REM sleep was selectively deprived across the entire night (sleep conditions counterbalanced across participants). Polysomnography recordings quantified precisely the amount of SWS and REM sleep that occurred during each of the sleep conditions, and spindle counts were recorded. In the morning, participants completed the experimental tasks in the same sequence as the night before. SWS deprivation disrupted the consolidation of explicit memories for visuospatial information (ηp2 = .23), and both SWS (ηp2 = .53) and REM sleep (ηp2 = .52) deprivation adversely affected explicit verbal recall. Neither SWS nor REM sleep deprivation affected aspects of short-term or working memory, and did not affect measures of verbal implicit memory. Spindle counts did not correlate significantly with memory performance. These findings demonstrate the importance of measuring the sleep cycles throughout the entire night, and the contribution of both SWS and REM sleep to memory consolidation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Devnani, Preeti; Fernandes, Racheal
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, impact on falls, and effect on polysomnography (PSG) while highlighting the non-motor, autonomic, and cognitive impact of this entity. PubMed databases were reviewed upto May 2013 in peer-reviewed scientific literature regarding the pathophysiology and management of RBD in adults. The literature was graded according to the Oxford centre of evidence-based Medicine Levels. An early intervention that helps prevent consequences such as falls and provides a base for intervention with neuroprotective mechanisms and allocates a unique platform that RBD portrays with its high risk of disease conversion with a sufficiently long latency. RBD provides a unique platform with its high risk of disease conversion with a sufficiently long latency, providing an opportunity for early intervention both to prevent consequences such as falls and provide a base for intervention with neuroprotective mechanisms.
Full Text Available Rapid eye movement (REM sleep behavior disorder (RBD is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, impact on falls, and effect on polysomnography (PSG while highlighting the non-motor, autonomic, and cognitive impact of this entity. PubMed databases were reviewed upto May 2013 in peer-reviewed scientific literature regarding the pathophysiology and management of RBD in adults. The literature was graded according to the Oxford centre of evidence-based Medicine Levels. An early intervention that helps prevent consequences such as falls and provides a base for intervention with neuroprotective mechanisms and allocates a unique platform that RBD portrays with its high risk of disease conversion with a sufficiently long latency. RBD provides a unique platform with its high risk of disease conversion with a sufficiently long latency, providing an opportunity for early intervention both to prevent consequences such as falls and provide a base for intervention with neuroprotective mechanisms.
Hobson, J Allan
Dreaming has fascinated and mystified humankind for ages: the bizarre and evanescent qualities of dreams have invited boundless speculation about their origin, meaning and purpose. For most of the twentieth century, scientific dream theories were mainly psychological. Since the discovery of rapid eye movement (REM) sleep, the neural underpinnings of dreaming have become increasingly well understood, and it is now possible to complement the details of these brain mechanisms with a theory of consciousness that is derived from the study of dreaming. The theory advanced here emphasizes data that suggest that REM sleep may constitute a protoconscious state, providing a virtual reality model of the world that is of functional use to the development and maintenance of waking consciousness.
Perchance to dream? Primordial motor activity patterns in vertebrates from fish to mammals: their prenatal origin, postnatal persistence during sleep, and pathological reemergence during REM sleep behavior disorder.
Corner, Michael A; Schenck, Carlos H
An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodically modulated, neurogenic bursts of non-purposive movements are a universal feature of larval and prenatal behavior, which in endothermic animals (i.e. birds and mammals) continue to occur periodically throughout life. Since the entire body musculature is involved in ever-shifting combinations, it is proposed that these spontaneously active periods be designated as 'rapid-BODY-movement' (RBM) sleep. The term 'rapid-EYE-movement (REM) sleep', characterized by attenuated muscle contractions and reduced tonus, can then be reserved for sleep at later stages of development. Mature stages of development in which sustained muscle atonia is combined with 'paradoxical arousal' of cortical neuronal firing patterns indisputably represent the evolutionarily most recent aspect of REM sleep, but more research with ectothermic vertebrates, such as fish, amphibians and reptiles, is needed before it can be concluded (as many prematurely have) that RBM is absent in these species. Evidence suggests a link between RBM sleep in early development and the clinical condition known as 'REM sleep behavior disorder (RBD)', which is characterized by the resurgence of periodic bouts of quasi-fetal motility that closely resemble RBM sleep. Early developmental neuromotor risk factors for RBD in humans also point to a relationship between RBM sleep and RBD.
La Berge, S P; Nagel, L E; Dement, W C; Zarcone, V P
The occurrence of lucid dreaming (dreaming while being conscious that one is dreaming) has been verified for 5 selected subjects who signaled that they knew they were dreaming while continuing to dream during unequivocal REM sleep. The signals consisted of particular dream actions having observable concomitants and were performed in accordance with pre-sleep agreement. The ability of proficient lucid dreamers to signal in this manner makes possible a new approach to dream research--such subjects, while lucid, could carry out diverse dream experiments marking the exact time of particular dream events, allowing derivation of of precise psychophysiological correlations and methodical testing of hypotheses.
Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Guo, Yang
Objectives We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Design Adult male Sprague Dawley rats were treated with either MD or MC procedures for ten days starting at postnatal day 4. At three months of age, sleep was recorded for 48 hours in one set of MD and MC rats while another set of MD and MC rats were measured for locomotor activity (under LD=12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Results Compared with the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared with the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Conclusion Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein. PMID:21805687
Kobayashi, T; Ishikawa, T; Arakawa, K
The effects of mental and physical daytime activities upon REM sleep cycle (REM cycle) during 1 night was studied in five university students (aged 19-25 years). Mental activity with high tension has effects upon the timing of REM sleep periods in the later part of the night. Physical activity has effects upon the timing of REM sleep in the early part of the night. The result suggests that mental and/or physical activities during daytime modulate REM cycle during the night.
Full Text Available Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students were separated into two groups (undisturbed sleep and selective REM-sleep deprived. Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever.
Morgenthaler, Jarste; Wiesner, Christian D; Hinze, Karoline; Abels, Lena C; Prehn-Kristensen, Alexander; Göder, Robert
Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional) between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever.
Drakatos, Panagis; Suri, Angula; Higgins, Sean E; Ebrahim, Irshaad O; Muza, Rexford T; Kosky, Christopher A; Williams, Adrian J; Leschziner, Guy D
The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N-C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N-C only 52% arose from NREM1. Within the N-C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.
Full Text Available Primary and secondary processes are the foundational axes of the Freudian mental apparatus: one horizontally as a tendency to associate, the primary process, and one vertically as the ability for perspective taking, the secondary process. Primary process mentation is not only supposed to be dominant in the unconscious but also, for example, in dreams. The present study tests the hypothesis that the mental activity during REM-sleep has more characteristics of the primary process, while during non-REM-sleep more secondary process operations take place. Because the solving of a rebus requires the ability to non-contexually condensate the literal reading of single stimuli into a new one, rebus solving is a primary process operation by excellence. In a replication of the dream-rebus study of Shevrin and Fisher (1967, a rebus, which consisted of an image of a comb (German: “Kamm” and an image of a raft (German: “Floß”, resulting in the German rebus word “kampflos” (Engl.: without a struggle, was flashed subliminally (at 1 ms to 20 participants before going to sleep. Upon consecutive awakenings participants were asked for a dream report, free associations and an image description. Based on objective association norms, there were significantly more conceptual associations referring to Kamm and Floß indexing secondary process mentation when subjects were awakened from non-REM sleep as compared to REM-awakenings. There were not significantly more rebus associations referring to kampflos indexing primary process mentation when awakened from REM-sleep as compared to non-REM awakenings. However, when the associations were scored on the basis of each subject’s individual norms, there was a rebus effect with more idiosyncratic rebus associations in awakenings after REM than after non-REM-sleep. Our results support the general idea that REM-sleep is characterized by primary process thinking, while non-REM-sleep mentation follows the rules of the
Full Text Available Numerous data show a reciprocal interaction between REM sleep and thermoregulation. During REM sleep, the function of thermoregulation appears to be impaired; from the other hand, the tonic activation of thermogenesis, such as during cold exposure, suppresses REM sleep occurrence. Recently, both the central neural network controlling REM sleep and the central neural network controlling thermoregulation have been progressively unraveled. Thermoregulation was shown to be controlled by a central “core” circuit, responsible for the maintenance of body temperature, modulated by a set of accessory areas. REM sleep was suggested to be controlled by a group of hypothalamic neurons overlooking at the REM sleep generating circuits within the brainstem. The two networks overlap in a few areas, and in this review, we will suggest that in such overlap may reside the explanation of the reciprocal interaction between REM sleep and thermoregulation. Considering the peculiar modulation of thermoregulation by REM sleep the result of their coincidental evolution, REM sleep may therefore be seen as a period of transient heterothermy.
Full Text Available Converging evidence from animal and human studies suggest that REM sleep modulates emotional processing. The aim of the present study was to explore the effects of selective REM sleep deprivation on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging (fMRI. Twenty healthy subjects were randomly assigned to two groups: selective REM sleep deprivation (REM-D, by awakening them at each REM sleep onset, or NREM sleep interruptions (NREM-I as control for potential non-specific effects of awakenings and lack of sleep. In a within-subject design, a visual emotional-reactivity task was performed in the scanner before and 24 hours after sleep manipulation. Behaviorally, emotional reactivity was enhanced relative to baseline in the REM deprived group only. In terms of fMRI signal, there was an overall decrease in activity in the NREM-I group the second time subjects performed the task, particularly in regions involved in emotional processing, such as occipital and temporal areas, as well as in the ventrolateral prefrontal cortex, involved in top-down emotion regulation. In contrast, activity in these areas remained the same level or even increased in the REM-D group, compared to their baseline level.Taken together, these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity, both at behavioral and neural levels, and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness.
Bennett, J R; Dunroy, H M A; Corfield, D R; Hart, N; Simonds, A K; Polkey, M I; Morrell, M J
The diaphragm is the main inspiratory muscle during REM sleep. It was hypothesized that patients with isolated bilateral diaphragm paralysis (BDP) might not be able to sustain REM sleep. Polysomnography with EMG recordings was undertaken from accessory respiratory muscles in patients with BDP and normal subjects. Patients with BDP had a normal quantity of REM sleep (mean +/- SD, 18.6 +/- 7.5% of total sleep time) achieved by inspiratory recruitment of extradiaphragmatic muscles in both tonic and phasic REM, suggesting brainstem reorganization.
Khemiri, S.; Aloui, K.; Naceur, M. S.
We describe in this paper a new approach of classifying the different sleep stages only by focusing on the polysomnographic ECG signals. We show the pre-processing technique of the ECG signals. At the same time the identifcation and elimination of the different types of artifacts which contain the signal and its reconstruction are shown. The automatic classification of the slow-deep sleep and the rapid eye movement sleep called in this work REM-sleep consists in extracting physiological indicators that characterize these two sleep stages through the polysomnographic ECG signal. In other words, this classification is based on the analysis of the cardiac rhythm during a night's sleep.
Liscombe, Marcus P; Hoffmann, Robert F; Trivedi, Madhukar H; Parker, Marc K; Rush, A John; Armitage, Roseanne
To determine if there are significant differences in the temporal organization of rapid eye movement (REM) sleep microarchitecture between healthy controls and outpatients with major depressive disorder (MDD). Forty age-matched subjects, 20 men and 20 women, half with MDD, were selected from an archive of sleep electroencephalography (EEG) data collected under identical conditions. Each participant spent 2 consecutive nights in the Sleep Study Unit of the University of Texas Southwestern Medical Center at Dallas, the first of which served as adaptation. The average amplitude in each of 5 conventional EEG frequency bands was computed for each REM period across the second night. Data were then coded for group and sex. Aside from REM latency, none of the key sleep macroarchitectural variables differentiated MDD patients from controls. REM latency was longest in men with MDD. Sleep microarchitecture, however, did show a number of between-group differences. In general, slower frequencies declined across REM periods, with a significant REM period effect for delta, theta and alpha amplitude. Group x sex interactions were also obtained for theta and alpha. Beta activity showed a unique temporal profile in each group, supported by a significant REM period x group x sex interaction. In addition, the temporal change in theta amplitude across REM periods was most striking in women with MDD. This study suggests that, like during non-REM sleep, EEG amplitude shows a systematic temporal change over successive REM sleep periods and also shows elements that are both disease- and sex-dependent.
Brooks, Patricia L; Peever, John H
During REM sleep the CNS is intensely active, but the skeletal motor system is paradoxically forced into a state of muscle paralysis. The mechanisms that trigger REM sleep paralysis are a matter of intense debate. Two competing theories argue that it is caused by either active inhibition or reduced excitation of somatic motoneuron activity. Here, we identify the transmitter and receptor mechanisms that function to silence skeletal muscles during REM sleep. We used behavioral, electrophysiological, receptor pharmacology and neuroanatomical approaches to determine how trigeminal motoneurons and masseter muscles are switched off during REM sleep in rats. We show that a powerful GABA and glycine drive triggers REM paralysis by switching off motoneuron activity. This drive inhibits motoneurons by targeting both metabotropic GABA(B) and ionotropic GABA(A)/glycine receptors. REM paralysis is only reversed when motoneurons are cut off from GABA(B), GABA(A) and glycine receptor-mediated inhibition. Neither metabotropic nor ionotropic receptor mechanisms alone are sufficient for generating REM paralysis. These results demonstrate that multiple receptor mechanisms trigger REM sleep paralysis. Breakdown in normal REM inhibition may underlie common sleep motor pathologies such as REM sleep behavior disorder.
Stefani, A; Heidbreder, A; Brandauer, E; Guaita, M; Neier, L M; Mitterling, T; Santamaria, J; Iranzo, A; Videnovic, A; Trenkwalder, C; Sixel-Döring, F; Wenning, G K; Chade, A; Poewe, W; Gershanik, O S; Högl, B
To evaluate the utility of multimodal low-cost approaches including actigraphy, a wrist-worn device monitoring rest/activity cycles, in identifying patients with idiopathic REM sleep behavior disorder (iRBD). Seventy patients diagnosed with sleep disorders causing different motor manifestations during sleep (iRBD, sleep apnea, restless legs syndrome) and 20 subjects without any relevant motor manifestation during sleep, underwent video-polysomnography (vPSG) and two-week actigraphy, completed six validated RBD screening questionnaires, and sleep apps use was assessed. Actigraphy was analyzed automatically, and visually by seven blinded sleep medicine experts who rated as "no", "possible" and "probable" RBD. Quantitative actigraphy analysis distinguished patients from controls, but not between patients with different types of motor activity during sleep. Visual actigraphy rating by blinded experts in sleep medicine using pattern recognition identified vPSG confirmed iRBD with 85-95% sensitivity, 79-91% specificity, 81-91% accuracy, 57.7±11.3% positive predictive value, 95.1±3.3% negative predictive value, 6.8±2.2 positive likelihood ratio, 0.14±0.05 negative likelihood ratio and 0.874-0.933 AUC. AUC of the best performing questionnaire was 0.868. Few patients used sleep apps, therefore their potential utility in the evaluated patients' groups is limited. Visual analysis of actigraphy using pattern recognition can identify subjects with iRBD, is able to distinguish iRBD from other motor activity during sleep, even when patients are not aware of the disease in contrast to questionnaires. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population.
Coble, P A; Reynolds, C F; Kupfer, D J; Houck, P
Using earlier developed computer-based measurement methods, delta and REM activity were examined during sleep as a function of age, gender, and time of night in 85 healthy, 6- to 16-year-old children. Chronological age was found to account most strongly for differences in automated delta and REM count measures in this age range. Increasing age was shown to be associated with a significant decline in both automated measures, but the effect was much greater for the delta count measure. The age-related decline in delta wave activity was reflected primarily in a linear decline in 2.0-3.0 Hz delta activity, that is, in the faster end of the delta frequency band. Examination of these measurements in successive NREM and REM sleep periods confirmed that, in children as in adults, delta activity decreases and REM activity increases across the night. Findings are discussed relative to those obtained in the same children using standard measurement methods.
Full Text Available Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a form to cope with the adverse stimuli. Chronic stress, conversely, has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, which confer more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the REM phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior.
Christensen, Julie Anja Engelhard; Jennum, Poul; Koch, Henriette; Frandsen, Rune; Zoetmulder, Marielle; Arvastson, Lars; Christensen, Søren Rahn; Sorensen, Helge Bjarrup Dissing
Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are at high risk of developing Parkinson's disease (PD). As wake/sleep-regulation is thought to involve neurons located in the brainstem and hypothalamic areas, we hypothesize that the neurodegeneration in iRBD/PD is likely to affect wake/sleep and REM/non-REM (NREM) sleep transitions. We determined the frequency of wake/sleep and REM/NREM sleep transitions and the stability of wake (W), REM and NREM sleep as measured by polysomnography (PSG) in 27 patients with PD, 23 patients with iRBD, 25 patients with periodic leg movement disorder (PLMD) and 23 controls. Measures were computed based on manual scorings and data-driven labeled sleep staging. Patients with PD showed significantly lower REM stability than controls and patients with PLMD. Patients with iRBD had significantly lower REM stability compared with controls. Patients with PD and RBD showed significantly lower NREM stability and significantly more REM/NREM transitions than controls. We conclude that W, NREM and REM stability and transitions are progressively affected in iRBD and PD, probably reflecting the successive involvement of brain stem areas from early on in the disease. Sleep stability and transitions determined by a data-driven approach could support the evaluation of iRBD and PD patients. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Madan, Vibha; Jha, Sushil K.
Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem, and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep–wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC) REM-OFF neurons...
Saxvig, Ingvild West; Lundervold, Astri Johansen; Grønli, Janne; Ursin, Reidun; Bjorvatn, Bjørn; Portas, Chiara Maria
Previous studies have suggested that memory is dependent on the occurrence of REM sleep. Research has mainly focused on two distinct types of memory function, declarative and procedural, and it seems that the latter may more directly depend on REM sleep. Memory consolidation has been more investigated than acquisition, maintenance, and recall, despite the fact that sleep may affect flow of information into/from storage. Moreover, tests have often been limited to stimuli within only one modality (usually visual or verbal). This study aimed to clarify the role of REM sleep in memory by investigating aspects of memory function, processing, and modality in the same experimental setting. Tests of acquisition and consolidation of multiple aspects of memory function within the visual and verbal modalities were administrated to subjects before and after REM sleep deprivation. Results show that test performance was not affected by REM sleep deprivation.
Fujii, Yoko; Okura, Mutsumi; Uemori, Hidekazu; Taniguchi, Mitsutaka; Ohi, Motoharu
The rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behaviors related to the loss of the normal generalized skeletal muscle atonia during REM sleep, and shows REM sleep without atonia (RWA) during polysomnography (PSG). Patients with idiopathic RBD have been known to have a siginificantly increased risk of developing one of the α-synucleiopathies later in life, therefore the diagnosis of RBD is very important and must be dealt with carefully. A 51-year-old man was identified presenting dream-enacting behaviors and unpleasant dreams suggesting the diagnosis of RBD, in addition to snoring and excessive daytime sleepiness. Attended video-PSG excluded RBD showing REM sleep with atonia and without increased phasic EMG activity, and diagnosed with severe obstructive sleep apnea (OSA) with an apnea-hypopnea index of 30.1 demonstrating that the reported abnormal sleep behaviors occurred only during respiratory event-induced arousals. Continuous positive airway pressure therapy eliminated the abnormal behaviors, unpleasant dreams, snoring and daytime hypersomnolence. This case shows that severe OSA mimic the symptoms of RBD and that attended video-PSG is necessary to establish the diagnosis of RBD, and identify or exclude other causes of dream-enacting behaviors.
Mandai, O; Guerrien, A; Sockeel, P; Dujardin, K; Leconte, P
Various experimental data indicate that rapid eye movement (REM) sleep is involved in learning processes. In animals, any complex task in a learning environment leads to an increase of the consecutive total REM sleep time, especially just before learning completion. In humans, the oculomotor activity during REM sleep seems to constitute an interesting marker of learning performance. In this work, we focus on the qualitative analysis of REM sleep characteristics after a Morse code learning session. Eight male subjects were polygraphically recorded during three consecutive nights. A computer aided teaching session was performed just before bedrest onset of the experimental night. The learning performance (percentage of saving) was checked on awakening. The Morse code learning led to some modifications in REM sleep components, particularly increases of REM sleep time and number of REM episodes. We did not observe any significant modification in the total number of REMs in the experimental night. However, the correlative analysis between learning performance and sleep parameters indicates a superior r for the oculomotor activity than for the tonic components. This is consistent with the information processing hypothesis in which the temporal distribution of REMs reflects the subject's ability to increase the signal-noise ratio from environmental information intake.
Fraigne, Jimmy J.; Orem, John M.
Objectives: In this study, we quantified the profiles of phasic activity in respiratory muscles (diaphragm, genioglossus and external intercostal) and non-respiratory muscles (neck and extensor digitorum) across REM sleep. We hypothesized that if there is a unique pontine structure that controls all REM sleep phasic events, the profiles of the phasic twitches of different muscle groups should be identical. Furthermore, we described how respiratory parameters (e.g., frequency, amplitude, and effort) vary across REM sleep to determine if phasic processes affect breathing. Methods: Electrodes were implanted in Wistar rats to record brain activity and muscle activity of neck, extensor digitorum, diaphragm, external intercostal, and genioglossal muscles. Ten rats were studied to obtain 313 REM periods over 73 recording days. Data were analyzed offline and REM sleep activity profiles were built for each muscle. In 6 animals, respiratory frequency, effort, amplitude, and inspiratory peak were also analyzed during 192 REM sleep periods. Results: Respiratory muscle phasic activity increased in the second part of the REM period. For example, genioglossal activity increased in the second part of the REM period by 63.8% compared to the average level during NREM sleep. This profile was consistent between animals and REM periods (η2 = 0.58). This increased activity seen in respiratory muscles appeared as irregular bursts and trains of activity that could affect rythmo-genesis. Indeed, the increased integrated activity seen in the second part of the REM period in the diaphragm was associated with an increase in the number (28.3%) and amplitude (30%) of breaths. Non-respiratory muscle phasic activity in REM sleep did not have a profile like the phasic activity of respiratory muscles. Time in REM sleep did not have an effect on nuchal activity (P = 0.59). Conclusion: We conclude that the concept of a common pontine center controlling all REM phasic events is not supported by our
Renouard, Leslie; Billwiller, Francesca; Ogawa, Keiko; Clément, Olivier; Camargo, Nutabi; Abdelkarim, Mouaadh; Gay, Nadine; Scoté-Blachon, Céline; Touré, Rouguy; Libourel, Paul-Antoine; Ravassard, Pascal; Salvert, Denise; Peyron, Christelle; Claustrat, Bruno; Léger, Lucienne; Salin, Paul; Malleret, Gael; Fort, Patrice; Luppi, Pierre-Hervé
Evidence in humans suggests that limbic cortices are more active during rapid eye movement (REM or paradoxical) sleep than during waking, a phenomenon fitting with the presence of vivid dreaming during this state. In that context, it seemed essential to determine which populations of cortical neurons are activated during REM sleep. Our aim in the present study is to fill this gap by combining gene expression analysis, functional neuroanatomy, and neurochemical lesions in rats. We find in rats that, during REM sleep hypersomnia compared to control and REM sleep deprivation, the dentate gyrus, claustrum, cortical amygdaloid nucleus, and medial entorhinal and retrosplenial cortices are the only cortical structures containing neurons with an increased expression of Bdnf, FOS, and ARC, known markers of activation and/or synaptic plasticity. Further, the dentate gyrus is the only cortical structure containing more FOS-labeled neurons during REM sleep hypersomnia than during waking. Combining FOS staining, retrograde labeling, and neurochemical lesion, we then provide evidence that FOS overexpression occurring in the cortex during REM sleep hypersomnia is due to projections from the supramammillary nucleus and the claustrum. Our results strongly suggest that only a subset of cortical and hippocampal neurons are activated and display plasticity during REM sleep by means of ascending projections from the claustrum and the supramammillary nucleus. Our results pave the way for future studies to identify the function of REM sleep with regard to dreaming and emotional memory processing. PMID:26601158
Frandsen, Rune; Nikolic, Miki; Zoetmulder, Marielle
. The method was stable and can be used to differentiate RBD from controls and to quantify motor activity during REM sleep in patients with neurodegeneration. No control had more than 30% of REM sleep with increased motor activity; patients with known RBD had as low activity as 4.5%. We developed and applied...
Full Text Available Sleep is characterized as rapid eye movement (REM and non-rapid eye movement (NREM sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep-wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO2 level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO2 level and respond accordingly. For example; one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC’s REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO2 level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.
Madan, Vibha; Jha, Sushil K
Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem, and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep-wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC) REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO(2) level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO(2) level and respond accordingly. For example, one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO(2) level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO(2) level for unperturbed sleep.
Madan, Vibha; Jha, Sushil K.
Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem, and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep–wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC) REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO2 level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO2 level and respond accordingly. For example, one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO2 level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep. PMID:22363318
Uguccioni, Ginevra; Pallanca, Olivier; Golmard, Jean-Louis; Dodet, Pauline; Herlin, Bastien; Leu-Semenescu, Smaranda; Arnulf, Isabelle
To determine if sleep talkers with REM sleep behavior disorder (RBD) would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep. Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test) in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation). In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall) was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges. Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words) as in controls (+9±18%, p=0.3). The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index). Daytime consolidation (-9±19%) was worse than night-time consolidation (+29±45%, p=0.03) in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally) related to the text learned before sleep. Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself) at the semantic level suggests a replay at a highly cognitive creative level.
Fraigne, Jimmy J; Orem, John M
In this study, we quantified the profiles of phasic activity in respiratory muscles (diaphragm, genioglossus and external intercostal) and non-respiratory muscles (neck and extensor digitorum) across REM sleep. We hypothesized that if there is a unique pontine structure that controls all REM sleep phasic events, the profiles of the phasic twitches of different muscle groups should be identical. Furthermore, we described how respiratory parameters (e.g., frequency, amplitude, and effort) vary across REM sleep to determine if phasic processes affect breathing. Electrodes were implanted in Wistar rats to record brain activity and muscle activity of neck, extensor digitorum, diaphragm, external intercostal, and genioglossal muscles. Ten rats were studied to obtain 313 REM periods over 73 recording days. Data were analyzed offline and REM sleep activity profiles were built for each muscle. In 6 animals, respiratory frequency, effort, amplitude, and inspiratory peak were also analyzed during 192 REM sleep periods. Respiratory muscle phasic activity increased in the second part of the REM period. For example, genioglossal activity increased in the second part of the REM period by 63.8% compared to the average level during NREM sleep. This profile was consistent between animals and REM periods (η(2)=0.58). This increased activity seen in respiratory muscles appeared as irregular bursts and trains of activity that could affect rythmo-genesis. Indeed, the increased integrated activity seen in the second part of the REM period in the diaphragm was associated with an increase in the number (28.3%) and amplitude (30%) of breaths. Non-respiratory muscle phasic activity in REM sleep did not have a profile like the phasic activity of respiratory muscles. Time in REM sleep did not have an effect on nuchal activity (P=0.59). We conclude that the concept of a common pontine center controlling all REM phasic events is not supported by our data. There is a drive in REM sleep that
Schaefer, Carolin; Kunz, Dieter; Bes, Frederik
REM sleep behavior disorder (RBD), with its main clinical symptoms of nightmares with dream-enacting behavior, is considered as a possible precursor of neurodegenerative disease. Obstructive Sleep Apnea Syndrome (OSAS) is known to be capable of provoking RBD-like symptoms by apneic event related arousals. The two sleep related pathologies must coincide in a relevant number of individuals because of overlapping prevalence in similar age groups. Until now RBD symptoms coexisting with OSAS are rarely described in scientific literature and in fact considered as OSAS mimicking RBD. We report four cases with a severe clinical RBD syndrome which were polysomnographically also diagnosed with concomitant OSAS (AHI range: 10.1 -53.2/h). Treatment with 2 mg prolonged release melatonin led to a relevant clinical improvement of RBD symptoms in all patients, so far untreated for the sleep related breathing disorder. Measure of REM sleep without atonia (RSWA) in polysomnography showed values ranging from 5.1 to 20.4% determined with the Montplaisir method. Surprisingly, RSWA values in PSG with melatonin were high, probably because of the still untreated OSAS. We presume that in patients with RBD and OSAS both pathologies contribute in varying degrees to the emergence of RBD symptoms by a destabilization of REM sleep. We suggest by consequence to consider a therapeutic strategy including the treatment of both disorders for an optimal therapeutic response. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Fraize, Nicolas; Carponcy, Julien; Joseph, Mickaël Antoine; Comte, Jean-Christophe; Luppi, Pierre-Hervé; Libourel, Paul-Antoine; Salin, Paul-Antoine; Malleret, Gaël; Parmentier, Régis
It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM. © 2016 Associated Professional Sleep Societies, LLC.
Janković Slavko M.; Sokić Dragoslav V.; Vojvodić Nikola M.; Ristić Aleksandar J.
The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats . In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepress...
Full Text Available The melanin-concentrating hormone (MCH is a peptidergic neuromodulator synthesized by neurons of the lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR and median (MR raphe nuclei, which are involved in the control of sleep and mood.Major Depression (MD is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability and anhedonia. A short REM sleep latency (i.e. the interval between sleep onset and the first REM sleep period, as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons.Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.
Arnulf, Isabelle; Neutel, Dulce; Herlin, Bastien; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Cochen de Cock, Valérie; Vidailhet, Marie
To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1-15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems. © 2015 Associated Professional Sleep Societies, LLC.
Ravassard, Pascal; Hamieh, Al Mahdy; Joseph, Mickaël Antoine; Fraize, Nicolas; Libourel, Paul-Antoine; Lebarillier, Léa; Arthaud, Sébastien; Meissirel, Claire; Touret, Monique; Malleret, Gaël; Salin, Paul-Antoine
Prolonged rapid-eye-movement (REM) sleep deprivation has long been used to study the role of REM sleep in learning and memory processes. However, this method potentially induces stress and fatigue that may directly affect cognitive functions. Here, by using a short-term and nonstressful REM sleep deprivation (RSD) method we assessed in rats the bidirectional influence of reduced and increased REM sleep amount on hippocampal-dependent emotional memory and plasticity. Our results indicate that 4 h RSD impaired consolidation of contextual fear conditioning (CFC) and induction of long-term potentiation (LTP), while decreasing density of Egr1/Zif268-expressing neurons in the CA1 region of the dorsal hippocampus. LTP and Egr1 expression were not affected in ventral CA1. Conversely, an increase in REM sleep restores and further facilitates CFC consolidation and LTP induction, and also increases Egr1 expression in dorsal CA1. Moreover, CFC consolidation, Egr1 neuron density, and LTP amplitude in dorsal CA1 show a positive correlation with REM sleep amount. Altogether, these results indicate that mild changes in REM sleep amount bidirectionally affect memory and synaptic plasticity mechanisms occurring in the CA1 area of the dorsal hippocampus. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Neu, D; Mairesse, O; Newell, J; Verbanck, P; Peigneux, P; Deliens, G
We investigated effects of NREM and REM predominant sleep periods on sleepiness and psychomotor performances measured with visual analog scales and the psychomotor vigilance task, respectively. After one week of stable sleep-wake rhythms, 18 healthy sleepers slept 3hours of early sleep and 3hours of late sleep, under polysomnographic control, spaced by two hours of sustained wakefulness between sleep periods in a within subjects split-night, sleep interruption protocol. Power spectra analysis was applied for sleep EEG recordings and sleep phase-relative power proportions were computed for six different frequency bands (delta, theta, alpha, sigma, beta and gamma). Both sleep periods presented with similar sleep duration and efficiency. As expected, phasic NREM and REM predominances were obtained for early and late sleep conditions, respectively. Albeit revealing additive effects of total sleep duration, our results showed a systematic discrepancy between psychomotor performances and sleepiness levels. In addition, sleepiness remained stable throughout sustained wakefulness during both conditions, whereas psychomotor performances even decreased after the second sleep period. Disregarding exchanges for frequency bands in NREM or stability in REM, correlations between outcome measures and EEG power proportions further evidenced directional divergence with respect to sleepiness and psychomotor performances, respectively. Showing that the functional correlation pattern changed with respect to early and late sleep condition, the relationships between EEG power and subjective or behavioral outcomes might however essentially be related to total sleep duration rather than to the phasic predominance of REM or NREM sleep. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
R. Ryan Williams
Full Text Available Rapid eye movement (REM sleep behavioral disorder is characterized by the absence of muscular atonia during REM sleep. In this disorder, patients can violently act out their dreams, placing them at risk for traumatic fractures during these episodes. REM sleep behavioral disorder (RBD can be a sign of future neurodegenerative disease and has also been found to be a side effect of certain psychiatric medications. We present a case of venlafaxine-induced RBD in a 55 year old female who presented with a 13 year history of intermittent parasomnia and dream enactment in addition to a recent history of two fractures requiring intervention.
Ota, Simone M; Moreira, Karin Di Monteiro; Suchecki, Deborah; Oliveira, Maria Gabriela M; Tiba, Paula A
Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. Wistar male rats weighing 300-400 g. Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained.
Bertini, Mario; Ferrara, Michele; De Gennaro, Luigi; Curcio, Giuseppe; Moroni, Fabio; Babiloni, Claudio; Infarinato, Francesco; Rossini, Paolo Maria; Vecchio, Fabrizio
The present electroencephalographic (EEG) study evaluated the hypothesis of a preferred directionality of communication flows between brain hemispheres across 24 h (i.e., during the whole daytime and nighttime), as an extension of a recent report showing changes in preferred directionality from pre-sleep wake to early sleep stages. Scalp EEGs were recorded in 10 normal volunteers during daytime wakefulness (eyes closed; first period: from 10:00 to 13:00 h; second period: from 14:00 to 18:00 h; third period: from 19:00 to 22:00 h) and nighttime sleep (four NREM-REM cycles). EEG rhythms of interest were delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz) and beta (16-28 Hz). The direction of the inter-hemispheric information flow was evaluated by computing the directed transfer function (DTF) from these EEG rhythms. Inter-hemispheric directional flows varied as a function of the state of consciousness (wake, NREM sleep, REM sleep) and in relation to different cerebral areas. During the daytime, alpha and beta rhythms conveyed inter-hemispheric signals with preferred Left-to-Right hemisphere direction in parietal and central areas, respectively. During the NREM sleep periods of nighttime, the direction of inter-hemispheric DTF information flows conveyed by central beta rhythms was again preponderant from Left-to-Right hemisphere in the stage 2, independent of cortical areas. No preferred direction emerged across the REM periods. These results support the hypothesis that specific directionality of communication flows between brain hemispheres is associated with wakefulness, NREM (particularly stage 2) and REM states during daytime and nighttime. They also reinforce the suggestive hypothesis of a relationship between inter-hemispheric directionality of EEG functional coupling and frequency of the EEG rhythms.
Aleisa, A M; Alzoubi, K H; Alkadhi, K A
Rapid eye movement sleep deprivation (REM-SD) is associated with spatial learning and memory impairment. During REM-SD, an increase in nicotine consumption among habitual smokers and initiation of tobacco use by non-smokers have been reported. We have shown recently that nicotine treatment prevented learning and memory impairments associated with REM-SD. We now report the interactive effects of post-learning REM-SD and/or nicotine. The animals were first trained on the radial arm water maze (RAWM) task, then they were REM-sleep deprived using the modified multiple platform paradigm for 24h. During REM-SD period, the rats were injected with saline or nicotine (1mg/kg s.c. every 12h: a total of 3 injections). The animals were tested for long-term memory in the RAWM at the end of the REM-SD period. The 24h post-learning REM-SD significantly impaired long-term memory. However, nicotine treatment reversed the post-learning REM-SD-induced impairment of long-term memory. On the other hand, post-learning treatment of normal rats with nicotine for 24h enhanced long-term memory. These results indicate that post-learning acute nicotine treatment prevented the deleterious effect of REM-SD on cognitive abilities. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Diagnostic thresholds for quantitative REM sleep phasic burst duration, phasic and tonic muscle activity, and REM atonia index in REM sleep behavior disorder with and without comorbid obstructive sleep apnea.
McCarter, Stuart J; St Louis, Erik K; Duwell, Ethan J; Timm, Paul C; Sandness, David J; Boeve, Bradley F; Silber, Michael H
We aimed to determine whether phasic burst duration and conventional REM sleep without atonia (RSWA) methods could accurately diagnose REM sleep behavior disorder (RBD) patients with comorbid OSA. We visually analyzed RSWA phasic burst durations, phasic, "any," and tonic muscle activity by 3-s mini-epochs, phasic activity by 30-s (AASM rules) epochs, and conducted automated REM atonia index (RAI) analysis. Group RSWA metrics were analyzed and regression models fit, with receiver operating characteristic (ROC) curves determining the best diagnostic cutoff thresholds for RBD. Both split-night and full-night polysomnographic studies were analyzed. N/A. Parkinson disease (PD)-RBD (n = 20) and matched controls with (n = 20) and without (n = 20) OSA. N/A. All mean RSWA phasic burst durations and muscle activities were higher in PD-RBD patients than controls (P sleep without atonia diagnostic thresholds applicable in Parkinson disease-REM sleep behavior disorder (PD-RBD) patient populations with comorbid OSA that may be useful toward distinguishing PD-RBD in typical outpatient populations. © 2014 Associated Professional Sleep Societies, LLC.
Kuzhuppilly Ramakrishnan, Nisha; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J.; Elsinga, Philip H.; Ishiwata, Kiichi; Dierckx, Rudi A. J. O.; van Waarde, Aren
Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model. Sigma-1 receptor occupancy (RO) in the rat brain by
Full Text Available It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.
Lassi, Glenda; Ball, Simon T; Maggi, Silvia; Colonna, Giovanni; Nieus, Thierry; Cero, Cheryl; Bartolomucci, Alessandro; Peters, Jo; Tucci, Valter
It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.
Full Text Available Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM sleep.To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2 or vesicular GABA-glycine transporter (VGAT genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG and lateral pontine tegmentum (LPT are not critically involved in REM sleep control.These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD.
Jozwiak, Natalia; Postuma, Ronald B; Montplaisir, Jacques; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Bourgouin, Pierre-Alexandre; Gagnon, Jean-François
REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD. One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language. PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024). RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail email@example.com.
Brylowski, A; Levitan, L; LaBerge, S
A single subject, a proficient lucid dreamer experienced with signaling the onset of lucidity (reflective consciousness of dreaming) by means of voluntary eye movements, spent 4 nonconsecutive nights in the sleep laboratory. The subject reported becoming lucid and signaling in 8 of the 18 rapid-eye movement (REM) periods recorded. Ten lucid dream reports were verified by polygraphic examination of signals, providing a total of 12.5 min of signal-verified lucid REM. H-Reflex amplitude was recorded every 5 s, along with continuous recording of electroencephalogram, electrooculogram, electromyogram, electrocardiogram, finger pulse, and respiration. Significant findings included greater mean H-reflex suppression during lucid REM sleep than during nonlucid REM and correlations of H-reflex suppression with increased eye movement density, heart rate, and respiration rate. These results support previous studies reporting that lucid REM is not, as might be supposed, a state closer to awakening than ordinary, or nonlucid, REM; rather, lucid dreaming occurs during unequivocal REM sleep and is characteristically associated with phasic REM activation.
Iranzo, Alex; Santamaría, Joan
To describe the clinical and video-polysomnographic (VPSG) features of a group of subjects with severe obstructive sleep apnea/hypopnea (OSAH) mimicking the symptoms of REM sleep behavior disorder (RBD). Evaluation of clinical and VPSG data. University hospital sleep laboratory unit. Sixteen patients that were identified during routine first evaluation visits. Patients' PSG measures were compared with those of 20 healthy controls and 16 subjects with idiopathic RBD of similar age and sex distribution and apnea/hypopnea index lower than 10. NA. Sixteen subjects were identified presenting with dream-enacting behaviors and unpleasant dreams suggesting the diagnosis of RBD, in addition to snoring and excessive daytime sleepiness. VPSG excluded RBD showing REM sleep with atonia and without increased phasic EMG activity, and was diagnostic of severe OSAH with a mean apnea-hypopnea index of 67.5 +/- 18.7 (range, 41-105) demonstrating that the reported abnormal sleep behaviors occurred only during apnea-induced arousals. Continuous positive airway pressure therapy eliminated the abnormal behaviors, unpleasant dreams, snoring and daytime hypersomnolence. Our study shows that severe OSAH may mimick the symptoms of RBD and that VPSG is mandatory to establish the diagnosis of RBD, and identify or exclude other causes of dream-enacting behaviors.
Full Text Available The function of REM sleep dreaming is still unknown. We situate our approach to understanding dream phenomenology and dream function within that part of evolutionary theory known as Costly Signaling Theory (CST. We contend that many of the signals produced by the dreaming brain can be and should be construed as “costly signals”—emotions or mental simulations that produce daytime behavioral dispositions that are costly to the dreamer. For example, often the dreamer will appear in the dream as handicapped in some way (i.e., no clothes, no ID, no money, is under attack, being chased etc.. The dreamer, during waking life, is then influenced by the carry-over effect of the unpleasant dream content. The informational and affective content of the dream creates a mental set in the dreamer that operates during the daytime to facilitate the signaling of a “handicapped” Self. The subtle signaling effect might be via display of the intense emotions or physical demeanor that had first appeared in the dream. When the dreamer shares his dream with others the dream has a more direct impact on waking life and social interactions. In effect, the dreamer uses his or her dreams to adopt a self-handicapping strategy when dealing with significant others. The increased use of costly signals (the self-handicapping strategy during the daytime then facilitates some vital communicative goal of the dreamer.
