Showing papers on "Rapid eye movement sleep published in 2019"

Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.

Abstract: Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.

Neural signatures of sleep in zebrafish

Abstract: Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show—using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate—that there are at least two major sleep signatures in zebrafish These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago Fluorescence-based polysomnography in zebrafish reveals two major sleep signatures that share features with those of amniotes, which suggests that common neural sleep signatures emerged in the vertebrate brain over 450 million years ago

Regional Delta Waves In Human Rapid Eye Movement Sleep.

Abstract: Although the EEG slow wave of sleep is typically considered to be a hallmark of nonrapid eye movement (NREM) sleep, recent work in mice has shown that slow waves can also occur in REM sleep. Here, we investigated the presence and cortical distribution of negative delta (1-4 Hz) waves in human REM sleep by analyzing high-density EEG sleep recordings obtained in 28 healthy subjects. We identified two clusters of delta waves with distinctive properties: (1) a frontal-central cluster characterized by ∼2.5-3.0 Hz, relatively large, notched delta waves (so-called "sawtooth waves") that tended to occur in bursts, were associated with increased gamma activity and rapid eye movements (EMs), and upon source modeling displayed an occipital-temporal and a frontal-central component and (2) a medial-occipital cluster characterized by more isolated, slower (<2 Hz), and smaller waves that were not associated with rapid EMs, displayed a negative correlation with gamma activity, and were also found in NREM sleep. Therefore, delta waves are an integral part of REM sleep in humans and the two identified subtypes (sawtooth and medial-occipital slow waves) may reflect distinct generation mechanisms and functional roles. Sawtooth waves, which are exclusive to REM sleep, share many characteristics with ponto-geniculo-occipital waves described in animals and may represent the human equivalent or a closely related event, whereas medial-occipital slow waves appear similar to NREM sleep slow waves.SIGNIFICANCE STATEMENT The EEG slow wave is typically considered a hallmark of nonrapid eye movement (NREM) sleep, but recent work in mice has shown that it can also occur in REM sleep. By analyzing high-density EEG recordings collected in healthy adult individuals, we show that REM sleep is characterized by prominent delta waves also in humans. In particular, we identified two distinctive clusters of delta waves with different properties: a frontal-central cluster characterized by faster, activating "sawtooth waves" that share many characteristics with ponto-geniculo-occipital waves described in animals and a medial-occipital cluster containing slow waves that are more similar to NREM sleep slow waves. These findings indicate that REM sleep is a spatially and temporally heterogeneous state and may contribute to explaining its known functional and phenomenological properties.

Sleep Disturbance as Potential Risk and Progression Factor for Parkinson's Disease.

Abstract: Sleep disturbances are common and a major source of disability in Parkinson's disease (PD). Primary and secondary insomnia, rapid eye movement sleep behavior disorder (RDB), central sleep apnea, restless legs, and nocturnal akinesia are common sleep disturbances in PD. Prodromal presence of RBD is associated with a more severe motor and non-motor PD subtype implying a significant disease-modifying effect of this parasomnia. Other disease-modifying mechanisms of sleep disturbances in PD include impaired glymphatic clearance, endoplasmic reticulum stress, nocturnal brain deoxygenation and inflammatory processes among others. Impairments of neural circuit switching and imbalance between inhibitory and excitatory neuronal populations are likely responsible for episodic sleep disturbances, in particular RBD. As neural circuits may predict patterns of α-synuclein propagation in the nervous system, impairments of such circuits are of high relevance for PD pathophysiology. Future research is needed to determine whether appropriate treatment for disturbed sleep might slow progression of PD.

Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior.

