Showing papers on "Rapid eye movement sleep published in 2023"

Accurate Detection of α‐Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort

Abstract: Misfolded α‐synuclein (αSyn) aggregates (αSyn‐seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn‐seeds have been detected in prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD).

Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool

Abstract: Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson's disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that α-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies.

Alzheimer's disease phenotypes show different sleep architecture.

Abstract: INTRODUCTION Sleep-wake disturbances are a prominent feature of Alzheimer's disease (AD). Atypical (non-amnestic) AD syndromes have different patterns of cortical vulnerability to AD. We hypothesized that atypical AD also shows differential vulnerability in subcortical nuclei that will manifest as different patterns of sleep dysfunction. METHODS Overnight electroencephalography monitoring was performed on 48 subjects, including 15 amnestic, 19 atypical AD, and 14 controls. AD was defined based on neuropathological or biomarker confirmation. We compared sleep architecture by visual scoring and spectral power analysis in each group. RESULTS Overall, AD cases showed increased sleep fragmentation and N1 sleep compared to controls. Compared to atypical AD groups, typical AD showed worse N3 sleep dysfunction and relatively preserved rapid eye movement (REM) sleep. DISCUSSION Results suggest differing effects of amnestic and atypical AD variants on slow wave versus REM sleep, respectively, corroborating the hypothesis of differential selective vulnerability patterns of the subcortical nuclei within variants. Optimal symptomatic treatment for sleep dysfunction in clinical phenotypes may differ. HIGHLIGHTS Alzheimer's disease (AD) variants show distinct patterns of sleep impairment. Amnestic/typical AD has worse N3 slow wave sleep (SWS) impairment compared to atypical AD. Atypical AD shows more rapid eye movement deficits than typical AD. Selective vulnerability patterns in subcortical areas may underlie sleep differences. Relatively preserved SWS may explain better memory scores in atypical versus typical AD.

Large Muscle Group Movements during Sleep in Healthy People: Normative Values and Correlation to Sleep Features.

Abstract: STUDY OBJECTIVE To investigate the frequency and characteristics of large muscle group movements (LMMs) during sleep in healthy adults. METHODS LMMs were scored following the International Restless Legs Syndrome Study Group criteria in 100 healthy subjects aged 19-77 years. A LMM was defined as a temporally overlapping increase in EMG activity and/or the occurrence of movement artifact in at least two channels. LMM indices and durations in total sleep time (TST), NREM and REM sleep, and association with arousals, awakenings, and/or respiratory events were calculated. Correlations of LMMs indices and durations with sleep architecture, respiratory and motor events, and subjective sleep quality were investigated. RESULTS Median LMMs index in TST was 6.8/h (interquartile range (IQR), 4.5/h-10.8/h), median mean duration 12.4s (IQR 10.7s-14.4s). Mean LMMs duration was longer in NREM (median 12.7s, IQR 11.1s-15.2s) versus REM sleep (median 10.3s, IQR 8.0s-13.5s), P<0.001. LMMs associated with awakening increased with age (P=0.029). LMMs indices in TST were higher in men than women (p=0.018). LMMs indices correlated positively with N1 sleep percentage (ρ=0.49, P<0.001), arousal index (ρ=0.40, P=0.002), sleep stages shift index (ρ=0.43, P<0.001, apnoea index (ρ=0.36, P=0.017), and video-visible movements indices (ρ=0.45, P<0.001), and negatively with N3 sleep (ρ=-0.38, P=0.004) percentage. CONCLUSIONS This is the first study providing normative data on LMMs frequency in healthy adults. LMMs are a ubiquitous phenomenon often associated with other events. Correlation with arousals and respiratory events suggests a potential clinical significance of LMMs in adults that awaits further investigation.

Obstructive sleep apnea in aboriginal Australians: polysomnographic outcomes and symptom perception post-continuous positive airway pressure implementation