Wasserman, M D
I have reviewed Hobson and McCarley's activation-synthesis hypothesis of dreaming which attempts to show that the instigation and certain formal aspects of dreaming are physiologically determined by a brainstem neuronal mechanism, their reasons for suggesting major revisions in psychoanalytic dream theory, and neurophysiological data that are inconsistent with their hypothesis. I then discussed the concept of mind-body isomorphism pointing out that they use this concept inconsistently, that despite their denials they regularly view physiology as primary and psychological processes as secondary, and that they frequently make the error of mixing the languages of physiology and psychology in their explanatory statements. Finally, in order to evaluate Hobson and McCarley's claim that their findings require revision of psychoanalytic dream theory, I examined their discussions of chase dreams, flying dreams, sexual dreams, the formal characteristics of dreams, the forgetting of dreams, and the instigation of dreams. I concluded that although their fascinating physiological findings may be central to understanding the neurobiology of REM sleep, they do not alter the meaning and interpretation of dreams gleaned through psychoanalytic study.
Machado, Ricardo Borges; Rocha, Murilo Ramos; Suchecki, Deborah
REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound. Copyright © 2016 Elsevier Inc. All rights reserved.
Mazzetti, Michela; Campi, Claudio; Mattarozzi, Katia; Plazzi, Giuseppe; Tuozzi, Giovanni; Vandi, Stefano; Vignatelli, Luca; Cipolli, Carlo
Patients with narcolepsy-cataplexy (NC) present excessive daytime sleepiness (EDS), cataplexy and an altered architecture of nocturnal sleep, with frequent episodes of REM-sleep at sleep onset (SOREM-sleep). This altered organization of nocturnal sleep may be accompanied by some differences in the functioning of the cognitive processes involved in the access, organization and consolidation of information during sleep. This study attempts to ascertain whether the activation of semantic memory during REM-sleep, as measured using a technique of semantic priming (namely, the facilitation of the activation of strongly-related rather than weakly-related and, overall, unrelated pairs of prime-target words) is different in NC patients compared to normal subjects. A lexical decision task (LDT) was carried out twice in wakefulness (at 10a.m. and after a 24h interval) and twice in the period of sleep inertia following awakening from SOREM and 4th-cycle REM-sleep on 12 NC patients and from 1st- and 4th-cycle REM-sleep on 12 matched controls. Reaction time (RT) to target words, taken as a measure of the semantic priming effect, proved to be longer (a) in NC patients than in control subjects; (b) in the period of REM-sleep inertia than in wakefulness; (c) in the first rather than the second session; and (d) for unrelated compared to weakly-related and, overall, strongly-related prime-target pairs. RT in post-REM-sleep sessions was less impaired, compared to waking sessions, and less dependent on the associative strength of prime-target pairs in NC patients than in normal subjects. Finally, RT of NC patients, although longer than that of normal subjects in waking sessions, significantly improved in the second session, as a consequence of either the amount of exercise or the consolidation advantage provided by REM-sleep for the procedural components of the task. The whole picture suggests a greater effectiveness of the activation of semantic memory during (SO)REM-sleep in NC
Sasai-Sakuma, Taeko; Frauscher, Birgit; Mitterling, Thomas; Ehrmann, Laura; Gabelia, David; Brandauer, Elisabeth; Inoue, Yuichi; Poewe, Werner; Högl, Birgit
Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease. Copyright © 2014 Elsevier B.V. All rights reserved.
Schwartz, Michael D; Nguyen, Alexander T; Warrier, Deepti R; Palmerston, Jeremiah B; Thomas, Alexia M; Morairty, Stephen R; Neylan, Thomas C; Kilduff, Thomas S
Hypocretin 1 and 2 (Hcrts; also known as orexin A and B), excitatory neuropeptides synthesized in cells located in the tuberal hypothalamus, play a central role in the control of arousal. Hcrt inputs to the locus coeruleus norepinephrine (LC NE) system and the posterior hypothalamic histaminergic tuberomammillary nuclei (TMN HA) are important efferent pathways for Hcrt-induced wakefulness. The LC expresses Hcrt receptor 1 (HcrtR1), whereas HcrtR2 is found in the TMN. Although the dual Hcrt/orexin receptor antagonist almorexant (ALM) decreases wakefulness and increases NREM and REM sleep time, the neural circuitry that mediates these effects is currently unknown. To test the hypothesis that ALM induces sleep by selectively disfacilitating subcortical wake-promoting populations, we ablated LC NE neurons (LCx) or TMN HA neurons (TMNx) in rats using cell-type-specific saporin conjugates and evaluated sleep/wake following treatment with ALM and the GABAA receptor modulator zolpidem (ZOL). Both LCx and TMNx attenuated the promotion of REM sleep by ALM without affecting ALM-mediated increases in NREM sleep. Thus, eliminating either HcrtR1 signaling in the LC or HcrtR2 signaling in the TMN yields similar effects on ALM-induced REM sleep without affecting NREM sleep time. In contrast, neither lesion altered ZOL efficacy on any measure of sleep-wake regulation. These results contrast with those of a previous study in which ablation of basal forebrain cholinergic neurons attenuated ALM-induced increases in NREM sleep time without affecting REM sleep, indicating that Hcrt neurotransmission influences distinct aspects of NREM and REM sleep at different locations in the sleep-wake regulatory network.
Gregory, Gavin G; Cabeza, Rafael
Rapid eye movement (REM) sleep is a recurring state throughout the sleeping period. Based on the examination of 45 sleep records of 3-mo-old male rats during the middle of the light phase, a stochastic model is proposed for the sequence X(1),Y(2), X(2),Y(2),. of REM sleep durations X and inter-REM sleep waiting times Y experienced by a rat during a sleeping period. In our model the probability distribution of any variable in the sequence, given the past, is allowed to depend on only the immediately previous variable. The conditional distributions f(y(i) | x(i)) and g(x(i+1) | y(i)) do not depend on the index i. It is shown that the marginal distributions tend to stationarity. Aggregations of the data on a discrete time scale suggest that the conditional distributions be formulated as two-component mixtures. These component distributions are modeled as Poisson and their means are called the means of short and long waiting time and the means of short and long REM sleep duration. Associated with each mean is a probability weight. Parametric forms are given to the means and probability weights. The model estimated by maximum likelihood shows a good fit to data of the 3-mo-old rats. The model fit to a smaller data set obtained from rats aged 15-22 mo shows a significant shortening of the means for both short and long REM sleep bout durations compared with the means of the 3-mo-old rats. Neuronal correlates for the behavior of the model are discussed in the context of the reciprocal interaction model of REM sleep regulation.
stereotyped behaviours , such as leaping, stalking, toying with prey. Their behaviour is normal when they are awake or are in slow-wave sleep . Jouvet supposes...that the period of paradoxical sleep is used to develop, and maintain, the organization of complicated sequences of motor behaviour : efferent...dream sleep . Nature 304, 111. Crick, F. & Mitchison, G. (1986) REM sleep and neural nets. Journal of Mind and Behaviour , 7, 229. Druckman, D. and
Rihm, Julia S; Rasch, Björn
Emotional memories are reprocessed during sleep, and it is widely assumed that this reprocessing occurs mainly during rapid eye movement (REM) sleep. In support for this notion, vivid emotional dreams occur mainly during REM sleep, and several studies have reported emotional memory enhancement to be associated with REM sleep or REM sleep-related parameters. However, it is still unknown whether reactivation of emotional memories during REM sleep strengthens emotional memories. Here, we tested whether re-presentation of emotionally learned stimuli during REM sleep enhances emotional memory. In a split-night design, participants underwent Pavlovian conditioning after the first half of the night. Neutral sounds served as conditioned stimuli (CS) and were either paired with a negative odor (CS+) or an odorless vehicle (CS-). During sound replay in subsequent late REM or N2 sleep, half of the CS+ and half of the CS- were presented again. In contrast to our hypothesis, replay during sleep did not affect emotional memory as measured by the differentiation between CS+ and CS- in expectancy, arousal and valence ratings. However, replay unspecifically decreased subjective arousal ratings of both emotional and neutral sounds and increased positive valence ratings also for both CS+ and CS- sounds, respectively. These effects were slightly more pronounced for replay during REM sleep. Our results suggest that re-exposure to previously conditioned stimuli during late sleep does not affect emotional memory strength, but rather influences the affective tone of both emotional and neutral memories. Copyright © 2015 Elsevier Inc. All rights reserved.
Gais, Steffen; Rasch, Bjorn; Dahmen, Johannes C.; Sara, Susan; Born, Jan
There is a long-standing assumption that low noradrenergic activity during sleep reflects mainly the low arousal during this brain state. Nevertheless, recent research has demonstrated that the locus coeruleus, which is the main source of cortical noradrenaline, displays discrete periods of intense firing during non-REM sleep, without any signs of…
Louter, M.; Arends, J.B.; Bloem, B.R.; Overeem, S.
BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is a common parasomnia in Parkinson's disease (PD) patients. The current International Classification of Sleep Disorders (ICSD-II) requires a clinical interview combined with video polysomnography (video-PSG) to diagnose. The latter
Full Text Available Noradrenaline, one of the main brain monoamines, has powerful central influences on neurobiological processes in the forebrain which support the mental activities occurring during the sleep–waking cycle. Noradrenergic neurons are activated during waking, decrease their firing rate during slow wave sleep, and become silent during REM sleep. Although a low level of noradrenaline is still maintained during REM sleep, the decrease observed during this period contributes to the mentation disturbances that occur with dreaming, which principally resemble symptoms of schizophrenia but seemingly also of attention deficit hyperactivity disorder.
Kirov, Roumen; Banaschewski, Tobias; Uebel, Henrik; Kinkelbur, Jörg; Rothenberger, Aribert
To characterize precisely the sleep pattern in children with co-existence of TD + ADHD. By means of polysomnography, sleep pattern was investigated in 19 children with TD + ADHD unmedicated before and during study and 19 healthy controls, matched for age, gender, and intelligence. Compared with healthy controls, children with TD + ADHD displayed shorter REM sleep latency and increased REM sleep duration. There was a negative correlational relationship between these REM-sleep alterations and they were determined by hyperactivity symptoms. Sleep in children with coexistence of TD + ADHD may be characterized by an elevated REM sleep drive. Common mechanisms are suggested to underpin hypermotor symptoms and REM sleep regulation.
Mari A. Watanabe
Full Text Available Background Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC frequency would correlate with measures of apnea and sympathetic activity.Methods Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI into Moderate (AHI 15 apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM. Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated.Results There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005 and by AHI (F=8.7, p<.005. In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011. In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19. Oxygen desaturation duration per apnea episode correlated positively with AHI (r2=.71, p<.0001, and was longer in REM than in non-REM (p<.0001. The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r2=.06, p=.014.Conclusions Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.
Valencia Garcia, Sara; Libourel, Paul-Antoine; Lazarus, Michael; Grassi, Daniela; Luppi, Pierre-Hervé; Fort, Patrice
SEE SCHENCK AND MAHOWALD DOI101093/AWW329 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Idiopathic REM sleep behaviour disorder is characterized by the enactment of violent dreams during paradoxical (REM) sleep in the absence of normal muscle atonia. Accumulating clinical and experimental data suggest that REM sleep behaviour disorder might be due to the neurodegeneration of glutamate neurons involved in paradoxical sleep and located within the pontine sublaterodorsal tegmental nucleus. The purpose of the present work was thus to functionally determine first, the role of glutamate sublaterodorsal tegmental nucleus neurons in paradoxical sleep and second, whether their genetic inactivation is sufficient for recapitulating REM sleep behaviour disorder in rats. For this goal, we first injected two retrograde tracers in the intralaminar thalamus and ventral medulla to disentangle neuronal circuits in which sublaterodorsal tegmental nucleus is involved; second we infused bilaterally in sublaterodorsal tegmental nucleus adeno-associated viruses carrying short hairpin RNAs targeting Slc17a6 mRNA [which encodes vesicular glutamate transporter 2 (vGluT2)] to chronically impair glutamate synaptic transmission in sublaterodorsal tegmental nucleus neurons. At the neuroanatomical level, sublaterodorsal tegmental nucleus neurons specifically activated during paradoxical sleep hypersomnia send descending efferents to glycine/GABA neurons within the ventral medulla, but not ascending projections to the intralaminar thalamus. These data suggest a crucial role of sublaterodorsal tegmental nucleus neurons rather in muscle atonia than in paradoxical sleep generation. In line with this hypothesis, 30 days after adeno-associated virus injections into sublaterodorsal tegmental nucleus rats display a decrease of 30% of paradoxical sleep daily quantities, and a significant increase of muscle tone during paradoxical sleep concomitant to a tremendous increase of abnormal motor dream
Speth, Clemens; Speth, Jana
Hallucinatory states are experienced not only in connection with drugs and psychopathologies but occur naturally and spontaneously across the human circadian cycle: Our nightly dreams bring multimodal experiences in the absence of adequate external stimuli. The current study proposes a new, tighter measure of these hallucinatory states: Sleep onset, REM sleep, and non-REM sleep are shown to differ with regard to (a) motor imagery indicating interactions with a rich imaginative world, and (b) cognitive agency that could enable sleepers to recognize their hallucinatory state. Mentation reports from the different states were analysed quantitatively with regard to two grammatical-semantic constructs, motor agency and cognitive agency. The present results support earlier physiological and psychological evidence in revealing a decline in cognitive functions and an increase in simulated interactions with a hallucinatory world, en route to normal REM sleep. This leads us to introduce the hypothesis that REM sleep, which exhibits remarkably high levels of (simulated) sensorimotor processes, may have evolved to serve as a virtual laboratory for the development and rehearsal of embodied cognition. The new measure of hallucinatory states presented here may also hold implications for the study of executive functions and (meta-)cognitions, which might be interesting, for example, for the investigation of lucid dreaming. Copyright © 2017 Cognitive Science Society, Inc.
Vetrugno, Roberto; Montagna, Pasquale
Sleep is a coordinated process involving more or less simultaneous changes in sensory, motor, autonomic, hormonal, and cerebral processes. On the other hand, none of the changes occurring with sleep are invariably coupled to sleep. EEG synchrony, heat loss, sleep-related hormone secretion, and even REM-related motoneuron paralysis may occur independent of the parent state. In REM sleep behaviour disorder (RBD) the muscle tone of wakefulness intrudes into REM sleep, allowing the release of dream-enacting behaviours. Status dissociatus (SD) is a condition in which brain and mind are in disarray along the boundaries of sleep and wakefulness. The existence of such dissociated behaviours shows that they have separate neuronal control systems and indicates that the whole organization of sleep is an emergent property of the collective neuronal systems to synchronize. Insults to the brain can drastically alter the circuitries responsible for maintaining the integrity of wakefulness, NREM sleep, and REM sleep. As a consequence, the basic states of existence can become admixed and interchanged with striking disturbances of consciousness, brain electrophysiology, and the behavioural and polygraphic expression of sleep and wakefulness. The evolution of RBD into SD may result from a disarray of (brainstem) structures that orchestrate the whole brain wake-sleep conditions, but with preserved discrete systems and dissociable strategies to still place navigation in wake and sleep. Advances in the fields of genetics, neuroimaging, and behavioural neurology will expand the understanding of the mechanisms underlying the organization of the states of being along with their somatic/behavioural manifestations. Copyright © 2011 Elsevier B.V. All rights reserved.
Manni, Raffaele; Terzaghi, Michele; Ratti, Pietro-Luca; Repetto, Alessandra; Zangaglia, Roberta; Pacchetti, Claudio
REM sleep behaviour disorder (RBD) is a REM sleep-related parasomnia which may be considered a "dissociated state of wakefulness and sleep", given that conflicting elements of REM sleep (dreaming) and of wakefulness (sustained muscle tone and movements) coexist during the episodes, leading to motor and behavioural manifestations reminiscent of an enacted dream. RBD has been reported in association with α-synucleinopathies: around a third of patients with Parkinson's disease (PD) have full-blown RBD. Recent data indicate that PD patients with RBD are more prone to hallucinations than PD patients without this parasomnia. However it is still not clear why RBD in PD is associated with an increased prevalence of VHs. Data exist which suggest that visual hallucinations in PD may be the result of untimely intrusions of REM visual imagery into wakefulness. RBD, which is characterised by a REM sleep dissociation pattern, might be a condition that particularly favours such intrusions. However, other hypotheses may be advanced. In fact, deficits in attentional, executive, visuoperceptual and visuospatial abilities have been documented in RBD and found to occur far more frequently in PD with RBD than in PD without RBD. Neuropsychological deficits involving visual perception and attentional processes are thought to play an important role in the pathophysiology of VHs. On this basis, RBD in PD could be viewed as a contributory risk factor for VHs. Copyright © 2010 Elsevier Inc. All rights reserved.
Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M
Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
Christensen, Julie Anja Engelhard; Kempfner, Jacob; Zoetmulder, Marielle
ObjectiveTo determine whether sleep spindles (SS) are potentially a biomarker for Parkinson’s disease (PD). MethodsFifteen PD patients with REM sleep behavior disorder (PD+RBD), 15 PD patients without RBD (PD−RBD), 15 idiopathic RBD (iRBD) patients and 15 age-matched controls underwent...... polysomnography (PSG). SS were scored in an extract of data from control subjects. An automatic SS detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine (SVM) was developed and applied to the PSG recordings. The SS densities in N1, N2, N3, all NREM combined and REM sleep were obtained...
Barsky, Murray M; Tucker, Matthew A; Stickgold, Robert
During wakefulness the brain creates meaningful relationships between disparate stimuli in ways that escape conscious awareness. Processes active during sleep can strengthen these relationships, leading to more adaptive use of those stimuli when encountered during subsequent wake. Performance on the Weather Prediction Task (WPT), a well-studied measure of implicit probabilistic learning, has been shown to improve significantly following a night of sleep, with stronger initial learning predicting more nocturnal REM sleep. We investigated this relationship further, studying the effect on WPT performance of a daytime nap containing REM sleep. We also added an interference condition after the nap/wake period as an additional probe of memory strength. Our results show that a nap significantly boosts WPT performance, and that this improvement is correlated with the amount of REM sleep obtained during the nap. When interference training is introduced following the nap, however, this REM-sleep benefit vanishes. In contrast, following an equal period of wake, performance is both unchanged from training and unaffected by interference training. Thus, while the true probabilistic relationships between WPT stimuli are strengthened by sleep, these changes are selectively susceptible to the destructive effects of retroactive interference, at least in the short term. Copyright © 2015 Elsevier Inc. All rights reserved.
Lauer, C.; Zulley, Jürgen; Krieg, J. C.; Riemann, D.; Berger, M.
The electroencephalographic (EEG) sleep of 20 anorexic patients, 10 bulimic patients, and 10 age-matched healthy controls was studied. In addition, six anorexic patients and six bulimic patients had a cholinergic rapid eye movement (REM) sleep induction test (RIT) performed with the cholinergic agent RS 86. The three samples showed no major differences in sleep patterns. The same held true when attention was focused on patients who additionally met DSM-III criteria for major depression. The R...
Leoni, Chiara; Cesarini, Laura; Dittoni, Serena; Battaglia, Domenica; Novelli, Antonio; Bernardini, Laura; Losurdo, Anna; Vollono, Catello; Testani, Elisa; Della Marca, Giacomo; Zampino, Giuseppe
We describe a 2-year-old baby affected by Smith-Magenis syndrome (SMS), due to 17p11.2 deletion, who presented repeated episodes of hemoglobin desaturation during REM sleep. The boy, aged 14 months, presented a phenotype characterized by psychomotor delay, right posterior plagiocephaly, telecanthus, strabismus, upslanting palpebral fissures, broad hypoplastic nasal bridge, short philtrum, deep ring shaped skin creases around the limbs, proximal syndactyly, bilateral hypoacusia. Polysomnographic (PSG) recording showed episodes of REM-related hypoventilation (hemoglobin desaturations without apneas or hypopneas). Sleep disorders are present in almost all the cases of SMS, but very few reports describe the sleep-related respiratory patterns. The finding of REM hypoventilation in SMS does not allow an unequivocal interpretation. It could reflect a subclinical restrictive respiratory impairment or, alternatively, an impairment of central respiratory control during REM sleep. In SMS children, respiratory abnormalities during sleep, and in particular during REM sleep, may cause sleep disruption, reduction of time spent in REM sleep, and daytime sleepiness. We therefore suggest that some sleep abnormalities described in SMS could be consequent to Sleep Disordered Breathing, and in particular to REM hypoventilation. Sleep studies in SMS should include the recording of respiratory parameters. (c) 2010 Wiley-Liss, Inc.
McGrane, Ian R; Leung, Jonathan G; St Louis, Erik K; Boeve, Bradley F
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish the evidence basis for melatonin and clonazepam as RBD therapies. Copyright © 2014 Elsevier B.V. All rights reserved.
Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F
Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.
Lau, Kristy Nga Ting; Hui, Florence Wai Ying; Tseng, Chia-huei
The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that “sleep gain” during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy. PMID:25970511
Esther Yuet Ying Lau
Full Text Available The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40 or stay awake (Wake-group, n=40 between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM and total sleep time during the nap. Our findings suggested that "sleep gain" during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression, which are also presented with cognitive dysfunctions (e.g. working memory deficits, this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy.
Lau, Esther Yuet Ying; Wong, Mark Lawrence; Lau, Kristy Nga Ting; Hui, Florence Wai Ying; Tseng, Chia-huei
The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that "sleep gain" during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy.
McNamara, Patrick; Auerbach, Sanford; Johnson, Patricia; Harris, Erica; Doros, Gheorghe
We tested the hypothesis that REM sleep contributes to core features of cognitive dysfunction of anxious depression including negative self-appraisals, biased memory processing and unpleasant dream content. After a habituation night in a sleep lab, a convenience sample of 35 healthy college students and 20 depressed/anxious students were awakened 10 min into a REM sleep episode and then 10 min into a NREM sleep episode. Awakenings were counterbalanced to control circadian effects. After each awakening participants reported a dream and then completed memory recall, mood and self-appraisal tasks. Self-appraisals of depressed/anxious participants were significantly less positive and significantly more negative after awakenings from REM sleep vs NREM sleep. Appraisal of the REM sleep dream self was negative for depressed/anxious subjects only. Recall of negative memories was significantly more frequent after REM vs NREM sleep awakenings for both depress/anxious and healthy participants. REM sleep dreams were associated with greater frequencies of negative emotion, greater aggression and victimization rates than dreams in NREM sleep for depressed/anxious participants. Depressed/anxious participants were classified as such on the basis of mood scales rather than clinical interview. All participants were drawn from a volunteer college student population and thus our results may not be applicable to some elderly clinical populations. REM appears to facilitate cognitive distortions of anxious depression. Copyright (c) 2009 Elsevier B.V. All rights reserved.
Walsh, Christine M.; Booth, Victoria; Poe, Gina R.
This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair…
Gujar, Ninad; McDonald, Steven Andrew; Nishida, Masaki
Although the impact of sleep on cognitive function is increasingly well established, the role of sleep in modulating affective brain processes remains largely uncharacterized. Using a face recognition task, here we demonstrate an amplified reactivity to anger and fear emotions across the day, without sleep. However, an intervening nap blocked and even reversed this negative emotional reactivity to anger and fear while conversely enhancing ratings of positive (happy) expressions. Most interestingly, only those subjects who obtained rapid eye movement (REM) sleep displayed this remodulation of affective reactivity for the latter 2 emotion categories. Together, these results suggest that the evaluation of specific human emotions is not static across a daytime waking interval, showing a progressive reactivity toward threat-related negative expressions. However, an episode of sleep can reverse this predisposition, with REM sleep depotentiating negative reactivity toward fearful expressions while concomitantly facilitating recognition and ratings of reward-relevant positive expressions. These findings support the view that sleep, and specifically REM neurophysiology, may represent an important factor governing the optimal homeostasis of emotional brain regulation. PMID:20421251
Virtanen, Jaakko; Näsi, Tiina; Noponen, Tommi; Toppila, Jussi; Salmi, Tapani; Ilmoniemi, Risto J.
Spontaneous cerebral hemodynamic oscillations below 100 mHz reflect the level of cerebral activity, modulate hemodynamic responses to tasks and stimuli, and may aid in detecting various pathologies of the brain. Near-infrared spectroscopy (NIRS) is ideally suited for both measuring spontaneous hemodynamic oscillations and monitoring sleep, but little research has been performed to combine these two applications. We analyzed 30 all-night NIRS-electroencephalography (EEG) sleep recordings to investigate spontaneous hemodynamic activity relative to sleep stages determined by polysomnography. Signal power of hemodynamic oscillations in the low-frequency (LF, 40-150 mHz) and very-low-frequency (VLF, 3-40 mHz) bands decreased in slow-wave sleep (SWS) compared to light sleep (LS) and rapid-eye-movement (REM) sleep. No statistically significant (p sleep in line with earlier studies with other modalities. These results increase our knowledge of the physiology of sleep, complement EEG data, and demonstrate the applicability of NIRS to studying spontaneous hemodynamic fluctuations during sleep.
Meles, Sanne K.; Vadasz, David; Renken, Remco J.; Sittig-Wiegand, Elisabeth; Mayer, Geert; Depboylu, Candan; Reetz, Kathrin; Overeem, Sebastiaan; Pijpers, Angelique; Reesink, Fransje E.; van Laar, Teus; Heinen, Lisette; Teune, Laura K.; Höffken, Helmut; Luster, Marcus; Kesper, Karl; Adriaanse, Sofie M.; Booij, Jan; Leenders, Klaus L.; Oertel, Wolfgang H.
Background: Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The
Meles, Sanne K; Vadasz, David; Renken, Remco J; Sittig-Wiegand, Elisabeth; Mayer, Geert; Depboylu, Candan; Reetz, Kathrin; Overeem, Sebastiaan; Pijpers, Angelique; Reesink, Fransje E; van Laar, Teus; Heinen, Lisette; Teune, Laura K; Höffken, Helmut; Luster, Marcus; Kesper, Karl; Adriaanse, Sofie M; Booij, Jan; Leenders, Klaus L; Oertel, Wolfgang H
BACKGROUND: Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The
Full Text Available Homeostatic regulation of REM sleep drive, as measured by an increase in the number of REM sleep transitions, plays a key role in neuronal and behavioral plasticity (i.e., learning and memory. Deficits in REM sleep homeostatic drive (RSHD are implicated in the development of many neuropsychiatric disorders. Yet, the cellular and molecular mechanisms underlying this RSHD remain to be incomplete. To further our understanding of this mechanism, the current study was performed on freely moving rats to test a hypothesis that a positive interaction between extracellular-signal-regulated kinase 1 and 2 (ERK1/2 activity and brain-derived neurotrophic factor (BDNF signaling in the pedunculopontine tegmentum (PPT is a causal factor for the development of RSHD. Behavioral results of this study demonstrated that a short period (<90 min of selective REM sleep restriction (RSR exhibited a strong RSHD. Molecular analyses revealed that this increased RSHD increased phosphorylation and activation of ERK1/2 and BDNF expression in the PPT. Additionally, pharmacological results demonstrated that the application of the ERK1/2 activation inhibitor U0126 into the PPT prevented RSHD and suppressed BDNF expression in the PPT. These results, for the first time, suggest that the positive interaction between ERK1/2 and BDNF in the PPT is a casual factor for the development of RSHD. These findings provide a novel direction in understanding how RSHD-associated specific molecular changes can facilitate neuronal plasticity and memory processing.
Markowitsch, Hans J; Staniloiu, Angelica
It is argued that Llewellyn's hypothesis about the lack of rapid eye movement (REM)-sleep dreaming leading to loss of personal identity and deficits in episodic memory, affectivity, and prospection is insufficiently grounded because it does not integrate data from neurodevelopmental studies and makes reference to an outdated definition of episodic memory.
Full Text Available The rock hyrax, Procavia capensis, is a highly social, diurnal mammal. In the current study several physiologically measurable parameters of sleep, as well as the accompanying behavior, were recorded continuously from five rock hyraxes, for 72 h under solitary (experimental animal alone in the recording chamber, and social conditions (experimental animal with 1 or 2 additional, non-implanted animals in the recording chamber. The results revealed no significant differences between solitary and social conditions for total sleep times, number of episodes, episode duration or slow wave activity (SWA for all states examined. The only significant difference observed between social and solitary conditions was the average duration of rapid eye movement (REM sleep episodes. REM sleep episode duration was on average 20 s and 40 s longer under social conditions daily and during the dark period, respectively. It is hypothesized that the increase in REM sleep episode duration under social conditions could possibly be attributed to improved thermoregulation strategies, however considering the limited sample size and design of the current study further investigations are needed to confirm this finding. Whether the conclusions and the observations made in this study can be generalized to all naturally socially sleeping mammals remains an open question.
Anderson, Kirstie N.; Shneerson, John M.
Study Objectives: REM sleep behavior disorder (RBD) is characterized by loss of the normal muscle atonia during REM sleep associated with disruptive motor activity related to the acting out of dreams. There is frequently injury to the patient or bed partner, and treatment is usually required. Clonazepam has been the first-line therapy for many years, with 2 large case series reporting efficacy with few side effects in the majority of patients. However, long-acting hypnotics in the elderly or those with cognitive impairment can be associated with adverse events especially unacceptable daytime sedation, confusion, and exacerbation of existing sleep apnea. Methods: We reviewed 39 patients with confirmed RBD who were treated within our regional sleep center, assessing both efficacy and side effects of drug therapies. Results: Adverse effects were reported by 58% of the patients using clonazepam, with 50% either discontinuing the drug or reducing the dose. This prompted us review the side effects of clonazepam in detail and to look for alternative therapies. We report several novel and effective therapies, in particular zopiclone, in a series of patients under long-term follow-up for RBD. Conclusions: There are alternatives to clonazepam therapy for RBD which can be as effective and may be better tolerated. Citation: Anderson KN; Shneerson JM. Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam. J Clin Sleep Med 2009;5(3):235–239. PMID:19960644
Poe, G R; Nitz, D A; McNaughton, B L; Barnes, C A
The idea that sleep could serve a cognitive function has remained popular since Freud stated that dreams were "not nonsense" but a time to sort out experiences [S. Freud, Letter to Wilhelm Fliess, May 1897, in The Origins of Psychoanalysis - Personal Letters of Sigmund Freud, M. Bonaparte, A. Freud, E. Kris (Eds.), Translated by E. Mosbacher, J. Strachey, Basic Books and Imago Publishing, 1954]. Rapid eye movement (REM) sleep, which is associated with dream reports, is now known to be is important for acquisition of some tasks [A. Karni, D. Tanne, B.S. Rubenstein, J.J.M. Askenasy, D. Sagi, Dependence on REM sleep of overnight improvement of a perceptual skill, Science 265 (1994) 679-682; C. Smith, Sleep states and learning: a review of the animal literature, Biobehav. Rev. 9 (1985) 157-168]; although why this is so remains obscure. It has been proposed that memories may be consolidated during REM sleep or that forgetting of unnecessary material occurs in this state [F. Crick, G. Mitchison, The function of dream sleep, Nature 304 (1983) 111-114; D. Marr, Simple memory: a theory for archicortex, Philos. Trans. R. Soc. B. 262 (1971) 23-81]. We studied the firing of multiple single neurons in the hippocampus, a structure that is important for episodic memory, during familiar and novel experiences and in subsequent REM sleep. Cells active in familiar places during waking exhibited a reversal of firing phase relative to local theta oscillations in REM sleep. Because firing-phase can influence whether synapses are strengthened or weakened [C. Holscher, R. Anwyl, M.J. Rowan, Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can be depotentiated by stimulation on the negative phase in area CA1 in vivo, J. Neurosci. 15 (1977) 6470-6477; P.T. Huerta, J.E. Lisman, Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro, Neuron 15 (1995) 1053-1063; C. Pavlides, Y
Diederich, Nico J; Rufra, Olivier; Pieri, Vannina; Hipp, Géraldine; Vaillant, Michel
Polysomnography (PSG) data are rare in patients who have early stage idiopathic Parkinson's disease (IPD). Thirty-three patients who had IPD with a disease duration ≤ 3 years and 37 age-matched controls were recruited. PSG analysis was performed on current medication. Patients with IPD had a reduced mean percentage of muscle atonia during rapid eye movement (REM) sleep (80% vs 93%; P sleep time, sleep efficiency, indices/hour of arousals, awakenings, apnea/hypopnea, and periodic leg movements were similar in both groups. Age, but not dopaminergic medication, had a negative impact on sleep architecture in patients with IPD. There was no correlation between sleep efficiency assessed by PSG and sleep quality assessed by questionnaire. The results confirmed a reduction in muscle atonia during REM sleep as a characteristic finding in early IPD. However, there were no further disease-inherent or medication-induced changes in sleep architecture. Although sleep disturbances are considered to be an integral part of IPD, PSG cannot yet identify them objectively at an early stage. © 2013 The Authors. Movement Disorders published by Wiley on behalf of the International Parkinson and Movement Disorder Society.
Baltzan, Marcel A; Scott, Adrienne S; Wolkove, Norman
Patients with unilateral diaphragmatic paralysis (UDP) have been reported to have varied respiratory symptoms and often reduced lung function. We sought to describe the polysomnographic respiratory characteristics in patients with UDP without obstructive sleep apnea. We prospectively collected 5 cases with clinical investigation regarding symptoms, lung function, and nocturnal polysomnography. The respiratory sleep characteristics were analyzed with standardized scoring of respiratory events in 30-sec epochs and comparison according to sleep-wake stages and body position with respect to oximetry. The cases were compared to 5 controls matched for age, gender, and body mass index. Three of 5 patients had significant awake lung restriction with a mean (range) forced vital capacity of 1.89 (1.48-2.24) liters, 72% (45% to 102%) predicted. All had REM sleep with few apneas and episodes of prolonged hypopneas characterized by important desaturation noted on oximetry. These desaturations were greatest during REM sleep when the patients slept supine with a mean (SD) saturation of 90.8% (4.5%) and minimum of 64% or on the side unaffected by UDP with a mean saturation of 87.8% (5.3%) and minimum of 67% (p sleep stages had few, if any significant desaturations and these events rarely occurred when the patient slept in the supine position. Saturation was lower in all sleep-wake stages and sleep positions compared to controls (p sleep with frequent desaturations.
Full Text Available Brain state alternations resembling those of sleep spontaneously occur in rats under urethane anesthesia and they are closely linked with sleep-like respiratory changes. Although rats are a common model for both sleep and respiratory physiology, we sought to determine if similar brain state and respiratory changes occur in mice under urethane. We made local field potential recordings from the hippocampus and measured respiratory activity by means of EMG recordings in intercostal, genioglossus, and abdominal muscles. Similar to results in adult rats, urethane anesthetized mice displayed quasi-periodic spontaneous forebrain state alternations between deactivated patterns resembling slow wave sleep (SWS and activated patterns resembling rapid eye movement (REM sleep. These alternations were associated with an increase in breathing rate, respiratory variability, a depression of inspiratory related activity in genioglossus muscle and an increase in expiratory-related abdominal muscle activity when comparing deactivated (SWS-like to activated (REM-like states. These results demonstrate that urethane anesthesia consistently induces sleep-like brain state alternations and correlated changes in respiratory activity across different rodent species. They open up the powerful possibility of utilizing transgenic mouse technology for the advancement and translation of knowledge regarding sleep cycle alternations and their impact on respiration.
Barbanoj, Manel J; Riba, Jordi; Clos, S; Giménez, S; Grasa, E; Romero, S
Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilian-based religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N,N-dimethyltryptamine (DMT) and beta-carboline alkaloids with monoamine oxidase-inhibiting properties that render DMT orally active. DMT interacts with serotonergic neurotransmission acting as a partial agonist at 5-HT(1A) and 5-HT(2A/2C) receptor sites. Given the role played by serotonin in the regulation of the sleep/wake cycle, we investigated the effects of daytime ayahuasca consumption in sleep parameters. Subjective sleep quality, polysomnography (PSG), and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of a placebo, an ayahuasca dose equivalent to 1 mg DMT kg(-1) body weight, and 20 mg d-amphetamine, a proaminergic drug, as a positive control. Results show that ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance, in contrast with d-amphetamine, which delayed sleep initiation, disrupted sleep maintenance, induced a predominance of 'light' vs 'deep' sleep and significantly impaired subjective sleep quality. PSG analysis also showed that similarly to d-amphetamine, ayahuasca inhibits rapid eye movement (REM) sleep, decreasing its duration, both in absolute values and as a percentage of total sleep time, and shows a trend increase in its onset latency. Spectral analysis showed that d-amphetamine and ayahuasca increased power in the high frequency range, mainly during stage 2. Remarkably, whereas slow-wave sleep (SWS) power in the first night cycle, an indicator of sleep pressure, was decreased by d-amphetamine, ayahuasca enhanced power in this frequency band. Results show that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an
Pace, Marta; Adamantidis, Antoine; Facchin, Laura; Bassetti, Claudio
Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke. Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR. A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group. Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.
Full Text Available Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH and orexin/hypocretin (OX systems. This study aims to 1 assess the relationship between sleep and recovery; 2 test the association between MCH and OX systems with the pathological mechanisms of stroke.Sprague-Dawley rats were assigned to four experimental groups: (i SD_IS: SD performed before ischemia; (ii IS: ischemia; (iii SD_Sham: SD performed before sham surgery; (iv Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.
St Louis, Erik K; Boeve, Angelica R; Boeve, Bradley F
Rapid eye movement sleep behavior disorder is characterized by dream enactment and complex motor behaviors during rapid eye movement sleep and rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia) during polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or symptomatic and in both settings is highly associated with synucleinopathy neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. Rapid eye movement sleep behavior disorder frequently manifests years to decades prior to overt motor, cognitive, or autonomic impairments as the presenting manifestation of synucleinopathy, along with other subtler prodromal "soft" signs of hyposmia, constipation, and orthostatic hypotension. Between 35% and 91.9% of patients initially diagnosed with idiopathic rapid eye movement sleep behavior disorder at a sleep center later develop a defined neurodegenerative disease. Less is known about the long-term prognosis of community-dwelling younger patients, especially women, and rapid eye movement sleep behavior disorder associated with antidepressant medications. Patients with rapid eye movement sleep behavior disorder are frequently prone to sleep-related injuries and should be treated to prevent injury with either melatonin 3-12 mg or clonazepam 0.5-2.0 mg to limit injury potential. Further evidence-based studies about rapid eye movement sleep behavior disorder are greatly needed, both to enable accurate prognostic prediction of end synucleinopathy phenotypes for individual patients and to support the application of symptomatic and neuroprotective therapies. Rapid eye movement sleep behavior disorder as a prodromal synucleinopathy represents a defined time point at which neuroprotective therapies could potentially be applied for the prevention of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. © 2017
Kato, T; Nakamura, N; Masuda, Y; Yoshida, A; Morimoto, T; Yamamura, K; Yamashita, S; Sato, F
Sleep-related movement disorders are characterized by the specific phenotypes of muscle activities and movements during sleep. However, the state-specific characteristics of muscle bursts and movement during sleep are poorly understood. In this study, jaw-closing and -opening muscle electromyographic (EMG) activities and jaw movements were quantified to characterize phenotypes of motor patterns during sleep in freely moving and head-restrained guinea pigs. During non-rapid eye movement (NREM) sleep, both muscles were irregularly activated in terms of duration, activity, and intervals. During rapid eye movement (REM) sleep, clusters of phasic bursts occurred in the two muscles. Compared with NREM sleep, burst duration, activity, and intervals were less variable during REM sleep for both muscles. Although burst activity was lower during the two sleep states than during chewing, burst duration and intervals during REM sleep were distributed within a similar range to those during chewing. A trigger-averaged analysis of muscle bursts revealed that the temporal association between the bursts of the jaw-closing and -opening muscles during REM sleep was analogous to the temporal association during natural chewing. The burst characteristics of the two muscles reflected irregular patterns of jaw movements during NREM sleep and repetitive alternating bilateral movements during REM sleep. The distinct patterns of jaw muscle bursts and movements reflect state-specific regulations of the jaw motor system during sleep states. Phasic activations in the antagonistic jaw muscles during REM sleep are regulated, at least in part, by the neural networks involving masticatory pattern generation, demonstrating that waking jaw motor patterns are replayed during sleep periods.