Abstract: Most brain neurons are active in waking, but hypothalamic neurons that synthesize the neuropeptide melanin-concentrating hormone (MCH) are claimed to be active only during sleep, particularly rapid eye movement (REM) sleep. Here we use deep-brain imaging to identify changes in fluorescence of the genetically encoded calcium (Ca2+) indicator GCaMP6 in individual hypothalamic neurons that contain MCH. An in vitro electrophysiology study determined a strong relationship between depolarization and Ca2+ fluorescence in MCH neurons. In 10 freely behaving MCH-cre mice (male and female), the highest fluorescence occurred in all recorded neurons (n = 106) in REM sleep relative to quiet waking or non-REM sleep. Unexpectedly, 70% of the MCH neurons had strong fluorescence activity when the mice explored novel objects. Spatial and temporal mapping of the change in fluorescence between pairs of MCH neurons revealed dynamic activation of MCH neurons during REM sleep and activation of a subset of the same neurons during exploratory behavior. Functional network activity maps will facilitate comparisons of not only single-neuron activity, but also network responses in different conditions and disease. SIGNIFICANCE STATEMENT Functional activity maps identify brain circuits responding to specific behaviors, including rapid eye movement sleep (REM sleep), a sleep phase when the brain is as active as in waking. To provide the first activity map of individual neurons during REM sleep, we use deep-brain calcium imaging in unrestrained mice to map the activity of hypothalamic melanin-concentrating hormone (MCH) neurons. MCH neurons were found to be synchronously active during REM sleep, and also during the exploration of novel objects. Spatial mapping revealed dynamic network activation during REM sleep and activation of a subset of the neurons during exploratory behavior. Functional activity maps at the cellular level in specific behaviors, including sleep, are needed to establish a brain connectome.

EEG Frontal Alpha Asymmetry and Dream Affect: Alpha Oscillations over the Right Frontal Cortex during REM Sleep and Presleep Wakefulness Predict Anger in REM Sleep Dreams

Abstract: Affective experiences are central not only to our waking life but also to rapid eye movement (REM) sleep dreams. Despite our increasing understanding of the neural correlates of dreaming, we know little about the neural correlates of dream affect. Frontal alpha asymmetry (FAA) is considered a marker of affective states and traits as well as affect regulation in the waking state. Here, we explored whether FAA during REM sleep and during evening resting wakefulness is related to affective experiences in REM sleep dreams. EEG recordings were obtained from 17 human participants (7 men) who spent 2 nights in the sleep laboratory. Participants were awakened 5 min after the onset of every REM stage after which they provided a dream report and rated their dream affect. Two-minute preawakening EEG segments were analyzed. Additionally, 8 min of evening presleep and morning postsleep EEG were recorded during resting wakefulness. Mean spectral power in the alpha band (8-13 Hz) and corresponding FAA were calculated over the frontal (F4-F3) sites. Results showed that FAA during REM sleep, and during evening resting wakefulness, predicted ratings of dream anger. This suggests that individuals with greater alpha power in the right frontal hemisphere may be less able to regulate (i.e., inhibit) strong affective states, such as anger, in dreams. Additionally, FAA was positively correlated across wakefulness and REM sleep. Together, these findings imply that FAA may serve as a neural correlate of affect regulation not only in the waking but also in the dreaming state.SIGNIFICANCE STATEMENT We experience emotions not only during wakefulness but also during dreaming. Despite our increasing understanding of the neural correlates of dreaming, we know little about the neural correlates of dream emotions. Here we used electroencephalography to explore how frontal alpha asymmetry (FAA)-the relative difference in alpha power between the right and left frontal cortical areas that is associated with emotional processing and emotion regulation in wakefulness-is related to dream emotions. We show that individuals with greater FAA (i.e., greater right-sided alpha power) during rapid eye movement sleep, and during evening wakefulness, experience more anger in dreams. FAA may thus reflect the ability to regulate emotions not only in the waking but also in the dreaming state.

Sleep disturbances are common in patients with autoimmune encephalitis.

Abstract: Autoimmune encephalitis (AE) is increasingly recognized as an important cause of subacute cognitive decline, seizures, and encephalopathy, with an ever-broadening clinical phenotype. Sleep disturbances are reported in AE patients, including rapid eye movement sleep behavior disorder, hypersomnia, fragmented sleep, and sleep-disordered breathing; however, the prevalence of sleep disturbances and contributions to outcomes in AE patients remain unknown. There is a need to determine the prevalence of sleep disturbances in AE patients, and to clarify the relationship between specific autoantibodies and disruptions in sleep. Clinical history, results of serum and cerebrospinal fluid testing, electroencephalography, and neuroimaging were reviewed from 26 AE patients diagnosed and managed at our tertiary care hospital. Polysomnography was performed in patients with clinical indications, yielding data from 12 patients. The median age of AE patients was 53 years (range 18–83). Autoantibodies against intracellular antigens (including Ma and Hu autoantibodies) were identified in 6/26 (23%) patients, while autoantibodies against cell-surface neuronal antigens (including NMDAR and LGI1) were identified in 20/26 (77%) patients. New sleep complaints were reported by 19/26 (73%) AE patients, including gasping or snoring (9/19, 47%), dream enactment behavior (6/19, 32%), insomnia (5/19, 29%), hypersomnia (4/19, 21%), other parasomnias (4/19, 21%), and dream-wake confusional states (2/19, 11%). Dream enactment behaviors were particularly common in AE associated with LGI1 autoantibodies, reported in 4/7 (57%) patients. Polysomnography showed reduced total sleep time, stage 3 and rapid eye movement sleep, and prominent sleep fragmentation. Sleep disturbances are common in AE, warranting active surveillance in affected patients. Improved identification and treatment of sleep disorders may reduce morbidity associated with AE and improve long-term outcomes.

Ability of the Fitbit Alta HR to quantify and classify sleep in patients with suspected central disorders of hypersomnolence: A comparison against polysomnography

Abstract: Measuring sleep duration and early onset rapid eye movement sleep (REMS) is critical in the assessment of suspected central disorders of hypersomnolence (CDH). Current multi-sensor activity trackers that integrate accelerometry and heart rate are purported to accurately quantify sleep time and REMS; however, their utility in suspected CDH has not been established. This investigation aimed to determine the ability of a current, multi-sensor tracker, Fitbit Alta HR (FBA-HR), to quantify and classify sleep in patients with suspected CDH relative to polysomnography (PSG). Forty-nine patients (46 female; mean age, 30.3 ± 9.84 years) underwent ad libitum PSG with concurrent use of the FBA-HR. FBA-HR sleep variable quantification was assessed using Bland-Altman analysis. FBA-HR all sleep (AS), light sleep (LS; PSG N1 + N2), deep sleep (DS; PSG N3) and REMS classification was evaluated using epoch-by-epoch comparisons. FBA-HR-detected sleep-onset rapid eye movement periods (SOREMPs) were compared against PSG SOMREMPs. FBA-HR displayed significant overestimation of total sleep time (11.6 min), sleep efficiency (1.98%) and duration of deep sleep (18.2 min). FBA-HR sensitivity and specificity were as follows: AS, 0.96, 0.58; LS, 0.73, 0.72;DS, 0.67, 0.92; REMS, 0.74, 0.93. The device failed to detect any nocturnal SOREMPs. Device performance did not differ appreciably among diagnostic subgroups. These results suggest FBA-HR cannot replace EEG-based measurements of sleep and wake in the diagnostic assessment of suspected CDH, and that improvements in device performance are required prior to adoption in clinical or research settings.

The Mesopontine Cholinergic System: A Dual Role in REM Sleep and Wakefulness

Abstract: The mesopontine tegmentum contains cholinergic neurons that project widely to the forebrain and brainstem. These neurons are distributed in the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei. Cholinergic neurons in the mesopontine tegmentum have long been thought to play a critical role in the generation of rapid eye movement sleep. Tegmental cholinergic neurons have long been thought to have an important role in behavioral wakefulness and cortical arousal as part of the ascending reticular activating system. Anatomically, cholinergic neurons in the mesopontine tegmentum are distributed in a continuum encompassing the PPT and LDT. Cholinergic neurons are not the only cell type found in the PPT and LDT, as non-cholinergic neurons are also present intermixed with cholinergic neurons. In conclusion, it is clear that non-cholinergic neurons vary in their morphology, projection, and neurotransmitter content.

Brain Microdialysate Monoamines in Relation to Circadian Rhythms, Sleep, and Sleep Deprivation – a Systematic Review, Network Meta-analysis, and New Primary Data

Abstract: Disruption of the monoaminergic system, e.g. by sleep deprivation (SD), seems to promote certain diseases. Assessment of monoamine levels over the circadian cycle, during different sleep stages and during SD is instrumental to understand the molecular dynamics during and after SD. To provide a complete overview of all available evidence, we performed a systematic review. A comprehensive search was performed for microdialysis and certain monoamines (dopamine, serotonin, noradrenaline, adrenaline), certain monoamine metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA)) and a precursor (5-hydroxytryptophan (5-HTP)) in PubMed and EMBASE. After screening of the search results by two independent reviewers, 94 publications were included. All results were tabulated and described qualitatively. Network-meta analyses (NMAs) were performed to compare noradrenaline and serotonin concentrations between sleep stages. We further present experimental monoamine data from the medial prefrontal cortical (mPFC). Monoamine levels varied with brain region and circadian cycle. During sleep, monoamine levels generally decreased compared to wake. These qualitative observations were supported by the NMAs: noradrenaline and serotonin levels decreased from wakefulness to slow wave sleep and decreased further during Rapid Eye Movement sleep. In contrast, monoamine levels generally increased during SD, and sometimes remained high even during subsequent recovery. Decreases during or after SD were only reported for serotonin. In our experiment, SD did not affect any of the mPFC monoamine levels. Concluding, monoamine levels vary over the light-dark cycle and between sleep stages. SD modifies the patterns, with effects sometimes lasting beyond the SD period.