Iranzo, Alex; Santamaria, Joan; Tolosa, Eduard
REM sleep behavior disorder (RBD) is characterized by vigorous movements associated with unpleasant dreams and increased electromyographic activity during REM sleep. Polysomnography with audiovisual recording is needed to confirm the diagnosis of RBD and to exclude other sleep disorders that can mimic its symptoms including obstructive sleep apnea, nocturnal hallucinations and confusional awakenings. RBD may be idiopathic or related to neurodegenerative diseases, particularly multiple system atrophy, Parkinson's disease and dementia with Lewy bodies. RBD may be the first manifestation of these disorders, antedating the onset of parkinsonism, cerebellar syndrome, dysautonomia, and dementia by several years. RBD should thus be considered an integral part of the disease process. When effective, neuroprotective strategies should be considered in subjects with idiopathic RBD. Patients with other neurodegenerative diseases, though, such as spinocerebellar ataxias, may also present with RBD. When clinically required, clonazepam at bedtime is effective in decreasing the intensity of dream-enacting behaviors and unpleasant dreams in both the idiopathic and secondary forms. When part of a neurodegenerative disorder the development of RBD is thought to reflect the location and extent of the underlying lesions involving the REM sleep centers of the brain (e.g., locus subceruleus, amygdala, etc.), leading to a complex multiple neurotransmitter dysfunction that involves GABAergic, glutamatergic and monoaminergic systems. RBD is mediated neither by direct abnormal alpha-synuclein inclusions nor by striatonigral dopaminergic deficiency alone.
Jeppesen, Jesper; Otto, Marit; Frederiksen, Yoon
OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent. METHODS: An EMG computer algorithm for scoring 'tonic', 'phasic' and 'any......' submental muscle activity during REM sleep was evaluated compared with human visual ratings. Subsequently, 52 subjects were analyzed with the algorithm. Duration and maximal amplitude of muscle activity, and self-awareness of RBD symptoms were assessed. RESULTS: The computer algorithm showed high congruency...... sleep without atonia. CONCLUSIONS: Our proposed algorithm was able to detect and rate REM sleep without atonia allowing identification of RBD. Increased duration and amplitude of muscle activity bouts were characteristics of RBD. Quantification of REM sleep without atonia represents a marker of RBD...
Gloria E Hoffman
Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.
Datta, Subimal; O'Malley, Matthew W .
Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372
Verhave, Peternella S; Jongsma, Marjan J; Van den Berg, Roland M; Vis, José C; Vanwersch, Raymond A P; Smit, August B; Van Someren, Eus J W; Philippens, Ingrid H C H M
Sleep problems are a common phenomenon in most neurological and psychiatric diseases. In Parkinson disease (PD), for instance, sleep problems may be the most common and burdensome non-motor symptoms in addition to the well-described classical motor symptoms. Since sleep disturbances generally become apparent in the disease before motor symptoms emerge, they may represent early diagnostic tools and a means to investigate early mechanisms in PD onset. The sleep disturbance, REM sleep behavior disorder (RBD), precedes PD in one-third of patients. We therefore investigated sleep changes in marmoset monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), the non-human primate model for idiopathic PD. Mild parkinsonism was induced in 5 marmoset monkeys (3M/2F) over a 2-week period of subchronic MPTP treatment. Electroencephalograms (EEGs) and electromyograms (EMGs) were recorded weekly. Motor activity and hand-eye coordination were also measured weekly, and any signs of parkinsonism were noted each day. Sleep parameters, motor activity, and performance data before and after MPTP treatment were compared between MPTP-treated marmosets and 4 control marmosets (1M/3F). MPTP increased the number of sleep epochs with high-amplitude EMG bouts during REM sleep relative to control animals (mean ± SEM percentage of REM 58.2 ± 9.3 vs. 29.6 ± 7.7; P sleep parameters measured, RBD-like measures discriminated best between MPTP-treated and control animals. On the other hand, functional motor behavior, as measured by hand-eye coordination, was not affected by MPTP treatment (correct trials MPTP: 23.40 ± 3.56 vs. control: 36.13 ± 5.88 correct trials; P = 0.32). This REM sleep-specific change, in the absence of profound changes in wake motor behaviors, suggests that the MPTP marmoset model of PD could be used for further studies into the mechanisms and treatment of RBD and other sleep disorders in premotor symptom PD.
Wiesner, Christian D; Pulst, Julika; Krause, Fanny; Elsner, Marike; Baving, Lioba; Pedersen, Anya; Prehn-Kristensen, Alexander; Göder, Robert
Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Gaig, Carles; Iranzo, Alex; Pujol, Montserrat; Perez, Hernando; Santamaria, Joan
To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS). Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center. Patients were 15 men and 2 women with a median age of 66 (range: 48-77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals. Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and
Shechter, Ari; Foster, Gary D; Lang, Wei; Reboussin, David M; St-Onge, Marie-Pierre; Zammit, Gary; Newman, Anne B; Millman, Richard P; Wadden, Thomas A; Jakicic, John M; Strotmeyer, Elsa S; Wing, Rena R; Pi-Sunyer, F Xavier; Kuna, Samuel T
The aim of this study was to determine if an intensive lifestyle intervention (ILI) reduces the severity of obstructive sleep apnea (OSA) in rapid-eye movement (REM) sleep, and to determine if longitudinal changes in glycaemic control are related to changes in OSA severity during REM sleep over a 4-year follow-up. This was a randomized controlled trial including 264 overweight/obese adults with type 2 diabetes (T2D) and OSA. Participants were randomized to an ILI targeted to weight loss or a diabetes support and education (DSE) control group. Measures included anthropometry, apnea-hypopnea index (AHI) during REM sleep (REM-AHI) and non-REM sleep (NREM-AHI) and glycated haemoglobin (HbA1c) at baseline and year 1, year 2 and year 4 follow-ups. Mean baseline values of REM-AHI were significantly higher than NREM-AHI in both groups. Both REM-AHI and NREM-AHI were reduced significantly more in ILI versus DSE, but these differences were attenuated slightly after adjustment for weight changes. Repeated-measure mixed-model analyses including data to year 4 demonstrated that changes in HbA1c were related significantly to changes in weight, but not to changes in REM-AHI and NREM-AHI. Compared to control, the ILI reduced REM-AHI and NREM-AHI during the 4-year follow-up. Weight, as opposed to REM-AHI and NREM-AHI, was related to changes in HbA1c. The findings imply that weight loss from a lifestyle intervention is more important than reductions in AHI for improving glycaemic control in T2D patients with OSA. © 2017 European Sleep Research Society.
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Mariana F. Aurich
Full Text Available Introduction: Olfactory dysfunction affects about 85-90% of Parkinson's disease (PD patients with severe deterioration in the ability of discriminate several types of odors. In addition, studies reported declines in olfactory performances during a short period of sleep deprivation. Besides, PD is also known to strongly affect the occurrence and maintenance of rapid eye movement (REM sleep. Methods: Therefore, we investigated the mechanisms involved on discrimination of a social odor (dependent on the vomeronasal system and a non-social odor (related to the main olfactory pathway in the rotenone model of PD. Also, a concomitant impairment in REM sleep was inflicted with the introduction of two periods (24 or 48 h of REM sleep deprivation (REMSD. Rotenone promoted a remarkable olfactory impairment in both social and non-social odors, with a notable modulation induced by 24 h of REMSD for the non-social odor. Results: Our findings demonstrated the occurrence of a strong association between the density of nigral TH-ir neurons and the olfactory discrimination capacity for both odorant stimuli. Specifically, the rotenone-induced decrease of these neurons tends to elicit reductions in the olfactory discrimination ability. Conclusions: These results are consistent with the participation of the nigrostriatal dopaminergic system mainly in the olfactory discrimination of a non-social odor, probably through the main olfactory pathway. Such involvement may have produce relevant impact in the preclinical abnormalities found in PD patients.
Full Text Available No abstract available. Article truncated after first 150 words. A 55 year old female with a past medical history significant for Parkinson disease status-post implantation of bilateral deep brain stimulators, depression, and restless legs syndrome, who initially presented to the sleep clinic on referral by neurology for evaluation of disordered sleep. Medications included carbidopa-levodopa, escitalopram, gabapentin, lorazepam, ambien, and pramipexole. Her subjective sleep complaints included snoring, restless sleep, difficulty in maintaining sleep, sleep related anxiety, dream enactment behavior, nightmares, and sleep talking. She was sent to the sleep laboratory for evaluation of suspected rapid eye movement behavior disorder (RBD. Overnight polysomnogram did not show evidence for sleep disordered breathing. The sleep study was notable for rapid eye movement (REM sleep without atonia, visible arm and leg movements, and audible moaning, speaking, and crying out. These findings corroborated the subjective complaints expressed by the patient and her husband. Her medication regimen was altered. Zolpidem and lorazepam were discontinued and she ...
Fernández-Mendoza, Julio; Lozano, Beatriz; Seijo, Fernando; Santamarta-Liébana, Elena; Ramos-Platón, Maria José; Vela-Bueno, Antonio; Fernández-González, Fernando
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. Citation: Fernández-Mendoza J; Lozano B; Seijo F; Santamarta-Liébana E; Ramos-Platón MJ; Vela-Bueno A; Fernández-González F. Evidence of subthalamic PGO-like waves during REM sleep in humans: a deep brain polysomnographic study. SLEEP 2009;32(9):1117-1126. PMID:19750916
Bhidayasiri, Roongroj; Sringean, Jirada; Rattanachaisit, Watchara; Truong, Daniel D
Sleep disorders are identified as common non-motor symptoms of Parkinson's disease (PD) and recently this recognition has been expanded to include parasomnias, encompassing not only REM sleep behaviour disorder (RBD), but also other non-REM forms. RBD, a prototypical parasomnia in PD, exists even in the prodromal stage of the disease, and is characterized by the presence of dream enactment behaviours occurring alongside a loss of normal skeletal muscle atonia during REM sleep. In contrast, non-REM parasomnias are more frequently observed in the late stage PD. However, the development of these disorders often overlaps and it is not uncommon for PD patients to meet the criteria for more than one type of parasomnias, thus making a clinical distinction challenging for practicing neurologists who are not sleep specialists. Indeed, clinical recognition of the predominant form of parasomnia does not just depend on video-polysomnography, but also on an individual physician's clinical acumen in delineating pertinent clinical history to determine the most likely diagnosis and proceed accordingly. In this review article, we highlight the various forms of parasomnias that have been reported in PD, including, but not limited to, RBD, with a focus on clinical symptomatology and implications for clinical practice. In addition, we review the differences in PD-related parasomnias compared to those seen in general populations. With advances in sleep research and better technology for ambulatory home monitoring, it is likely that many unanswered questions on PD-related parasomnias will soon be resolved resulting in better management of this nocturnal challenge in PD. Copyright © 2017 Elsevier B.V. All rights reserved.
Zhong, George; Bolitho, Samuel; Grunstein, Ronald; Naismith, Sharon Linda; Lewis, Simon John Geoffrey
This study explored the relationship between symptoms of rapid eye movement sleep behaviour disorder, thermoregulation and sleep in Parkinson's Disease. The study group comprised 12 patients with Parkinson's Disease and 11 healthy age-matched controls. We investigated markers of thermoregulation (core-body temperature profile), circadian rhythm (locomotor actigraphy) and sleep (polysomnography). The mesor (the mean value around which the core temperature rhythm oscillates) of the core-body temperature in patients with Parkinson's Disease was significantly lower than that of controls. In addition, the nocturnal fall in CBT (the difference between the mesor and the nadir temperature) was also significantly reduced in PD patients relative to controls. Furthermore, in patients the reduction in the amplitude of their core-body temperature profile was strongly correlated with the severity of self-reported rapid eye movement sleep behaviour disorder symptom, reduction in the percentage of REM sleep and prolonged sleep latency. By contrast, these disturbances of thermoregulation and sleep architecture were not found in controls and were not related to other markers of circadian rhythm or times of sleep onset and offset. These findings suggest that the brainstem pathology associated with disruption of thermoregulation in Parkinson's disease may also contribute to rapid eye movement sleep behavioural disorder. It is possible that detailed analysis of the core-body temperature profile in at risk populations such as those patients with idiopathic rapid eye movement sleep behaviour disorder might help identify those who are at high risk of transitioning to Parkinson's Disease.
Ronald B. Postuma
Full Text Available Rapid eye movement (REM sleep behavior disorder (RBD is characterized by loss of normal atonia during REM sleep, such that patients appear to act out their dreams. The most important implication of research into this area is that patients with idiopathic RBD are at very high risk of developing synucleinmediated neurodegenerative disease (Parkinson's disease [PD], dementia with Lewy bodies [DLB], and multiple system atrophy, with risk estimates that approximate 40–65% at 10 years. Thus, RBD disorder is a very strong feature of prodromal synucleinopathy. This provides several opportunities for future research. First, patients with REM sleep behavior disorder can be studied to test other predictors of disease, which could potentially be applied to the general population. These studies have demonstrated that olfactory loss, decreased color vision, slowing on quantitative motor testing, and abnormal substantia nigra neuroimaging findings can predict clinical synucleinopathy. Second, prospectively studying patients with RBD allows a completely unprecedented opportunity to directly evaluate patients as they transition into clinical neurodegenerative disease. Studies assessing progression of markers of neurodegeneration in prodromal PD are beginning to appear. Third, RBD are very promising subjects for neuroprotective therapy trials because they have a high risk of disease conversion with a sufficiently long latency, which provides an opportunity for early intervention. As RBD research expands, collaboration between centers will become increasingly essential.
Full Text Available Ten years ago the sleep disorder narcolepsy was linked to the neuropeptide hypocretin (HCRT, also known as orexin. This disorder is characterized by excessive day time sleepiness, inappropriate triggering of rapid-eye movement (REM sleep and cataplexy, which is a sudden loss of muscle tone during waking. It is still not known how HCRT regulates REM sleep or muscle tone since HCRT neurons are localized only in the lateral hypothalamus while REM sleep and muscle atonia are generated from the brainstem. To identify a potential neuronal circuit, the neurotoxin hypocretin-2-saporin (HCRT2-SAP was used to lesion neurons in the ventral lateral periaquaductal gray (vlPAG. The first experiment utilized hypocretin knock-out (HCRT-ko mice with the expectation that deletion of both HCRT and its target neurons would exacerbate narcoleptic symptoms. Indeed, HCRT-ko mice (n = 8 given the neurotoxin HCRT2-SAP (16.5 ng/23nl/sec each side in the vlPAG had levels of REM sleep and sleep fragmentation that were considerably higher compared to HCRT-ko given saline (+39%; n = 7 or wildtype mice (+177%; n = 9. However, cataplexy attacks did not increase, nor were levels of wake or non-REM sleep changed. Experiment 2 determined the effects in mice where HCRT was present but the downstream target neurons in the vlPAG were deleted by the neurotoxin. This experiment utilized an FVB-transgenic strain of mice where eGFP identifies GABA neurons. We verified this and also determined that eGFP neurons were immunopositive for the HCRT-2 receptor. vlPAG lesions in these mice increased REM sleep (+79% versus saline controls and it was significantly correlated (r = 0.89 with loss of eGFP neurons. These results identify the vlPAG as one site that loses its inhibitory control over REM sleep, but does not cause cataplexy, as a result of hypocretin deficiency.
... REM sleep? What is the effect of sleep deprivation? What are sleep myths? What are sleep disorders? ... Some hormones produced during sleep affect the body's use of energy. This may be how inadequate sleep ...
Full Text Available 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.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle
Godin, Isabelle; Montplaisir, Jaques; Gagnon, Jean-François; Nielsen, Tore
Idiopathic REM sleep behavior disorder (iRBD) is characterized by atypical REM sleep motor activity, vivid dreams and nightmares, and dream-enacting behaviors that can result in injuries to the patient and bed partner. It is also a known predictor of Parkinson disease (PD). Alexithymia has been associated with disturbances in sleep and dreaming (e.g., nightmares) and is a non-motor symptom of PD. We assessed alexithymia and disturbed dreaming in iRBD patients with the aim of determining if these two factors are elevated and interrelated among this population. Questionnaire study of clinically diagnosed patients. Clinical sleep disorders center. Thirty-two iRBD patients and 30 healthy age- and sex-matched control participants. Participants completed the 20-item Toronto Alexithymia Scale (TAS-20), the Dream Questionnaire, and the Beck Depression Inventory. iRBD patients obtained higher TAS-20 total scores (62.16 ± 13.90) than did controls (52.84 ± 7.62; F 1,59 = 10.44, P sleep behavior disorder patients, and especially a difficulty in identifying feelings, parallels evidence of dysautonomia in this population. The higher incidence of distressing nightmares and the association of nightmares with alexithymia further extend similar findings for both clinical and non-clinical samples and suggest that an affect regulation disturbance may be common to the two sets of symptoms.
Tan, Shian Ming; Wan, Yi Min
While widely accepted as a first-line treatment for rapid eye movement sleep (REM) behaviour disorder, clonazepam (CNZP) has side effects that limit its applicability. Pramipexole is a possible alternative, but limited literature on its effectiveness exists. This review aims to summarize the available data on the use of pramipexole in REM sleep behaviour disorder. A systematic search of major databases was conducted to look for published and on-going trials. This search yielded a total of five articles, all of which are observational in nature. Factors associated with effectiveness include low doses (less than 1.5mg/day) and idiopathic rapid eye movement sleep behaviour disorder/absence of neurodegenerative disease. Overall, the evidence is inconclusive. This is due to the lack of randomised controlled trials and the challenges in interpreting polysomgraphy findings in rapid eye movement sleep behaviour disorder. Suggestions are given on how future trials evaluating pramipexole treatment in rapid eye movement sleep behaviour disorder could overcome current methodological issues in extant literature. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Alkadhi, Karim A; Alhaider, Ibrahim A
We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available Rapid eye movement (REM sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase controls acetylcholine (Ach availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12. Two additional groups, a home-cage control (N = 6 and a large platform control (N = 6, were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant, membrane-bound (100,000 g pellet and soluble (100,000 g supernatant Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1 in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8. There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2. Our results
Deliens, Gaétane; Schwartz, Sophie; Peigneux, Philippe
Llewellyn suggests that episodic memories undergo "elaborative encoding" during rapid eye movement (REM) dreams, generating novel associations between recent and remote memories that are then instantiated during non-REM (NREM) sleep. This hypothesis conflicts with our knowledge of the physiology of NREM and then REM sleep stages and their ordered succession. Moreover, associations during sleep might also involve the extraction of hidden patterns rather than de novo associations.
Qureshi, Munazah F; Jha, Sushil K
The conditioning tasks have been widely used to model fear and anxiety and to study their association with sleep. Many reports suggest that sleep plays a vital role in the consolidation of fear memory. Studies have also demonstrated that fear-conditioning influences sleep differently in mice strains having a low or high anxiety level. It is, therefore, necessary to know, how sleep influences fear-conditioning and how fear-conditioning induces changes in sleep architecture in moderate anxious strains. We have used Swiss mice, a moderate anxious strain, to study the effects of: (i) sleep deprivation on contextual fear conditioned memory, and also (ii) contextual fear conditioning on sleep architecture. Animals were divided into three groups: (a) non-sleep deprived (NSD); (b) stress control (SC); and (c) sleep-deprived (SD) groups. The SD animals were SD for 5 h soon after training. We found that the NSD and SC animals showed 60.57% and 58.12% freezing on the testing day, while SD animals showed significantly less freezing (17.13% only; p sleep. REM sleep, however, significantly decreased in NSD and SC animals on the training and testing days. Interestingly, REM sleep did not decrease in the SD animals on the testing day. Our results suggest that short-term sleep deprivation impairs fear memory in moderate anxious mice. It also suggests that NREM sleep, but not REM sleep, may have an obligatory role in memory consolidation.
Qureshi, Munazah F.; Jha, Sushil K.
The conditioning tasks have been widely used to model fear and anxiety and to study their association with sleep. Many reports suggest that sleep plays a vital role in the consolidation of fear memory. Studies have also demonstrated that fear-conditioning influences sleep differently in mice strains having a low or high anxiety level. It is, therefore, necessary to know, how sleep influences fear-conditioning and how fear-conditioning induces changes in sleep architecture in moderate anxious strains. We have used Swiss mice, a moderate anxious strain, to study the effects of: (i) sleep deprivation on contextual fear conditioned memory, and also (ii) contextual fear conditioning on sleep architecture. Animals were divided into three groups: (a) non-sleep deprived (NSD); (b) stress control (SC); and (c) sleep-deprived (SD) groups. The SD animals were SD for 5 h soon after training. We found that the NSD and SC animals showed 60.57% and 58.12% freezing on the testing day, while SD animals showed significantly less freezing (17.13% only; p sleep. REM sleep, however, significantly decreased in NSD and SC animals on the training and testing days. Interestingly, REM sleep did not decrease in the SD animals on the testing day. Our results suggest that short-term sleep deprivation impairs fear memory in moderate anxious mice. It also suggests that NREM sleep, but not REM sleep, may have an obligatory role in memory consolidation. PMID:29238297
He, Bin; Peng, Hua; Zhao, Ying; Zhou, Hui; Zhao, Zhongxin
Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats. 2011. Published by Elsevier B.V.
Di Fabio, Nadia; Poryazova, Rositsa; Oberholzer, Michael; Baumann, Christian R; Bassetti, Claudio L
In a questionnaire survey, we identified 36 (9%) of 417 Parkinson's disease (PD) patients with sleepwalking (SW); 72% of them also had a history of REM sleep behaviour disorder (RBD). We aimed to assess the clinical and polysomnographic characteristics of SW in PD and to compare them to patients with PD with and without a history of RBD. We performed video-polysomnography and detailed clinical examination in 30 PD patients from the above-mentioned survey: 10 patients with a history of SW, 10 patients with a history of RBD, and 10 patients with no history of either SW or RBD. PD patients with SW had higher depression, anxiety and Hoehn & Yahr scores and lower activities of daily living scores than patients without a history of RBD but did not differ from patients with RBD. Patients with SW and RBD also had more often dyskinesia and hallucinations. By polysomnography, RBD was observed in 8 patients with SW and in all patients with a history of RBD. A total of 5 patients without a history of either SW or RBD had REM sleep without atonia without behavioural peculiarities. SW in PD is associated with depression, higher disease severity and functional disability. The simultaneous occurrence of SW and RBD (overlap parasomnia) in most patients suggests a common underlying disturbance of motor control during sleep in PD, with variable manifestations in different sleep stages. Copyright © 2013 S. Karger AG, Basel.
Lara-Carrasco, Jessica; Nielsen, Tore A; Solomonova, Elizaveta; Levrier, Katia; Popova, Ani
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 dream negativity (P dream sadness (P 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.
Cellini, Nicola; Torre, Jacopo; Stegagno, Luciano; Sarlo, Michela
Sleep may play a role in consolidating emotional memories. However, studies on the effects of REM sleep on negative vs. neutral memories have produced inconsistent evidence. Here, we assess the role of NREM and REM sleep before and after learning in promoting the consolidation of neutral and arousing pleasant and unpleasant memories. Forty-six (32 F) healthy university students were exposed to a set of pictures at 1:00PM (Session 1) and to an equivalent set at 4:45PM (Session 2). All the pictures in Session 1 and Session 2 were presented again, intermixed with new similar pictures at 5:15PM in a memory recognition task. Following Session 1, participants took a 90/120-min nap (NAP group), while 16 participants remained awake (WAKE group). Via polysomnographic recording, the NAP group was segregated into REM (N=14) and NoREM groups (N=16). Indices of memory consolidation for both stimuli presented before (discriminability of Session 1 pictures in Session 3) and after sleep (discriminability of Session 2 pictures in Session 3) were calculated. Memory consolidation for pictures presented both before and after the sleep period was higher in the NAP group as compared to the WAKE group, but no differential role of REM sleep emerged. A memory consolidation advantage was evident for neutral over pleasant (but not unpleasant) pictures. Taken together, these results indicate that a daytime nap (with or without REM sleep) facilitates consolidation of declarative memories presented before and after sleep irrespective of their valence. Copyright © 2016 Elsevier Inc. All rights reserved.
Mellman, Thomas A; Kobayashi, Ihori; Lavela, Joseph; Wilson, Bryonna; Hall Brown, Tyish S
To determine relationships of polysomnographic (PSG) measures with posttraumatic stress disorder (PTSD) in a young adult, urban African American population. Cross-sectional, clinical and laboratory evaluation. Community recruitment, evaluation in the clinical research unit of an urban University hospital. Participants (n = 145) were Black, 59.3% female, with a mean age of 23.1 y (SD = 4.8). One hundred twenty-one participants (83.4%) met criteria for trauma exposure, the most common being nonsexual violence. Thirty-nine participants (26.9%) met full (n = 19) or subthreshold criteria (n = 20) for current PTSD, 41 (28.3%) had met lifetime PTSD criteria and were recovered, and 65 (45%) were negative for PTSD. Evaluations included the Clinician Administered PTSD Scale (CAPS) and 2 consecutive nights of overnight PSG. Analysis of variance did not reveal differences in measures of sleep duration and maintenance, percentage of sleep stages, and the latency to and duration of uninterrupted segments of rapid eye movement (REM) sleep by study group. There were significant relationships between the duration of PTSD and REM sleep percentage (r = 0.53, P = 0.001), REM segment length (r = 0.43, P = 0.006), and REM sleep latency (r = -0.34, P sleep with posttraumatic stress disorder (PTSD) relatively proximate to trauma exposure and nondisrupted or increased REM sleep with chronic PTSD. Mellman TA, Kobayashi I, Lavela J, Wilson B, Hall Brown TS. A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population.
Sivakumar, Siddharth S; Namath, Amalia G; Galán, Roberto F
Previous work from our lab has demonstrated how the connectivity of brain circuits constrains the repertoire of activity patterns that those circuits can display. Specifically, we have shown that the principal components of spontaneous neural activity are uniquely determined by the underlying circuit connections, and that although the principal components do not uniquely resolve the circuit structure, they do reveal important features about it. Expanding upon this framework on a larger scale of neural dynamics, we have analyzed EEG data recorded with the standard 10-20 electrode system from 41 neurologically normal children and adolescents during stage 2, non-REM sleep. We show that the principal components of EEG spindles, or sigma waves (10-16 Hz), reveal non-propagating, standing waves in the form of spherical harmonics. We mathematically demonstrate that standing EEG waves exist when the spatial covariance and the Laplacian operator on the head's surface commute. This in turn implies that the covariance between two EEG channels decreases as the inverse of their relative distance; a relationship that we corroborate with empirical data. Using volume conduction theory, we then demonstrate that superficial current sources are more synchronized at larger distances, and determine the characteristic length of large-scale neural synchronization as 1.31 times the head radius, on average. Moreover, consistent with the hypothesis that EEG spindles are driven by thalamo-cortical rather than cortico-cortical loops, we also show that 8 additional patients with hypoplasia or complete agenesis of the corpus callosum, i.e., with deficient or no connectivity between cortical hemispheres, similarly exhibit standing EEG waves in the form of spherical harmonics. We conclude that spherical harmonics are a hallmark of spontaneous, large-scale synchronization of neural activity in the brain, which are associated with unconscious, light sleep. The analogy with spherical harmonics in
Takeuchi, Tomoka; Ogilvie, Robert D; Murphy, Timothy I; Ferrelli, Anthony V
To be the first to compare EEG power spectra during sleep onset REM periods (SOREMP) and sleep onset NREM periods (NREMP) in normal individuals and relate this to dream appearance processes underlying these different types of sleep periods. Eight healthy undergraduates spent 7 consecutive nights in the sleep lab including 4 nights for SOREMP elicitation using the Sleep Interruption Technique. This enabled us to control preceding sleep processes between SOREMP and NREMP. EEG power spectra when participants did and did not report 'dreams' were compared between both types of sleep. Sleep stages, subjective measurements including dream property scores, sleepiness, mood, and tiredness after awakenings were also examined to determine their consistency with EEG findings. Increased alpha EEG activities (11.72-13.67 Hz) observed mainly in the central area were related to the absence of SOREMP dreams and appearance of NREMP dreams. Analyses of sleep stages combining two studies (16 participants) also supported the Fast Fourier Transform findings, showing that when dreams were reported there were decreased amounts of stage 2 and increased stage REM in SOREMP and increased stage W in NREMP. SOREMP dreams were more bizarre than NREMP dreams. Participants felt more tired after SOREMP with dreams than without dreams, while the opposite was observed after NREMP episodes. EEG power spectra patterns reflected different physiological mechanisms underlying generation of SOREMP and NREMP dreams. The same relationships were also reflected by sleep stage analyses as well as subjective measurements including dream properties and tiredness obtained after awakenings. This study not only supports the hypothesized relationships between REM mechanisms and REM dreams as well as arousal processes and NREM dreams, it also provides a new perspective to dream research due to its unique techniques to awaken participants and collect REM dreams during experimentally induced SOREMP.
Full Text Available Paradoxical sleep (PS is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons are principally located in the ventrolateral periaqueductal gray (vlPAG and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe. Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.
Cowdin, Nancy; Kobayashi, Ihori
Emotional memory consolidation has been associated with rapid eye movement (REM) sleep, and recent evidence suggests that increased electroencephalogram spectral power in the theta (4–8 Hz) frequency range indexes this activity. REM sleep has been implicated in posttraumatic stress disorder (PTSD) as well as in emotional adaption. In this cross-sectional study, thirty young healthy African American adults with trauma exposure were assessed for PTSD status using the Clinician Administered PTSD Scale. Two consecutive night polysomnographic (PSG) recordings were performed and data scored for sleep stages. Quantitative electroencephalographic spectral analysis was used to measure theta frequency components sampled from REM sleep periods of the second-night PSG recordings. Our objective was to compare relative theta power between trauma-exposed participants who were either resilient or had developed PTSD. Results indicated higher right prefrontal theta power during the first and last REM periods in resilient participants compared with participants with PTSD. Right hemisphere prefrontal theta power during REM sleep may serve as a biomarker of the capacity for adaptive emotional memory processing among trauma-exposed individuals. PMID:24531640
Cohen, Daniel J.; Begley, Amy; Alman, Jennie J.; Cashmere, J. David; Pietrone, Regina N.; Seres, Robert J.; Germain, Anne
Summary Sleep disturbances are a hallmark feature of posttraumatic stress disorder (PTSD), and associated with poor clinical outcomes. Few studies have examined sleep quantitative electroencephalography (qEEG), a technique able to detect subtle differences polysomnography does not capture. We hypothesized greater high-frequency qEEG would reflect “hyperarousal” in in combat veterans with PTSD (n=16) compared to veterans without PTSD (n=13). EEG power in traditional EEG frequency bands was computed for artifact-free sleep epochs across an entire night. Correlations were performed between qEEG and ratings of PTSD symptoms and combat exposure. The groups did not differ significantly in whole night qEEG measures for either REM or NREM. Non-significant medium effect sizes suggest less REM beta (opposite to our hypothesis), less REM and NREM sigma, and more NREM gamma in combat veterans with PTSD. Positive correlations were found between combat exposure and NREM beta (PTSD group only), and REM and NREM sigma (non-PTSD group only). Results did not support global hyperarousal in PTSD as indexed by increased beta qEEG activity. The correlation of sigma activity with combat exposure in those without PTSD, and the non-significant trend towards less sigma activity during both REM and NREM sleep in combat veterans with PTSD suggests that differential information processing during sleep may characterize combat-exposed military veterans with and without PTSD. PMID:22845675
Herlin, Bastien; Leu-Semenescu, Smaranda; Chaumereuil, Charlotte; Arnulf, Isabelle
To determine whether non-dreamers do not produce dreams or do not recall them, subjects were identified with no dream recall with dreamlike behaviours during rapid eye movement sleep behaviour disorder, which is typically characterised by dream-enacting behaviours congruent with sleep mentation. All consecutive patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye movement sleep behaviour disorder associated with Parkinson's disease who underwent a video-polysomnography were interviewed regarding the presence or absence of dream recall, retrospectively or upon spontaneous arousals. The patients with no dream recall for at least 10 years, and never-ever recallers were compared with dream recallers with rapid eye movement sleep behaviour disorder regarding their clinical, cognitive and sleep features. Of the 289 patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients had no dream recall, including four (1.4%) patients who had never ever recalled dreams, and four patients who had no dream recall for 10-56 years. All non-recallers exhibited, daily or almost nightly, several complex, scenic and dreamlike behaviours and speeches, which were also observed during rapid eye movement sleep on video-polysomnography (arguing, fighting and speaking). They did not recall a dream following sudden awakenings from rapid eye movement sleep. These eight non-recallers with rapid eye movement sleep behaviour disorder did not differ in terms of cognition, clinical, treatment or sleep measures from the 17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex and disease. The scenic dreamlike behaviours reported and observed during rapid eye movement sleep in the rare non-recallers with rapid eye movement sleep behaviour disorder (even in the never-ever recallers) provide strong evidence that non-recallers produce dreams, but do not recall them. Rapid eye movement sleep behaviour disorder provides a new model to
Kang, Won Sub; Park, Hae Jeong; Chung, Joo-Ho; Kim, Jong Woo
Recently, evidence has suggested the possible involvement of inflammatory cytokines in sleep deprivation (SD). In this study, we assessed the patterns of inflammatory gene regulation in the hypothalamus of REM SD mice. C57BL/6 mice were randomly assigned to two groups, SD (n=15) and control groups (n=15). Mice in the SD group were sleep-deprived for 72h using modified multiple platforms. Microarray analysis on inflammatory genes was performed in mice hypothalamus. In addition, interleukin 1 beta (IL1β) protein expression was analyzed by the immunochemistry method. Through microarray analysis, we found that expressions of IL subfamily genes, such as IL1β (2.55-fold), IL18 (1.92-fold), IL11 receptor alpha chain 1 (1.48-fold), IL5 (1.41-fold), and IL17E genes (1.31-fold), were up-regulated in the hypothalamus of SD mice compared to the control. The increase in the expression of these genes was also confirmed by RT-PCR. Among these genes, the expression of IL1β was particularly increased in the hypothalamus of SD mice. Interestingly, we found that the protein expression of endogenous IL1β was also elevated in the hypothalamus of SD mice compared to the control mice. These results implicate that IL subfamily genes, and in particular, IL1β, may play a role in sleep regulation in the hypothalamus of REM SD mice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Limousin, Nadège; Dehais, Caroline; Gout, Olivier; Héran, Françoise; Oudiette, Delphine; Arnulf, Isabelle
A 40-year-old woman with no prior parasomnia developed an acute inflammatory rhombencephalitis with multiple cranial nerve palsies and cerebellar ataxia, followed by myelitis 6 months later, and by an intracranial thrombophlebitis 1 month after. Between and after these episodes, she had a persistent, mild right internuclear ophtalmoplegia, a mild cerebellar ataxia, and a severe REM sleep behavior disorder (RBD) lasting for 2 years. She talked, sang and moved nightly while asleep, and injured her son (cosleeping with her) while asleep. In addition, she walked asleep nightly. During video-polysomnography, there were two arousals during slow wave sleep without abnormal behavior, while 44% of REM sleep was without chin muscle atonia with bilateral arm and leg movements. There were small hypointensities in the right pontine tegmentum and in the right dorsal medulla on T1-weighted magnetic resonance imaging, suggesting post-inflammatory lesions that persisted between acute episodes. The RBD and sleepwalking did not improve with clonazepam, but improved with melatonin 9 mg/d. The unilateral small lesion of the pontine tegmentum could be responsible for the parasomnia overlap disorder as in other rare lesional cases.
Full Text Available Background: Parkinson's disease (PD represents a major public health challenge that will only grow in our aging population. Understanding the connection between PD and associated prodromal conditions, such as rapid eye movement sleep behavioral disorder (RBD, is critical to identifying prevention strategies. However, the relationship between RBD and severity of motor findings in early PD is unknown. This study aims to examine this relationship. Methods: The study population consisted of 418 PD patients who completed the Movement Disorders Society‐United Parkinson's Disease Rating Scale (MDS‐UPDRS and rapid eye movement sleep (REM disorder questionnaires at the baseline visit of the Michael J. Fox's Parkinson's Progression Markers Initiative (PPMI. Cross‐sectional analysis was carried out to assess the association between REM Sleep Behavior Screening Questionnaire score and MDS UPDRS‐3 (motor score categories. Correlation with a higher score category was described as “worse motor findings”. A score of 5 on the REM disorder questionnaire was defined as predictive of RBD.Results: Out of the 418 PD patients, 113 (27.0% had RBD. With univariate logistic regression analysis, individuals with scores predictive of RBD were 1.66 times more likely to have worse motor findings (p = 0.028. Even with age, gender, and Geriatric Depression Scale scores taken into account, individuals with scores predictive of RBD were 1.69 times more likely to have worse motor findings (p = 0.025.Discussion: PD patients with RBD symptoms had worse motor findings than those unlikely to have RBD. This association provides further evidence for the relationship between RBD and PD.
Walsh, Christine M.; Booth, Victoria; Poe, Gina R.
This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation–associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items. PMID:21677190
Miguel Meira e Cruz
Full Text Available Parasomnias with sexual behavior or sexsomnias are considered a subtype of NREM parasomnias. Obstructive sleep apnea/hypopnea (OSAH has been described as a known triggering factor for parasomnias including sexsomnia. Nasal continuous positive airway pressure (nCPAP has been the standard of treatment for OSAH but mandibular advancement devices (MAD are becoming an important treatment alternative. We present the case of a patient with mild OSAH and sexsomnia who had resolution of both conditions with a MAD. This patient had the added uniqueness of having REM-predominant OSAH
Ramakrishnan, Nisha K; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J; Elsinga, Philip H; Ishiwata, Kiichi; Dierckx, Rudi A J O; van Waarde, Aren
Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model. Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [(11)C]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test. Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition. The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.
Christensen, Julie A E; Kempfner, Jacob; Zoetmulder, Marielle; Leonthin, Helle L; Arvastson, Lars; Christensen, Søren R; Sorensen, Helge B D; Jennum, Poul
To determine whether sleep spindles (SS) are potentially a biomarker for Parkinson's disease (PD). Fifteen PD patients with REM sleep behavior disorder (PD+RBD), 15 PD patients without RBD (PD-RBD), 15 idiopathic RBD (iRBD) patients and 15 age-matched controls underwent polysomnography (PSG). SS were scored in an extract of data from control subjects. An automatic SS detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine (SVM) was developed and applied to the PSG recordings. The SS densities in N1, N2, N3, all NREM combined and REM sleep were obtained and evaluated across the groups. The SS detector achieved a sensitivity of 84.7% and a specificity of 84.5%. At a significance level of α=1%, the iRBD and PD+RBD patients had a significantly lower SS density than the control group in N2, N3 and all NREM stages combined. At a significance level of α=5%, PD-RBD had a significantly lower SS density in N2 and all NREM stages combined. The lower SS density suggests involvement in pre-thalamic fibers involved in SS generation. SS density is a potential early PD biomarker. It is likely that an automatic SS detector could be a supportive diagnostic tool in the evaluation of iRBD and PD patients. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Tekriwal, Anand; Kern, Drew S; Tsai, Jean; Ince, Nuri F; Wu, Jianping; Thompson, John A; Abosch, Aviva
Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterised by complex motor enactment of dreams and is a potential prodromal marker of Parkinson's disease (PD). Of note, patients with PD observed during RBD episodes exhibit improved motor function, relative to baseline states during wake periods. Here, we review recent epidemiological and mechanistic findings supporting the prodromal value of RBD for PD, incorporating clinical and electrophysiological studies. Explanations for the improved motor function during RBD episodes are evaluated in light of recent publications. In addition, we present preliminary findings describing changes in the activity of the basal ganglia across the sleep-wake cycle that contribute to our understanding of RBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Abenza Abildúa, M J; Miralles Martinez, A; Arpa Gutiérrez, F J; Lores Gutiérrez, V; Algarra Lucas, C; Jimeno Montero, C; Sánchez García, B; Mata Álvarez-Santullano, M; Borrue Fernández, C; Cordero Martín, G; Gutiérrez Cueto, G; Torrecillas Narváez, M D; Thuissard Vasallo, I; Gómez Aceña, A
REM sleep behaviour disorder (RBD) is characterised by violent behaviours (screaming, kicking, vivid dreams) during REM sleep. It has a prevalence of 1% to 2% of the general population and is especially frequent in men and the population older than 60. In the last decade, RBD has been suggested to be a prodrome of neurodegenerative disease. We analysed associated neurological diseases and responses to drug treatment in 33 patients with RBD treated in the multidisciplinary sleep disorders unit at Hospital Infanta Sofía. We conducted an observational descriptive retrospective analysis of patients diagnosed with RBD and treated in our multidisciplinary sleep disorders unit between October 2012 and December 2015. We recorded age, sex, associated diseases, and treatments administered to these patients. A total of 365 patients were attended at our unit, including 33 with RBD: 13 women (40%) and 20 men (60%). Mean age was 62.72 years. An associated disorder was identified in 48%, with the most common being mild cognitive impairment (69%). The percentage of patients with RBD and an associated disorder among patients older than 60 was 68%. Eighty-two percent of the patients required treatment. The most commonly used drug was clonazepam (76%), followed by melatonin (9%), gabapentin (6%), and trazodone (3%). In our series, 48% of the patients had an associated disorder. The likelihood of detecting an associated disorder increases with patients' age. The vast majority of patients required drug treatment due to symptom severity; the most frequently administered drug was clonazepam (76%). Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.