Dynamic modulation of theta-gamma coupling during rapid eye movement sleep.

Abstract: Theta phase modulates gamma amplitude in hippocampal networks during spatial navigation and rapid eye movement (REM) sleep. This cross-frequency coupling has been linked to working memory and spatial memory consolidation; however, its spatial and temporal dynamics remains unclear. Here, we first investigate the dynamics of theta-gamma interactions using multiple frequency and temporal scales in simultaneous recordings from hippocampal CA3, CA1, subiculum, and parietal cortex in freely moving mice. We found that theta phase dynamically modulates distinct gamma bands during REM sleep. Interestingly, we further show that theta-gamma coupling switches between recorded brain structures during REM sleep and progressively increases over a single REM sleep episode. Finally, we show that optogenetic silencing of septohippocampal GABAergic projections significantly impedes both theta-gamma coupling and theta phase coherence. Collectively, our study shows that phase-space (i.e. cross-frequency coupling) coding of information during REM sleep is orchestrated across time and space consistent with region-specific processing of information during REM sleep including learning and memory.

Sleep in Huntington’s disease: a systematic review and meta-analysis of polysomongraphic findings

Abstract: Study objectives Disturbed overnight sleep is a prominent feature of advanced stage Huntington's disease (HD). Several polysomnography (PSG) studies have reported significant changes of sleep in HD patients, but the findings are not unequivocal. To date, no meta-analysis has investigated the PSG changes in HD patients. The present study meta-analyzed results from studies examining the PSG changes in HD patients compared with controls. Methods A literature search performed in MEDLINE, EMBASE, All EBM databases, PsycINFO, and CINAHL databases identified seven studies involving 152 HD patients and 144 controls which were included in our meta-analysis. Results Pooled results indicated decreased sleep efficiency, percentage of slow wave sleep and rapid eye movement sleep, and increased percentage of N1 sleep, wake time after sleep onset, and rapid eye movement sleep latency in HD patients compared with controls. We found high heterogeneity in the effect sizes and no indication of systematic publication biases across studies. Meta-regression analyses showed that some of the heterogeneity was explained by age, body mass index (BMI), CAG repeat length, and disease severity of HD patients. Conclusions Our study showed that polysomnographic abnormalities are present in HD. Our findings also underscore the need for a comprehensive PSG assessment of sleep changes in patients with HD. Furthermore, the effects of age, BMI and CAG repeat length on sleep changes should be carefully considered and closely monitored in the management of HD.

Obstructive sleep apnea, nighttime arousals, and leukocyte telomere length: the Multi-Ethnic Study of Atherosclerosis.

Abstract: Study objectives Sleep disturbances and sleep apnea are associated with increased vulnerability to age-related disease, altering molecular pathways affecting biological aging. Telomere length captures one component of biological aging. We evaluated whether objectively assessed sleep and sleep apnea relate to leukocyte telomere length (LTL) in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods Men and women aged 44-84 years (n = 672) from the MESA Stress and MESA Sleep studies underwent polysomnography and 7 day actigraphy (at Exam 5) and assessment of LTL (at baseline [Exam 1] and about 10 years later [Exam 5]). Results General linear models adjusting for age, sex, race/ethnicity, BMI, physical activity, and smoking found that severe obstructive sleep apnea (OSA; apnea-hypopnea index > 30) was cross-sectionally associated with shorter LTL (p = 0.007). Modest associations of shorter LTL with less rapid eye movement sleep, more stage 1 sleep, wake after sleep onset >30 min, and long sleep duration were found, but these effects were diminished after adjusting for lifestyle and OSA. Exploratory analyses found that higher arousal index at Exam 5 was associated with greater LTL decline over the prior 10 years (p = 0.004). Conclusions OSA was associated with shorter LTL. Individuals with high-arousal frequency had greater leukocyte telomere attrition over the prior decade. These findings suggest that sleep apnea and sleep fragmentation are associated with accelerated biological aging.

Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice

Abstract: The regulatory network of genes and molecules in sleep/wakefulness remains to be elucidated. Here we describe the methodology and workflow of the dominant screening of randomly mutagenized mice and discuss theoretical basis of forward genetics research for sleep in mice. Our high-throughput screening employs electroencephalogram (EEG) and electromyogram (EMG) to stage vigilance states into a wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS). Based on their near-identical sleep/wake behavior, C57BL/6J (B6J) and C57BL/6N (B6N) are chosen as mutagenized and counter strains, respectively. The total time spent in the wake and NREMS, as well as the REMS episode duration, shows sufficient reproducibility with small coefficients of variance, indicating that these parameters are most suitable for quantitative phenotype-driven screening. Coarse linkage analysis of the quantitative trait, combined with whole-exome sequencing, can identify the gene mutation associated with sleep abnormality. Our simulations calculate the achievable LOD score as a function of the phenotype strength and the numbers of mice examined. A pedigree showing a mild decrease in total wake time resulting from a heterozygous point mutation in the Cacna1a gene is described as an example.

Associations between quantitative sleep EEG and subsequent cognitive decline in older women.

Abstract: The pathophysiological processes of Alzheimer’s dementia predate its clinical manifestation. Sleep disturbances can accelerate the aging process and are common features of dementia. This study examined whether quantitative sleep electroencephalogram changes predate the clinical development of mild cognitive impairment and/or incident dementia. We collected data from a nested case-control sample of women (mean age 83 years) from the Sleep and Cognition Study, an ancillary study to the longitudinal Study of Osteoporotic Fractures, who were characterized as cognitively normal at the time of a baseline polysomnography study (Study of Osteoporotic Fractures visit 8) based on a Mini-Mental Status Exam (MMSE) score >24. Cases (n = 85) were women who developed new mild cognitive impairment or dementia by objective cognitive testing 5 years after polysomnography. Controls were women with no mild cognitive impairment/dementia (n = 85) at baseline or at follow-up. Differences in electroencephalogram absolute and relative power density were observed between the two groups. Specifically, higher electroencephalogram power values were found in the dementia/mild cognitive impairment group, for the alpha (p = .01) and theta bands (p = .04) in non-rapid eye movement sleep, as well as alpha (p = .04) and sigma (p = .04) bands in rapid eye movement sleep. In contrast, there were no group differences in traditional polysomnography measures of sleep architecture and sleep stage distribution, as well as sleep apnea and periodic limb movement indices. Our results provide evidence for quantitative electroencephalogram changes, which precede the clinical onset of cognitive decline and the diagnosis of dementia in elderly women, and support the application of quantitative sleep electroencephalogram analysis as a promising biomarker for imminent cognitive decline.

Increased creative thinking in narcolepsy

Abstract: Some studies suggest a link between creativity and rapid eye movement sleep. Narcolepsy is characterized by falling asleep directly into rapid eye movement sleep, states of dissociated wakefulness and rapid eye movement sleep (cataplexy, hypnagogic hallucinations, sleep paralysis, rapid eye movement sleep behaviour disorder and lucid dreaming) and a high dream recall frequency. Lucid dreaming (the awareness of dreaming while dreaming) has been correlated with creativity. Given their life-long privileged access to rapid eye movement sleep and dreams, we hypothesized that subjects with narcolepsy may have developed high creative abilities. To test this assumption, 185 subjects with narcolepsy and 126 healthy controls were evaluated for their level of creativity with two questionnaires, the Test of Creative Profile and the Creativity Achievement Questionnaire. Creativity was also objectively tested in 30 controls and 30 subjects with narcolepsy using the Evaluation of Potential Creativity test battery, which measures divergent and convergent modes of creative thinking in the graphic and verbal domains, using concrete and abstract problems. Subjects with narcolepsy obtained higher scores than controls on the Test of Creative Profile (mean ± standard deviation: 58.9 ± 9.6 versus 55.1 ± 10, P = 0.001), in the three creative profiles (Innovative, Imaginative and Researcher) and on the Creative Achievement Questionnaire (10.4 ± 25.7 versus 6.4 ± 7.6, P = 0.047). They also performed better than controls on the objective test of creative performance (4.3 ± 1.5 versus 3.7 ± 1.4; P = 0.009). Most symptoms of narcolepsy (including sleepiness, hypnagogic hallucinations, sleep paralysis, lucid dreaming, and rapid eye movement sleep behaviour disorder, but not cataplexy) were associated with higher scores on the Test of Creative Profile. These results highlight a higher creative potential in subjects with narcolepsy and further support a role of rapid eye movement sleep in creativity.