Salsone, M; Cerasa, A; Arabia, G; Morelli, M; Gambardella, A; Mumoli, L; Nisticò, R; Vescio, B; Quattrone, A
REM sleep behavior disorder (RBD) is a common non motor feature of Parkinson's Disease (PD) affecting about half the patients with this disease. Distinct structural brain tissue abnormalities have been reported in several regions modulating REM sleep of the patients with idiopathic RBD. At the present time, there are no conventional MRI studies investigating patients with PD associated with RBD. Herein, we used voxel-based morphometry (VBM) to detect the neuroanatomical profile of PD patients with and without RBD. Optimized VBM was applied to the MRI brain images in 11 PD patients with RBD (PD-RBD), 11 PD patients without RBD (PD) and 18 age-and sex-matched controls. To corroborate VBM findings we used automated volumetric method (FreeSurfer) to quantify subcortical brain regions volumes. Patients and controls also underwent DAT-SPECT and cardiac MIBG scintigraphies. The VBM analysis showed markedly reduced gray matter volume in the right thalamus of PD-RBD patients in comparison with PD patients and controls. Automatic thalamic segmentation in PD-RBD patients showed a bilaterally reduced thalamic volume as compared with PD patients or controls. All PD patients (with and without RBD) showed a reduced tracer uptake on DAT-SPECT and cardiac MIBG scintigraphies as compared to controls. Our findings suggest that the presence of RBD symptoms in PD patients is associated with a reduced thalamic volume suggesting a pathophysiologic role of the thalamus in the complex circuit causing RBD. Copyright © 2014. Published by Elsevier Ltd.
Bellosta Diago, E; Lopez Del Val, L J; Santos Lasaosa, S; López Garcia, E; Viloria Alebesque, A
The relationship between impulse control disorder (ICD) and REM sleep behaviour disorder (RBD) has not yet been clarified, and the literature reports contradictory results. Our purpose is to analyse the association between these 2 disorders and their presence in patients under dopaminergic treatment. A total of 73 patients diagnosed with Parkinson's disease and treated with a single dopamine agonist were included in the study after undergoing clinical assessment and completing the single-question screen for REM sleep behaviour disorder and the short version of the questionnaire for impulsive-compulsive behaviours in Parkinson's disease. Mean age was 68.88 ± 7.758 years. Twenty-six patients (35.6%) were classified as probable-RBD. This group showed a significant association with ICD (P=.001) and had a higher prevalence of non-tremor akinetic rigid syndrome and longer duration of treatment with levodopa and dopamine agonists than the group without probable-RBD. We found a significant correlation between the use of oral dopamine agonists and ICD. Likewise, patients treated with oral dopamine agonists demonstrated a greater tendency toward presenting probable-RBD than patients taking dopamine agonists by other routes; the difference was non-significant. The present study confirms the association between RBD and a higher risk of developing symptoms of ICD in Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J
The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs
Venancio, Daniel Paulino; Suchecki, Deborah
Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (pmetabolic syndrome-related alterations that may be mediated by inflammation of the RPAT. Copyright © 2014 Elsevier Inc. All rights reserved.
Full Text Available Background Stress induced by sleep deprivation can cause degradation of learning in the acquisition phase, and low-intensity exercise can prevent the negative effects of stress. Objectives The aim of this study was to investigate the moderating role of aerobic exercise on spatial memory and learning following stress-induced insomnia (sleep REM in animal models. Materials and Methods This experimental study was conducted on adult male Wistar rats that were randomly divided into two groups. Both groups were exposed to sleep deprivation induced stress, following which the experimental group was exposed to exercise training (experimental, n = 8; control, n = 8. The stress intervention was undertaken through 24 hours of sleep deprivation using a modified sleep deprivation platform (MMD. The exercise protocol included mild aerobic exercise on a treadmill (30 minutes a day, seven days, and Morris Water Maze (MWM protocols were applied to assess spatial memory and learning. Data were analyzed by an independent t-test and dependent t-test. Results The results showed that, after seven days of aerobic exercise on a treadmill, the experimental group showed better performance escape latency (P < 0.05 and distance traveled (P < 0.05 than the control group in the MWM, while there was no difference between these two groups in the pre-test. Conclusions The role of exercise is greater in the retention than the acquisition phase for recalling past experiences.
Dijk, D. J.
In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.
Janković Slavko M.
Full Text Available The perplexing and tantalizing disease of rapid eye movement (REM sleep behavior disorder (RBD is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats . In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication , and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse . However, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986 [4-7]. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia . To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al  in 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. . The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep" . Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene
Cui, Su-Ying; Cui, Xiang-Yu; Zhang, Juan; Wang, Zi-Jun; Yu, Bin; Sheng, Zhao-Fu; Zhang, Xue-Qiong; Shi, Xiao-Lei; Zhang, Yong-He
Our previous studies indicated that L-type calcium channel blocker diltiazem could potentiate pentobarbital-induced hypnosis through serotonergic system. In view of the important role of dorsal raphe nucleus (DRN) on the sleep regulation and the pharmacological actions of calcium channel blocker, we presumed that Ca(2+) in the DRN may play an important role in sleep regulation in pentobarbital treated rats. Therefore, we investigated whether the Ca(2+) modulation in DRN by the microinjection of L-type Ca(2+) channel antagonist diltiazem, agonist BAY-K-8644, Ca(2+) chelator EGTA and CaCl(2) would alter the sleep parameters in pentobarbital treated rats. Results showed that perfusion of the agents attenuating Ca(2+) function, such as diltiazem (5 or 20 nmol) or EGTA (3 or 6 pmol) into DRN significantly increased pentobarbital (35 mg/kg, i.p.)-induced total sleep (TS), non-rapid eye movement (NREM) sleep and the slow wave sleep (SWS) ratio in NREM sleep. On the contrary, the DRN injection of the agents improving Ca(2+) function, such as BAY-K-8644 (10 nmol) or CaCl(2) (50 or 100 nmol) significantly reduced pentobarbital (35 mg/kg, i.p.)-induced TS, NREM sleep, rapid eye movement (REM) sleep and REM sleep ratio in TS without influence on SWS. These results suggested that the suppression of Ca(2+) function in DRN could increase NREM sleep including SWS, and the elevation of Ca(2+) function could reduce both NREM and REM sleep in pentobarbital treated rats. Copyright © 2011 Elsevier B.V. All rights reserved.
Alves, R; Alóe, F; Tavares, S; Vidrio, S; Yáñez, L; Aguilar-Roblero, R; Rosenthal, L; Villalobos, L; Fernández-Cancino, F; Drucker-Colín, R; Chagoya De Sanchez, V
Seven cases of sexual behavior during sleep (SBS) have been recently reported. The subjects had histories of behavioral parasomnias as well as positive family histories of parasomnia. A 27 year-old man with a history of sexual behavior during sleep was reported. His sleep history disclosed sleepwalking (SW) since 9 years of age. He also developed episodes of highly disruptive and violent nocturnal behavior with dream enactment at age 20 years, which often resulted in physical injuries either to himself or his wife and infant. His wife also reported episodes of amnestic sexual behavior that began 4 years before referral. During the episodes, the patient typically procured his wife, achieving complete sexual intercourse with total amnesia. Physical and neurological diagnostic workups were unremarkable. Family history disclosed sleepwalking in his brother. He was put on 2mg/day of bedtime clonazepam with a remarkable clinical improvement. This case involves either the combination of violent and non-violent sleepwalking with SBS, or the superimposition of presumed REM sleep behavior disorder (RBD) on top of preexisting SW in a man who also developed SBS in adulthood. Thus, this is a case report of probable parasomnia overlap syndrome.
Munazah F. Qureshi
Full Text Available The conditioning tasks have been widely used to model fear and anxiety and to study their association with sleep. Many reports suggest that sleep plays a vital role in the consolidation of fear memory. Studies have also demonstrated that fear-conditioning influences sleep differently in mice strains having a low or high anxiety level. It is, therefore, necessary to know, how sleep influences fear-conditioning and how fear-conditioning induces changes in sleep architecture in moderate anxious strains. We have used Swiss mice, a moderate anxious strain, to study the effects of: (i sleep deprivation on contextual fear conditioned memory, and also (ii contextual fear conditioning on sleep architecture. Animals were divided into three groups: (a non-sleep deprived (NSD; (b stress control (SC; and (c sleep-deprived (SD groups. The SD animals were SD for 5 h soon after training. We found that the NSD and SC animals showed 60.57% and 58.12% freezing on the testing day, while SD animals showed significantly less freezing (17.13% only; p < 0.001 on the testing day. Further, we observed that contextual fear-conditioning did not alter the total amount of wakefulness and non-rapid eye movement (NREM sleep. REM sleep, however, significantly decreased in NSD and SC animals on the training and testing days. Interestingly, REM sleep did not decrease in the SD animals on the testing day. Our results suggest that short-term sleep deprivation impairs fear memory in moderate anxious mice. It also suggests that NREM sleep, but not REM sleep, may have an obligatory role in memory consolidation.
Solomonova, Elizaveta; Stenstrom, Philippe; Schon, Emilie; Duquette, Alexandra; Dubé, Simon; O'Reilly, Christian; Nielsen, Tore
Face recognition is a highly specialized capability that has implicit and explicit memory components. Studies show that learning tasks with facial components are dependent on rapid eye movement and non-rapid eye movement sleep features, including rapid eye movement sleep density and fast sleep spindles. This study aimed to investigate the relationship between sleep-dependent consolidation of memory for faces and partial rapid eye movement sleep deprivation, rapid eye movement density, and fast and slow non-rapid eye movement sleep spindles. Fourteen healthy participants spent 1 night each in the laboratory. Prior to bed they completed a virtual reality task in which they interacted with computer-generated characters. Half of the participants (REMD group) underwent a partial rapid eye movement sleep deprivation protocol and half (CTL group) had a normal amount of rapid eye movement sleep. Upon awakening, they completed a face recognition task that contained a mixture of previously encountered faces from the task and new faces. Rapid eye movement density and fast and slow sleep spindles were detected using in-house software. The REMD group performed worse than the CTL group on the face recognition task; however, rapid eye movement duration and rapid eye movement density were not related to task performance. Fast and slow sleep spindles showed differential relationships to task performance, with fast spindles being positively and slow spindles negatively correlated with face recognition. The results support the notion that rapid eye movement and non-rapid eye movement sleep characteristics play complementary roles in face memory consolidation. This study also raises the possibility that fast and slow spindles contribute in opposite ways to sleep-dependent memory consolidation. © 2017 European Sleep Research Society.
Zhou, Junying; Zhang, Jihui; Lam, Siu Ping; Chan, Joey Wy; Mok, Vincent; Chan, Anne; Li, Shirley Xin; Liu, Yaping; Tang, Xiangdong; Yung, Wing Ho; Wing, Yun Kwok
To determine the association of excessive daytime sleepiness (EDS) with the conversion of neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (iRBD). A total of 179 patients with iRBD (79.1% males, mean age = 66.3 ± 9.8 years) were consecutively recruited. Forty-five patients with Epworth Sleepiness Scale score ≥14 were defined as having EDS. Demographic, clinical, and polysomnographic data were compared between iRBD patients with and without EDS. The risk of developing neurodegenerative diseases was examined using Cox proportional hazards model. After a mean follow-up of 5.8 years (SD = 4.3 years), 50 (27.9%) patients developed neurodegenerative diseases. There was a significantly higher proportion of conversion in patients with EDS compared to those without EDS (42.2 % vs. 23.1%, p = .01). EDS significantly predicted an increased risk of developing neurodegenerative diseases (adjusted hazard ratios [HR] = 2.56, 95% confidence interval [CI] 1.37 to 4.77) after adjusting for age, sex, body mass index, current depression, obstructive sleep apnea, and periodic limb movements during sleep. Further analyses demonstrated that EDS predicted the conversion of Parkinson's disease (PD) (adjusted HR = 3.55, 95% CI 1.59 to 7.89) but not dementia (adjusted HR = 1.48, 95% CI 0.44 to 4.97). EDS is associated with an increased risk of developing neurodegenerative diseases, especially PD, in patients with iRBD. Our findings suggest that EDS is a potential clinical biomarker of α-synucleinopathies in iRBD. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail firstname.lastname@example.org.
Iaccarino, Leonardo; Marelli, Sara; Iannaccone, Sandro; Magnani, Giuseppe; Ferini-Strambi, Luigi; Perani, Daniela
To evaluate the prevalence of REM sleep behavior disorder (RBD) in a sample of Dementia with Lewy Bodies (DLB) and Alzheimer's Disease (AD) patients and compare the patterns of brain glucose metabolism in DLB patients with or without the sleep disturbances. In this retrospective study, the presence of probable RBD was ascertained for 27 clinically diagnosed DLB patients and 11 AD patients by a self-administered RBD Single-Question Screen (RBD1Q), followed by a sleep structured interview by experts in sleep disorders blinded to clinical information. For 18F-FDG-PET metabolic comparisons, we considered an additional 13 DLB patients with negative history for sleep disturbance. We performed DLB within-group comparisons covarying for age and disease duration. The RBD1Q questionnaire identified 20 out of 27 DLB RBD+ and 7 out of 27 DLB RBD-. None of the AD patients was positive to RBD1Q test. 18F-FDG-PET hypometabolism at the single- and group-level tested by means of an optimized SPM approach revealed the typical DLB metabolic pattern. Each DLB patient showed a predominant occipital hypometabolism. The SPM voxel-based comparisons revealed significant brain metabolic differences, namely a more severe metabolic decrease in DLB RBD+ in the dorsolateral and medial frontal regions, left precuneus, bilateral superior parietal lobule and rolandic operculum, and amygdala. We found a high prevalence of RBD in DLB and none in AD, as identified by the RBD1Q questionnaire, indicating its utility in clinical practice. DLB patients with or without RBD show different hypometabolism patterns that might reflect differences in underlying pathology.
Li, Xudong; Zhou, Zhi; Jia, Shuhong; Hou, Chunlei; Zheng, Wenjing; Rong, Pei; Jiao, Jinsong
We investigated cognitive abnormalities using standard tests in Chinese patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with those in normal controls. Twenty-three patients with iRBD and 23 normal controls were included in this study. All of the participants underwent one night of video-polysomnography (PSG) monitoring to certify REM sleep without atonia or abnormal behaviors. The cognitive assessments were administered and scored according to a standard procedure, including global cognitive screening and attention/processing speed, executive function, memory, language, and visuospatial ability testing. Patients with iRBD had similar scores of the Mini Mental State Examination (MMSE) but lower Montreal Cognitive Assessment (MoCA) scores compared with controls (p>0.05, p=0.013). The iRBD patients performed poorly on verbal memory tests, which included immediate recall (pfalse recognitions (p=0.002) of the Rey Auditory Verbal Learning Test (RAVLT). The visual memory and visuospatial abilities were also impaired in iRBD patients, as reflected by the copy (p=0.005) and immediate (p=0.004) and delayed (p=0.003) recall of the Rey-Osterrieth complex figure, although no difference was found after Bonferroni correction. The duration of RBD was 6.98±8.10years. After controlling for age, the duration of RBD was only correlated with the Trail Making Test B (r=0.613, p=0.045) and block design (r=-0.667, p=0.025). Impaired verbal memory was observed in iRBD patients who identified as Chinese. MoCA could detect cognitive abnormalities and serve as a screening scale. The present study further confirmed cognitive deficits in iRBD as an early clinical marker in the prodromal stage of synucleinopathy. Copyright © 2016 Elsevier B.V. All rights reserved.
Sinton, C M; Fitch, T E; Gershenfeld, H K
Leptin (ob protein) is an adipose tissue derived circulating hormone that acts at specific receptors in the hypothalamus to reduce food intake. The protein is also critically involved in energy balance and metabolic status. Here the effect of leptin on sleep architecture in rats was evaluated because food consumption and metabolic status are known to influence sleep. Sprague-Dawley rats were chronically implanted with electrodes for EEG and EMG recording and diurnal sleep parameters were quantified over 9-h periods following leptin administration. Murine recombinant leptin (rMuLep) was administered systemically to rats that either had undergone 18 h of prior food deprivation or had received food ad libitum. In the normally fed rats, leptin significantly decreased the duration of rapid eye movement sleep (REMS) by about 30% and increased the duration of slow wave sleep (SWS) by about 13%, the latter effect reflecting enhanced power in the delta frequency band. These results are consistent with studies that have linked changes in metabolic rate with effects on sleep. Leptin administration has previously been shown to alter neuroendocrine parameters that could have mediated these changes in sleep architecture. Unexpectedly, prior food deprivation negated the effect of leptin on both REMS and SWS, a result that emphasizes the significance of the apparent coupling between sleep parameters and energy status.
Full Text Available Background/Aim. Sleep is prompted by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM sleep and non-rapid eye movement (NREM sleep. REM sleep behavior disorder (RBD is characterized by violent motor and vocal behavior during REM sleep which represents dream enactment. The normal loss of muscle tone, with the exception of respiratory, sphincter, extra ocular and middle ear muscles, is absent in patients with RBD. The origin of RBD is frequently unknown, but can be associated with degenerative neurological disorders, such as Parkinson’s disease (PD. PD patients do not necessarily express features of RBD, which is identified in approximately third to a half of them. The aim of this study was to estimate the prevalence of RBD in a cohort of PD patients, as well as to identify risk-factors for its development. Methods. In the period from December 2010 to September 2011 we recruited 97 consecutive PD outpatients, treated in the Institute of Neurology, Clinical Center of Serbia, Belgrade. After establishing the diagnosis, all the patients filled out a specially constructed questionnaire with the following items: actual age, sex, age at disease onset, disease duration, form of the disease, type of treatment, duration of treatment, the presence of constipation, lessening of smell sense, and family history of PD. At entring the study, patients disability was scored using the Unified Parkinson’s Disease Rating Scale (motor part - UPDRS. Cognitive abilities were assessed by the Mini Mental Status Examination (MMSE scale, and depression symptoms by the 21-item Hamilton Depression Rating Scale (HDRS. The patients with PD were dichotomized to those with and without RBD using the RBD Questionnaire - Hong Kong (RBDQ-HK in the manner of an interview. Forms of PD, mode of treatment, sex, constipation and family history were investigated using the Fishers χ2 test. Symptoms and treatment duration, the presence of
Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen
STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...... in rapid eye movement (REM) and nonrapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...
Hobson, J A
The most important recent work on the neurobiology of sleep has focused on the precise cellular and biochemical mechanisms of rapid eye movement sleep mediation. Direct and indirect evidence implicates acetylcholine-containing neurons in the peribrachial pons as critical in the triggering and maintenance of rapid eye movement sleep. Other new studies provide support for the hypothesis that the cholinergic generator system is gated during waking by serotonergic and noradrenergic influences. A growing consensus regarding the basic neurobiology has stimulated new thinking about the brain basis of consciousness during waking and dreaming.
Iranzo, Alex; Schenck, Carlos H; Fonte, Jorge
During a viewing of Disney's animated film Cinderella (1950), one author (AI) noticed a dog having nightmares with dream-enactment that strongly resembled RBD. This prompted a study in which all Disney classic full-length animated films and shorts were analyzed for other examples of RBD. Three additional dogs were found with presumed RBD in the classic films Lady and the Tramp (1955) and The Fox and the Hound (1981), and in the short Pluto's Judgment Day (1935). These dogs were elderly males who would pant, whine, snuffle, howl, laugh, paddle, kick, and propel themselves while dreaming that they were chasing someone or running away. In Lady and the Tramp the dog was also losing both his sense of smell and his memory, two associated features of human RBD. These four films were released before RBD was first formally described in humans and dogs. In addition, systematic viewing of the Disney films identified a broad range of sleep disorders, including nightmares, sleepwalking, sleep related seizures, disruptive snoring, excessive daytime sleepiness, insomnia and circadian rhythm sleep disorder. These sleep disorders were inserted as comic elements. The inclusion of a broad range of accurately depicted sleep disorders in these films indicates that the Disney screenwriters were astute observers of sleep and its disorders.
O'Reilly, Christian; Godin, Isabelle; Montplaisir, Jacques; Nielsen, Tore
To investigate differences in sleep spindle properties and scalp topography between patients with rapid eye movement sleep behaviour disorder (RBD) and healthy controls, whole-night polysomnograms of 35 patients diagnosed with RBD and 35 healthy control subjects matched for age and sex were compared. Recordings included a 19-lead 10-20 electroencephalogram montage and standard electromyogram, electrooculogram, electrocardiogram and respiratory leads. Sleep spindles were automatically detected using a standard algorithm, and their characteristics (amplitude, duration, density, frequency and frequency slope) compared between groups. Topological analyses of group-discriminative features were conducted. Sleep spindles occurred at a significantly (e.g. t34 = -4.49; P = 0.00008 for C3) lower density (spindles ∙ min(-1) ) for RBD (mean ± SD: 1.61 ± 0.56 for C3) than for control (2.19 ± 0.61 for C3) participants. However, when distinguishing slow and fast spindles using thresholds individually adapted to the electroencephalogram spectrum of each participant, densities smaller (31-96%) for fast but larger (20-120%) for slow spindles were observed in RBD in all derivations. Maximal differences were in more posterior regions for slow spindles, but over the entire scalp for fast spindles. Results suggest that the density of sleep spindles is altered in patients with RBD and should therefore be investigated as a potential marker of future neurodegeneration in these patients. © 2015 European Sleep Research Society.
Full Text Available ObjectivesREM sleep behavior disorder (RBD is associated with cognitive dysfunctions and is a risk factor for development of mild cognitive impairment and dementia. However, it is unknown whether RBD is associated with faster cognitive decline in already established dementia. The main goal of this study was to determine if patients with mild dementia with and without RBD differ in progression rate and in specific neuropsychological measures over 4-year follow-up.MethodsThis longitudinal, prospective study based on data from the DemVest study compares neuropsychological measures in a mild dementia cohort. A diagnosis of probable RBD (pRBD was made based on the Mayo Sleep Questionnaire. Neuropsychological domains were assessed by Mini Mental State Examination, total score and figure copying, California Verbal Learning Test-II, Visual Object and Space Perception Cube and Silhouettes, Boston Naming Test, Stroop test, Verbal Category Fluency, Trail Making Test A and B.ResultsAmong the 246 subjects, 47 (19.1% had pRBD at the baseline, and pRBD group was younger and with male predominance. During 4-year follow-up, we did not observe any significant differences in the rate of decline in neuropsychological measures. Patients with pRBD performed generally poorer in visuoconstructional, visuoperceptual, and executive/attention tests in comparison to RBD negative.ConclusionWe did not find any significant differences in progression rate of neurocognitive outcomes between dementia patients with and without RBD.
Aleisa, A M; Helal, G; Alhaider, I A; Alzoubi, K H; Srivareerat, M; Tran, T T; Al-Rejaie, S S; Alkadhi, K A
Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long-term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD-induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg(-1) s.c.) twice a day. In the radial arm water maze (RAWM) task, 24- or 48-h SD significantly impaired learning and short-term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24- and 48-h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity. Copyright © 2010 Wiley-Liss, Inc.
Meerlo, P; Easton, A; Bergmann, B M; Turek, F W
Sleep is generally considered to be a recovery from prior wakefulness. The architecture of sleep not only depends on the duration of wakefulness but also on its quality in terms of specific experiences. In the present experiment, we studied the effects of restraint stress on sleep architecture and sleep electroencephalography (EEG) in different strains of mice (C57BL/6J and BALB/cJ). One objective was to determine if the rapid eye movement (REM) sleep-promoting effects of restraint stress previously reported for rats would also occur in mice. In addition, we examined whether the effects of restraint stress on sleep are different from effects of social defeat stress, which was found to have a non-REM (NREM) sleep-promoting effect. We further measured corticosterone and prolactin levels as possible mediators of restraint stress-induced changes in sleep. Adult male C57BL/6J and BALB/cJ mice were subjected to 1 h of restraint stress in the middle of the light phase. To control for possible effects of sleep loss per se, the animals were also kept awake for 1 h by gentle handling. Restraint stress resulted in a mild increase in NREM sleep compared with baseline, but, overall, this effect was not significantly different from sleep deprivation by gentle handling. In contrast, restraint stress caused a significant increase in REM sleep compared with handling in the C57BL/6J mice but not in BALB/cJ mice. Corticosterone levels were significantly and similarly elevated after restraint in both strains, but prolactin was increased only in the C57BL/6J mice. In conclusion, this study shows that the restraint stress-induced increase in REM sleep in mice is strongly strain dependent. The concomitant increases in prolactin and REM sleep in the C57BL/6J mice, but not in BALB/cJ mice, suggest prolactin may be involved in the mechanism underlying restraint stress-induced REM sleep. Furthermore, this study confirms that different stressors differentially affect NREM and REM sleep
Maturana, Maira J; Pudell, Cláudia; Targa, Adriano D S; Rodrigues, Laís S; Noseda, Ana Carolina D; Fortes, Mariana H; Dos Santos, Patrícia; Da Cunha, Cláudio; Zanata, Sílvio M; Ferraz, Anete C; Lima, Marcelo M S
There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD.
Barber, Thomas R; Lawton, Michael; Rolinski, Michal; Evetts, Samuel; Baig, Fahd; Ruffmann, Claudio; Gornall, Aimie; Klein, Johannes C; Lo, Christine; Dennis, Gary; Bandmann, Oliver; Quinnell, Timothy; Zaiwalla, Zenobia; Ben-Shlomo, Yoav; Hu, Michele T M
Rapid eye movement (REM) sleep behavior disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models. Clinical assessments were performed in 171 RBD, 296 control, and 119 untreated Parkinson's (PD) participants. Putative risk measures were assessed as predictors of prodromal neurodegeneration, and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common leucine-rich repeat kinase 2 (LRRK2)/glucocerebrosidase gene (GBA) gene mutations. Compared to controls, participants with RBD had higher rates of solvent exposure, head injury, smoking, obesity, and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD participants performed significantly worse than controls on Unified Parkinson's Disease Rating Scale (UPDRS)-III, timed "get-up-and-go", Flamingo test, Sniffin Sticks, and cognitive tests and had worse measures of constipation, quality of life (QOL), and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD participants were equally impaired. Depression, anxiety, and apathy were worse in RBD compared to PD participants. Stratification of people with RBD according to antidepressant use, obesity, and age altered the odds ratio (OR) of hyposmia compared to controls from 3.4 to 45.5. 74% (95% confidence interval [CI] 66%, 80%) of RBD participants met the MDS criteria for probable prodromal Parkinson's compared to 0.3% (95% CI 0.009%, 2%) of controls. RBD are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe nonmotor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].
Lee, Hyeong Gon; Choi, Jae Won; Lee, Yu Jin; Jeong, Do-Un
Objective REM sleep behavior disorder (RBD) is associated with psychiatric symptoms, such as anxiety and alexithymia. However, only a few studies on the relationship between depression and RBD have been published. In this study, we investigated the occurrence of depression and associated factors in patients with RBD. Methods In total 94 patients (mean age: 61.9?12.7 years, male: 70.2%) diagnosed as RBD were examined using detailed clinical histories, the Beck Depression Inventory (BDI), the E...
Schenck, C H; Boyd, J L; Mahowald, M W
A series of 33 patients with combined (injurious) sleepwalking, sleep terrors, and rapid eye movement (REM) sleep behavior disorder (viz. "parasomnia overlap disorder") was gathered over an 8-year period. Patients underwent clinical and polysomnographic evaluations. Mean age was 34 +/- 14 (SD) years; mean age of parasomnia onset was 15 +/- 16 years (range 1-66); 70% (n = 23) were males. An idiopathic subgroup (n = 22) had a significantly earlier mean age of parasomnia onset (9 +/- 7 years) than a symptomatic subgroup (n = 11) (27 +/- 23 years, p = 0.002), whose parasomnia began with either of the following: neurologic disorders, n = 6 [congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response/atypical cataplexy)]; nocturnal paroxysmal atrial fibrillation, n = 1; posttraumatic stress disorder/major depression, n = 1; chronic ethanol/amphetamine abuse and withdrawal, n = 1; or mixed disorders (schizophrenia, brain trauma, substance abuse), n = 2. The rate of DSM-III-R (Diagnostic and Statistical Manual, 3rd edition, revised) Axis 1 psychiatric disorders was not elevated; group scores on various psychometric tests were not elevated. Forty-five percent (n = 15) had previously received psychologic or psychiatric therapy for their parasomnia, without benefit. Treatment outcome was available for n = 20 patients; 90% (n = 18) had substantial parasomnia control with bedtime clonazepam (n = 13), alprazolam and/or carbamazepine (n = 4), or self-hypnosis (n = 1). Thus, "parasomnia overlap disorder" is a treatable condition that emerges in various clinical settings and can be understood within the context of current knowledge on parasomnias and motor control/dyscontrol during sleep.
Conwell, Walter; Patel, Bhakti; Doeing, Diana; Pamidi, Sushmita; Knutson, Kristen L; Ghods, Farbod; Mokhlesi, Babak
Due to inconsistent definitions used in the literature, the prevalence of rapid eye movement (REM)-related sleep-disordered breathing (SDB) has been quite variable and its clinical significance remains unclear. This study aimed to compare the prevalence of and clinical characteristics between various criteria for defining REM-related SDB. We also investigated how frequently CPAP therapy was recommended in patients with REM-related SDB and if they had lower CPAP adherence compared to non-stage-specific SDB. In this cross-sectional study, we evaluated 1,019 consecutive adults referred for a polysomnogram for suspicion of SDB. The prevalence of REM-related SDB was calculated based on "traditional criteria" commonly reported in the literature and a "strict criteria" that minimized the contribution of SDB during non-REM sleep. The prevalence of REM-related SDB ranged from 13.5% to 36.7%. There were no clinically significant differences between the strict definition and the traditional definition of REM-related SDB. REM-related SDB was more prevalent in women, younger individuals and African Americans. Compared to non-stage-specific obstructive sleep apnea (OSA), patients with REM-related SDB were equally symptomatic and hypersomnolent. CPAP titration was recommended in 88% of patients with REM-related SDB vs. 94% of patients with non-stage-specific OSA (p < 0.001). There was no significant difference in CPAP adherence between the two groups. Regardless of how REM-related SDB is defined, it was highly prevalent in our large clinical cohort. Compared to non-stage-specific OSA, these patients were equally hypersomnolent and adherent to CPAP therapy despite having overall significantly milder OSA. Further research is needed to better establish whether these patients will derive any benefit from long-term CPAP therapy.
Ferri, Raffaele; Marelli, Sara; Ferini-Strambi, Luigi; Oldani, Alessandro; Colli, Francesca; Schenck, Carlos H; Zucconi, Marco
To analyze the differences in sleep structure and nocturnal motor activity between drug-free REM sleep behavior disorder (RBD) patients and those under therapy with clonazepam, and to evaluate the long-term longitudinal changes under continued therapy with clonazepam. Fifty-seven consecutive iRBD patients were recruited (52 men and 5 women, mean age 68.8±6.03years). Forty-two patients were not taking any medication at the time of the evaluation (iRBD-Clo) while 15 were taking clonazepam (0.5-1mg) at bedtime (iRBD+Clo). The Clinical Global Impression-Severity (CGI-S) scale was obtained. Sleep was video-polysomnographically recorded and the RBD severity scale (RBDSS) obtained. The chin EMG amplitude was quantitatively assessed and the Atonia Index computed. Disease duration was significantly longer in iRBD+Clo patients who also showed a lower rate of stage shifts, higher sleep efficiency and lower percentage of wakefulness after sleep onset and of sleep stage 1, and an increased percentage of sleep stage 2. The longitudinal long-term follow up study in a subgroup of 13 patients showed moderately increased total sleep time, sleep efficiency, sleep stage 2, slow-wave sleep and decreased wakefulness after sleep onset and sleep stage 1, under clonazepam treatment. The CGI scale clearly tended to improve after treatment, but no common trend was evident for RBDSS or Atonia Index. This study provides evidence of important objective effects of clonazepam on NREM sleep in RBD; this data might be very important for the development of new and effective treatments for this condition. Copyright © 2012 Elsevier B.V. All rights reserved.
Sansa, Gemma; Falup-Pecurariu, Cristian; Salamero, Manel; Iranzo, Alex; Santamaria, Joan
The diagnosis of narcolepsy is supported by the presence of two or more sleep onset REM periods (SOREMPs) in the multiple latency sleep test (MSLT). The distribution of SOREMPs throughout the MSLT has not been systematically studied in narcolepsy. We studied the temporal distribution of SOREMPs in the MSLT of a large series of narcoleptics and calculated the effects of age and the diagnostic value of shorter versions of the test. 129 patients consecutively diagnosed with narcolepsy (73.4% with cataplexy) underwent nocturnal polysomnography followed by a five-nap MSLT. 429 SOREMPs were recorded in 645 MSLT naps (66.5%). The probability of presenting SOREMPs in the fourth nap (3:30 pm) was significantly lower than in the remaining naps: 22.4% SOREMPs in the first nap, 20.5% in the second, 20.5% in the third, 16% in the fourth and 20.5% in the fifth nap (p<0.034). Patients older than 29 years had less SOREMPs than the younger ones (p:0.045). Shortening the MSLT to three or four naps decreased the capability of the test to support the diagnosis of narcolepsy in 14.7 and 10% respectively. The temporal distribution of SOREMPs in the MSLT is not even in narcolepsy, with the fourth nap having the lowest probability of presenting a SOREMP. This should be taken into account when evaluating the results of the MSLT, and particularly when using shorter versions of the test. Copyright © 2014 Elsevier B.V. All rights reserved.
May, Michael E; Harvey, Mark T; Valdovinos, Maria G; Kline, Robert H; Wiley, Ronald G; Kennedy, Craig H
REM sleep deprivation (REMSD) has been shown to increase rates of negatively reinforced operant behavior, but not operant responding maintained by positive reinforcement. The reason for this differential effect is currently unknown. We hypothesize that REMSD can increase sensitivity to noxious stimuli. In the present study, we sought to determine if REMSD was associated with a change in response to noxious heat (i.e., altered nociceptive sensitivity). Two groups of rats, aged 6 and 22 months, were subjected to hotplate algesia testing at two different temperatures (44 and 52 degrees C). Initially, baseline numbers of responses and total response time were obtained at 44 degrees C. Animals then were exposed to 48 h of REMSD or control conditions. The frequency and duration of hindpaw responses (licking and guarding) increased for young animals only after REMSD and none of the control conditions. Old rats showed increased duration of nocifensive responding after REMSD and tank control conditions without a change in the number of responses at 44 degrees C. Latency to first nocifensive response was significantly longer in the 44 degrees C hotplate tests, but decreased to levels observed throughout the 52 degrees C hotplate tests following REMSD and TC conditions. These findings suggest that REMSD increases nociceptive sensitivity under conditions of sustained, selective C nociceptor activation (42 degrees C), but not under conditions of phasic A-delta activation (52 degrees C). The findings also indicate that age can be a significant variable in REMSD studies.
Ansari, Mina; Rahmani, Farzaneh; Dolatshahi, Mahsa; Pooyan, Atefe; Aarabi, Mohammad Hadi
REM (rapid eye movement) sleep behavior disorder (RBD) is characterized by increased muscle tone and violent limb movements and is a usual symptom of the early stages of Parkinson's disease (PD). PD patients with RBD represent faster motor and cognitive dysfunction progression. However, there are limited studies on possible structural brain changes underpinning this disorder. Diffusion magnetic resonance imaging (DMRI) was used to assess whether microstructural abnormalities in the brain of 23 RBD positive PD are detectable compared to 31 RBD negative PD. DMRI scans were analyzed without a prior hypothesis. Diffusion MRI connectometry was used to carry out group analysis between age and gender matched PD patients with and without RBD. Diffusion MRI connectometry is based on spin distribution function (SDF) which quantifies the density of diffusing water and is more sensitive to psychological differences between groups. Patients with RBD positive showed microstructural white matter changes in the left and right cingulum, inferior front occipital fasciculus (IFOF), bilateral corticospinal tracts (CST), and middle cerebellar peduncles (MCPs), compared to patients without RBD. White matter alterations in the cingulum, IFOF regions, and corpus callosum might explain faster cognitive deterioration in PD patients with RBD, in terms of visual recognition and visuospatial dysfunction and executive function. Disturbed brain structural tissue markers in CST in PD + RBD patients, could be justified in the light of faster motor progression in these patients.
Dresler, Martin; Wehrle, Renate; Spoormaker, Victor I; Koch, Stefan P; Holsboer, Florian; Steiger, Axel; Obrig, Hellmuth; Sämann, Philipp G; Czisch, Michael
To investigate the neural correlates of lucid dreaming. Parallel EEG/fMRI recordings of night sleep. Sleep laboratory and fMRI facilities. Four experienced lucid dreamers. N/A. Out of 4 participants, one subject had 2 episodes of verified lucid REM sleep of sufficient length to be analyzed by fMRI. During lucid dreaming the bilateral precuneus, cuneus, parietal lobules, and prefrontal and occipito-temporal cortices activated strongly as compared with non-lucid REM sleep. In line with recent EEG data, lucid dreaming was associated with a reactivation of areas which are normally deactivated during REM sleep. This pattern of activity can explain the recovery of reflective cognitive capabilities that are the hallmark of lucid dreaming.
Thompson, Robert S; Roller, Rachel; Greenwood, Benjamin N; Fleshner, Monika
Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise.
Full Text Available GABA is the major inhibitory neurotransmitter in the mammalian central nervous system that has been strongly implicated in the regulation of sleep. GABA transporter subtype 1 (GAT1 constructs high affinity reuptake sites for GABA and regulates GABAergic transmission in the brain. However, the role of GAT1 in sleep-wake regulation remains elusive. In the current study, we characterized the spontaneous sleep-wake cycle and responses to sleep deprivation in GAT1 knock-out (KO mice. GAT1 KO mice exhibited dominant theta-activity and a remarkable reduction of EEG power in low frequencies across all vigilance stages. Under baseline conditions, spontaneous rapid eye movement (REM sleep of KO mice was elevated both during the light and dark periods, and non-REM (NREM sleep was reduced during the light period only. KO mice also showed more state transitions from NREM to REM sleep and from REM sleep to wakefulness, as well as more number of REM and NREM sleep bouts than WT mice. During the dark period, KO mice exhibited more REM sleep bouts only. Six hours of sleep deprivation induced rebound increases in NREM and REM sleep in both genotypes. However, slow wave activity, the intensity component of NREM sleep was briefly elevated in WT mice but remained completely unchanged in KO mice, compared with their respective baselines. These results indicate that GAT1 plays a critical role in the regulation of REM sleep and homeostasis of NREM sleep.
Koban, Michael; Swinson, Kevin L
A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.
Cooper, Denise C.; Ziegler, Michael G.; Milic, Milos S.; Ancoli-Israel, Sonia; Mills, Paul J.; Loredo, José S.; von Känel, Roland; Dimsdale, Joel E.
Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh ...
Meles, Sanne Katherina; Renken, Remco J; Janzen, Annette; Vadasz, David; Pagani, Marco; Arnaldi, Dario; Morbelli, Silvia; Nobili, Flavio; Mayer, Geert; Leenders, Klaus L; Oertel, Wolfgang H O
Rationale: Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson's disease (PD) and other Lewy-body disorders. Spatial covariance analysis of [ 18 F]-Fluorodeoxyglucose Positron Emission Tomography ( 18 F-FDG-PET) data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it to the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we study the expression of the iRBD pattern in de novo PD patients. Methods: The iRBD-related pattern was identified in 18 F-FDG-PET scans of 21 patients with polysomnographically-confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in 18 F-FDG-PET scans of 44 controls and 38 de novo, treatment-naïve PD patients. Of these 38 PD patients, 24 had probable RBD according to the Mayo Sleep Questionnaire. Neuropsychological evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom sixteen also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms. Results: The iRBD-related pattern was characterized by relative hypermetabolism in cerebellum, brainstem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in middle cingulate, temporal, occipital and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBD-related pattern was significantly expressed in PD patients compared to controls (Ppattern expression was not significantly different between PD patients with and without probable RBD, or between PD patients with unilateral or bilateral parkinsonism. iRBD-related pattern expression was higher in PD-MCI patients, compared to PD patients with preserved cognition ( P = 0.001). Subject scores on the iRBD-related pattern were highly correlated to subject scores on the PDRP (r=0.94, Ppatterns
Abd Rashid, Norlinda; Hapidin, Hermizi; Abdullah, Hasmah; Ismail, Zalina; Long, Idris
REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep-deprived rats hippocampus upon nicotine treatment. Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze (MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis. MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein. This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats.
Doppler, Kathrin; Jentschke, Hanna-Maria; Schulmeyer, Lena; Vadasz, David; Janzen, Annette; Luster, Markus; Höffken, Helmut; Mayer, Geert; Brumberg, Joachim; Booij, Jan; Musacchio, Thomas; Klebe, Stephan; Sittig-Wiegand, Elisabeth; Volkmann, Jens; Sommer, Claudia; Oertel, Wolfgang H
Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = -0.377, p = 0.048), with olfactory function (ρ = -0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs.
Sikka, Pilleriin; Valli, Katja; Virta, Tiina; Revonsuo, Antti
We investigated whether inconsistencies in previous studies regarding emotional experiences in dreams derive from whether dream emotions are self-rated or externally evaluated. Seventeen subjects were monitored with polysomnography in the sleep laboratory and awakened from every rapid eye movement (REM) sleep stage 5 min after the onset of the stage. Upon awakening, participants gave an oral dream report and rated their dream emotions using the modified Differential Emotions Scale, whereas external judges rated the participants' emotions expressed in the dream reports, using the same scale. The two approaches produced diverging results. Self-ratings, as compared to external ratings, resulted in greater estimates of (a) emotional dreams; (b) positively valenced dreams; (c) positive and negative emotions per dream; and (d) various discrete emotions represented in dreams. The results suggest that this is mostly due to the underrepresentation of positive emotions in dream reports. Possible reasons for this discrepancy are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.