A New Metabolic Network Correlated with Olfactory and Executive Dysfunctions in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

Abstract: BACKGROUND AND PURPOSE To identify a metabolic network reflecting neurodegeneration in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS We recruited a prospective cohort comprising patients with de novo Parkinson's disease (PD) with probable REM sleep behavior disorder (PDRBD, n=21), polysomnography-confirmed iRBD patients (n=28), and age-matched healthy controls (HC) (n=24). PDRBD-related spatial covariance pattern (PDRBD-RP) were determined from ¹⁸F-fluorodeoxyglucose PET images of the PDRBD group and validated by reproduction in a separate PD cohort with polysomnography-confirmed REM sleep behavior disorder (n=11). We also confirmed via ¹⁸F-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane PET that none of our iRBD patients had any loss of dopamine transporters (DATs) suggestive of PD. Differences in the PDRBD-RP across groups were compared, and the clinical significance of these metabolic patterns in iRBD patients was further evaluated based on relationships with olfactory and cognitive functions, and striatal DAT densities. RESULTS The PDRBD-RP reflected the previously reported PD-related covariance pattern and additionally showed relative metabolic increases in the hippocampus and premotor cortex. The PDRBD-RP gradually increased from the HC to iRBD patients and to the de novo and validation PDRBD groups. In iRBD patients, the PDRBD-RP was negatively correlated with olfactory and frontal executive functions (age-controlled p<0.01 for both), and tended to be negatively correlated with the striatal DAT density, although this was insignificant after age adjustment. During the mean follow-up period of 3.5 years, 5 of 11 iRBD patients with PDRBD-RP elevation had developed Lewy body diseases, whereas those without PDRBD-RP elevation had not. CONCLUSIONS Our results suggest that PDRBD-RP is an effective biomarker for monitoring the progression to neurodegenerative disease in iRBD patients.

Rapid eye movement sleep and neuronal development.

Abstract: Purpose of review To understand the importance of rapid eye movement (REM) sleep in the cognitive and sensorimotor development via neural plasticity during embryonic development and infants. Recent findings REM sleep has remained a mystery as many of the underlying mechanisms of REM sleep remain unclear. Recent findings have demonstrated that REM sleep selectively prunes newly formed dendritic spines in the developing brain as well as strengthening new synapses in the developing brain. This process is critical for normal neuronal circuit development and behavioral improvement after learning. Summary Although many mechanisms of REM sleep remain unclear, recent findings strongly suggest that REM sleep is vitally important in pruning synapses as well as maintaining new synapses for the development of a healthy brain. Developmental neuroplasticity refers to the continuous change of the developing brain during fetal development. Lack of plasticity may result in reduced intellectual ability, reduced learning and memory consolidation, and mental illness.

Clinical and video-polysomnographic analysis of rapid eye movement sleep behavior disorder and other sleep disturbances in dementia with Lewy bodies.

Abstract: Objective The main objective of this study was to study rapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disorders in dementia with Lewy bodies (DLB). Methods Consecutive patients with DLB and mild dementia severity were recruited irrespective of sleep complaints. Patients underwent clinical interview, assessment of sleep scales, and video-polysomnography (V-PSG). RBD was diagnosed with V-PSG based on electromyographic and audiovisual analysis. Results Thirty-five patients (65.7% men; mean age 77.7 ± 6.1 years) were evaluated. Poor sleep quality (54.3%), hypersomnia (37.1%), snoring (60%), and abnormal nocturnal behaviors (77.1%) were reported. Sleep-wake architecture abnormalities occurred in 75% patients and consisted of occipital slowing on awake electroencephalography (EEG; 34.4%), the absence of sleep spindles and K complexes (12.9%), slow frequency sleep spindles (12.9%), delta activity in REM sleep (19.2%), and REM sleep without atonia (44%). Three patients showed hallucinatory-like behaviors and 10 patients showed abnormal behaviors during arousals mimicking RBD. RBD was diagnosed in 50% of those patients in whom sufficient REM sleep was attained. Of these, 72.7% were not aware of displaying dream-enacting behaviors and in 63.7% RBD preceded the onset of cognitive impairment. For RBD diagnosis, the sensitivity of Mayo Sleep Questionnaire was 50%, specificity was 66.7%, positive predictive value was 83.3%, and negative predictive value was 28%. False-positive RBD cases according to clinical history had hallucinatory-like behaviors, severe obstructive sleep apnea, and prominent periodic limb movements in sleep. Occipital EEG frequency while awake and rate of electromyographic activity in REM sleep were negatively correlated, suggesting a common subcortical origin. Conclusion In DLB, RBD and sleep-wake disorders are common, heterogeneous, and complex, challenging their identification without performing V-PSG.

Increased Awakenings From Non-rapid Eye Movement Sleep Explain Differences in Dream Recall Frequency in Healthy Individuals.

Abstract: Background Dreaming is a universal experience, yet there is considerable inter-individual variability in dream recall frequency (DRF). One dominant model, the "arousal-retrieval" model, posits that intra-sleep wakefulness is required for dream traces to be encoded into long-term storage, essentially proposing that a better memory for dreams underlie increased DRF. A recent study utilizing polysomnography combined with an event-related potentials paradigm, provides direct support for this model by demonstrating increased intra-sleep wakefulness in a healthy population by comparing high frequency recallers (HFRs) and low frequency recallers (LFRs). Another study by the same group demonstrated increased regional cerebral blood flow in regions associated with dream production, supporting the premise that HFRs also may produce more dreams. Hypotheses This study investigated the profile of nocturnal awakenings and dream production in healthy HFRs and LFRs. Hypothesis (1a): HFRs will spend significantly more time awake after sleep onset; (1b): HFRs will experience significantly more awakenings across the night, and from rapid eye movement (REM) sleep in particular; (2) HFRs will have significantly higher rates of dream production across the night as measured by REM density. Methods We studied two groups of healthy adults: HFRs (n = 19) and LFRs (n = 17) who underwent polysomnographic recordings on two non-consecutive nights. Results Hypothesis (1a) was confirmed: HFRs spent significantly more time awake after sleep onset. Hypothesis (1b) was partially confirmed: HFRs experienced significantly more awakenings across the night; however, awakenings from REM sleep were comparable. Interestingly, HFRs had significantly more awakenings, as well as a higher number of longer awakenings, from non-rapid eye movement (NREM) stage 2 sleep. Hypothesis (2) was not confirmed: There was no significant difference in rates of REM density between groups. Conclusion This is the first study to provide evidence that awakenings from NREM 2 sleep might underlie increased DRF in HFRs. This finding coupled with null findings in relation to REM sleep variables, support the premise that inter-individual variability in DRF cannot be ascribed to differences in REM sleep parameters in healthy individuals. Instead, the data indicates that awakenings from NREM sleep is of particular importance in relation to DRF in a healthy population.

Isolated rapid eye movement sleep behavior disorder and cyclic alternating pattern: is sleep microstructure a predictive parameter of neurodegeneration?

Abstract: Objective To evaluate the role of sleep cyclic alternating pattern (CAP) in patients with isolated REM sleep behavior disorder (IRBD) and ascertain whether CAP metrics might represent a marker of phenoconversion to a defined neurodegenerative condition. Methods Sixty-seven IRBD patients were included and classified into patients who phenoconverted to a neurodegenerative disease (RBD converters: converter REM sleep behavior disorder [cRBD]; n = 34) and remained disease-free (RBD non-converters: non-converter REM sleep behavior disorder [ncRBD]; n = 33) having a similar follow-up duration. Fourteen age- and gender-balanced healthy controls were included for comparisons. Results Compared to controls, CAP rate and CAP index were significantly decreased in IRBD mainly due to a decrease of A1 phase subtypes (A1 index) despite an increase in duration of both CAP A and B phases. The cRBD group had significantly lower values of CAP rate and CAP index when compared with the ncRBD group and controls. A1 index was significantly reduced in both ncRBD and cRBD groups compared to controls. When compared to the ncRBD group, A3 index was significantly decreased in the cRBD group. The Kaplan-Meier curve applied to cRBD estimated that a value of CAP rate below 32.9% was related to an average risk of conversion of 9.2 years after baseline polysomnography. Conclusion IRBD is not exclusively a rapid eye movement (REM) sleep parasomnia, as non-rapid eye movement (non-REM) sleep microstructure can also be affected by CAP changes. Further studies are necessary to confirm that a reduction of specific CAP metrics is a marker of neurodegeneration in IRBD.

Rapid eye movement sleep mediates age-related decline in prospective memory consolidation.