Fujishiro, Hiroshige; Okuda, Masato; Iwamoto, Kunihiro; Miyata, Seiko; Otake, Hironao; Noda, Akiko; Iritani, Shuji; Ozaki, Norio
Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with Lewy body disease, narcolepsy, or depression. In contrast, the relationship between REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, and clinical characteristics remains unclear. The purpose of this study is to investigate the clinical features of psychiatric patients exhibiting RWA and its relevance to Lewy body disease. Of 55 consecutive patients who underwent polysomnography at the psychiatric ward, 25 patients with sleep apnea syndrome were excluded, and 12 patients exhibiting RWA were identified. The clinical profiles were compared between the groups with and without RWA. The mean age and the frequency of neurocognitive disorders were significantly higher in 12 patients with RWA than in 18 without. Only five of the 12 patients exhibiting RWA had episodes of dream-enactment behavior, and fulfilled the clinical criteria for RBD. Two young patients were diagnosed with narcolepsy, while the other middle-aged and older patients fulfilled the clinical criteria for Parkinson's disease (n = 1), dementia with Lewy bodies (n = 4), idiopathic RBD (n = 2), and major depressive disorder (MDD) (n = 3). The patients with MDD exhibited constipation and/or olfactory dysfunction. Moreover, neuroimaging examinations in the patients with MDD revealed isolated occipital hypoperfusion in three patients and mild dopamine transporter deficit in one patient. Rapid eye movement sleep without atonia itself may be associated with specific clinical profiles, even when dream-enactment behavior is absent. Continued follow-up of the patients with MDD exhibiting RWA is warranted to determine if they represent the prodromal Parkinson's disease/dementia with Lewy bodies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Javad-Moosavi, Bibi-Zahra; Vaezi, Gholamhassan; Nasehi, Mohammad; Haeri-Rouhani, Seyed-Ali; Zarrindast, Mohammad-Reza
Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). A modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to determine the effects of SD and its changes by physostigmine (as cholinesterase inhibitor) or scopolamine (muscarinic receptor antagonist) on memory formation. Because locomotor activity and pain perception induce critical roles in passive avoidance memory formation, we also measured these factors by open field and hot-plate instruments, respectively. The results showed that TSD and RSD for 24 hours impaired memory formation but they did not alter locomotor activity. TSD also induced analgesia effect, but RSD did not alter it. Intra-CA1 injection of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) did not alter memory acquisition in the sham-TSD or sham-RSD, by themselves. Moreover, intra-CA1 injection of sub-threshold dose of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) could restore the memory acquisition deficit induced by RSD, while scopolamine could restore TSD-induced amnesia. Both drugs reversed analgesia induced by TSD. None of previous interventions altered locomotor activity. According to this study, CA1 cholinergic muscarinic receptors play an important role in
Haridi, Mehdi; Weyn Banningh, Sebastian; Clé, Marion; Leu-Semenescu, Smaranda; Vidailhet, Marie; Arnulf, Isabelle
This study sought to determine if there is any overlap between the two major non-rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep terrors and rapid eye movement sleep behaviour disorder. We assessed adult patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour disorder screening questionnaires and determined if they had enhanced muscle tone during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep behaviour disorder patients using the Paris Arousal Disorders Severity Scale and determined if they had more N3 awakenings. The 251 participants included 64 patients with rapid eye movement sleep behaviour disorder (29 with idiopathic rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep behaviour disorder associated with Parkinson's disease), 62 patients with sleepwalking/sleep terrors, 66 old healthy controls (age-matched with the rapid eye movement sleep behaviour disorder group) and 59 young healthy controls (age-matched with the sleepwalking/sleep terrors group). They completed the rapid eye movement sleep behaviour disorder screening questionnaire, rapid eye movement sleep behaviour disorder single question and Paris Arousal Disorders Severity Scale. In addition, all the participants underwent a video-polysomnography. The sleepwalking/sleep terrors patients scored positive on rapid eye movement sleep behaviour disorder scales and had a higher percentage of 'any' phasic rapid eye movement sleep without atonia when compared with controls; however, these patients did not have higher tonic rapid eye movement sleep without atonia or complex behaviours during rapid eye movement sleep. Patients with rapid eye movement sleep behaviour disorder had moderately elevated scores on the Paris Arousal Disorders Severity Scale but did not exhibit more N3 arousals (suggestive of non-rapid eye movement parasomnia) than the control group. These results indicate that dream
Smith, C; Lapp, L
Animal studies have recently demonstrated that increases in rapid eye movement (REM) sleep and actual number of rapid eye movements (REMs) over normal levels followed successful learning of an avoidance task. These increases persisted for many days following the end of the training sessions. It was hypothesized that similar extended increases in REM sleep parameters would follow an intensive learning task in humans. Senior college students were sleep monitored following the end of their Christmas examinations. Results showed that there was a significant increase in the number of REMs observed following the exams as compared to baseline and control subject values. The number of extra REMs was mot prominent during the fifth REM period of the night. A significantly increased REM density was observed at the fourth REM sleep period of the night. Results support the idea of REM sleep and/or the REMs themselves being involved in long-term memory processing several days after the end of training.
Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vis, J.C.; Vanwersch, R.A.P.; Smit, A.B.; Someren, E.J.W. van; Philippens, I.H.C.H.M.
Study Objectives: Sleep problems are a common phenomenon in most neurological and psychiatric diseases. In Parkinson disease (PD), for instance, sleep problems may be the most common and burdensome non-motor symptoms in addition to the well-described classical motor symptoms. Since sleep
Iotchev, I.B.; Kis, A.; Bodizs, R.; Luijtelaar, E.L.J.M. van; Kubinyi, E.
Sleep spindles are phasic bursts of thalamo-cortical activity, visible in the cortex as transient oscillations in the sigma range (usually defined in humans as 12-14 or 9-16 Hz). They have been associated with sleep-dependent memory consolidation and sleep stability in humans and rodents.
Llewellyn, Sue; Hobson, J Allan
This article argues both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep contribute to overnight episodic memory processes but their roles differ. Episodic memory may have evolved from memory for spatial navigation in animals and humans. Equally, mnemonic navigation in world and mental space may rely on fundamentally equivalent processes. Consequently, the basic spatial network characteristics of pathways which meet at omnidirectional nodes or junctions may be conserved in episodic brain networks. A pathway is formally identified with the unidirectional, sequential phases of an episodic memory. In contrast, the function of omnidirectional junctions is not well understood. In evolutionary terms, both animals and early humans undertook tours to a series of landmark junctions, to take advantage of resources (food, water and shelter), whilst trying to avoid predators. Such tours required memory for emotionally significant landmark resource-place-danger associations and the spatial relationships amongst these landmarks. In consequence, these tours may have driven the evolution of both spatial and episodic memory. The environment is dynamic. Resource-place associations are liable to shift and new resource-rich landmarks may be discovered, these changes may require re-wiring in neural networks. To realise these changes, REM may perform an associative, emotional encoding function between memory networks, engendering an omnidirectional landmark junction which is instantiated in the cortex during NREM Stage 2. In sum, REM may preplay associated elements of past episodes (rather than replay individual episodes), to engender an unconscious representation which can be used by the animal on approach to a landmark junction in wake. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available BACKGROUND: During non-rapid eye movement (NREM sleep synchronous neural oscillations between neural silence (down state and neural activity (up state occur. Sleep Slow Oscillations (SSOs events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL FINDINGS: We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. CONCLUSIONS/SIGNIFICANCE: This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.
Full Text Available This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM and from non-Rapid Eye Movement Sleep (NREM. This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2 dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation.
Blagrove, Mark; Fouquet, Nathalie C; Henley-Einion, Josephine A; Pace-Schott, Edward F; Davies, Anna C; Neuschaffer, Jennifer L; Turnbull, Oliver H
This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation.
Sorensen, Gertrud Laura; Kempfner, Jacob; Zoetmulder, Marielle
The objective of this study was to determine whether patients with Parkinson's disease with and without rapid‐eye‐movement sleep behavior disorder and patients with idiopathic rapid‐eye‐movement sleep behavior disorder have an attenuated heart rate response to arousals or to leg movements during...... sleep compared with healthy controls. Fourteen and 16 Parkinson's patients with and without rapid‐eye‐movement sleep behavior disorder, respectively, 11 idiopathic rapid‐eye‐movement sleep behavior disorder patients, and 17 control subjects underwent 1 night of polysomnography. The heart rate response...... and the idiopathic rapid‐eye‐movement sleep behavior disorder group. The heart rate response to leg movement was significantly lower in both Parkinson's groups and in the idiopathic rapid‐eye‐movement sleep behavior disorder group compared with the control group. The heart rate response for the idiopathic rapid...
Paulo Sérgio A. Henriques-Filho
Full Text Available BACKGROUND: Chiari malformations (CM may result in the appearance of REM sleep behavior disorder (RBD and sleep apnea syndrome (SAS that can be considered markers of brain stem dysfunction. PURPOSE: To evaluate the frequency of RBD and SAS in patients with CM type I and II. METHOD: Were evaluated 103 patients with CM by means of full night polysomnography. Were scoring different sleep stages, frequency of abnormal movements (through video monitoring and abnormal respiratory events. RESULTS: Of the 103 patients, 36 showed CM type I and 67 CM type II. Episodes of RBD were observed in 23 patients. Abnormal apnea-hypopnea index (AHI was observed in 65 patients. CONCLUSION: The high rate of RBD suggests that this parassomnia and the increased frequency of central sleep apnea episodes, may be considered as a marker of progressive brain stem dysfunction.INTRODUÇÃO: Malformações de Chiari (MC podem gerar o aparecimento de distúrbio comportamental da fase do sono com REM (DCR e síndrome da apnéia do sono (SAS, sugerindo a ocorrência de disfunção do tronco cerebral. OBJETIVO: Avaliar a freqüência de DCR e SAS em pacientes com MC I ou II. MÉTODO: Utilizou-se a polissonografia de noite inteira para a avaliação de 103 pacientes. Classificaram-se as diferentes fases do sono e analisou-se a freqüência de movimentos anormais (monitorada por vídeo e de eventos respiratórios anormais. RESULTADOS: Dos 103 pacientes analisados, 36 eram portadores de MC I e 67 de MC II. Episódios de DCR foram observados em 23 pacientes. O índice de apnéia/hipopnéia foi considerado anormal em 65 pacientes. CONCLUSÃO: A alta freqüência de DCR e o aumento da freqüência de episódios de apnéia central do sono podem ser considerados manifestação de disfunção progressiva do tronco cerebral.
Drakatos, Panagis; Patel, Kishankumar; Thakrar, Chiraag; Williams, Adrian J; Kent, Brian D; Leschziner, Guy D
Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep-stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 ± 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2. © 2015 European Sleep Research Society.
Viola, Antoine U; Tobaldini, Eleonora; Chellappa, Sarah L; Casali, Karina Rabello; Porta, Alberto; Montano, Nicola
Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects. A polysomnographic study was performed in 12 healthy young (21.1±0.8 years) and 12 healthy older subjects (64.9±1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1-2 (S1-2), Stage 3-4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCE(min) measuring the minimum amount of information that cannot be derived from the knowledge of previous values. Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCE(min). In the older group, SE(3) and CCE(min) were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCE(min). This decrease of entropy measures was more evident during REM sleep. Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events.
Tseng, CH; Wong, ML; Lau, EYY; Hui, FWY; Lau, KNT
The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-wat...
Md Dilshad Manzar
Full Text Available To study spontaneous K-complex (KC densities during slow-wave sleep. The secondary objective was to estimate intra-non-rapid eye movement (NREM sleep differences in KC density.It is a retrospective study using EEG data included in polysomnographic records from the archive at the sleep research laboratory of the Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, India. The EEG records of 4459 minutes were used. The study presents a manual identification investigation of KCs in 17 healthy young adult male volunteers (age = 23.82±3.40 years and BMI = 23.42±4.18 kg/m2.N3 had a higher KC density than N2 (Z = -2.485, p = 0.013 for all of the probes taken together. Four EEG probes had a higher probe-specific KC density during N3. The inter-probe KC density differed significantly during N2 (χ2 = 67.91, p < .001, N3 (χ2 = 70.62, p < .001 and NREM (χ2 = 68.50, p < .001. The percent distribution of KC decreased uniformly with sleep cycles.The inter-probe differences during N3 establish the fronto-central dominance of the KC density regardless of sleep stage. This finding supports one local theory of KC generation. The significantly higher KC density during N3 may imply that the neuro-anatomical origin of slow-wave activity and KC is the same. This temporal alignment with slow-wave activity supports the sleep-promoting function of the KC.
Manzar, Md Dilshad; Rajput, Mohammad Muntafa; Zannat, Wassilatul; Pandi-Perumal, Seithikurippu R; BaHammam, Ahmed S; Hussain, M Ejaz
To study spontaneous K-complex (KC) densities during slow-wave sleep. The secondary objective was to estimate intra-non-rapid eye movement (NREM) sleep differences in KC density. It is a retrospective study using EEG data included in polysomnographic records from the archive at the sleep research laboratory of the Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, India. The EEG records of 4459 minutes were used. The study presents a manual identification investigation of KCs in 17 healthy young adult male volunteers (age = 23.82±3.40 years and BMI = 23.42±4.18 kg/m2). N3 had a higher KC density than N2 (Z = -2.485, p = 0.013) for all of the probes taken together. Four EEG probes had a higher probe-specific KC density during N3. The inter-probe KC density differed significantly during N2 (χ2 = 67.91, p < .001), N3 (χ2 = 70.62, p < .001) and NREM (χ2 = 68.50, p < .001). The percent distribution of KC decreased uniformly with sleep cycles. The inter-probe differences during N3 establish the fronto-central dominance of the KC density regardless of sleep stage. This finding supports one local theory of KC generation. The significantly higher KC density during N3 may imply that the neuro-anatomical origin of slow-wave activity and KC is the same. This temporal alignment with slow-wave activity supports the sleep-promoting function of the KC.
Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Guaita, Marc; Salamero, Manel; Santamaria, Joan
To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail email@example.com.
These results point to bistability as the underlying critical mechanism that prevents the emergence of complex interactions in human thalamocortical networks during NREM sleep. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions(Casali et al., 2013; Rosanova et al., 2012 where cortico-cortical communication and consciousness are impaired in spite of preserved neuronal activity.
Full Text Available Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1 control, (2 REMSD, (3 melatonin (10 mg/kg plus REMSD, (4 melatonin and intraperitoneal luzindole (once a day at 5 mg/kg plus REMSD, and (5 luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P<0.021. The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.
Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Soto-Rodríguez, Sofía; González-Perez, Oscar
Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149
López-Armas, Gabriela; Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Jave-Suarez, Luis Felipe; Soto-Rodríguez, Sofía; Rusanova, Iryna; Acuña-Castroviejo, Dario; González-Perez, Oscar; González-Castañeda, Rocío Elizabeth
Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.
Becchetti, Andrea; Amadeo, Alida
The ascending fibers releasing norepinephrine and acetylcholine are highly active during wakefulness. In contrast, during rapid-eye-movement sleep, the neocortical tone is sustained mainly by acetylcholine. By comparing the different physiological features of the norepinephrine and acetylcholine systems in the light of the GANE (glutamate amplifies noradrenergic effects) model, we suggest how to interpret some functional differences between waking and rapid-eye-movement sleep.
Leminen, Miika M; Virkkala, Jussi; Saure, Emma; Paajanen, Teemu; Zee, Phyllis C; Santostasi, Giovanni; Hublin, Christer; Müller, Kiti; Porkka-Heiskanen, Tarja; Huotilainen, Minna; Paunio, Tiina
Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality. We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].
Kitamura, Junichi; Tsuruta, Kazuhito; Yamamura, Yoshinori; Kurihara, Teruyuki; Matsukura, Shigeru
Four male and one female patients of a new Joseph disease family in southern Kyushu are presented. This disorder is inherited by autosomal dominant trait. The clinical symptoms are characterized by bulging eyes, ophthalmoplegia, dysarthria, rigospasticity of the lower limbs, marked dystonia and bradykinesia. In our cases, extrapyramidal symptoms were improved by amantadine and L-Dopa therapy. CSF homovanilic acid (HVA) was markedly reduced. Muscle biopsy and electromyographic studies revealed neurogenic changes. MRI revealed mild atrophy of frontal lobe and cerebellum, and marked atrophy of brain stem. These findings were consistent with the clinical manifestations. Our case had central type sleep apnea by sleep EEG and polygraphic studies. This is the first report about sleep apnea and MRI of Joseph disease. (author)
Kitamura, Junichi; Tsuruta, Kazuhito; Yamamura, Yoshinori; Kurihara, Teruyuki; Matsukura, Shigeru
Four male and one female patients of a new Joseph disease family in southern Kyushu are presented. This disorder is inherited by autosomal dominant trait. The clinical symptoms are characterized by bulging eyes, ophthalmoplegia, dysarthria, rigospasticity of the lower limbs, marked dystonia and bradykinesia. In our cases, extrapyramidal symptoms were improved by amantadine and L-dopa therapy. CSF homovanilic acid (HVA) was markedly reduced. Muscle biopsy and electromyographic studies revealed neurogenic changes. MRI revealed mild atrophy of frontal lobe and cerebellum, and marked atrophy of brain stem. These findings were consistent with the clinical manifestations. Our case had central type sleep apnea by sleep EEG and polygraphic studies. This is the first report about sleep apnea and MRI of Joseph disease.
Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J
We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Sound-attenuated sleep research room. Twenty-four long-term meditators and twenty-four meditation-naïve controls. Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. We found an increase in EEG low-frequency oscillatory activities (1-12 Hz, centered around 7-8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25-40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators.
Full Text Available We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity.High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention.Sound-attenuated sleep research room.Twenty-four long-term meditators and twenty-four meditation-naïve controls.Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation.We found an increase in EEG low-frequency oscillatory activities (1-12 Hz, centered around 7-8 Hz over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25-40 Hz. There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience.This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators.
Simor, Péter; Gombos, Ferenc; Szakadát, Sára; Sándor, Piroska; Bódizs, Róbert
Rapid eye movement sleep is composed of phasic and tonic periods, two distinguishable microstates in terms of arousal thresholds and sensory processing. Background electroencephalogram oscillations are also different between periods with (phasic state) and periods without (tonic state) eye movements. In Study 1, previous findings analysing electroencephalogram spectral power in phasic and tonic rapid eye movement sleep were replicated, and analyses extended to the high gamma range (52-90 Hz). In Study 2, phasic and tonic spectral power differences within a group of 4-8-year-old children were examined. Based on the polysomnographic data of 20 young adults, the phasic state yielded increased delta and theta power in anterior sites, as well as generally decreased high alpha and beta power in comparison to the tonic state. Moreover, phasic periods exhibited greater spectral power in the lower and the higher gamma band. Interestingly, children (n = 18) exhibited a different pattern, showing increased activity in the low alpha range during phasic periods. Moreover, during phasic in contrast to tonic rapid eye movement sleep, increased low and high gamma and enhanced low gamma band power emerged in anterior and posterior regions, respectively. The current findings show that spectral activity within the high gamma range substantially contributes to the differences between phasic and tonic rapid eye movement sleep, especially in adults. Moreover, the current data underscore the heterogeneity of rapid eye movement sleep, and point to marked differences between young adults and children regarding phasic/tonic electroencephalogram spectral power. These results suggest that the differentiation between phasic and tonic rapid eye movement periods undergoes maturation. © 2016 European Sleep Research Society.
Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan
Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.
Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M
SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep
D'Agostino, Armando; Manni, Raffaele; Limosani, Ivan; Terzaghi, Michele; Cavallotti, Simone; Scarone, Silvio
Dreams are commonly described as violent, threatening, and aggressive in patients with REM behavior disorder (RBD), but very few studies have directly investigated dream content in this population. We systematically assessed dreams in subjects with a confirmed diagnosis of idiopathic RBD (iRBD) and explored psychological traits within the group with specific focus on aggressiveness. A total of 129 dream reports was collected, of which 77 belonged to 12 iRBD patients and 52 belonged to 12 control subjects. Transcripts were analyzed with measures of both form and content. The Thematic Apperception Test was used to assess patients' personality traits and to yield information on formal aspects of waking thought processes. No statistically significant differences were found between the dreams of iRBD patients and those of normal controls in any of the applied measures. In wakefulness, passivity was found to differ between the two populations and was being higher in the iRBD group (F(9,14)=4.84, pdreams of RBD patients contain more aggressive elements than those of the general population. However, over 80% of the patients were on treatment at the time of data collection. The "mild" waking temperament could be interpreted as an early subtle sign of the apathy that is commonly described in the context of neurodegenerative disorders. Copyright © 2012 Elsevier B.V. All rights reserved.
Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A.; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J.
Study Objectives We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. Design High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Setting Sound-attenuated sleep research room. Patients or Participants Twenty-four long-term meditators and twenty-four meditation-naïve controls. Interventions Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. Measurements and Results We found an increase in EEG low-frequency oscillatory activities (1–12 Hz, centered around 7–8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25–40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. Conclusions This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior
Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc
Summary Background Autoimmunity may be involved in sleep and neurodegenerative disorders. We aimed to describe a neurological syndrome with prominent sleep dysfunction and antibodies to a previously unknown neuronal antigen. Methods In this observational study, clinical and video-polysomnography (V- PSG) investigations identified a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic University of Barcelona for abnormal sleep behaviors and obstructive sleep apnea(OSA). They had antibodies against a neuronal surface antigen also present in five additional patients referred to our laboratory for antibody studies. These five patients had been evaluated with PSG and in two, the study was done or reviewed in our Sleep Unit. Two patients underwent postmortem brain examination. Immunoprecipitation and mass spectrometry were used to characterize the antigen and to develop a diagnostic test. Serum or CSF from 285 patients with neurodegenerative, sleep, or autoimmune disorders served as controls. Findings All eight patients (five women; range: 52–76 years, median 59) had abnormal sleep movements and behaviors and OSA confirmed by PSG. Six patients had a chronic evolution (range 2–12 years, median 5.5); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability, and followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid evolution with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died two and six months after symptom onset. In 5/5 patients, the V-PSG reviewed in our Unit disclosed OSA, stridor, and abnormal sleep architecture with undifferentiated NREM sleep or poorly structured stage N2 with simple movements and finalistic behaviors, normalization of NREM sleep by the end of the night, and REM sleep behavior disorder. Four/4 patients carried the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. All patients had antibodies (mainly IgG4
Liu, Yia-Ping; Tung, Che-Se; Chuang, Chia-Hsin; Lo, Shih-Mao; Ku, Yu-Chi
Prepulse inhibition (PPI) is a phenomenon in which a mild stimulus attenuates a cross-modality startle response to later intense stimulation. PPI is thought to index the central inhibitory mechanism through which behavioural responses are filtered. The present study compared the effects of two stress paradigms on the acoustic startle response (ASR) and on PPI in a rat model. The tail-pinch (TP) method produces an acute and immediate stressful condition, whereas rapid eye movement (REM) sleep deprivation (REMSD) leads to a more persistent and long-term stress. Our results demonstrated that in rats, TP stress reduced the size of the ASR, and REMSD impaired PPI. The wake-promoting agent modafinil (MOD) had no effect on PPI if given alone. However, MOD reduced the ASR and PPI under TP stress, whereas only PPI was reduced by MOD after 96 h of REMSD. These results suggest that distinct stress paradigms differentially mediated sensorimotor gating abilities in terms of either responsiveness to the stimulus or information-filtering capabilities. Copyright © 2010 Elsevier B.V. All rights reserved.
Targa, Adriano D S; Noseda, Ana Carolina D; Rodrigues, Lais S; Aurich, Mariana F; Lima, Marcelo M S
Cognitive impairment is an important non-motor symptom of Parkinson's disease (PD). The neuronal death in nigrostriatal pathway is the main factor for motor symptoms and recent studies indicate a possible influence in non-motor symptoms as well. The pedunculopontine tegmental nucleus (PPT) and basal ganglia are closely related anatomically and functionally and, since they are affected by neurodegeneration in PD, they might be involved in recognition memory. To investigate this, we promoted an ibotenic acid lesion within the PPT or a rotenone lesion within substantia nigra pars compacta (SNpc) of Wistar rats, followed by 24h of REM sleep deprivation (REMSD). Then, we administered a dopaminergic D2 receptor agonist (piribedil, 3μg/μl), antagonist (raclopride, 10μg/μl) or vehicle (dimethylsulfoxide) directly in the striatum and the animals were submitted to the object recognition test (ORT). We observed that raclopride administration impaired object recognition memory as well as rotenone and ibotenic acid lesion. Interestingly, REMSD reversed the deleterious effects induced by these drugs. Also, raclopride administration after rotenone lesion allowed the animal to explore the new object for a longer time compared to the familiar object, suggesting that raclopride has a dual effect, dependent of the treatments. These findings suggest a role for PPT, SNpc and striatum in recognition memory and points the D2 receptors modulation and REMSD as possible targets for cognitive deficits in Parkinson's disease. Copyright © 2017 Elsevier B.V. All rights reserved.
Bastlund, Jesper F; Jennum, Poul; Mohapel, Paul; Penschuck, Silke; Watson, William P
The goal of the present study was to investigate the relationship between sleep, hypothalamic pathology, and seizures in spontaneous epileptic rats. Rats were implanted with radiotelemetry transmitters for measuring electrocorticogram (ECoG) and stimulation electrodes in the hippocampus. Epileptogenesis was triggered by 2 h of electical stimulation-induced self-sustained status epilepticus (SSSE). After SSSE, ECoGs were monitored over a 15-week period for the occurrence of interictal high-amplitude low-frequency (HALF) acitvity and spontaneous reoccurring seizures (SRSs). Spontaneous epileptic rats showed clinical features of temporal lobe epilepsy (TLE), such as spontaneous seizures, interictal activity and neuronal cell loss in the dorsomedial hypothalamus, a region important for normal sleep regulation. Interestingly, epileptic rats showed disturbances in sleep architecture, with a high percentage of the seizures occurring during sleep. Therefore we conclude that a close association exists between epileptiform activity and alterations in sleep architecture that may be related to hypothalamic pathology.
Pujol, Montserrat; Pujol, Jesús; Alonso, Tomás; Fuentes, Araceli; Pallerola, Mercè; Freixenet, Jovita; Barbé, Ferran; Salamero, Manel; Santamaría, Joan; Iranzo, Alex
To examine the presence and characteristics of idiopathic REM sleep behavior disorder (IRBD) in a representative Caucasian sample from the elderly community of Lleida, Spain, attending primary care centers. Participants were individuals aged 60 years or older who underwent routine visits in two primary care centers. They underwent a two-stage study; a validated screening single question for IRBD diagnosis (RBD1Q) followed by, in those who endorsed positive answer, clinical assessment by a neurologist plus video-polysomnography (V-PSG). Of 539 individuals (56.4% women, mean age 72.86 ± 8.20 years), 28 (5.2%) endorsed positively the RBD1Q. Four of these 28 refused further assessments. Four of the 24 remaining subjects underwent clinical assessment but refused V-PSG. Of the 20 who underwent clinical assessment plus V-PSG, REM sleep was not recorded in four (20%, all four taking antidepressants). V-PSG ruled out RBD in 12 subjects who had obstructive sleep apnea (n = 9), periodic limb movement disorder in sleep (n = 2) and normal sleep (n = 1). IRBD was diagnosed in four individuals giving an estimated prevalence of 0.74% (95% CI = 0.29-1.89). They were three men and one woman between 74 and 82 years of age who never reported dream-enacting behaviors to their doctors because they thought they represented a normal phenomenon despite suffering sleep-related injuries. These patients had history of violent sleep behaviors with an interval between estimated RBD onset and V-PSG of 4.5 ± 4.2 years. IRBD is not uncommon in the elderly community and its demographic and clinical profile is similar to those diagnosed in sleep centers. Copyright © 2017. Published by Elsevier B.V.
Full Text Available We examined the question whether the role of EEG oscillations in predicting presence/absence of dream recall (DR is explained by state- or trait-like factors. Six healthy subjects were awakened from REM sleep in a within-subjects design with multiple naps, until a recall (REC and a non-recall (NREC condition were obtained. Naps were scheduled in the early afternoon and were separated by one week. Topographical EEG data of the 5-min of REM sleep preceding each awakening were analyzed by power spectral analysis [Fast Fourier Transform (FFT] and by a method to detect oscillatory activity [Better OSCillations (BOSC].Both analyses show that REC is associated to higher frontal theta activity (5-7 Hz and theta oscillations (6.06 Hz compared to NREC condition, but only the second comparison reached significance. Our pilot study provides support to the notion that sleep and wakefulness share similar EEG correlates of encoding in episodic memories, and supports the state-like hypothesis: dream recall may depend on the physiological state related to the sleep stage from which the subject is awakened rather than on a stable individual EEG pattern.
Full Text Available Long-term changes in dopaminergic signaling are thought to underlie the pathophysiology of a number of psychiatric disorders. Several conditions are associated with cognitive deficits such as disturbances in attention processes and learning and memory, suggesting that persistent changes in dopaminergic signaling may alter neural mechanisms underlying these processes. Dopamine transporter knockout (DAT-KO mice exhibit a persistent five-fold increase in extracellular dopamine levels. Here, we demonstrate that DAT-KO mice display lower hippocampal theta oscillation frequencies during baseline periods of waking and rapid-eye movement sleep. These altered theta oscillations are not reversed via treatment with the antidopaminergic agent haloperidol. Thus, we propose that persistent hyperdopaminergia, together with secondary alterations in other neuromodulatory systems, results in lower frequency activity in neural systems responsible for various cognitive processes.
Laís Soares Rodrigues
Full Text Available Olfactory and rapid eye movement (REM sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson's disease (PD. Besides different studies reported declines in olfactory performances during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood although the impairment in the dopamine (DA neurotransmission in the olfactory bulb and in the nigrostriatal pathway may have important roles in olfactory as well as in REM sleep disturbances. Therefore, we have led to the hypothesis that a modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and after a short period of REM sleep deprivation (REMSD. We decided to investigate the olfactory, neurochemical and histological alterations generated by the administration of piribedil (a selective D2 agonist or raclopride (a selective D2 antagonist, within the glomerular layer of the olfactory bulb, in rats submitted to intranigral rotenone and REMSD. Our findings provided a remarkable evidence of the occurrence of a negative correlation (r = - 0.52, P = 0.04 between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham groups. A significant positive correlation (r = 0.34, P = 0.03 was observed between nigral DA and olfactory discrimination index (DI, for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc are associated to enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA induced by piribedil in the rotenone control and rotenone REMSD groups were consistent with reduced amounts of DI. The present evidence reinforce that DA produced by periglomerular neurons, and particularly the bulbar dopaminergic D2 receptors, are essential participants in the olfactory discrimination processes, as well as SNpc
Zhang, Baolin; Li, Xiuqin; Wang, Tingchu
Research the sleep structure of the OSAHS and snores, explore the reason that patients feel drowsy in daytime. Monitor the sleep of 46 OSAHS, 16 snores and 20 normal control, calculate the percent of stages of NREM and REM, count the RDI, AI, HI, total MI, MI associated with leg movement, MI associated with RDI, MI associated with snore, spontaneous MI. OSAHS has sleep structure disturbance obviously. The light sleep (stage I) increase obviously, but deep one decrease (stage II + V) obviously. The sleep structure is insufficient. The patients are deprived of a number of the REM sleep. The waking time is longer than normal control group. During the light sleep, the microarousal that is associated with both apnea and leg movement increase obviously. During the sleep, OSAHS has obvious sleep deprivation, frequent arousal, disturbance sleep structure and blood desaturation, etc. These resulted in disturbances of brain metabolize. This is the reason that patients feel drowsy, feeble decline, etc.
Lancel, Marike; Droste, Susanne K; Sommer, Susanne; Reul, Johannes M H M
To investigate the impact of regular physical exercise on sleep, we assessed sleep-wake behaviour in male C57BL/6N mice with and without long-term access (i.e. 4 weeks) to a running wheel. We studied sleep-wake behaviour during undisturbed conditions as well as after social stress. The exercising mice ran approximately 4 km/day, which affected their physical constitution, their spontaneous sleep-wake pattern and their endocrine and sleep responses to stress. When compared with the control mice, exercising animals had more muscle substance, less body fat and heavier adrenal glands. At baseline, exercising mice showed fewer, but longer-lasting, sleep episodes (indicating improved sleep consolidation) and less rapid-eye-movement sleep. In both control and exercising mice, mild social stress (elicited by a 15-min social conflict) evoked elevated plasma levels of adrenocorticotrophic hormone and corticosterone, an increase in non-rapid-eye-movement sleep, an enhancement of low-frequency activity in the electroencephalogram within non-rapid-eye-movement sleep (indicating increased sleep intensity) and a decrease in wakefulness. However, as compared with the control animals, exercising mice responded to social stress with higher corticosterone levels, but not adrenocorticotrophic hormone levels, suggesting an increased sensitivity of their adrenal glands to adrenocorticotrophic hormone. Moreover, in control mice, social stress increased rapid-eye-movement sleep in parallel to non-rapid-eye-movement sleep, whereas this stressor selectively decreased rapid-eye-movement sleep in exercising animals. Corticosterone is known to decrease rapid-eye-movement sleep. Therefore, changes in the regulation of the hypothalamic-pituitary-adrenocortical axis as a result of the long-term exercise may contribute to the observed differences in spontaneous and social stress-affected sleep. In conclusion, regular exercise appears to increase sleep quality and reverses the effects of mild
Baig, Fahd; Lawton, Michael A; Rolinski, Michal; Ruffmann, Claudio; Klein, Johannes C; Nithi, Kannan; Okai, David; Ben-Shlomo, Yoav; Hu, Michele T M
Changes in personality have been described in Parkinson's disease (PD), with suggestion that those with established disease tend to be risk averse with a disinclination for addictive behaviour. However, little is known about the earliest and prodromal stages. Personality and its relationship with addictive behaviours can help answer important questions about the mechanisms underlying PD and addiction. 941 population-ascertained PD subjects within 3.5 years of diagnosis, 128 patients with rapid eye movement sleep behaviour disorder (RBD) and 292 control subjects were fully characterised for motor symptoms, non-motor symptoms and across the following 5 personality domains: 1) neuroticism 2) extraversion 3) conscientiousness 4) agreeableness 5) openness using the Big Five Inventory. Patients with early PD were more neurotic (p personality changes is seen in PD and RBD compared to a control population. Personality characteristics were associated with addictive behaviours, suggestive of a common link, but the lower rates of addictive behaviours before and after the onset of motor symptoms in PD persisted after accounting for personality. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Odoi, Alexsandria; Andrew, Shanelle; Wong, Flora Y; Yiallourou, Stephanie R; Horne, Rosemary S C
Impaired arousal from sleep has been implicated in sudden infant death syndrome (SIDS). Sleeping in the prone position is a major risk factor for SIDS. Epidemiological studies have shown that pacifier use decreases the risk of SIDS, even when infants sleep prone. We examined spontaneous arousability in infants slept prone and supine over the first 6 months of life and hypothesised that spontaneous arousals would be increased in pacifier users, particularly in the prone position. Healthy term infants (n = 30) were studied on three occasions over the first 6 months after birth. Spontaneous cortical arousals and subcortical activations were scored and converted into frequency per hour of sleep. There was no effect of pacifier use on total time spent sleeping or awake or the number of spontaneous awakenings at any age. There was also no effect of pacifier use on the frequency or duration of the total number of spontaneous arousals or on cortical arousals and subcortical activations. Pacifier use did not alter infant spontaneous arousability at any of the three ages studied, in either the prone or supine sleeping position. Any preventative effect of pacifiers for SIDS may be through physiological mechanisms other than increased arousability. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Hamdi, A; Brock, J W; Payne, S; Ross, K D; Bond, S P; Prasad, C
L-Tyrosine is a non-essential amino acid that is produced as an intermediary metabolite in the conversion of phenylalanine to 3,4-dihyroxyphenylalanine (DOPA), and is a precursor of the neurotransmitter dopamine. In previous studies, tyrosine pretreatment was shown to protect against the neurochemical and behavioral deficits of acute stress caused by tail shock or cold exposure in rodents. The present study addressed the hypothesis that tyrosine administration may be an effective counter-measure to dopamine-mediated behaviors induced by rapid eye-movement sleep deprivation (RSD). In order to test the hypothesis, Sprague-Dawley rats were divided into 9 treatment groups: RSD-treated rats on normal-protein diet (20% casein: 1% tyrosine, 1% valine); tank control (TC) rats on a normal diet; cage control (CC) rats on normal diet; RSD-treated rats on 4% tyrosine diet; TC rats on 4% tyrosine diet; CC rats on 4% tyrosine diet; RSD-treated rats on 4% valine diet; TC rats on 4% valine diet; CC rats on 4% valine diet. In the RSD group receiving tyrosine, there was no apparent change in Bmax for binding of the dopamine D2 receptor ligand [(3)H]YM-09151-2 in the striata as compared to the respective TC and CC groups; whereas RSD-treated rats maintained on the normal diet and valine supplementation demonstrated expected increases in Bmax for ligand binding. The TC group on the tyrosine diet showed attenuated catalepsy compared to the corresponding CC group, while the RSD group consuming tyrosine showed a catalepsy that was significantly increased, and similar to that of cage control animais on a control diet. These data suggest that the tyrosine-supplemented diet significantly attenuated RSD-induced changes in striatal dopamine D2 receptors, and the effect appeared sufficient to influence RSD-induced behaviors.
Kim, Hee-Jin; Im, Hyung Kyun; Kim, Juhan; Han, Jee-Young; de Leon, Mony; Deshpande, Anup; Moon, Won-Jin
Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. We investigated that dementia with RBD might show distinctive cortical atrophic patterns. A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.
Fantini, M L; Macedo, L; Zibetti, M; Sarchioto, M; Vidal, T; Pereira, B; Marques, A; Debilly, B; Derost, P; Ulla, M; Vitello, N; Cicolin, A; Lopiano, L; Durif, F
To assess the frequency of symptoms of impulse control disorders (ICD, namely pathological gambling, compulsive sexual behaviour, compulsive eating and compulsive shopping) and related behaviours (hobbyism, punding, walkabout and dopamine dysregulation syndrome) in patients with Parkinson's disease (PD) with and without probable rapid eye movement, sleep behaviour disorder (pRBD). Two hundred and sixteen consecutive PD patients, attending two university-based movement disorders clinics, were screened for p-RBD using the RBD Single Question and the RBD Screening Questionnaire (RBDSQ). Current ICDs and related behaviours symptoms were assessed with the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP)-short form. PD-pRBD patients (n=106/216;49%) had a longer PD duration, a higher Hoehn & Yahr score, a greater levodopa-equivalent daily dose (LEDD), but no difference in dopamine agonist use, compared to PD-without pRBD. A higher proportion of one or more current ICDs and related behaviours symptoms was reported in PD-pRBD compared to PD-without RBD (53% vs28%; p=0.0002). In a multivariate regression analysis accounting for gender, age of onset, PD duration, PD severity, depression score and total and dopaminergic agonist-LEDD, RBD was associated to a relative risk of 1.84 for any ICD or related behaviours symptoms (p=0.01), and to a risk of 2.59 for any ICD symptoms only (p=0.001). Furthermore, PD-pRBD had a more than fourfold risk for symptoms of pathological gambling (relative risk (RR): 4.87; p=0.049) compared to PD-without pRBD. The present study indicates that RBD is associated with an increased risk of developing symptoms of ICDs in PD. Identifying RBD in PD may help clinicians to choose the best therapeutic strategy. AU1023 Institutional Ethics Committee. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Simor, Péter; Gombos, Ferenc; Blaskovich, Borbála; Bódizs, Róbert
Rapid Eye Movement (REM) sleep is characterized by the alternation of two markedly different microstates, phasic and tonic REM. These periods differ in awakening and arousal thresholds, sensory processing, and spontaneous cortical oscillations. Previous studies indicate that whereas in phasic REM, cortical activity is independent of the external environment, attentional functions and sensory processing are partially maintained during tonic periods. Large-scale synchronization of oscillatory activity, especially in the alpha and beta frequency ranges can accurately distinguish different states of vigilance and cognitive processes of enhanced alertness and attention. Therefore, we examined long-range inter-and intrahemispheric, as well as short-range EEG synchronization during phasic and tonic REM periods quantified by the weighted phase lag index. Based on the nocturnal polysomnographic data of 19 healthy, adult participants we showed that long-range inter-and intrahemispheric alpha and beta synchrony were enhanced in tonic REM states in contrast to phasic ones, and resembled alpha and beta synchronization of resting wakefulness. On the other hand, short-range synchronization within the gamma frequency range was higher in phasic as compared to tonic periods. Increased short-range synchrony might reflect local, and inwardly driven sensorimotor activity during phasic REM periods, whereas enhanced long-range synchrony might index frontoparietal activity that reinstates environmental alertness after phasic REM periods. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail firstname.lastname@example.org.
Kajeepeta, Sandhya; Sanchez, Sixto E; Gelaye, Bizu; Qiu, Chunfang; Barrios, Yasmin V; Enquobahrie, Daniel A; Williams, Michelle A
Preterm birth is a leading cause of perinatal morbidity and mortality worldwide, resulting in a pressing need to identify risk factors leading to effective interventions. Limited evidence suggests potential relationships between maternal sleep or vital exhaustion and preterm birth, yet the literature is generally inconclusive. We examined the relationship between maternal sleep duration and vital exhaustion in the first six months of pregnancy and spontaneous (non-medically indicated) preterm birth among 479 Peruvian women who delivered a preterm singleton infant (exhaustion were ascertained through in-person interviews. Spontaneous preterm birth cases were further categorized as those following either spontaneous preterm labor or preterm premature rupture of membranes. In addition, cases were categorized as very (exhaustion was also associated with increased odds of preterm birth (aOR = 2.41; 95% CI 1.79-3.23) compared to no exhaustion (Ptrend exhaustion on the odds of spontaneous preterm birth. The results of this case-control study suggest maternal sleep duration, particularly short sleep duration, and vital exhaustion may be risk factors for spontaneous preterm birth. These findings call for increased clinical attention to maternal sleep and the study of potential intervention strategies to improve sleep in early pregnancy with the aim of decreasing risk of preterm birth.
Steiger, A.; Dresler, M.; Kluge, M.; Schussler, P.
In patients with depression, characteristic changes of sleep electroencephalogram and nocturnal hormone secretion occur including rapid eye movement (REM) sleep disinhibition, reduced non-REM sleep and impaired sleep continuity. Neuropeptides are common regulators of the sleep electroencephalogram
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Liu, Yia-Ping; Tung, Che-Se; Lin, Yu-Lung; Chuang, Chia-Hsin
Individuals who experience sleep loss may exhibit certain physiological abnormalities. Central stimulant drugs have been studied in sleep-loss conditions, and some of them might be therapeutically beneficial. Modafinil (diphenyl-methyl-sulfinyl-2-acetamide, MOD) has been increasingly employed for elevating alertness and vigilance in recent years, yet the underlying mechanism of actions for MOD is not fully understood. To examine the behavioral effect of MOD following rapid eye movement sleep deprivation (REMD) in rats. A five-choice serial reaction time task (5-CSRTT) was employed to investigate animals' attentional performance and impulsive reactivity. Rats of different ages were trained to learn the 5-CSRTT. REMD with the water platform method was applied for 96 h. The impacts of REMD on 5-CSRTT in middle-age (32-weeks-old) and young-adult (12-week-old) rats were compared with baseline or a condition with shorter visual stimulus duration. The results revealed that following REMD, young-adult but not middle-age rats were liable to be affected in their performances of the 5-CSRTT. In young-adult rats, while MOD had no contributions to the effect of REMD, it worsened rats' performance following REMD when the stimulus duration was shortened, as shown by the reduced number of correct responses and prolonged magazine latency. These results suggest that aging might be a crucial factor for the physiological impact following REMD. MOD should be used cautiously, particularly, in conditions that require REM sleep.
Sforza, Emilia; Chapotot, Florian; Pigeau, Ross; Paul, Paul Naitoh; Buguet, Alain
The hierarchical definition of arousals from sleep includes a range of physiologic responses including microarousals, delta and K-complex bursts, and variations in autonomic system. Whether patterns in slow-wave electroencephalographic activity and autonomic activation are primary forms of arousal response can be addressed by studying effects of total sleep deprivation. We therefore examined changes in arousal density during recovery sleep in healthy subjects. Participants spent 6 consecutive 24-hour periods in the laboratory. Nights 1 and 2 were baseline nights followed by 64-hour total sleep deprivation, then 2 consecutive recovery nights. Sleep-deprivation protocol was conducted under laboratory conditions with continuous behavioral and electrophysiologic monitoring. Twelve drug-free men aged 27.4 +/- 7.9 years were studied. None reported sleepiness or altered sleep-wake cycle, and none had neurologic, psychiatric or sleep disorders. N/A. Arousals were classified into 4 levels: microarousals, phases of transitory activation, and delta and K-complex bursts. Sleep deprivation induced changes in the density of considered arousals except phases of transitory activation, with a distinct pattern among the different types. The greatest change was found for microarousals, which showed a significant decrease in the first recovery night (P = .01), with return to baseline thereafter. A fall in K-complex and delta-burst density was noted in the first recovery night, not, however, reaching statistical significance. The phases of transitory activation rate were virtually unaffected throughout the experimental nights. We conclude that homeostatic sleep processes exert an inhibitory effect on arousal response from sleep with a significant effect only on the microarousal density. Decreased delta and K-complex burst rates, though not significant, support the hypothesis that they may be activating processes, probably modulated by factors independent from those implicated in
I comportamenti violenti nel sonno REM: aspetti clinici, criminologici e medico-legali / Les comportements violents pendant le sommeil MOR : aspects cliniques, criminologiques et médico-légaux / The Violent Behaviour in REM Sleep-related: Clinical, Criminological and Forensic Aspects
Full Text Available The violent behaviour of sleep represents a new frontier of forensic interest. After examining the clinical aspects of a particular form of parasomnia related to REM stage of sleep, called REM Behavior Disorder-RBD, the author highlights the criminological and forensic implications emphasizing the distinctive features in terms of responsibility and imputability.Les comportements violents pendant le sommeil MOR représentent une nouvelle “frontière” d’intérêt de la psychologie médico-légale. Après avoir examiné les aspects cliniques d’une forme particulière de parasomnie liée à la phase MOR du sommeil (denominata REM Behaviour Disorders-RBD, l’auteur de l’article met en évidence ses implications criminologiques et médico-légales; en outre, il souligne les aspects particuliers de cette parasomnie en matière de responsabilité et d’imputabilité.I comportamenti violenti del sonno rappresentano una nuova “frontiera” di interesse forense. L’autore, dopo aver esaminato gli aspetti clinici di una particolare forma di parasonnia legata alla fase REM del sonno, denominata REM Behaviour Disorders-RBD, ne sottolinea le implicazioni criminologiche e medico-legali sottolineandone gli aspetti peculiari in tema di colpa ed imputabilità.
Kostyalik, Diána; Kátai, Zita; Vas, Szilvia; Pap, Dorottya; Petschner, Péter; Molnár, Eszter; Gyertyán, István; Kalmár, Lajos; Tóthfalusi, László; Bagdy, Gyorgy
Several multi-target drugs used in treating psychiatric disorders, such as antidepressants (e.g. agomelatine, trazodone, nefazodone, amitriptyline, mirtazapine, mianserin, fluoxetine) or most atypical antipsychotics, have 5-hydroxytryptamine 2C (5-HT2C) receptor-blocking property. Adaptive changes in 5-HT2C receptor-mediated functions are suggested to contribute to therapeutic effects of selective serotonin reuptake inhibitor (SSRI) antidepressants after weeks of treatment, at least in part. Beyond the mediation of anxiety and other functions, 5-HT2C receptors are involved in sleep regulation. Anxiety-related adaptive changes caused by antidepressants have been studied extensively, although sleep- and electroencephalography (EEG)-related functional studies are still lacking. The aim of this study was to investigate the effects of chronic SSRI treatment on 5-HT2C receptor antagonist-induced functions in different vigilance stages and on quantitative EEG (Q-EEG) spectra. Rats were treated with a single dose of the selective 5-HT2C receptor antagonist SB-242084 (1 mg/kg, i.p.) or vehicle at the beginning of passive phase following a 20-day-long SSRI (escitalopram; 10 mg/kg/day, osmotic minipump) or VEHICLE pretreatment. Fronto-parietal electroencephalogram, electromyogram and motility were recorded during the first 3 h of passive phase. We found that the chronic escitalopram pretreatment attenuated the SB-242084-caused suppression in rapid eye movement sleep (REMS). On the contrary, the 5-HT2C receptor antagonist-induced elevations in passive wake and theta (5-9 Hz) power density during active wake and REMS were not affected by the SSRI. In conclusion, attenuation in certain, but not all vigilance- and Q-EEG-related functions induced by the 5-HT2C receptor antagonist, suggests dissociation in 5-HT2C receptor adaptation.
Karle, W; Hopper, M; Switzer, A; Corriere, R; Woldenberg, L
This study investigated the effect of a functional psychotherapy on the sleep EEG patterns of 6 patients. Contrary to original expectations no significant group differences in REM time and REM latency were found between two nights following therapy sessions and two normal nights. However, across the 4 nights the patients exhibited an average REM latency of 71 min. which was significantly shorter than that recorded in an independent study with the same design and a similar subject population. Clausen, Sersen, and Lidsky (1974) reported an average REM latency of 107.3 min. for 10 normal subjects also recorded across four nights. This result is compared with those in several other studies and discussed in relation to possible changes in dream patterns.
Gagnadoux, Frédéric; Pevernagie, Dirk; Jennum, Poul
the performance of the System One RemStar Auto A-Flex (Philips Respironics, Murrysville, PA, USA) automatically adjusted positive airway pressure (APAP) mode to manually titrated, fixed pressure CPAP and to validate the device's breathing event detection capabilities against attended in-laboratory PSG. METHODS......STUDY OBJECTIVES: Autotitrating continuous positive airway pressure (CPAP) devices adjust pressure in response to changes in airflow and are an alternative to attended in-laboratory titration polysomnography (PSG) to determine optimal pressure levels. The aim of this study was to compare......: Sixty-one patients investigated in five centers for moderate to severe obstructive sleep apnea between May 2012 and June 2013 were invited to participate. Participants underwent two full-night attended polysomnograms in random order with manually titrated, fixed pressure CPAP versus APAP. RESULTS: Fifty...
Zagaar, Munder; Alhaider, Ibrahim; Dao, An; Levine, Amber; Alkarawi, Ahmed; Alzubaidy, Mariam; Alkadhi, Karim
Inadequate sleep is prevalent in modern societies and is known to profoundly impair cognitive function. We examined the impact of 4 weeks of regular treadmill exercise on sleep deprivation induced spatial learning and memory, synaptic plasticity and related signaling molecules in area CA1 of the rat hippocampus. Rats were exercised on a treadmill and subsequently sleep-deprived for 24h using the modified multiple platform technique. Testing of learning and short-term memory performance in the radial arm water maze showed that although sedentary sleep deprived rats were severely impaired, exercised sleep deprived rats' performance was normal. Extracellular recording from area CA1 of anesthetized rats revealed that early phase LTP (E-LTP) was markedly impaired in the sedentary sleep deprived animals, but was normal in the exercised sleep deprived group. Additionally, immunoblot analysis of CA1 area before (basal) and after expression of E-LTP indicated that the significant down-regulation of the brain derived neurotrophic factor (BDNF) and phosphorylated calcium-calmodulin dependent protein kinase II (P-CaMKII) levels in sleep deprived animals was prevented by the regular exercise regimen. The results suggest that the regular exercise protocol prevents the sleep deprivation induced impairments in short-term memory and E-LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CaMKII and BDNF associated with sleep deprivation. Copyright © 2011 Elsevier Inc. All rights reserved.
Drosopoulos, Spyridon; Schulze, Claudia; Fischer, Stefan; Born, Jan
Building on 2 previous studies (B. R. Ekstrand, 1967; B. R. Ekstrand, M. J. Sullivan, D. F. Parker, & J. N. West, 1971), the authors present 2 experiments that were aimed at characterizing the role of retroactive interference in sleep-associated declarative memory consolidation. Using an A-B, A-C paradigm with lists of word pairs in Experiment 1,…
Luik, Annemarie I; Zuurbier, Lisette A; Whitmore, Harry; Hofman, Albert; Tiemeier, Henning
Alterations in rapid eye movement sleep have been consistently related to depression in clinical studies. So far, there is limited evidence from population-based studies for this association of rapid eye movement sleep alterations with depressive symptoms. In 489 participants of the Rotterdam Study, we assessed rapid eye movement sleep latency, rapid eye movement sleep duration and rapid eye movement density with ambulant polysomnography, and depressive symptoms with the Center of Epidemiologic Studies-Depression Scale. A longer rapid eye movement sleep latency (B = 0.002, P = 0.025) and higher rapid eye movement density (B = 0.015, P = 0.046) were related to depressive symptoms after age-sex adjustment. When we excluded persons who used sleep medication or medication for the nervous system (n = 124), only rapid eye movement density remained related to depressive symptoms (B = 0.018, P = 0.027). Our results suggest that rapid eye movement density is a marker of depressive symptoms in the general population, and that associations of rapid eye movement sleep with depressive symptoms are modified by the use of medication. © 2015 European Sleep Research Society.
Full Text Available What is the function of sleep in humans? One claim is that sleep consolidates learning. Slow wave activity (SWA, i.e. slow oscillations of frequency < 4 Hz, has been observed in electroencephalograms (EEG during sleep; it increases with prior wakefulness and decreases with sleep. Studies have claimed that increase in SWA in specific regions of the sleeping brain is correlated with overnight improved performance, i.e. overnight consolidation, on a demanding motor learning task. We wondered if SWA change during sleep is attributable to overnight consolidation or to metabolic demand. Participants executed out-and-back movements to a target using a pen-like cursor with their dominant hand while the target and cursor position were displayed on a screen. They trained on three different conditions on separate nights, differing in the amount and degree of rotation between the actual hand movement direction and displayed cursor movement direction. In the no-rotation (NR condition, there was no rotation. In the single rotation (SR condition, the amount of rotation remained the same throughout, and performance improved both across pre-sleep training and after sleep, i.e. overnight consolidation occurred; in the random rotation (RR condition, the amount of rotation varied randomly from trial to trial, and no overnight consolidation occurred; SR and RR were cognitively demanding. The average EEG power density of SWA for the first 30 min. of non-rapid eye movement sleep after training was computed. Both SR and RR elicited increase in SWA in the parietal region; furthermore, the topographic distribution of SWA in each was remarkably similar. No correlation was found between the overnight performance improvement on SR and the SWA change in the parietal region on measures of learning. Our results argue that regulation of SWA in early sleep is associated with high levels of cognitive effort during prior wakefulness, and not just overnight consolidation.
Li, Ziyang; Sheth, Aarohi B; Sheth, Bhavin R
What is the function of sleep in humans? One claim is that sleep consolidates learning. Slow wave activity (SWA), i.e. slow oscillations of frequency sleep; it increases with prior wakefulness and decreases with sleep. Studies have claimed that increase in SWA in specific regions of the sleeping brain is correlated with overnight improved performance, i.e. overnight consolidation, on a demanding motor learning task. We wondered if SWA change during sleep is attributable to overnight consolidation or to metabolic demand. Participants executed out-and-back movements to a target using a pen-like cursor with their dominant hand while the target and cursor position were displayed on a screen. They trained on three different conditions on separate nights, differing in the amount and degree of rotation between the actual hand movement direction and displayed cursor movement direction. In the no-rotation (NR) condition, there was no rotation. In the single rotation (SR) condition, the amount of rotation remained the same throughout, and performance improved both across pre-sleep training and after sleep, i.e. overnight consolidation occurred; in the random rotation (RR) condition, the amount of rotation varied randomly from trial to trial, and no overnight consolidation occurred; SR and RR were cognitively demanding. The average EEG power density of SWA for the first 30 min. of non-rapid eye movement sleep after training was computed. Both SR and RR elicited increase in SWA in the parietal region; furthermore, the topographic distribution of SWA in each was remarkably similar. No correlation was found between the overnight performance improvement on SR and the SWA change in the parietal region on measures of learning. Our results argue that regulation of SWA in early sleep is associated with high levels of cognitive effort during prior wakefulness, and not just overnight consolidation.
Dauvilliers, Yves; Postuma, Ronald B; Ferini-Strambi, Luigi
To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort.......To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort....
Sato, Nobuo; Marui, Shuri; Ozaki, Makoto; Nagashima, Kei
We assessed the relationship between core temperature (Tc) and sleep rhythms in mice, and examined the effects of ambient temperature and fasting. Tc, electroencephalograms (EEG), electromyograms (EMG), and spontaneous activity in male ICR mice (n=9) were measured by telemetry for 3 days under a 12:12h dark-light cycle. Mice were fed or fasted at an ambient temperature (Ta) of 27°C or 20°C for the final 30h of the experiment. The vigilance state was categorized into a wake state, rapid-eye movement (REM) sleep, and non-REM (NREM) sleep, and the total sleep time (TST) was assessed. Relationships between Tc and TST, NREM periods, and REM sleep were estimated using Pearson's correlation coefficient. During cold exposure, Tc decreased during the dark and light phases, and TST and the periods of NREM and REM sleep decreased during the dark phase. Throughout the fasting period, Tc also decreased during the dark and light phases. Furthermore, the decrease in Tc was augmented when fasting and cold were combined. TST and NREM sleep periods decreased in the light and dark phases, respectively, whereas REM sleep periods decreased in both phases. Negative linear correlations (r=-0.884 to -0.987) were observed between Tc and TST, NREM sleep periods, and REM sleep periods, except for Tc and REM sleep periods where fasting and cold conditions were combined. The correlations between sleep and Tc rhythms were well maintained during cold exposure and fasting. However, when cold and fasting were combined, REM sleep and Tc rhythms were desynchronized. Copyright © 2015 Elsevier Inc. All rights reserved.
Eydipour, Zainab; Vaezi, Gholamhassan; Nasehi, Mohammad; Haeri-Rouhani, Seyed-Ali; Zarrindast, Mohammad-Reza
Serotonin receptors such as 5-HT3 plays critical role in regulation of sleep, wake cycle and cognitive process. Thus, we investigated the role of CA1 5HT3 serotonin receptors in memory acquisition deficit induced by total sleep deprivation (TSD; for 24 hour) and REM sleep deprivation (RSD; for 24 hour). Pain perception and locomotor activity were also assessed as factors that may affect the memory process. Modified water box and multi-platform apparatus were used to induce TSD or RSD, respectively. Passive avoidance, hot plate and open field devices were used for assessment of memory acquisition, pain and locomotor activity, respectively. Totally, 152 male Wistar rats were used in the study. Pre-training, intra-CA1 injection of 5-HT3 receptor agonist Chlorophenylbiguanide (Mchl; 0.01 and 0.001 µg/rat; P memory acquisition and did not alter pain response, while higher dose of both drugs increased locomotor activity in normal rats. Both TSD and RSD reduced memory acquisition (P effect. The amnesia induced by TSD was restored by subthreshold dose of Y25130 (0.001 µg/rat; P effect (P memory acquisition deficit and increased locomotor activity (P < 0.001 for Mchl and P < 0.01 for Y25130), while the Y25130 (P < 0.001), but not Mchl induced analgesia in the RSD rats. Based on the above data, CA1 5HT3 receptors seem to play a critical role in cognitive and non-cognitive behaviors induced by TSD and RSD.
Andrews, Colin G; Pagliardini, Silvia
Breathing is more vulnerable to apneas and irregular breathing patterns during rapid eye movement (REM) sleep in both humans and rodents. We previously reported that robust and recurrent recruitment of expiratory abdominal (ABD) muscle activity is present in rats during REM epochs despite ongoing REM-induced muscle atonia in skeletal musculature. To develop a further understanding of the characteristics of ABD recruitment during REM epochs and their relationship with breathing patterns and irregularities, we sought to compare REM epochs that displayed ABD muscle recruitment with those that did not, within the same rats. Specifically, we investigated respiratory characteristics that preceded and followed recruitment. We hypothesized that ABD muscle recruitment would be likely to occur following respiratory irregularities and would subsequently contribute to respiratory stability and the maintenance of good ventilation following recruitment. Our data demonstrate that epochs of REM sleep containing ABD recruitments (REM(ABD+)) were characterized by increased respiratory rate variability and increased presence of spontaneous brief central apneas. Within these epochs, respiratory events that displayed ABD muscle activation were preceded by periods of increased respiratory rate variability. Onset of ABD muscle activity increased tidal volume, amplitude of diaphragmatic contractions, and minute ventilation compared with the periods preceding ABD muscle activation. These results show that expiratory muscle activity is more likely recruited when respiration is irregular and its recruitment is subsequently associated with an increase in minute ventilation and a more regular respiratory rhythm. Copyright © 2015 the American Physiological Society.
Full Text Available The recently discovered Nesfatin-1 plays a role in appetite regulation as a satiety factor through hypothalamic leptin-independent mechanisms. Nesfatin-1 is co-expressed with Melanin-Concentrating Hormone (MCH in neurons from the tuberal hypothalamic area (THA which are recruited during sleep states, especially paradoxical sleep (PS. To help decipher the contribution of this contingent of THA neurons to sleep regulatory mechanisms, we thus investigated in rats whether the co-factor Nesfatin-1 is also endowed with sleep-modulating properties. Here, we found that the disruption of the brain Nesfatin-1 signaling achieved by icv administration of Nesfatin-1 antiserum or antisense against the nucleobindin2 (NUCB2 prohormone suppressed PS with little, if any alteration of slow wave sleep (SWS. Further, the infusion of Nesfatin-1 antiserum after a selective PS deprivation, designed for elevating PS needs, severely prevented the ensuing expected PS recovery. Strengthening these pharmacological data, we finally demonstrated by using c-Fos as an index of neuronal activation that the recruitment of Nesfatin-1-immunoreactive neurons within THA is positively correlated to PS but not to SWS amounts experienced by rats prior to sacrifice. In conclusion, this work supports a functional contribution of the Nesfatin-1 signaling, operated by THA neurons, to PS regulatory mechanisms. We propose that these neurons, likely releasing MCH as a synergistic factor, constitute an appropriate lever by which the hypothalamus may integrate endogenous signals to adapt the ultradian rhythm and maintenance of PS in a manner dictated by homeostatic needs. This could be done through the inhibition of downstream targets comprised primarily of the local hypothalamic wake-active orexin- and histamine-containing neurons.
Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.
Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye
Sato, Kiminori; Chitose, Shun-Ichi; Sato, Kiminobu; Umeno, Hirohito
Deglutition was extremely infrequent and displayed unique patterns during sleep in the aged. The deglutition and respiratory phase patterns during sleep in the healthy aged were investigated in this study. Ten aged adults (average age = 71 years) were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid muscles) related to swallowing. During sleep, swallowing was extremely infrequent and absent for long periods in the aged. The median number of swallows per hour during total sleep time was 0.6, and the median longest deglutition-free period was 134.8 minutes. Most deglutition occurred in association with spontaneous electroencephalographic arousal both in REM and non-REM sleep. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the mean deglutition frequency. There was no deglutition during deep sleep. Overall muscle tone is inhibited during REM sleep. However, deglutition also occurred in association with spontaneous EEG arousal. The deeper the sleep stage, the lower the mean arousal frequency, and the lower the mean ratio of arousal with deglutition to arousal. Approximately one-third of swallows occurred after inspiration and were followed by inspiration.
The dysynchronization of human circadian rhythms during 7 long-term (2 to 6 months) confinement experiments in temporal isolation in caves was studied. Five subjects abandon the circadian period of sleep and wakefulness (S-W) and spontaneously reach a circabidian S-W cycle (34 to 36 hr waking, 14 to 12 hr sleep) they maintain during weeks. Some subjects reach the 48 hr cycle very quickly (8 to 15 days), others after months. Polygraphic analyses of sleep show that rapid eye movement state (REMS) duration is directly proportional to the total duration of sleep and that the ultradian periodicity of REMS remains constant when S-W cycle is circadian or circabidian. When S-W cycle desynchronizes from circadian to circabidian, REMS and S-4 increase at the expense of stages I-2 and remain in constant relationship with the duration of previous wakefulness period.
Fereshtehnejad, Seyed-Mohammad; Montplaisir, Jacques Y; Pelletier, Amelie; Gagnon, Jean-François; Berg, Daniela; Postuma, Ronald B
Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies. This prospective cohort study was performed on 121 individuals with rapid eye movement sleep behavior disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post-test probability of the criteria were calculated at baseline and during each follow-up visit. Forty-eight (39.7%) individuals with rapid eye movement sleep behavior disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P conversion time in a rapid eye movement sleep behavior disorder cohort, with high sensitivity and high specificity with long follow-up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.
Orem, J; Lovering, A T; Dunin-Barkowski, W; Vidruk, E H
A putative endogenous excitatory drive to the respiratory system in rapid eye movement (REM) sleep may explain many characteristics of breathing in that state, e.g. its irregularity and variable ventilatory responses to chemical stimuli. This drive is hypothetical, and determinations of its existence and character are complicated by control of the respiratory system by the oscillator and its feedback mechanisms. In the present study, endogenous drive was studied during apnoea caused by mechanical hyperventilation. We reasoned that if there was a REM-dependent drive to the respiratory system, then respiratory activity should emerge out of the background apnoea as a manifestation of the drive. Diaphragmatic muscle or medullary respiratory neuronal activity was studied in five intact, unanaesthetized adult cats who were either mechanically hyperventilated or breathed spontaneously in more than 100 REM sleep periods. Diaphragmatic activity emerged out of a background apnoea caused by mechanical hyperventilation an average of 34 s after the onset of REM sleep. Emergent activity occurred in 60 % of 10 s epochs in REM sleep and the amount of activity per unit time averaged approximately 40 % of eupnoeic activity. The activity occurred in episodes and was poorly related to pontogeniculo-occipital waves. At low CO2 levels, this activity was non-rhythmic. At higher CO2 levels (less than 0.5 % below eupnoeic end-tidal percentage CO2 levels in non-REM (NREM) sleep), activity became rhythmic. Medullary respiratory neurons were recorded in one of the five animals. Nineteen of twenty-seven medullary respiratory neurons were excited in REM sleep during apnoea. Excited neurons included inspiratory, expiratory and phase-spanning neurons. Excitation began about 43 s after the onset of REM sleep. Activity increased from an average of 6 impulses s-1 in NREM sleep to 15.5 impulses s-1 in REM sleep. Neuronal activity was non-rhythmic at low CO2 levels and became rhythmic when levels were
Fujishiro, Hiroshige; Iseki, Eizo; Murayama, Norio; Yamamoto, Ryoko; Higashi, Shinji; Kasanuki, Koji; Suzuki, Masaru; Arai, Heii; Sato, Kiyoshi
Previous longitudinal studies have revealed that specific patterns on [(18) F]-fluoro-d-glucose (FDG) positron emission tomography (PET) scans in patients with amnesic mild cognitive impairment can predict Alzheimer's disease (AD). However, the significance of particular patterns on [(18) F]-FDG PET scans in prodromal patients with dementia with Lewy bodies (DLB) remains unclear. Based on the prevailing evidence that rapid eye movement (REM) sleep behavior disorder (RBD) often precedes the onset of DLB, [(18) F]-FDG PET scans of nine non-demented patients reporting recurrent nocturnal dream-enactment behavior in our memory clinic were compared with the normative database using three-dimensional stereotactic surface projection (3D-SSP) images. All patients underwent clinical and neuropsychological examinations as well as cardiac [(123) I]-metaiodobenzylguanidine ([(123) I]-MIBG) scintigraphy. Four patients were found to have diffuse areas of reduced cerebral metabolic rate of glucose (CMRglc), predominantly in the occipital lobe, which is the preferentially affected region in DLB patients. In contrast, five patients showed no such occipital hypometabolism; instead, these five patients showed hypometabolism in the left anterior cingulate gyrus (Broadmann area (BA) 24), right frontal lobe (BA 32) and right anterior temporal lobe (BA 38), which are the preferentially affected regions in Parkinson's disease rather than DLB. The extent of the reduction in CMRglc in the left occipital lobe was correlated with scores on the Bender Gestalt Test, which reflects visuospatial ability, but not with global cognitive measures. All patients showed reduced cardiac [(123) I]-MIBG levels, consistent with underlying Lewy body disease. These variations in [(18) F]-FDG PET scans raise the possibility that the specific pattern of CMRglc reduction may predict developing DLB in patients with idiopathic RBD. Further follow-up studies are needed, particularly on patients with diffuse
Previously I demonstrated that the slow wave sleep (SWS) functioned to adjust the emotional balance disrupted by emotional memories randomly accumulated during waking, while the rapid eye movement (REM) sleep played the opposite role. Many experimental results have unambiguously shown that various emotional memories are processed during REM sleep. In this article, it is attempted to combine this confirmed function of REM sleep with the atonic state unique to REM sleep, and to integrate a new theory suggesting that improvement of muscular efficiency be a new function of REM sleep. This new function of REM sleep is more advantageous than the function of REM sleep in emotional memories and disinhibited drives to account for the phylogenetic variations of REM sleep, especially the absence of REM sleep in dolphins and short duration of REM sleep in birds in contrary to that in humans and rodents, the absence of penile erections in REM sleep in armadillo, as well as the higher voltage in EEG during REM sleep in platypus and ostrich. Besides, this new function of REM sleep is also advantageous to explain the association of REM sleep with the atonic episodes in SWS, the absence of drastic menopausal change in duration of REM sleep, and the effects of ambient temperature on the duration of REM sleep. These comparative and experimental evidences support the improvement of muscular efficiency as a new and major function of REM sleep. Copyright © 2015 Elsevier Inc. All rights reserved.
Bjørnarå, Kari Anne; Pihlstrøm, Lasse; Dietrichs, Espen; Toft, Mathias
Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype. We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibility variants for Parkinson's disease located in the α-synuclein (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations between genetic risk variants and RBD were investigated by logistic regression, and an independent dataset of 382 patients from the Parkinson's Progression Marker Initiative (PPMI) study was used for replication. pRBD was associated with rs3756063 located in the 5' region of SNCA (two-sided p = 0.018, odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p = 0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p = 0.0032, odds ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and the MAPT variant showed no association with pRBD. Our findings provide proof of principle that a largely stable, dichotomous clinical feature of Parkinson's disease can be linked to a specific genetic susceptibility profile. Indirectly, it also supports the hypothesis of RBD as relevant marker for a distinct subtype of the disorder.
This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.
Sapin, Emilie; Bérod, Anne; Léger, Lucienne; Herman, Paul A; Luppi, Pierre-Hervé; Peyron, Christelle
We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD(67) mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD(67)in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD(+), Fos-ir/MCH(+), and GAD(+)/MCH(+) double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD(+) neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.
Full Text Available We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD(67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD(67in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD(+, Fos-ir/MCH(+, and GAD(+/MCH(+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD(+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.
John A Lesku
Full Text Available Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS and rapid eye movement (REM sleep. SWS is characterized by slow, high amplitude brain waves, while REM sleep is characterized by fast, low amplitude waves, known as activation, occurring with rapid eye movements and reduced muscle tone. However, monotremes (platypuses and echidnas, the most basal (or 'ancient' group of living mammals, show only a single sleep state that combines elements of SWS and REM sleep, suggesting that these states became temporally segregated in the common ancestor to marsupial and eutherian mammals. Whether sleep in basal birds resembles that of monotremes or other mammals and birds is unknown. Here, we provide the first description of brain activity during sleep in ostriches (Struthio camelus, a member of the most basal group of living birds. We found that the brain activity of sleeping ostriches is unique. Episodes of REM sleep were delineated by rapid eye movements, reduced muscle tone, and head movements, similar to those observed in other birds and mammals engaged in REM sleep; however, during REM sleep in ostriches, forebrain activity would flip between REM sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in the platypus. Moreover, the amount of REM sleep in ostriches is greater than in any other bird, just as in platypuses, which have more REM sleep than other mammals. These findings reveal a recurring sequence of steps in the evolution of sleep in which SWS and REM sleep arose from a single heterogeneous state that became temporally segregated into two distinct states. This common trajectory suggests that forebrain activation during REM sleep is an evolutionarily new feature, presumably involved in performing new sleep functions not found in more basal animals.
Lesku, John A; Meyer, Leith C R; Fuller, Andrea; Maloney, Shane K; Dell'Omo, Giacomo; Vyssotski, Alexei L; Rattenborg, Niels C
Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS) and rapid eye movement (REM) sleep. SWS is characterized by slow, high amplitude brain waves, while REM sleep is characterized by fast, low amplitude waves, known as activation, occurring with rapid eye movements and reduced muscle tone. However, monotremes (platypuses and echidnas), the most basal (or 'ancient') group of living mammals, show only a single sleep state that combines elements of SWS and REM sleep, suggesting that these states became temporally segregated in the common ancestor to marsupial and eutherian mammals. Whether sleep in basal birds resembles that of monotremes or other mammals and birds is unknown. Here, we provide the first description of brain activity during sleep in ostriches (Struthio camelus), a member of the most basal group of living birds. We found that the brain activity of sleeping ostriches is unique. Episodes of REM sleep were delineated by rapid eye movements, reduced muscle tone, and head movements, similar to those observed in other birds and mammals engaged in REM sleep; however, during REM sleep in ostriches, forebrain activity would flip between REM sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in the platypus. Moreover, the amount of REM sleep in ostriches is greater than in any other bird, just as in platypuses, which have more REM sleep than other mammals. These findings reveal a recurring sequence of steps in the evolution of sleep in which SWS and REM sleep arose from a single heterogeneous state that became temporally segregated into two distinct states. This common trajectory suggests that forebrain activation during REM sleep is an evolutionarily new feature, presumably involved in performing new sleep functions not found in more basal animals.
Full Text Available Objective To compare the clinical differences between Parkinson's disease (PD patients with and without rapid eye movement sleep behavior disorder (RBD. Methods PubMed, EMBASE, Cochrane Library, Chinese Biology Medicine (CBM and China National Knowledge Infrastructure (CNKI databases were used to search for studies on RBD in PD patients. Meticulous data were extracted and Meta-analysis was performed. All analyses were conducted with the software of Revman Manager 5.2.4. Results Five clinical studies involving total 650 PD patients were included. The Meta-analysis showed that PD patients with RBD had an older mean age (WMD = 2.870, 95%CI: 1.490-4.260; P = 0.000, a higher Hoehn-Yahr stage (WMD = 0.300, 95% CI: 0.160-0.450; P = 0.000, higher Unified Parkinson's Disease Rating Scale (UPDRS motor scores during the "on" state (WMD = 2.370, 95%CI: 0.260-4.490; P = 0.030, and larger levodopa dose (WMD = 90.550, 95% CI: 31.040-150.060; P = 0.003 in comparison with PD patients without RBD. In addition, PD patients with RBD were more likely to develop motor fluctuation (OR = 1.520, 95% CI: 1.080-2.140; P = 0.020 and orthostatic hypotension (OR = 11.390, 95% CI: 4.790-27.090; P = 0.000 as compared to PD patients without RBD. However, gender (OR = 1.850, 95%CI: 0.810-4.230; P = 0.150, disease duration (WMD = 0.130, 95% CI: -1.230-1.500; P = 0.850 and Mini-Mental State Examination (MMSE scores (WMD = - 0.220, 95%CI: - 0.600-0.160; P = 0.260 did not differ between PD patients with and without RBD. Conclusion PD patients with RBD were more likely to be associated with older age, more severe motor disability, higher levodopa usage, higher incidence of motor fluctuation and orthostatic hypotension, indicating that PD with RBD might be at an advanced stage and had more widespread and severe neurodegeneration.
Full Text Available No abstract available. Article truncated after 150 words. A 78 year-old man with a past medical history of Parkinson’s disease (PD presented to the sleep medicine clinic for evaluation of obstructive sleep apnea (OSA. An overnight polysomnogram (PSG study was consistent with sleep apnea and revealed frequent leg and arm movements and sleep-talking during rapid eye movement (REM sleep. REM sleep behavior disorder (RBD is a parasomnia characterized by repeated episodes of abnormal behavior occurring during REM sleep (1,2. On PSG, REM sleep without atonia is seen while features of “normal REM” such as number of REM periods and REM cycling remain intact (2. RBD emerges most often in the context of alpha-synucleinopathies, and occurs in up to 60% of PD patients (3. The presence of RBD may be an important preclinical symptom prior to the onset of PD. Cases of PD with RBD are associated with a unique phenotype with an older age of onset, longer disease ...
Isabel Camilla Hutchison
Full Text Available While NREM sleep has been strongly implicated in the reactivation and consolidation of memory traces, the role of REM sleep remains unclear. A growing body of research on humans and animals provide behavioral evidence for a role of REM sleep in the strengthening and modulation of emotional memories. Theta activity – which describes low frequency oscillations in the local field potential within the hippocampus, amygdala and neocortex – is a prominent feature of both wake and REM sleep in humans and rodents. Theta coherence between the hippocampus and amygdala drives large-scale PGO waves, the density of which predicts increases in plasticity-related gene expression. This could potentially facilitate the processing of emotional memory traces within the hippocampus during REM sleep. Further, the timing of hippocampal activity in relation to theta phase is vital in determining subsequent potentiation of neuronal activity. This could allow the emotionally modulated strengthening of novel and the gradual weakening of consolidated hippocampal memory traces observed in both wake and REM sleep. Hippocampal theta activity is also correlated with REM sleep acetylcholine levels – which are thought to reduce hippocampal afferent inputs in the neocortex. The additional low levels of noradrenaline during REM sleep, which facilitate recurrent activation within the neocortex, could allow the integration of novel memory traces previously consolidated during NREM sleep. We therefore propose that REM sleep mediates the prioritized processing of emotional memories within the hippocampus, the integration of previously consolidated memory traces within the neocortex, as well as the disengagement of consolidated neocortical memory traces from the hippocampus.
Handan İnönü Köseoğlu
Full Text Available Objective: Rapid eye movement (REM is an entity in which the collapsibility of upper respiratory tract increases. Different opinions have been proposed with regard to the definition of REM-related obstructive sleep apnea syndrome (OSAS. Some authors consider REM-related OSAS as the first presentation, and others consider it as a different clinical type of OSAS. We aimed to compare the clinical and polysomnographic findings of REM-related and non-REM-related OSAS patients to test whether REM-related OSAS is a different clinical type OSAS or the manifestation of early stage or the onset of OSAS. Methods: The study had a retrospective design. Patients with an initial diagnosis of sleep-related breathing disorders were later diagnosed to have OSAS based on an apnea–hypopnea index (AHI of ≥5 and were divided into the following two groups: patients with AHINREM of 2 whose REM recordings were obtained for at least 30 min were defined as having “REM-related OSAS,” and those who did not meet this description were defined as having “non-REM-related OSAS.” Results: A total of 329 patients with a mean age of 51±10 years were included in the study. Thirty-five (10.6% patients with OSAS were REM-related and 294 (89.4% were non-REM-related. Age, body mass index, smoking status, and concomitant diseases were comparable between groups (p>0.05. In REM-related patients, AHI was lower, REM duration was longer, and mean oxygen saturations were comparatively higher (p<0.05. Conclusion: Similarities between groups in age, body mass index, and concomitant disease suggest that REM-related OSAS is a different clinical type of OSAS, rather than the early phase of OSAS.
Batterink, Laura J; Creery, Jessica D; Paller, Ken A
Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned arbitrary spatial locations for objects that were each paired with a characteristic sound (eg, cat-meow). Then, during SWS periods of an afternoon nap, one-half of the sounds were presented at low intensity. When object location memory was subsequently tested, recall accuracy was significantly better for those objects cued during sleep. We report here for the first time that this memory benefit was predicted by slow-wave phase at the time of stimulation. For cued objects, location memories were categorized according to amount of forgetting from pre- to post-nap. Conditions of high versus low forgetting corresponded to stimulation timing at different slow-oscillation phases, suggesting that learning-related stimuli were more likely to be processed and trigger memory reactivation when they occurred at the optimal phase of a slow oscillation. These findings provide insight into mechanisms of memory reactivation during sleep, supporting the idea that reactivation is most likely during cortical upstates. Slow-wave sleep (SWS) is characterized by synchronized neural activity alternating between active upstates and quiet downstates. The slow-oscillation upstates are thought to provide a
Smith, C; Weeden, K
Sleep activity was monitored in 20 freshman college students for two consecutive nights. Subjects were assigned to 4 equal groups and all were asked to learn a complex logic task before bed on the second night. Two groups of subjects learned the task with a constant clicking noise in the background (cued groups), while two groups simply learned the task (non cued). During the night, one cued and one non cued group were presented with auditory clicks during REM sleep such as to coincide with all REMs of at least 100 microvolts. The second cued group was given auditory clicks during REM sleep, but only during the REMs "quiet" times. The second non-cued control group was never given any nighttime auditory stimulations. The cued REMs coincident group showed a significant 23% improvement in task performance when tested one week later. The non cued REMs coincident group showed only an 8.8% improvement which was not significant. The cued REMs quiet and non-stimulated control groups showed no change in task performance when retested. The results were interpreted as support for the idea that the cued auditory stimulation induced a "recall" of the learned material during the REM sleep state in order for further memory processing to take place.