Abstract: STUDY OBJECTIVES Prospective memory, or remembering to execute future intentions, accounts for half of everyday forgetting in older adults. Sleep intervals benefit prospective memory consolidation in young adults, but it is unknown whether age-related changes in slow wave activity, sleep spindles, and/or rapid eye movement (REM) sleep mediate hypothesized effects of aging on prospective memory consolidation. METHODS After an adaptation night, 76 adults aged 18-84 completed two experimental nights of in-laboratory polysomnography recording. In the evening, participants encoded and practiced a prospective memory task and were tested the next morning. On a counterbalanced night, they encoded and practiced a control task, and were tested the following morning. RESULTS Increasing age predicted worse prospective memory consolidation (r = -.34), even when controlling for encoding, speed, and control-task performance (all ps < .05). Frontal delta power, slow oscillations, and spindle density were not related to prospective memory consolidation. REM sleep duration, however, explained significant variance in prospective memory consolidation when controlling for age (∆R2 = .10). Bootstrapping mediation showed that less REM sleep significantly mediated the aging effect on prospective memory consolidation [b = -.0016, SE = 0.0009 (95% confidence interval [CI] = -0.0042 to -0.0004)]. REM sleep continued to mediate 24.29% of the total effect of age on prospective memory after controlling for numerous demographic, cognitive, mental health, and sleep variables. CONCLUSION Age-related variance in REM sleep is informative to how prospective memory consolidation changes with increasing age. Future work should consider how both REM sleep and slow wave activity contribute, perhaps in a sequential or dynamic manner, to preserving cognitive functioning with increasing age.

Reboxetine and hyoscine butylbromide improve upper airway function during nonrapid eye movement and suppress rapid eye movement sleep in healthy individuals

Abstract: Study objectives Recent findings indicate that noradrenergic and antimuscarinic processes are crucial for sleep-related reductions in pharyngeal muscle activity. However, there are few human studies. Accordingly, this study aimed to determine if a combined noradrenergic and antimuscarinic intervention increases pharyngeal dilator muscle activity and improves airway function in sleeping humans. Methods Genioglossus (GG) and tensor palatini electromyography (EMG), pharyngeal pressure, upper airway resistance, and breathing parameters were acquired in 10 healthy adults (5 female) during two overnight sleep studies after 4 mg of reboxetine (REB) plus 20 mg of hyoscine butylbromide (HBB) or placebo using a double-blind, placebo-controlled, randomized, cross-over design. Results Compared with placebo, peak and tonic GG EMG were lower (Mean ± SD: 83 ± 73 vs. 130 ± 75, p = 0.021 and 102 ± 102 vs. 147 ± 123 % wakefulness, p = 0.021, respectively) but the sleep-related reduction in tensor palatini was less (Median [25th, 75th centiles]: 53[45, 62] vs. 34[28, 38] % wakefulness, p = 0.008) with the drug combination during nonrapid eye movement (non-REM) sleep. These changes were accompanied by improved upper airway function including reduced pharyngeal pressure swings, airway resistance, respiratory load compensation, and increased breathing frequency during N2. REB and HBB significantly reduced rapid eye movement sleep compared with placebo (0.6 ± 1.1 vs. 14.5 ± 6.8 % total sleep time, p Conclusions Contrary to our hypothesis, GG muscle activity (% wakefulness) during non-REM sleep was lower with REB and HBB. However, sleep-related reductions in tensor palatini activity were less and upper airway function improved. These findings provide mechanistic insight into the role of noradrenergic and antimuscarinic processes on upper airway function in humans and have therapeutic potential for obstructive sleep apnea. Clinical trial registration Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au, trial ID: ACTRN12616000469415.

The effect of dream report collection and dream incorporation on memory consolidation during sleep.

Abstract: Collecting dream reports typically requires waking subjects up from their sleep-a method that has been used to study the relationship between dreams and memory consolidation. However, it is unclear whether these awakenings influence sleep-associated memory consolidation processes. Furthermore, it is unclear how the incorporation of the learning task into dreams is related to memory consolidation. In this study we compared memory performance in a word-picture association learning task after a night with and without awakenings in 22 young and healthy participants. We then examined if the stimuli from the learning task are successfully incorporated into dreams, and if this incorporation is related to the task performance the next morning. We show that while the awakenings impaired both subjective and objective sleep quality, they did not affect sleep-associated memory consolidation. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. When dreams were collected in the morning, no incorporations were detected. Task incorporation into non-rapid eye movement sleep dreams, but not rapid eye movement sleep dreams positively predicted memory performance the next morning. We conclude that the method of awakenings to collect dream reports is suitable and necessary for dream and memory studies. Furthermore, our study suggests that dreams in non-rapid eye movement rather than rapid eye movement sleep might be related to processes of memory consolidation during sleep.