Full Text Available Sleep is essential for nervous system functioning and sleep disorders are associated with several neurodegenerative diseases. However, the macroscale connectivity changes in brain networking during different sleep states are poorly understood. One of the hindering factors is the difficulty to combine functional connectivity investigation methods with spontaneously sleeping animals, which prevents the use of numerous preclinical animal models. Recent studies, however, have implicated that urethane anesthesia can uniquely induce different sleep-like brain states, resembling rapid eye movement (REM and non-REM (NREM sleep, in rodents. Therefore, the aim of this study was to assess changes in global connectivity and topology between sleep-like states in urethane anesthetized rats, using blood oxygenation level dependent (BOLD functional magnetic resonance imaging. We detected significant changes in corticocortical (increased in NREM-like state and corticothalamic connectivity (increased in REM-like state. Additionally, in graph analysis the modularity, the measure of functional integration in the brain, was higher in NREM-like state than in REM-like state, indicating a decrease in arousal level, as in normal sleep. The fMRI findings were supported by the supplementary electrophysiological measurements. Taken together, our results show that macroscale functional connectivity changes between sleep states can be detected robustly with resting-state fMRI in urethane anesthetized rats. Our findings pave the way for studies in animal models of neurodegenerative diseases where sleep abnormalities are often one of the first markers for the disorder development.
Hanzer, Marie; Zotter, Heinz; Sauseng, Werner; Pfurtscheller, Klaus; Müller, Wilhelm; Kerbl, Reinhold
It has been reported that pacifiers might reduce the risk of SIDS by favouring infants' arousability from sleep. We evaluated the influence of a pacifier on the frequency and duration of spontaneous arousals in healthy infants. Polygraphic recordings were performed in 14 infants with an age of 51.7+/-19.9 days (means+/-SD) who regularly used a pacifier during sleep. Cortical and subcortical arousals were scored according to the recommendations of the "International Paediatric Work Group on Arousals." The number of arousals per 10-min-period and the duration of arousals were determined for periods of pacifier use as well as for periods after pacifier dislodgement and were compared with the data of 10 control infants (age 49.8+/-16.5 days) who never used a pacifier. Altogether, 211 arousals in pacifier users and 225 arousals in non-users were scored. In pacifier users, 2.0+/-1.6 arousals per 10-min-period with a duration of 12.2+/-3.0 s occurred during pacifier use, and 1.7+/-1.6 arousals per 10-min-period with a duration of 12.2+/-3.1s occurred during periods without pacifier. In pacifier non-users, 2.3+/-1.2 arousals per 10-min-period (duration 13.9+/-2.9s) were scored. The results did not show a significant difference concerning frequency and duration of spontaneous arousals between pacifier users and non-users. Our findings suggest that factors other than arousal mechanisms might be responsible for the efficacy of pacifiers in SIDS prophylaxis.
Zhang, Zhongxing; Khatami, Ramin
The hemodynamic changes during natural human sleep are still not well understood. NIRS is ideally suited for monitoring the hemodynamic changes during sleep due to the properties of local measurement, totally safe application and good tolerance to motion. Several studies have been conducted using NIRS in both normal subjects and patients with various sleep disorders during sleep to characterize the hemodynamic changing patterns during different sleep stages and during different symptoms such as obstructive apneas. Here we assessed brain and muscle oxygenation changes in 7 healthy adults during all-night sleep with combined polysomnography measurement to test the notion if hemodynamic changes in sleep are indeed brain specific. We found that muscle and brain showed similar hemodynamic changes during sleep initiation. A decrease in HbO2 and tissue oxygenation index (TOI) while an increase in HHb was observed immediately after sleep onset, and an opposite trend was found after transition with progression to deeper slow-wave sleep (SWS) stage. Spontaneous low frequency oscillations (LFO) and very low frequency oscillations (VLFO) were smaller (Levene's test, psleep (LS) and rapid-eye-movement (REM) sleep in both brain and muscle. Spectral analysis of the NIRS signals measured from brain and muscle also showed reductions in VLFO and LFO powers during SWS with respect to LS and REM sleep. These results indicate a systemic attenuation rather than local cerebral reduction of spontaneous hemodynamic activity in SWS. A systemic physiological mechanism may exist to regulate the hemodynamic changes in brain and muscle during sleep.
Full Text Available Abstract Background Paradoxical sleep deprivation (PSD associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group. To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg or testosterone (0.5 mg/kg or 1.0 mg/kg administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role
Ishikawa, Hiroko; Yamada, Kazuo; Pavlides, Constantine; Ichitani, Yukio
Effects of sleep deprivation (SD) on one-trial recognition memory were investigated in rats using either a spontaneous novel-object or object-place recognition test. Rats were allowed to explore a field in which two identical objects were presented. After a delay period, they were placed again in the same field in which either: (1) one of the two objects was replaced by another object (novel-object recognition); or (2) one of the sample objects was moved to a different place (object-place recognition), and their exploration behavior to these objects was analyzed. Four hours SD immediately after the sample phase (early SD group) disrupted object-place recognition but not novel-object recognition, while SD 4-8h after the sample phase (delayed SD group) did not affect either paradigm. The results suggest that sleep selectively promotes the consolidation of hippocampal dependent memory, and that this effect is limited to within 4h after learning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
De Gennaro, Luigi; Marzano, Cristina; Moroni, Fabio; Curcio, Giuseppe; Ferrara, Michele; Cipolli, Carlo
The study investigated the effect of one night of sleep deprivation on dream recall at morning awakening after recovery sleep. Forty healthy subjects were studied after adaptation (A) and baseline nights (B), and a recovery (R) night following 40 h of prolonged wakefulness. Parallel to the well-known recovery sleep changes (slow-wave sleep--SWS--rebound, decreased number of awakenings and of REM sleep amount), an almost complete abolition of dream recall was found, with an around 75% decrease with respect to the adaptation and baseline nights. The number of dreams recalled by those subjects with successful recall (REC) did not significantly differ between nights. Moreover, gender and sleep stage at awakening did not affect either the proportion of REC subjects or the number of dreams recalled by REC subjects during each night. Finally, the drastic impairment of dream recall after R night was associated to a larger increase of SWS and a shorter REM sleep duration. We suggest that dream recall could have been impaired during R night because: (i) the lower number of spontaneous awakenings over the night reduced the contents available in memory as possible cues for the retrieval of dream experiences at morning; (ii) mental experiences, having been elaborated during SWS more than in the other nights, were less dreamlike (i.e., perceptually vivid and bizarre) and, thus less accessible at morning recall than those elaborated during the nights with a higher proportion of REM sleep; (iii) dream contents, as a peculiar type of episodic information, were less consolidated because of the lower effectiveness of declarative memory during recovery sleep.
Gagnadoux, Frédéric; Pevernagie, Dirk; Jennum, Poul
the performance of the System One RemStar Auto A-Flex (Philips Respironics, Murrysville, PA, USA) automatically adjusted positive airway pressure (APAP) mode to manually titrated, fixed pressure CPAP and to validate the device's breathing event detection capabilities against attended in-laboratory PSG. METHODS...
Kempfner, Jacob; Sørensen, Gertrud Laura; Zoetmulder, Marielle
Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection...... recordings were scored, according to the new sleep-scoring standard from the American Academy of Sleep Medicine, by two independent sleep specialists. A follow-up analysis of the scoring consensus between the two specialists has been conducted. Based on the agreement of the two manual scorings...
Kempfner, Jacob; Sorensen, Gertrud; Zoetmulder, Marielle
Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection...... recordings were scored, according to the new sleep-scoring standard from the American Academy of Sleep Medicine, by two independent sleep specialists. A follow-up analysis of the scoring consensus between the two specialists has been conducted. Based on the agreement of the two manual scorings...
Beldzik, Ewa; Chialvo, Dante R.; Domagalik, Aleksandra; Fafrowicz, Magdalena; Gudowska-Nowak, Ewa; Marek, Tadeusz; Nowak, Maciej A.; Oginska, Halszka; Szwed, Jerzy
The timing and dynamics of many diverse behaviors of mammals, e.g., patterns of animal foraging or human communication in social networks exhibit complex self-similar properties reproducible over multiple time scales. In this paper, we analyze spontaneous locomotor activity of healthy individuals recorded in two different conditions: during a week of regular sleep and a week of chronic partial sleep deprivation. After separating activity from rest with a pre-defined activity threshold, we have detected distinct statistical features of duration times of these two states. The cumulative distributions of activity periods follow a stretched exponential shape, and remain similar for both control and sleep deprived individuals. In contrast, rest periods, which follow power-law statistics over two orders of magnitude, have significantly distinct distributions for these two groups and the difference emerges already after the first night of shortened sleep. We have found steeper distributions for sleep deprived individuals, which indicates fewer long rest periods and more turbulent behavior. This separation of power-law exponents is the main result of our investigations, and might constitute an objective measure demonstrating the severity of sleep deprivation and the effects of sleep disorders. PMID:25222128
Jeremi K Ochab
Full Text Available The timing and dynamics of many diverse behaviors of mammals, e.g., patterns of animal foraging or human communication in social networks exhibit complex self-similar properties reproducible over multiple time scales. In this paper, we analyze spontaneous locomotor activity of healthy individuals recorded in two different conditions: during a week of regular sleep and a week of chronic partial sleep deprivation. After separating activity from rest with a pre-defined activity threshold, we have detected distinct statistical features of duration times of these two states. The cumulative distributions of activity periods follow a stretched exponential shape, and remain similar for both control and sleep deprived individuals. In contrast, rest periods, which follow power-law statistics over two orders of magnitude, have significantly distinct distributions for these two groups and the difference emerges already after the first night of shortened sleep. We have found steeper distributions for sleep deprived individuals, which indicates fewer long rest periods and more turbulent behavior. This separation of power-law exponents is the main result of our investigations, and might constitute an objective measure demonstrating the severity of sleep deprivation and the effects of sleep disorders.
Uludag, Irem Fatma; Tiftikcioglu, Bedile Irem; Ertekin, Cumhur
Spontaneous saliva swallows (SS) appear especially during sleep. The rate of SS was rarely investigated in all-night sleep in patients with Parkinson disease (PD). Dysphagia is a frequent symptom in PD, but the rate of SS was never studied with an all-night sleep electroencephalogram (EEG). A total of 21 patients with PD and 18 age-matched healthy controls were included in the study. Frequencies of SS and coughing were studied in all-night sleep recordings of patients with PD and controls. During all-night sleep, video-EEG 12-channel recording was used including the electromyography (EMG) of the swallowing muscles, nasal airflow, and recording of vertical laryngeal movement using a pair of EEG electrodes over the thyroid cartilage. The total number of SS was increased while the mean duration of sleep was decreased in PD when compared to controls. Sialorrhea and clinical dysphagia, assessed by proper questionnaires, had no effect in any patient group. The new finding was the so-called salvo type of consecutive SS in one set of swallowing. The amount of coughing was significantly increased just after the salvo SS. In PD, the rate of SS was not sufficient to demonstrate the swallowing disorder, such as oropharyngeal dysphagia, but the salvo type of SS was quite frequent. This is a novel finding and may contribute to the understanding of swallowing problems in patients with dysphagic or nondysphagic PD. © 2016 Associated Professional Sleep Societies, LLC.
Meerlo, Peter; Easton, Amy; Bergmann, Bernard M.; Turek, Fred W.
Sleep is generally considered to be a recovery from prior wakefulness. The architecture of sleep not only depends on the duration of wakefulness but also on its quality in terms of specific experiences. In the present experiment, we studied the effects of restraint stress on sleep architecture and
Beersma, Domien G.M.
Non-REM sleep deprivation and REM sleep deprivation both lead to specific rebounds, suggesting that these states fulfil physiological needs. In view of impaired performance after sleep deprivation, a recovery function of sleep seems likely. The timing of this recovery is restricted to a narrow time
Dijk, Derk Jan; Beersma, Domien G.M.
In order to test predictions of the 2-process model of sleep regulation, the effects of slow wave sleep (SWS) deprivation by acoustic stimulation during the first part of the sleep period on EEG power density and sleep duration were investigated in 2 experiments. In the first experiment, 8 subjects
Vita, Maria Gabriella; Batocchi, Anna Paola; Dittoni, Serena; Losurdo, Anna; Cianfoni, Alessandro; Stefanini, Maria Chiara; Vollono, Catello; Della Marca, Giacomo; Mariotti, Paolo
An 11 year-old-boy acutely developed complex visual and acoustic hallucinations. Hallucinations, consisting of visions of a threatening, evil character of the Harry Potter saga, persisted for 3 days. Neurological and psychiatric examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of hyperintense signal in the brainstem, along the paramedian and lateral portions of pontine tegmentum, one of which showed post-contrast enhancement. These lesions were likely of inflammatory origin, and treatment with immunoglobulins was started. Polysomnography was normal, multiple sleep latency test showed a mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine tegmentum is responsible for REM sleep regulation, and contains definite "REM-on" and "REM-off" regions. The anatomical distribution of the lesions permits us to hypothesize that hallucinations in this boy were consequent to a transient impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like hallucinations during wake.
Kumar, Velayudhan Mohan
Sleep is a complex neurological state, with its primary function of providing rest and restoring the body's energy levels. The importance of sleep could be seen from the fact that people spend about one-third of their lifespan in sleep. Normal human sleep is divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and the alteration between NREM and REM occurs about 4-5 times during a night of normal sleep. Human NREM sleep could be classified into four stages, namely, stage I, II, III and IV, representing successively deeper stages of sleep. Sleep is an active rhythmic neural process produced by several brain areas, of which the preoptic and other basal forebrain areas play a major role in the generation of NREM sleep. Interaction of the pedenculo-pontine and lateral dorsal tegmental areas with the dorsal raphae nucleus and locus coeruleus, is important for REM sleep generation. Suprachiasmatic nucleus of the hypothalamus and the pineal gland ensure that sleep and wakefulness follow a circadian periodicity of nearly 24 hours. Alterations in the quality, quantity and pattern of sleep result in sleep disorders. Persistent and repeated interruption of sleep affects the health of an individual. Undiagnosed and untreated wake/sleep complaints cause not only misery to the sufferer, but it also has socio-economic consequences. Sleep disorders cover a wide spectrum of diseases. Though there are more than 100 identified sleep/wake disorders, most sleep complaints can be categorised into five, namely, hypersomnia, insomnia, circadian rhythm disorders, parasomnias, and sleep disorders associated with mental, neurological, and other medical disorders. Researches during the last 50 years, and the advances made in clinical sleep medicine, have lead to more effective treatments for the myriad human sleep disorders. It is not possible to assign a specific reason for many of the sleep disorders, but some aspects of sleep and wakefulness are genetically
Hanif, Umaer; Trap, Lotte; Jennum, Poul
Idiopathic REM sleep behavior disorder (iRBD) is a very strong predictor for later development of Parkinson's disease (PD), and is characterized by REM sleep without atonia (RSWA), resulting in increased muscle activity during REM sleep. Abundant studies have shown the loss of atonia during REM...
van Rijn, E; Eichenlaub, J-B; Lewis, P A; Walker, M P; Gaskell, M G; Malinowski, J E; Blagrove, M
Incorporation of details from waking life events into Rapid Eye Movement (REM) sleep dreams has been found to be highest on the night after, and then 5-7 nights after events (termed, respectively, the day-residue and dream-lag effects). In experiment 1, 44 participants kept a daily log for 10 days, reporting major daily activities (MDAs), personally significant events (PSEs), and major concerns (MCs). Dream reports were collected from REM and Slow Wave Sleep (SWS) in the laboratory, or from REM sleep at home. The dream-lag effect was found for the incorporation of PSEs into REM dreams collected at home, but not for MDAs or MCs. No dream-lag effect was found for SWS dreams, or for REM dreams collected in the lab after SWS awakenings earlier in the night. In experiment 2, the 44 participants recorded reports of their spontaneously recalled home dreams over the 10 nights following the instrumental awakenings night, which thus acted as a controlled stimulus with two salience levels, high (sleep lab) and low (home awakenings). The dream-lag effect was found for the incorporation into home dreams of references to the experience of being in the sleep laboratory, but only for participants who had reported concerns beforehand about being in the sleep laboratory. The delayed incorporation of events from daily life into dreams has been proposed to reflect REM sleep-dependent memory consolidation. However, an alternative emotion processing or emotional impact of events account, distinct from memory consolidation, is supported by the finding that SWS dreams do not evidence the dream-lag effect. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Kempfner, Jacob; Sorensen, Gertrud; Zoetmulder, Marielle
Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection...... is proposed by analyzing the motor activity during sleep. Method: A total number of twelve patients have been involved in this study, six normal controls and six patients diagnosed with Parkinsons Disease (PD) with RBD. All subjects underwent at least one ambulant polysomnographic (PSG) recording. The sleep...
Steiger, Axel; Pawlowski,Marcel; Kimura,Mayumi
Axel Steiger, Marcel Pawlowski, Mayumi Kimura Max Planck Institute of Psychiatry, Munich, Germany Abstract: The sleep electroencephalogram (EEG) provides biomarkers of depression, which may help with diagnosis, prediction of therapy response, and prognosis in the treatment of depression. In patients with depression, characteristic sleep EEG changes include impaired sleep continuity, disinhibition of rapid-eye-movement (REM) sleep, and impaired non-REM sleep. Most antidepressants suppress REM...
Full Text Available O estudo de estratégias neurais para a organização do comportamento em vertebrados constitui um desafio maior para a neurociencia. O avanço do conhecimento nessa área depende criticamente da utilização de modelos experimentais adequados que suportem múltiplos níveis de análise (por exemplo: comportamental, circuital, celular, sináptico e molecular e abordagens por múltiplas técnicas. Decidiu-se analisar in vitro uma rede neural da união mesopontina do tronco encefálico criticamente envolvida no controle do sono de movimentos oculares rápidos (S-REM. Apesar da riqueza de provas que sustentam o papel desta rede em relação ao S-REM, os mecanismos celulares e sinápticos subjacentes a este controle são pouco conhecidos e permanecem sob intensa investigação. Para avançar no conhecimento desses mecanismos, caracterizou-se morfológica e funcionalmente uma fatia de tronco encefálico de rato, na qual as estruturas críticas para o controle do S-REM, i.e.: núcleos tegmentais laterodorsal e pedunculopontino, e sua projeção para o núcleo reticular pontis oralis (PnO estão presentes e operantes. A inclusão do núcleo motor do trigêmeo na fatia permitiu detectar mudanças da excitabilidade das motoneuronas provocadas por manipulações farmacológicas do PnO, representativas das alterações do tônus muscular associados com operações semelhantes quando realizados in vivo. A utlização deste modelo in vitro de S-REM permitirá contribuir para a elucidação de estratégias neurais que operam em níveis intermedios de organização do SN de mamíferos para a geração e regulação de um estado comportamental.
Walter, Lisa M; Nixon, Gillian M; Davey, Margot J; O'Driscoll, Denise M; Trinder, John; Horne, Rosemary S C
Sleep-disordered breathing in children is most prevalent in the pre-school years and has been associated with sleep fragmentation and hypoxia. We aimed to compare the sleep and spontaneous arousal characteristics of 3-5-year-old children with obstructive sleep apnoea (OSA) with that of non-snoring control children, and to further characterise the arousal responses to obstructive respiratory events. A total of 73 children (48 male) underwent overnight polysomnography: 51 for assessment of snoring who were subsequently diagnosed with OSA (obstructive apnoea hypopnoea index (OAHI)>1 event per h) and 22 control children recruited from the community (OAHI ≤ 1 and no history of snoring). The OSA group had poorer sleep efficiency (ptime in rapid eye movement (REM) (p<0.05), and had significantly fewer spontaneous arousals (p<0.001) compared with controls. One-quarter of the children with OSA had a sleep pressure score above the cut-off point for increased sleep pressure. In children with OSA, 62% of obstructive respiratory events terminated in a cortical arousal and 21% in a sub-cortical arousal. A significantly higher proportion of obstructive respiratory events terminated in a cortical arousal during non-REM (NREM) compared with REM (p<0.001). These findings suggest that in pre-school children OSA has a profound effect on sleep and arousal patterns. Given that these children are at a critical period for brain development, the impact of OSA may have more severe consequences than in older children. Copyright © 2011 Elsevier B.V. All rights reserved.
Koulack, D; De Koninck, J; Oczkowski, G
Recently a number of studies have concerned the possible function of rapid eye movement (REM) sleep and the mastery of stress. The present study was designed to explore the possibility that REM sleep might play a function in reducing the potency of a stressful physiological stimulus, thirst, as well as the possibility that such a function might be specific to individuals falling at different points along the field-dependence dimension. While there was no difference between REM deprivation and non-REM awakening nights in subsequent morning thirst, there was a significant interaction between field dependence and night on morning thirst measures for 10 college students. These results are discussed in light of previous work on stylistic differences in dreaming and their possible role in adaptation to stress.
Menicucci, D; Gentili, C; Piarulli, A; Laurino, M; Pellegrini, S; Mastorci, F; Bedini, R; Montanaro, D; Sebastiani, L; Gemignani, A
Brain connectivity is associated to behavioral states (e.g. wake, sleep) and modified by physical activity although, to date, it is not clear which components (e.g. hypothalamus-pituitary-adrenal axis hormones, cytokines) associated to the exercise are involved. In this pilot study, we used extreme exercise (UltraTriathlon) as a model to investigate physical-activity-related changes of brain connectivity. We studied post-race brain synchronization during wakefulness and sleep as well as possible correlations between exercise-related cytokines/hormones and synchronization features. For wakefulness, global synchronization was evaluated by estimating from fMRI data (12 athletes) the brain global connectivity (GC). GC increased in several brain regions, mainly related to sensory-motor activity, emotional modulation and response to stress that may foster rapid exchange of information across regions, and reflect post-race internally-focused mental activity or disengagement from previous motor programs. No significant correlations between cytokines/hormones and GC were found. For sleep (8 athletes), synchronization was evaluated by estimating the local-(cortical) and global-related (thalamo- cortical) EEG features associated to the phenomenon of Sleep Slow Oscillations (SSO) of NREM sleep. Results showed that: power of fast rhythms in the baseline preceding the SSO increased in midline and parietal regions; amplitude and duration of SSOs increased, mainly in posterior areas; sigma modulation in the SSO up state decreased. In the post race, IL-10 positively correlated with fast rhythms baseline, SSO rate and positive slope; IL-1ra and cortisol inversely correlated with SSO duration; TNF-α and C-reactive protein positively correlated with fast rhythm modulation in the SSO up state. Sleep results suggest that: arousal during sleep, estimated by baseline fast rhythms, is increased; SSO may be sustained by cortical excitability, linked to anti-inflammatory markers (IL-10
Chen, Chieh-Wen; Kuo, Terry B J; Chen, Chun-Yu; Yang, Cheryl C H
Ambulatory blood pressure (BP) monitoring with a lack of nocturnal BP fall (BP nondipping) has been reported to be more prevalent among hypertensive populations and is a risk factor for cardiovascular disease than in patients with dipping pattern. However, its underlying mechanism is not fully understood. This study hypothesized that spontaneously hypertensive rats (SHRs) with a nondipping profile have an exaggerated disruption of both autonomic functioning and sleep compared with Wistar-Kyoto rats (WKYs) with a nondipping profile. Continuous power spectral analysis of electroencephalogram, electromyogram, and cardiovascular variability was performed in WKYs and SHRs over 24 h. BP dipping was assessed as the percentage decline in SBP from dark active waking to light quiet sleep (lQS). According to the human definition of BP dipping (10%), we divided WKYs and SHRs into dipper and nondipper groups individually. Of the four groups, both parasympathetic activity and baroreflex sensitivity in sleep were the lowest in the SHR nondippers. Compared with the WKY nondippers, the SHR nondippers spent more time awake and less time asleep during the light period and the opposite during the dark period. Moreover, they showed more interruptions and a lower delta power percentage of lQS. Correlation analysis revealed that baroreflex sensitivity during lQS was correlated with the BP dipping percentage in SHRs. SHR nondippers exhibit poor sleep quality and impaired autonomic functioning to a greater degree than do SHR dippers and WKY nondippers, which may account for a higher cardiovascular risk in this population.
Jennum, Poul; Christensen, Julie Anja Engelhard; Zoetmulder, Marielle
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities ha...
Jones, D; Gershon, S; Sitaram, N; Keshavan, M
Manifestations of sleep disturbances can potentially serve as external criteria for the diagnosis of specific subtypes of major depressive disorder (MDD). Depressed patients generally experience disturbances of sleep continuity and rapid eye movement (REM) sleep. Disturbances in nonrapid eye movement (NREM) sleep (stages III and IV) also occur. Characteristic of primary sleep disturbance in many depressed patients are shortened REM latency periods and instabilities in NREM sleep identified by increases in the number of stage shifts, decreases in the duration of stage III and IV sleep, and a shift towards lighter sleep stages (sleep efficiency disturbances). Treatment modalities for these sleep disturbances include sleep deprivation therapy and antidepressant therapy. Sleep deprivation alone has been only moderately successful, while antidepressant therapy usually results in symptomatic improvement. To restore normative sleep, REM sleep periods and stage III and IV sleep must be returned to normal. Trazodone therapy has been shown to reduce the frequency of arousals, the severity of drowsiness, and the duration of REM sleep, and increase restorative slow wave sleep and stage III and IV NREM sleep.
Scarone, S; Spoto, G; Penati, G; Canger, R; Moja, E A
The modifications of spontaneous sleep in schizophrenic patients following N-ethyl-2(2-methoxy-5-sulfamido-benzamidomethyl)-pyrrolidine (sulpiride, Dobren) administration are reported in this study. No significant modifications in the quantitative distribution of the various sleep phases (LST, SWS, REM) were observed, while a significant percent increase of SWS was noted, together with a significant decrease in the number of awakenings during the night and an increase of the sleep onset time. The patients' own difficulty to fall asleep, however, decreased significantly, and also a significant increase of dream recall could be observed.
Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP) - in fitting the data well - successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN...
Full Text Available Neurons that utilize the neuropeptide melanin-concentrating hormone (MCH as a neuromodulator are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows:1. The areas related to the control of sleep and wakefulness have an important density of MCHergic fibers and receptors.2. MCHergic neurons are active during sleep, especially during REM sleep.3. Genetically-modified animals without MCH have less REM sleep, notably under conditions of negative energy balance. 4. Systemically administered MCHR1 antagonists reduce sleep. 5. Intraventricular microinjection of MCH increases both slow wave sleep (SWS and REM sleep; however, the increment in REM sleep is more pronounced.6. Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus.7. Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency.All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.
Ribeiro, Sidarta; Nicolelis, Miguel A. L.
In mammals and birds, long episodes of nondreaming sleep ("slow-wave" sleep, SW) are followed by short episodes of dreaming sleep ("rapid-eye-movement" sleep, REM). Both SW and REM sleep have been shown to be important for the consolidation of newly acquired memories, but the underlying mechanisms remain elusive. Here we review…
Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe
Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized...
Ming, Xue; Sun, Ye-Ming; Nachajon, Roberto V.; Brimacombe, Michael; Walters, Arthur S.
The prevalence of sleep related complaints is reported by questionnaire studies to be as high as 83.3% in children with autism spectrum disorders (ASD). Questionnaire studies report the presence of various parasomnia in ASD. However, no polysomnographic study reports non-REM parasomnias and only a single study reports REM related parasomnias in ASD. We investigated the prevalence and characteristics of sleep disorders by polysomnographic study and questionnaires in a cohort of 23 children with ASD and 23 age-matched children of a non-autistic comparison group. The results showed significantly more non-REM parasomnias in 14 children with ASD on polysomnograms (PSG) and 16 ASD children by questionnaire, a finding that was not associated with medication use, other comorbid medical or psychiatric disorders, or sleep disordered breathing. Of the 14 children with ASD who had PSG evidence of parasomnia, 11 of them had a history suggestive of parasomnia by questionnaire. There was a high sensitivity but a low specificity of parasomnia in ASD by questionnaire in predicting the presence of parasomnia in the PSG. Of the parasomnias recorded in the laboratory, 13 ASD children had Disorders of Partial Arousal, consistent with sleep terrors or confusional arousals. Furthermore, multiple episodes of partial arousal occurred in 11 of the 13 ASD children who had PSG evidence of Disorders of Partial Arousal. Of the 11 ASD children with multiple episodes of partial arousal, 6 ASD children had multiple partial arousals during both nights’ PSG study. Sleep architecture was abnormal in children with ASD, characterized by increased spontaneous arousals, prolonged REM latency and reduced REM percentage. These results suggest a high prevalence of parasomnia in this cohort of children with ASD and a careful history intake of symptoms compatible with parasomnia could be prudent to diagnose parasomnia in ASD children when performing a PSG is not possible. PMID:23818789
Arthur S. Walters
Full Text Available The prevalence of sleep related complaints is reported by questionnaire studies to be as high as 83.3% in children with autism spectrum disorders (ASD. Questionnaire studies report the presence of various parasomnia in ASD. However, no polysomnographic study reports non-REM parasomnias and only a single study reports REM related parasomnias in ASD. We investigated the prevalence and characteristics of sleep disorders by polysomnographic study and questionnaires in a cohort of 23 children with ASD and 23 age-matched children of a non-autistic comparison group. The results showed significantly more non-REM parasomnias in 14 children with ASD on polysomnograms (PSG and 16 ASD children by questionnaire, a finding that was not associated with medication use, other comorbid medical or psychiatric disorders, or sleep disordered breathing. Of the 14 children with ASD who had PSG evidence of parasomnia, 11 of them had a history suggestive of parasomnia by questionnaire. There was a high sensitivity but a low specificity of parasomnia in ASD by questionnaire in predicting the presence of parasomnia in the PSG. Of the parasomnias recorded in the laboratory, 13 ASD children had Disorders of Partial Arousal, consistent with sleep terrors or confusional arousals. Furthermore, multiple episodes of partial arousal occurred in 11 of the 13 ASD children who had PSG evidence of Disorders of Partial Arousal. Of the 11 ASD children with multiple episodes of partial arousal, 6 ASD children had multiple partial arousals during both nights’ PSG study. Sleep architecture was abnormal in children with ASD, characterized by increased spontaneous arousals, prolonged REM latency and reduced REM percentage. These results suggest a high prevalence of parasomnia in this cohort of children with ASD and a careful history intake of symptoms compatible with parasomnia could be prudent to diagnose parasomnia in ASD children when performing a PSG is not possible.
Arnulf, I.; Nielsen, J.; Lohmann, E.
Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages...... interview, nighttime video and sleep monitoring, and daytime multiple sleep latency tests. Their results were compared with those of patients with narcolepsy and control patients. Results: The HD patients had frequent insomnia, earlier sleep onset, lower sleep efficiency, increased stage I sleep, delayed......: The sleep phenotype of HD includes insomnia, advanced sleep phase, periodic leg movements, REM sleep behavior disorders, and reduced REM sleep but not narcolepsy. Reduced REM sleep may precede chorea. Mutant huntingtin may exert an effect on REM sleep and motor control during sleep Udgivelsesdato: 2008/4...
Sleep disorders are serious issues in modern society. There has been marked scientific interest in sleep for a century, with the discoveries of the electrical activity of the brain (EEG), sleep-wake system, rapid eye movement (REM) sleep, and circadian rhythm system. Additionally, the advent of video-polysomnography in clinical research has revealed some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. Decades of clinical research have demonstrated that sleep disorders are intimately tied to not only physical disease (e. g., lifestyle-related disease) but psychiatric illness. According to The International Classification of Sleep Disorders (2005), sleep disorders are classified into 8 major categories: 1) insomnia, 2) sleep-related breathing disorders, 3) hypersomnias of central origin, 4) circadian rhythm sleep disorders, 5) parasomnias, 6) sleep-related movement disorders, 7) isolated symptoms, and 8) other sleep disorders. Several sleep disorders, including obstructive sleep apnea syndrome, restless legs syndrome, periodic limb movement disorder, sleepwalking, REM sleep behavior disorder, and narcolepsy, may be comorbid or possibly mimic numerous psychiatric disorders, and can even occur due to psychiatric pharmacotherapy. Moreover, sleep disorders may exacerbate underlying psychiatric disorders when left untreated. Therefore, psychiatrists should pay attention to the intimate relationship between sleep disorders and psychiatric symptoms. Sleep psychiatry is an academic field focusing on interrelations between sleep medicine and psychiatry. This mini-review summarizes recent findings in sleep psychiatry. Future research on the bidirectional relation between sleep disturbance and psychiatric symptoms will shed light on the pathophysiological view of psychiatric disorders and sleep disorders.
Full Text Available Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG, we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP--in fitting the data well--successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN activity we show that the SCN has the information required to provide a threshold-triggered flip-flop for TIMING the towards-and-away alternations, information provided by sleep-relevant feedback to the SCN. NTP then determines the PATTERN of spectral power within each dynamic-state. NTP was fitted to individual NREM episodes 1-4, using data from 30 healthy subjects aged 20-30 years, and the quality of fit for each NREM measured. We show that the model fits well all NREM episodes and the best-fit probability-set is found to be effectively the same in fitting all subject data. The significant model-data agreement, the constant probability parameter and the proposed role of the SCN add considerable strength to the model. With it we link for the first time findings at cellular level and detailed time-course data at EEG level, to give a coherent picture of NREM dynamics over the entire night and over hierarchic brain levels all the way from the SCN
Kempfner, Jacob; Jennum, Poul; Nikolic, Miki
Idiopathic Rapid-Eye-Movement (REM) sleep Behavior Disorder (iRBD) is one of the most potential biomarkers for Parkinson's Disease (PD) and some atypical PD (AP). It is characterized by REM sleep with abnormal high surface EMG (sEMG) activity. Some twitching during REM sleep is normal, but no one...... has defined what normal is, and no well-defined methodology for measuring muscle activity in REM sleep exists. The purpose of this study is to investigate the possibility of detecting abnormal high muscle activity during REM sleep in subjects diagnosed with iRBD. This has been achieved by considering...
McNamara, Patrick; McLaren, Deirdre; Durso, Kate
The authors hypothesized that representations of the Self (or the dreamer) in dreams would change systematically, from a prereflective form of Self to more complex forms, as a function of both age and sleep state (REM vs. non-REM). These hypotheses were partially confirmed. While the authors found that all the self-concept-related dream content indexes derived from the Hall/Van de Castle dream content scoring system did not differ significantly between the dreams of children and adults, adult Selves were more likely to engage in “successful” social interactions. The Self never acted as aggressor in NREM dream states and was almost always the befriender in friendly interactions in NREM dreams. Conversely, the REM-related dream Self preferred aggressive encounters. Our results suggests that while prereflective forms of Self are the norm in children’s dreams, two highly complex forms of Self emerge in REM and NREM dreams. PMID:19169371
Espie, Colin A.; Paul, Audrey; McFie, Joyce; Amos, Pat; Hamilton, David; McColl, John H.; And Others
A study of the sleep patterns of 28 people with severe or profound mental retardation and epilepsy found atypical sleep stages with significant depletion of REM sleep and a predominance of indiscriminate non-REM sleep. Sleep diaries completed by caregivers reveal lengthy sleep periods, especially among those with profound mental retardation.…
Ferini-Strambi, Luigi; Oertel, Wolfgang; Dauvilliers, Yves
to study the disorders of the autonomic nervous system in Parkinson's disease (PD) patients, the SCOPA-AUT, was administered to all the patients and controls. The SCOPA-AUT consists of 25 items assessing the following domains: gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor......Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic...... symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale...
Gotthard G. Tribl
Full Text Available Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD. This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson’s disease (WD and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.
Yetton, Benjamin D; Niknazar, Mohammad; Duggan, Katherine A; McDevitt, Elizabeth A; Whitehurst, Lauren N; Sattari, Negin; Mednick, Sara C
Rapid eye movements (REMs) are a defining feature of REM sleep. The number of discrete REMs over time, or REM density, has been investigated as a marker of clinical psychopathology and memory consolidation. However, human detection of REMs is a time-consuming and subjective process. Therefore, reliable, automated REM detection software is a valuable research tool. We developed an automatic REM detection algorithm combining a novel set of extracted features and the 'AdaBoost' classification algorithm to detect the presence of REMs in Electrooculogram data collected from the right and left outer canthi (ROC/LOC). Algorithm performance measures of Recall (percentage of REMs detected) and Precision (percentage of REMs detected that are true REMs) were calculated and compared to the gold standard of human detection by three expert sleep scorers. REM detection by four non-experts were also investigated and compared to expert raters and the algorithm. The algorithm performance (78.1% Recall, 82.6% Precision) surpassed that of the average (expert & non-expert) single human detection performance (76% Recall, 83% Precision). Agreement between non-experts (Cronbach Alpha=0.65) is markedly lower than experts (Cronbach Alpha=0.80). By following reported methods, we implemented all previously published LOC and ROC based detection algorithms on our dataset. Our algorithm performance exceeded all others. The automatic detection algorithm presented is a viable and efficient method of REM detection as it reliably matches the performance of human scorers and outperforms all other known LOC- and ROC-based detection algorithms. Copyright © 2015 Elsevier B.V. All rights reserved.
Madsen, P L; Holm, S; Vorstrup, S
tomography and the new tracer 99mTc-dl-hexamethylpropyleneamine. Eleven healthy volunteers aged between 22 and 27 years were studied. CBF was measured on separate nights during REM sleep and during EEG-verified wakefulness. On awakening from REM sleep, all subjects reported visual dreams. During REM sleep...... dream experiences. On the other hand, the reduced involvement of the inferior frontal cortex observed during REM sleep might explain the poor temporal organization and bizarreness often experienced in dreams....
Hernández-Chan, Nancy G; Góngora-Alfaro, José L; Álvarez-Cervera, Fernando J; Solís-Rodríguez, Francisco A; Heredia-López, Francisco J; Arankowsky-Sandoval, Gloria
Anatomical and functional studies have shown that the NADPH-diaphorase-positive cholinergic neurons of the pedunculopontine nucleus (PPN) send projections to several areas in the brain. The purpose of this work was to investigate whether bilateral lesions with quinolinic acid, a neurotoxin with greater selectivity for NADPH-diaphorase-positive neurons, aimed at the compact portion of the PPN would affect the performance of adaptive behaviors, such as sleep, locomotion, and spontaneous alternation. Lesioned animals were divided in a low lesion group (LL, sleep patterns, as compared to controls. In contrast, the HL group showed a significant increase in the number of REM sleep periods, and a reduction of REM sleep average duration, but did not differ in the total time spent in REM sleep. HL animals also showed an increase in the number of SWS periods, though wakefulness parameters did not show significant alterations. The duration and number of both REM and SWS sleep episodes were significantly correlated with the number of NADPH-diaphorase-positive neurons in the PPN. The short-term habituation pattern of locomotion, the vertical exploratory activity, as well as the thigmotaxis (an index of emotionality), displayed by LL and HL rats in a novel environment were similar to those of control animals. Likewise, there were no significant differences in spontaneous alternation among the groups. Our results indicate that quinolinic acid lesions of NADPH-diaphorase-positive cholinergic neurons localized in the posterior region of the PPN disrupt normal sleep structure, while motor activity and spontaneous alternation remain unaffected. Copyright © 2011 Elsevier B.V. All rights reserved.
Brandon H. Cline
Full Text Available Central insulin receptor-mediated signalling is attracting the growing attention of researchers because of rapidly accumulating evidence implicating it in the mechanisms of plasticity, stress response and neuropsychiatric disorders including depression. Dicholine succinate (DS, a mitochondrial complex II substrate, was shown to enhance insulin-receptor mediated signaling in neurons and is regarded as a sensitizer of the neuronal insulin receptor. Compounds enhancing neuronal insulin receptor-mediated transmission exert an antidepressant-like effect in several pre-clinical paradigms of depression; similarly, such properties for DS were found with a stress-induced anhedonia model. Here, we additionally studied the effects of DS on several variables which were ameliorated by other insulin receptor sensitizers in mice. Pre-treatment with DS of chronically stressed C57BL6 mice rescued normal contextual fear conditioning, hippocampal gene expression of NMDA receptor subunit NR2A, the NR2A/NR2B ratio and increased REM sleep rebound after acute predation. In 18-month-old C57BL6 mice, a model of elderly depression, DS restored normal sucrose preference and activated the expression of neural plasticity factors in the hippocampus as shown by Illumina microarray. Finally, young naïve DS-treated C57BL6 mice had reduced depressive- and anxiety-like behaviours and, similarly to imipramine-treated mice, preserved hippocampal levels of the phosphorylated (inactive form of GSK3 beta that was lowered by forced swimming in pharmacologically naïve animals. Thus, DS can ameliorate behavioural and molecular outcomes under a variety of stress- and depression-related conditions. This further highlights neuronal insulin signalling as a new factor of pathogenesis and a potential pharmacotherapy of affective pathologies.
Kohyama, J; Hasegawa, T; Shimohira, M; Fukumizu, M; Iwakawa, Y
One-night polysomnography was performed on seven subjects suffering from breath-holding spells, including one whose death was suggested to be a consequence of a breath-holding spell. The fatal case showed no rapid eye movements (REMs) during REM sleep, although he exhibited REMs during wakefulness. The average numbers of both REMs and bursts of REMs in REM sleep in the other six breath holders were significantly lower than those in age-matched controls. The breath holders showed no airway obstruction, desaturation, or sleep fragmentation. Since the rapid ocular activity in REM sleep is generated in the brain stem, we hypothesized that a functional brainstem disturbance is involved in the occurrence of breath-holding spells.
Irfan, Muna; Schenck, Carlos H; Howell, Michael J
This article reviews the spectrum of non-rapid eye movement (non-REM) sleep parasomnias, including sleepwalking, confusional arousals, and sleep terrors, which represent the range of phenotypic disorders of arousal from non-REM sleep that occurs in children and adults. The International Classification of Sleep Disorders, Third Edition (ICSD-3) classifies parasomnias according to the sleep stage they emerge from: REM, non-REM, or other. Demographics, clinical features, and diagnosis of non-REM parasomnias are reviewed in this article, and an up-to-date synopsis of guidelines for management strategies to assist in the treatment of these sleep disorders is provided. The non-REM parasomnias are most common in children and adolescents but may persist into adulthood. They can be distinguishable from REM parasomnias and nocturnal epilepsies, and, importantly, may lead to injury. Additionally, other parasomnias in this spectrum include sleep-related eating disorder and sexsomnia. Overlap parasomnia disorder includes one or more manifestations of a non-REM parasomnia seen in combination with REM sleep behavior disorder, representing an apparent erosion of the normally distinct stages of non-REM and REM sleep. A similar yet much more extreme dissociation of states underlies agrypnia excitata and status dissociatus, which represent rare, severe dissociations between non-REM, REM, and wake states resulting clinically in oneiric behaviors and severe derangement of normal polysomnographic wake and sleep stage characteristics. Management of non-REM and overlap parasomnias and state dissociation disorders include ensuring bedroom safety and prescription of clonazepam or hypnosis, in select cases, although in children and adolescents with noninjurious behaviors, non-REM parasomnias are often age-limited developmental disorders, which may ultimately remit by adulthood, and, in these cases, counseling and education alone may suffice. Timely and accurate recognition of the non-REM and
Yanik, G.M. Jr.
Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.
Yanik, G.M. Jr.
Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A 1 receptors, 3 H-L-PIA binding was measured. The Bmax values for 3 H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in 3 H-L-PIA binding resulted from REM sleep deprivation and not from stress
Full Text Available Sleep changes were studied in mice (n = 59 from early adolescence to adulthood (postnatal days P19–111. REM sleep declined steeply in early adolescence, while total sleep remained constant and NREM sleep increased slightly. Four hours of sleep deprivation starting at light onset were performed from ages P26 through adulthood (>P60. Following this acute sleep deprivation all mice slept longer and with more consolidated sleep bouts, while NREM slow wave activity (SWA showed high interindividual variability in the younger groups, and increased consistently only after P42. Three parameters together explained up to 67% of the variance in SWA rebound in frontal cortex, including weight-adjusted age and increase in alpha power during sleep deprivation, both of which positively correlated with the SWA response. The third, and strongest predictor was the SWA decline during the light phase in baseline: mice with high peak SWA at light onset, resulting in a large SWA decline, were more likely to show no SWA rebound after sleep deprivation, a result that was also confirmed in parietal cortex. During baseline, however, SWA showed the same homeostatic changes in adolescents and adults, declining in the course of sleep and increasing across periods of spontaneous wake. Thus, we hypothesize that, in young adolescent mice, a ceiling effect and not the immaturity of the cellular mechanisms underlying sleep homeostasis may prevent the SWA rebound when wake is extended beyond its physiological duration.
Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K
We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy.
Full Text Available The lateral paragigantocellular nucleus (LPGi is located in the ventrolateral medulla and is known as a sympathoexcitatory area involved in the control of blood pressure. In recent experiments, we showed that the LPGi contains a large number of neurons activated during PS hypersomnia following a selective deprivation. Among these neurons, more than two-thirds are GABAergic and more than one fourth send efferent fibers to the wake-active locus coeruleus nucleus. To get more insight into the role of the LPGi in PS regulation, we combined an electrophysiological and anatomical approach in the rat, using extracellular recordings in the head-restrained model and injections of tracers followed by the immunohistochemical detection of Fos in control, PS-deprived and PS-recovery animals. With the head-restrained preparation, we showed that the LPGi contains neurons specifically active during PS (PS-On neurons, neurons inactive during PS (PS-Off neurons and neurons indifferent to the sleep-waking cycle. After injection of CTb in the facial nucleus, the neurons of which are hyperpolarized during PS, the largest population of Fos/CTb neurons visualized in the medulla in the PS-recovery condition was observed in the LPGi. After injection of CTb in the LPGi itself and PS-recovery, the nucleus containing the highest number of Fos/CTb neurons, moreover bilaterally, was the sublaterodorsal nucleus (SLD. The SLD is known as the pontine executive PS area and triggers PS through glutamatergic neurons. We propose that, during PS, the LPGi is strongly excited by the SLD and hyperpolarizes the motoneurons of the facial nucleus in addition to local and locus coeruleus PS-Off neurons, and by this means contributes to PS genesis.
Andrews, Colin G.; Pagliardini, Silvia
Breathing is more vulnerable to apneas and irregular breathing patterns during rapid eye movement (REM) sleep in both humans and rodents. We previously reported that robust and recurrent recruitment of expiratory abdominal (ABD) muscle activity is present in rats during REM epochs despite ongoing REM-induced muscle atonia in skeletal musculature. To develop a further understanding of the characteristics of ABD recruitment during REM epochs and their relationship with breathing patterns and ir...
Kimberly A Cote
Full Text Available Sleep difficulties are commonly reported following traumatic brain injury (TBI, but few studies have systematically examined the neurophysiological characteristics of sleep. Sleep EEG was quantified over multiple nights to examine mechanisms underlying sleep disruption in individuals who had sustained a TBI and to explore the relationship between sleep disruption and waking function. Sleep was recorded from 20 individuals with a TBI (18-64 years and 20 age-matched controls over two uninterrupted nights, as well as during a night where auditory stimuli were delivered. All participants underwent neuropsychological testing and waking performance assessment. Compared to controls, the TBI group had subjective complaints of falling asleep, delayed sleep onset on polysomnography (PSG, less Slow Wave (< 1 Hz and delta (1-4 Hz EEG power in non-REM sleep, fewer spontaneous and evoked k-complexes, reduced periodicity of spontaneous k-complexes, and lower amplitude of evoked k-complexes. While for controls, the density, duration and periodicity of sleep spindles diminished with deepening of non-REM as typically observed, this pattern was disrupted in the TBI group with peak spindle presentation occurring in Stage 3 sleep. Night-to-night-stability of Stage 2 spindles was high for controls but absent for the TBI group. Greater injury severity was related to fewer evoked k-complexes and lower spindle density. Greater spindle production predicted better waking function in the TBI group. Taken together, these data demonstrate impairment in sleep regulatory and inhibitory mechanisms as factors underlying sleep complaints following a TBI. Spindle generation may be adaptive or a marker of resiliency following TBI.
Arnulf, Isabelle; Nielsen, Jørgen; Lohmann, Ebba; Schiefer, Johannes; Schieffer, Johannes; Wild, Edward; Jennum, Poul; Konofal, Eric; Walker, Matthew; Oudiette, Delphine; Tabrizi, Sarah; Durr, Alexandra
Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages and the length of CAG repeats. Because a mild hypocretin deficiency has been found in the brains of some patients with HD (hereinafter referred to as HD patients), we also tested the HD patients for narcolepsy. Twenty-five HD patients (including 2 premanifest carriers) underwent clinical interview, nighttime video and sleep monitoring, and daytime multiple sleep latency tests. Their results were compared with those of patients with narcolepsy and control patients. The HD patients had frequent insomnia, earlier sleep onset, lower sleep efficiency, increased stage 1 sleep, delayed and shortened rapid eye movement (REM) sleep, and increased periodic leg movements. Three HD patients (12%) had REM sleep behavior disorders. No sleep abnormality correlated with CAG repeat length. Reduced REM sleep duration (but not REM sleep behavior disorders) was present in premanifest carriers and patients with very mild HD and worsened with disease severity. In contrast to narcoleptic patients, HD patients had no cataplexy, hypnagogic hallucinations, or sleep paralysis. Four HD patients had abnormally low (< 8 minutes) daytime sleep latencies, but none had multiple sleep-onset REM periods. The sleep phenotype of HD includes insomnia, advanced sleep phase, periodic leg movements, REM sleep behavior disorders, and reduced REM sleep but not narcolepsy. Reduced REM sleep may precede chorea. Mutant huntingtin may exert an effect on REM sleep and motor control during sleep.
Whitmire, Alexandra; Orr, Martin; Arias, Diana; Rueger, Melanie; Johnston, Smith; Leveton, Lauren
While ground research has clearly shown that preserving adequate quantities of sleep is essential for optimal health and performance, changes in the progression, order and /or duration of specific stages of sleep is also associated with deleterious outcomes. As seen in Figure 1, in healthy individuals, REM and Non-REM sleep alternate cyclically, with stages of Non-REM sleep structured chronologically. In the early parts of the night, for instance, Non-REM stages 3 and 4 (Slow Wave Sleep, or SWS) last longer while REM sleep spans shorter; as night progresses, the length of SWS is reduced as REM sleep lengthens. This process allows for SWS to establish precedence , with increases in SWS seen when recovering from sleep deprivation. SWS is indeed regarded as the most restorative portion of sleep. During SWS, physiological activities such as hormone secretion, muscle recovery, and immune responses are underway, while neurological processes required for long term learning and memory consolidation, also occur. The structure and duration of specific sleep stages may vary independent of total sleep duration, and changes in the structure and duration have been shown to be associated with deleterious outcomes. Individuals with narcolepsy enter sleep through REM as opposed to stage 1 of NREM. Disrupting slow wave sleep for several consecutive nights without reducing total sleep duration or sleep efficiency is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. Depression has been shown to be associated with a reduction of slow wave sleep and increased REM sleep. Given research that shows deleterious outcomes are associated with changes in sleep structure, it is essential to characterize and mitigate not only total sleep duration, but also changes in sleep stages.
Full Text Available Abstract Background In humans, rapid eye movements (REM density during REM sleep plays a prominent role in psychiatric diseases. Especially in depression, an increased REM density is a vulnerability marker for depression. In clinical practice and research measurement of REM density is highly standardized. In basic animal research, almost no tools are available to obtain and systematically evaluate eye movement data, although, this would create increased comparability between human and animal sleep studies. Methods We obtained standardized electroencephalographic (EEG, electromyographic (EMG and electrooculographic (EOG signals from freely behaving mice. EOG electrodes were bilaterally and chronically implanted with placement of the electrodes directly between the musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG and EOG signals were obtained for four days. Subsequent to the implantation process, we developed and validated an Eye Movement scoring in Mice Algorithm (EMMA to detect REM as singularities of the EOG signal, based on wavelet methodology. Results The distribution of wakefulness, non-REM (NREM sleep and rapid eye movement (REM sleep was typical of nocturnal rodents with small amounts of wakefulness and large amounts of NREM sleep during the light period and reversed proportions during the dark period. REM sleep was distributed correspondingly. REM density was significantly higher during REM sleep than NREM sleep. REM bursts were detected more often at the end of the dark period than the beginning of the light period. During REM sleep REM density showed an ultradian course, and during NREM sleep REM density peaked at the beginning of the dark period. Concerning individual eye movements, REM duration was longer and amplitude was lower during REM sleep than NREM sleep. The majority of single REM and REM bursts were associated with micro-arousals during NREM sleep, but not during REM sleep. Conclusions Sleep
Sikka, Pilleriin; Revonsuo, Antti; Sandman, Nils; Tuominen, Jarno; Valli, Katja
The aim of this study was to compare the emotional content of dream reports collected at home upon morning awakenings with those collected in the laboratory upon early and late rapid eye movement (REM) sleep awakenings. Eighteen adults (11 women, seven men; mean age = 25.89 ± 4.85) wrote down their home dreams every morning immediately upon awakening during a 7-day period. Participants also spent two non-consecutive nights in the sleep laboratory where they were awoken 5 min into each continuous REM sleep stage, upon which they gave a verbal dream report. The content of a total of 151 home and 120 laboratory dream reports was analysed by two blind judges using the modified Differential Emotions Scale. It was found that: (1) home dream reports were more emotional than laboratory early REM dream reports, but not more emotional than laboratory late REM dream reports; (2) home dream reports contained a higher density of emotions than laboratory (early or late REM) dream reports; and (3) home dream reports were more negative than laboratory dream reports, but differences between home and early REM reports were larger than those between home and late REM reports. The results suggest that differences between home and laboratory dream reports in overall emotionality may be due to the time of night effect. Whether differences in the density of emotions and negative emotionality are due to sleep environment or due to different reporting procedures and time spent in a sleep stage, respectively, remains to be determined in future studies. © The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.
Askenasy, J J M
The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment
Fanfulla, Francesco; Ceriana, Piero; D'Artavilla Lupo, Nadia; Trentin, Rossella; Frigerio, Francesco; Nava, Stefano
Severe sleep disruption is a well-documented problem in mechanically ventilated, critically ill patients during their time in the intensive care unit (ICU), but little attention has been paid to the period when these patients become clinically stable and are transferred to a step-down unit (SDU). We monitored the 24-h sleep pattern in 2 groups of patients, one on mechanical ventilation and the other breathing spontaneously, admitted to our SDU to assess the presence of sleep abnormalities and their association with mechanical ventilation. Twenty-two patients admitted to an SDU underwent 24-h polysomnography with monitoring of noise and light. One patient did not complete the study. At night, 10 patients showed reduced sleep efficiency, 6 had reduced percentage of REM sleep, and 3 had reduced percentage of slow wave sleep (SWS). Sleep amount and quality did not differ between patients breathing spontaneously and those on mechanical ventilation. Clinical severity (SAPS(II) score) was significantly correlated with daytime total sleep time and efficiency (r = 0.51 and 0.5, P sleep quantity and quality; and higher PaO(2) was correlated with increased SWS (r = 0.49; P = 0.02). Patients admitted to an SDU after discharge from an ICU still have a wide range of sleep abnormalities. These abnormalities are mainly associated with a high severity score and alkalosis. Mechanical ventilation does not appear to be a primary cause of sleep impairment.
Full Text Available Axel Steiger, Marcel Pawlowski, Mayumi Kimura Max Planck Institute of Psychiatry, Munich, Germany Abstract: The sleep electroencephalogram (EEG provides biomarkers of depression, which may help with diagnosis, prediction of therapy response, and prognosis in the treatment of depression. In patients with depression, characteristic sleep EEG changes include impaired sleep continuity, disinhibition of rapid-eye-movement (REM sleep, and impaired non-REM sleep. Most antidepressants suppress REM sleep in depressed patients, healthy volunteers, and in animal models. REM suppression appears to be an important, but not an absolute requirement, for antidepressive effects of a substance. Enhanced REM density, a measure for frequency of REM, characterizes high-risk probands for affective disorders. REM-sleep changes were also found in animal models of depression. Sleep-EEG variables were shown to predict the response to treatment with antidepressants. Furthermore, certain clusters of sleep EEG variables predicted the course of the disorder for several years. Some of the predicted sleep EEG markers appear to be related to hypothalamic–pituitary–adrenal system activity. Keywords: biomarkers, depression, sleep EEG, antidepressants, prediction, animal models
Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul
Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.
Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul
Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain......'s sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype....
Kruger, Jean-Leigh; Gravett, Nadine; Bhagwandin, Adhil; Bennett, Nigel C; Archer, Elizabeth K; Manger, Paul R
The Cape mole rat Georychus capensis is a solitary subterranean rodent found in the western and southern Cape of South Africa. This approximately 200-gram bathyergid rodent shows a nocturnal circadian rhythm, but sleep in this species is yet to be investigated. Using telemetric recordings of the electroencephalogram (EEG) and electromyogram (EMG) in conjunction with video recordings, we were able to show that the Cape mole rat, like all other rodents, has sleep periods composed of both rapid eye movement (REM) and slow-wave (non-REM) sleep. These mole rats spent on average 15.4 h awake, 7.1 h in non-REM sleep and 1.5 h in REM sleep each day. Cape mole rats sleep substantially less than other similarly sized terrestrial rodents but have a similar percentage of total sleep time occupied by REM sleep. In addition, the duration of both non-REM and REM sleep episodes was markedly shorter in the Cape mole rat than has been observed in terrestrial rodents. Interestingly, these features (total sleep time and episode duration) are similar to those observed in another subterranean bathyergid mole rat, i.e. Fukomys mechowii. Thus, there appears to be a bathyergid type of sleep amongst the rodents that may be related to their environment and the effect of this on their circadian rhythm. Investigating further species of bathyergid mole rats may fully define the emerging picture of sleep in these subterranean African rodents. © 2016 S. Karger AG, Basel.
Peter-Derex, Laure; Magnin, Michel; Bastuji, Hélène
Wakefulness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep are characterized by specific brain activities. However, recent experimental findings as well as various clinical conditions (parasomnia, sleep inertia) have revealed the presence of transitional states. Brief intrusions of wakefulness into sleep, namely, arousals, appear as relevant phenomena to characterize how brain commutes from sleep to wakefulness. Using intra-cerebral recordings in 8 drug-resistant epileptic patients, we analyzed electroencephalographic (EEG) activity during spontaneous or nociceptive-induced arousals in NREM and REM sleep. Wavelet spectral analyses were performed to compare EEG signals during arousals, sleep, and wakefulness, simultaneously in the thalamus, and primary, associative, or high-order cortical areas. We observed that 1) thalamic activity during arousals is stereotyped and its spectral composition corresponds to a state in-between wakefulness and sleep; 2) patterns of cortical activity during arousals are heterogeneous, their manifold spectral composition being related to several factors such as sleep stages, cortical areas, arousal modality ("spontaneous" vs nociceptive-induced), and homeostasis; 3) spectral compositions of EEG signals during arousal and wakefulness differ from each other. Thus, stereotyped arousals at the thalamic level seem to be associated with different patterns of cortical arousals due to various regulation factors. These results suggest that the human cortex does not shift from sleep to wake in an abrupt binary way. Arousals may be considered more as different states of the brain than as "short awakenings." This phenomenon may reflect the mechanisms involved in the negotiation between two main contradictory functional necessities, preserving the continuity of sleep, and maintaining the possibility to react. Copyright © 2015 Elsevier Inc. All rights reserved.
Tassi, Patricia; Muzet, Alain
Sleep inertia is a transitional state of lowered arousal occurring immediately after awakening from sleep and producing a temporary decrement in subsequent performance. Many factors are involved in the characteristics of sleep inertia. The duration of prior sleep can influence the severity of subsequent sleep inertia. Although most studies have focused on sleep inertia after short naps, its effects can be shown after a normal 8-h sleep period. One of the most critical factors is the sleep stage prior to awakening. Abrupt awakening during a slow wave sleep (SWS) episode produces more sleep inertia than awakening in stage 1 or 2, REM sleep being intermediate. Therefore, prior sleep deprivation usually enhances sleep inertia since it increases SWS. There is no direct evidence that sleep inertia exhibits a circadian rhythm. However, it seems that sleep inertia is more intense when awakening occurs near the trough of the core body temperature as compared to its circadian peak. A more controversial issue concerns the time course of sleep inertia. Depending on the studies, it can last from 1 min to 4 h. However, in the absence of major sleep deprivation, the duration of sleep inertia rarely exceeds 30 min. But all these results should be analysed as a function of type of task and dependent variables. Different cognitive functions are probably not sensitive to the same degree to sleep inertia and special attention should be provided to dependent variables as a result of the cognitive processes under review. Finally, sleep disorders represent risk factors which deserve new insight in treatment strategies to counteract the adverse effects of sleep inertia.
According to the sequential hypothesis (SH) memories acquired during wakefulness are processed during sleep in two serial steps respectively occurring during slow wave sleep (SWS) and rapid eye movement (REM) sleep. During SWS memories to be retained are distinguished from irrelevant or competing traces that undergo downgrading or elimination. Processed memories are stored again during REM sleep which integrates them with preexisting memories. The hypothesis received support from a wealth of ...
Dresler, Martin; Konrad, Boris N
We studied the world's most distinguished experts in the use of mnemonic techniques: the top participants of the World Memory Championships. They neither feel the use of mnemonics to be dreamlike, nor does their REM sleep differ from mnemonic-naive control subjects. Besides these empirical data, also theoretical considerations contradict an isomorphism between features of REM sleep dreaming and mnemonic principles.
Zoetmulder, Marielle; Jennum, Poul
Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...
Fanfulla, Francesco; Ceriana, Piero; D'Artavilla Lupo, Nadia; Trentin, Rossella; Frigerio, Francesco; Nava, Stefano
Background: Severe sleep disruption is a well-documented problem in mechanically ventilated, critically ill patients during their time in the intensive care unit (ICU), but little attention has been paid to the period when these patients become clinically stable and are transferred to a step-down unit (SDU). We monitored the 24-h sleep pattern in 2 groups of patients, one on mechanical ventilation and the other breathing spontaneously, admitted to our SDU to assess the presence of sleep abnormalities and their association with mechanical ventilation. Methods: Twenty-two patients admitted to an SDU underwent 24-h polysomnography with monitoring of noise and light. Results: One patient did not complete the study. At night, 10 patients showed reduced sleep efficiency, 6 had reduced percentage of REM sleep, and 3 had reduced percentage of slow wave sleep (SWS). Sleep amount and quality did not differ between patients breathing spontaneously and those on mechanical ventilation. Clinical severity (SAPSII score) was significantly correlated with daytime total sleep time and efficiency (r = 0.51 and 0.5, P Nava S. Sleep disturbances in patients admitted to a step-down unit after ICU discharge: the role of mechanical ventilation. SLEEP 2011;34(3):355-362. PMID:21358853
Mallick, Birendra Nath; Singh, Abhishek; Khanday, Mudasir Ahmad
Interactions among REM-ON and REM-OFF neurons form the basic scaffold for rapid eye movement sleep (REMS) regulation; however, precise mechanism of their activation and cessation, respectively, was unclear. Locus coeruleus (LC) noradrenalin (NA)-ergic neurons are REM-OFF type and receive GABA-ergic inputs among others. GABA acts postsynaptically on the NA-ergic REM-OFF neurons in the LC and presynaptically on the latter's projection terminals and modulates NA-release on the REM-ON neurons. Normally during wakefulness and non-REMS continuous release of NA from the REM-OFF neurons, which however, is reduced during the latter phase, inhibits the REM-ON neurons and prevents REMS. At this stage GABA from substantia nigra pars reticulate acting presynaptically on NA-ergic terminals on REM-ON neurons withdraws NA-release causing the REM-ON neurons to escape inhibition and being active, may be even momentarily. A working-model showing neurochemical-map explaining activation of inactivation process, showing contribution of GABA-ergic presynaptic inhibition in withdrawing NA-release and dis-inhibition induced activation of REM-ON neurons, which in turn activates other GABA-ergic neurons and shutting-off REM-OFF neurons for the initiation of REMS-generation has been explained. Our model satisfactorily explains yet unexplained puzzles (i) why normally REMS does not appear during waking, rather, appears following non-REMS; (ii) why cessation of LC-NA-ergic-REM-OFF neurons is essential for REMS-generation; (iii) factor(s) which does not allow cessation of REM-OFF neurons causes REMS-loss; (iv) the association of changes in levels of GABA and NA in the brain during REMS and its deprivation and associated symptoms; v) why often dreams are associated with REMS. Copyright © 2012 Elsevier Ltd. All rights reserved.
Dijk, Derk-Jan; Brunner, Daniel P.; Beersma, Domien G.M.; Borbély, Alexander A.
Human sleep electroencephalograms, recorded in four experiments, were subjected to spectral analysis. Waking prior to sleep varied from 12 to 36 h and sleep was initiated at different circadian phases. Power density of delta and theta frequencies in rapid-eye-movement (REM) sleep and non-REM (NREM)
Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu
Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.
Carr, Michelle; Nielsen, Tore
The goal of the study was to assess semantic priming to emotion and nonemotion cue words using a novel measure of associational breadth for participants who either took rapid eye movement (REM) or nonrapid eye movement (NREM) naps or who remained awake; assess relation of priming to REM sleep consolidation and REM sleep inertia effects. The associational breadth task was applied in both a priming condition, where cue-words were signaled to be memorized prior to sleep (primed), and a nonpriming condition, where cue words were not memorized (nonprimed). Cue words were either emotional (positive, negative) or nonemotional. Participants were randomly assigned to either an awake (WAKE) or a sleep condition, which was subsequently split into NREM or REM groups depending on stage at awakening. Hospital-based sleep laboratory. Fifty-eight healthy participants (22 male) ages 18 to 35 y (Mage = 23.3 ± 4.08 y). The REM group scored higher than the NREM or WAKE groups on primed, but not nonprimed emotional cue words; the effect was stronger for positive than for negative cue words. However, REM time and percent correlated negatively with degree of emotional priming. Priming occurred for REM awakenings but not for NREM awakenings, even when the latter sleep episodes contained some REM sleep. Associational breadth may be selectively consolidated during REM sleep for stimuli that have been tagged as important for future memory retrieval. That priming decreased with REM time and was higher only for REM sleep awakenings is consistent with two explanatory REM sleep processes: REM sleep consolidation serving emotional downregulation and REM sleep inertia. © 2015 Associated Professional Sleep Societies, LLC.
Full Text Available In this study we have constructed a mathematical model of a recently proposed functional model known to be responsible for inducing waking, NREMS and REMS. Simulation studies using this model reproduced sleep-wake patterns as reported in normal animals. The model helps to explain neural mechanism(s that underlie the transitions between wake, NREMS and REMS as well as how both the homeostatic sleep-drive and the circadian rhythm shape the duration of each of these episodes. In particular, this mathematical model demonstrates and confirms that an underlying mechanism for REMS generation is pre-synaptic inhibition from substantia nigra onto the REM-off terminals that project on REM-on neurons, as has been recently proposed. The importance of orexinergic neurons in stabilizing the wake-sleep cycle is demonstrated by showing how even small changes in inputs to or from those neurons can have a large impact on the ensuing dynamics. The results from this model allow us to make predictions of the neural mechanisms of regulation and patho-physiology of REMS.
Although sleep appears to simply be a body and mind at rest, it is actually a dynamic and complex physiologic state that is necessary for survival. Normal sleep is characterized by behavioral and physiologic changes as well as 2 distinct sleep states, rapid eye movement (REM) and non-REM (NREM). Throughout the course of a night, people cycle between NREM and REM sleep via an ultradian rhythm, with most of sleep spent in NREM. Determinants involved in the regulation of sleep are the homeostatic and circadian processes. Despite being highly regulated, sleep is fragile, and its stages and duration may be affected by multiple factors, such as age, drugs, temperature, and medical and psychiatric disease. Variations in nighttime sleep impact subsequent sleep periods as well as daytime function.
Andrillon, Thomas; Pressnitzer, Daniel; Léger, Damien; Kouider, Sid
Sleep and memory are deeply related, but the nature of the neuroplastic processes induced by sleep remains unclear. Here, we report that memory traces can be both formed or suppressed during sleep, depending on sleep phase. We played samples of acoustic noise to sleeping human listeners. Repeated exposure to a novel noise during Rapid Eye Movements (REM) or light non-REM (NREM) sleep leads to improvements in behavioral performance upon awakening. Strikingly, the same exposure during deep NREM sleep leads to impaired performance upon awakening. Electroencephalographic markers of learning extracted during sleep confirm a dissociation between sleep facilitating memory formation (light NREM and REM sleep) and sleep suppressing learning (deep NREM sleep). We can trace these neural changes back to transient sleep events, such as spindles for memory facilitation and slow waves for suppression. Thus, highly selective memory processes are active during human sleep, with intertwined episodes of facilitative and suppressive plasticity.Though memory and sleep are related, it is still unclear whether new memories can be formed during sleep. Here, authors show that people could learn new sounds during REM or light non-REM sleep, but that learning was suppressed when sounds were played during deep NREM sleep.
Hofman, W.F.; Talamini, L.M.; Watson, R.R.
Normal sleep consists of two states: NREM (light and deep sleep) and REM, alternating in a cyclical pattern. The sleep/wake rhythm is regulated by two processes: the sleep propensity, building up during wake, and the circadian rhythm, imposed by the suprachiasmatic nucleus. The arousal pathways in
Learning and memory can be impaired by sleep loss during specific vulnerable "windows" for several days after new tasks have been learned. Different types of tasks are differentially vulnerable to the loss of different stages of sleep. Memory required to perform cognitive procedural tasks is affected by the loss of rapid-eye-movement (REM) sleep on the first night after learning occurs and again on the third night after learning. REM-sleep deprivation on the second night after learning does not produce memory deficits. Declarative memory, which is used for the recall of specific facts, is not similarly affected by REM-sleep loss. The learning of procedural motor tasks, including those required in many sports, is impaired by the loss of stage 2 sleep, which occurs primarily in the early hours of the morning. These findings have implications for the academic and athletic performance of students and for anyone whose work involves ongoing learning and demands high standards of performance.
Garcia-Molina, G.; Baehr, K.; Steele, B.; Tsoneva, T.K.; Pfundtner, S.; Mahadevan, A.; Papas, N.; Riedner, B.; Tononi, G.; White, D.
Introduction: In the two-process model of sleep regulation, slow-wave activity (SWA, EEG power in the 0.5–4 Hz band) is a direct indicator of sleep need. SWA builds up during NREM sleep, declines before the onset of REM sleep, remains low during REM and the level of increase in successive NREM
Paradoxical (REM) sleep deprivation in mice using the small-platforms-over-water method: polysomnographic analyses and melanin-concentrating hormone and hypocretin/orexin neuronal activation before, during and after deprivation.
Arthaud, Sebastien; Varin, Christophe; Gay, Nadine; Libourel, Paul-Antoine; Chauveau, Frederic; Fort, Patrice; Luppi, Pierre-Herve; Peyron, Christelle
Studying paradoxical sleep homeostasis requires the specific and efficient deprivation of paradoxical sleep and the evaluation of the subsequent recovery period. With this aim, the small-platforms-over-water technique has been used extensively in rats, but only rare studies were conducted in mice, with no sleep data reported during deprivation. Mice are used increasingly with the emergence of transgenic mice and technologies such as optogenetics, raising the need for a reliable method to manipulate paradoxical sleep. To fulfil this need, we refined this deprivation method and analysed vigilance states thoroughly during the entire protocol. We also studied activation of hypocretin/orexin and melanin-concentrating hormone neurones using Fos immunohistochemistry to verify whether mechanisms regulating paradoxical sleep in mice are similar to those in rats. We showed that 48 h of deprivation was highly efficient, with a residual amount of paradoxical sleep of only 2.2%. Slow wave sleep and wake quantities were similar to baseline, except during the first 4 h of deprivation, where slow wave sleep was strongly reduced. After deprivation, we observed a 124% increase in paradoxical sleep quantities during the first hour of rebound. In addition, 34% of hypocretin/orexin neurones were activated during deprivation, whereas melanin-concentrated hormone neurones were activated only during paradoxical sleep rebound. Corticosterone level showed a twofold increase after deprivation and returned to baseline level after 4 h of recovery. In summary, a fairly selective deprivation and a significant rebound of paradoxical sleep can be obtained in mice using the small-platforms-over-water method. As in rats, rebound is accompanied by a selective activation of melanin-concentrating hormone neurones. © 2014 European Sleep Research Society.
Lee Kavanau, J
A major controversy over REM sleep's role in memory processing may owe to inadequate allowances for the highly conservative nature of evolutionary adaptations. The controversy hinges on whether NREM sleep, alone, retains primitive memory processing capabilities. The selective pressure for primitive sleep, is thought to have been the need to obviate conflicts between enormous neural processing requirements of complex visual analysis and split-second control of movements, on the one hand, and memory processing, on the other. The most efficient memory processing during mammalian and avian sleep appears to be a two-step process: synapses in individual component circuits of events are reinforced primarily by slow brain waves during NREM sleep, with the reinforced components temporally bound by fast waves, and manifested as dreams, during REM sleep. This dual action could account for partitioning of sleep periods into multiple NREM-REM cycles. It is proposed that in the absence of REM sleep, all needed memory processing can be accomplished by NREM sleep, alone, though less efficiently. Many symptoms of fatal familial insomnia are attributed to subnormal nightly reinforcement of brain circuitry because of almost total loss of sleep, and compensatory responses thereto during waking. During this disorder, sensory circuitry seemingly is spared by virtue of its supernormal reinforcement during almost continuous waking. Contrariwise, sparing of an adult's 'higher faculties' in encephalitis lethargica appears to owe to supernormal circuit reinforcement during almost continuous sleep.
Barloese, M C J; Jennum, P J; Lund, N T
BACKGROUND AND PURPOSE: Cluster headache (CH) is a primary headache disorder characterized by severe attacks of unilateral pain following a chronobiological pattern. There is a close connection with sleep as most attacks occur during sleep. Hypothalamic involvement and a particular association...... with rapid eye movement (REM) sleep have been suggested. Sleep in a large, well-characterized population of CH patients was investigated. METHODS: Polysomnography (PSG) was performed on two nights in 40 CH patients during active bout and one night in 25 age, sex and body mass index matched controls...... in hospital. Macrostructure and other features of sleep were analyzed and related to phenotype. Clinical headache characterization was obtained by semi-structured interview. RESULTS: Ninety-nine nights of PSG were analyzed. Findings included a reduced percentage of REM sleep (17.3% vs. 23.0%, P = 0...
Krueger, J.M.; Opp, M.R.
Sleep is profoundly altered during the course of infectious diseases. The typical response to infection includes an initial increase in nonrapid eye movement sleep (NREMS) followed by an inhibition in NREMS. REMS is inhibited during infections. Bacterial cell wall components, such as peptidoglycan and lipopolysaccharide, macrophage digests of these components, such as muramyl peptides, and viral products, such as viral double-stranded RNA, trigger sleep responses. They do so via pathogen-asso...
... NICHD Research Information Find a Study More Information Preterm Labor and Birth Condition Information NICHD Research Information ... NIH-funded researchers identify risk factors for sleep apnea during pregnancy NICHD scientists identify molecule that may ...
The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 3 H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by α-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S 2 episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. 3 H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system
Kishi, Akifumi; Struzik, Zbigniew R.; Natelson, Benjamin H.; Togo, Fumiharu; Yamamoto, Yoshiharu
Sleep dynamics emerges from complex interactions between neuronal populations in many brain regions. Annotated sleep stages from electroencephalography (EEG) recordings could potentially provide a non-invasive way to obtain valuable insights into the mechanisms of these interactions, and ultimately into the very nature of sleep regulation. However, to date, sleep stage analysis has been restricted, only very recently expanding the scope of the traditional descriptive statistics to more dynamical concepts of the duration of and transitions between vigilance states and temporal evaluation of transition probabilities among different stages. Physiological and/or pathological implications of the dynamics of sleep stage transitions have, to date, not been investigated. Here, we study detailed duration and transition statistics among sleep stages in healthy humans and patients with chronic fatigue syndrome, known to be associated with disturbed sleep. We find that the durations of waking and non-REM sleep, in particular deep sleep (Stages III and IV), during the nighttime, follow a power-law probability distribution function, while REM sleep durations follow an exponential function, suggestive of complex underlying mechanisms governing the onset of light sleep. We also find a substantial number of REM to non-REM transitions in humans, while this transition is reported to be virtually non-existent in rats. Interestingly, the probability of this REM to non-REM transition is significantly lower in the patients than in controls, resulting in a significantly greater REM to awake, together with Stage I to awake, transition probability. This might potentially account for the reported poor sleep quality in the patients because the normal continuation of sleep after either the lightest or REM sleep is disrupted. We conclude that the dynamical transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with a
Dijk, D.J.; Strijkstra, A.; Daan, S.; Beersma, D.G.M.; Hoofdakker, R.H. van den
Sleep was recorded in the diurnal rodent Eutamias sibiricus, chronically implanted with EEG and EMG electrodes. The tricyclic antidepressant drug clomipramine suppressed the duration of REM sleep and EEG power density in the frequencies between 1.5 and 13.5 Hz in nonREM sleep. During the
Costa e Silva, Jorge Alberto
Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal
Schoch, Sarah F; Werth, Esther; Poryazova, Rositsa; Scammell, Thomas E; Baumann, Christian R; Imbach, Lukas L
Patients with narcolepsy experience poor maintenance of wakefulness and fragmented night sleep, but the underlying mechanism of sleep boundary dysregulation remains little understood. The goal of this study was to quantify abnormal sleep-wake regulation in narcolepsy patients. Using a model-based approach (state space analysis), we analyzed overnight electroencephalography recordings in 10 patients with narcolepsy type 1 and age- and gender-matched healthy control subjects. We analyzed consolidated sleep states using cluster analysis in state space and transitional sleep periods as trajectories between stable clusters. Patients with narcolepsy showed a dislocation of rapid eye movement (REM) sleep in state space and overlap of REM and WAKE behavioral states. Narcolepsy patients had more trajectories between the REM and the WAKE clusters and also between the non-rapid eye movement (NREM) and WAKE clusters. Point density analysis showed more transitional periods between WAKE and REM in narcolepsy, less consolidated NREM sleep, and higher velocities between WAKE and NREM in patients. Conventional sleep analysis revealed increased NREM1 and decreased NREM2 sleep and reduced REM latency in narcolepsy patients. This study provides further evidence for narcolepsy as a disorder of state boundaries including but not limited to REM sleep and wakefulness. In particular, the increase in transitional periods between REM and WAKE but also between NREM and WAKE indicates abnormal state dynamics in narcolepsy. This pattern may be a consequence of disrupted sleep/wake stabilizing mechanisms due to loss of hypocretin/orexin neurons in the hypothalamus. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail email@example.com.
Kempfner, Jacob; Sorensen, Helge B D; Nikolic, Miki
SUMMARY: Idiopathic rapid-eye-movement (REM) sleep behavior disorder (iRBD) is most likely the earliest sign of Parkinson's Disease (PD) and is characterized by REM sleep without atonia (RSWA) and consequently increased muscle activity. However, some muscle twitching in normal subjects occurs...
Full Text Available Aim: to evaluate potential efficacy of a new therapeutic approach in posttraumatic stress disorder in comparison with eye movement desensitization and reprocessing (EMDR, a standard treatment approach and controls. Methods: the study was designed using a randomized controlled trial methodology. Participants were recruited from military servicemen aged between 25 to 50 years who were admitting hospitals of Bushehr, Iran, with the final diagnosis of PTSD. Finally 33 male patients were devided into three subgroups: G1: EMDR; G2: REM Desensitization; and group 3: controls who received no therapy. Mississippi Scale for Posttraumatic Stress Disorder, Pittsburgh Sleep Quality Index (PSQI and a 37 item death anxiety questionnaire were used for measures. Results: multiple comparisons showed that intrusive thoughts were significantly more likely to improve with REM Desensitization versus EMDR (P=0.03, while depression was more responsive to EMDR (p=0.03. Among the Pittsburgh scale for the quality of sleep items, sleep quality (p=0.02, sleep duration (p=0.001, and total sleep quality score (p=0.002 were significantly more likely to improve in the REM Desensitization group. Change in the absolute death anxiety scores was not different between subgroups excepting EMDR versus control group (p=0.05. Conclusion: REM, desensitization, the new therapeutic approach to PTSD is a highly effective strategy, even more than EMDR, the standard treatment, in most of the evaluated subjects, with special emphasis on sleep symptoms, and also in the management of intrusive thoughts. Depression is the only factor in which, REM Desensitization was significantly less likely to represent a superior therapeutic effect than EMDR. Key words: post traumatic stress disorder (PTSD, eye movement desensitization and reprocessing, new treatment.
Schwartz, Michael D.; Kilduff, Thomas S.
SYNOPSIS Since the discovery of Rapid Eye Movement (REM) sleep in the late 1950s, identification of the neural circuitry underlying wakefulness, sleep onset and the alternation between REM and non-REM (NREM) sleep has been an active area of investigation. Synchronization and desynchronization of cortical activity as detected in the electroencephalogram (EEG) is due to a corticothalamocortical loop, intrinsic cortical oscillators, monoaminergic and cholinergic afferent input to the thalamus, and the basal forebrain cholinergic input directly to the cortex. The monoaminergic and cholinergic systems are largely wake-promoting; the brainstem cholinergic nuclei are also involved in REM sleep regulation. These wake-promoting systems receive excitatory input from the hypothalamic hypocretin/orexin system. Sleep-promoting nuclei are GABAergic in nature and found in the preoptic area, brainstem and lateral hypothalamus. Although the pons is critical for the expression of REM sleep, recent research has suggested that melanin-concentrating hormone/GABAergic cells in the lateral hypothalamus "gate" REM sleep. The temporal distribution of sleep and wakefulness is due to interaction between the circadian system and the sleep homeostatic system. Although the hypothalamic suprachiasmatic nuclei contain the circadian pacemaker, the neural circuitry underlying the sleep homeostat is less clear. Prolonged wakefulness results in the accumulation of extracellular adenosine, possibly from glial sources, which is an important feedback molecule for the sleep homeostatic system. Cortical neuronal nitric oxide (nNOS) neurons may also play a role in propagating slow waves through the cortex in NREM sleep. Several neuropeptides and other neurochemicals likely play important roles in sleep/wake control. Although the control of sleep and wakefulness seemingly involves multiple redundant systems, each of these systems provides a vulnerability that can result in sleep/wake dysfunction that may
Yang, C; Brown, R E
Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods
McGuire, Sarah M.
occurrence of rapid eye movements, sleep spindles, and slow wave sleep. Using these features an approach for classifying sleep stages every one second during the night was developed. From observation of the results of the