Abstract: Abstract Study Objectives Obstructive sleep apnea (OSA) is reported to be highly prevalent among Aboriginal Australians. However, no studies have assessed the implementation and efficacy of continuous positive airway pressure (CPAP) therapy in this population. Hence, we compared the clinical, self-reported perception of sleep quality and polysomnographic (PSG) characteristics among Aboriginal patients with OSA. Methods Adult Aboriginal Australians who underwent both diagnostic (Type 1 and 2) and in-lab CPAP implementation studies were included. Results Total of 149 patients were identified (46% female, median age 49 years, body mass index 35 kg/m2). The OSA severity was 6% mild, 26% moderate, and 68% severe on the diagnostic PSG. On application of CPAP, there were significant improvements in; total arousal index (diagnostic 29 to 17/h on CPAP), total apnea–hypopnea index (AHI) (diagnostic 48 to 9/h on CPAP), non-rapid eye movement AHI (diagnostic 47 to 8/h on CPAP), rapid eye movement (REM) AHI (diagnostic 56 to 8/h on CPAP) and oxygen saturation (SpO2) nadir (diagnostic 77% to 85% on CPAP) (p < 0.001 for each). Following a single night of CPAP, 54% of patients reported sleeping “better than normal” compared to 12% following the diagnostic study (p = 0.003). In multivariate regression models, males had a significantly lesser change in REM AHI than females (5.7 events/hour less change (IQR 0.4, 11.1), p = 0.029). Conclusions There is substantial improvement in several sleep-related domains on the application of CPAP among Aboriginal patients with a good initial acceptance of treatment. Whether the positive impact observed in this study translates to better sleep health outcomes with long-term adherence to CPAP therapy is yet to be assessed.

B lymphocyte responses in Parkinson’s disease and their possible significance in disease progression

Abstract: Abstract Inflammation contributes to Parkinson’s disease pathogenesis. We hypothesized that B lymphocytes are involved in Parkinson’s disease progression. We measured antibodies to alpha-synuclein and tau in serum from patients with rapid eye movement sleep behaviour disorder (n = 79), early Parkinson’s disease (n = 50) and matched controls (n = 50). Rapid eye movement sleep behaviour disorder cases were stratified by risk of progression to Parkinson’s disease (low risk = 30, high risk = 49). We also measured B-cell activating factor of the tumour necrosis factor receptor family, C-reactive protein and total immunoglobulin G. We found elevated levels of antibodies to alpha-synuclein fibrils in rapid eye movement sleep behaviour disorder patients at high risk of Parkinson’s disease conversion (ANOVA, P < 0.001) and lower S129D peptide-specific antibodies in those at low risk (ANOVA, P < 0.001). An early humoral response to alpha-synuclein is therefore detectable prior to the development of Parkinson’s disease. Peripheral B lymphocyte phenotyping using flow cytometry in early Parkinson’s disease patients and matched controls (n = 41 per group) revealed reduced B cells in Parkinson’s disease, particularly in those at higher risk of developing an early dementia [t(3) = 2.87, P = 0.01]. Patients with a greater proportion of regulatory B cells had better motor scores [F(4,24) = 3.612, P = 0.019], suggesting they have a protective role in Parkinson’s disease. In contrast, B cells isolated from Parkinson’s disease patients at higher risk of dementia had greater cytokine (interleukin 6 and interleukin 10) responses following in vitro stimulation. We assessed peripheral blood lymphocytes in alpha-synuclein transgenic mouse models of Parkinson’s disease: they also had reduced B cells, suggesting this is related to alpha-synuclein pathology. In a toxin-based mouse model of Parkinson’s disease, B-cell deficiency or depletion resulted in worse pathological and behavioural outcomes, supporting the conclusion that B cells play an early protective role in dopaminergic cell loss. In conclusion, we found changes in the B-cell compartment associated with risk of disease progression in rapid eye movement sleep behaviour disorder (higher alpha-synuclein antibodies) and early Parkinson’s disease (lower levels of B lymphocytes that were more reactive to stimulation). Regulatory B cells play a protective role in a mouse model, potentially by attenuating inflammation and dopaminergic cell loss. B cells are therefore likely to be involved in the pathogenesis of Parkinson’s disease, albeit in a complex way, and thus warrant consideration as a therapeutic target.

A medullary hub for controlling REM sleep and pontine waves

Abstract: Rapid-eye-movement (REM) sleep is a distinct behavioral state associated with vivid dreaming and memory processing. Phasic bursts of electrical activity, measurable as spike-like pontine (P)-waves, are a hallmark of REM sleep implicated in memory consolidation. However, the brainstem circuits regulating P-waves, and their interactions with circuits generating REM sleep, remain largely unknown. Here, we show that an excitatory population of dorsomedial medulla (dmM) neurons expressing corticotropin-releasing-hormone (CRH) regulates both REM sleep and P-waves in mice. Calcium imaging showed that dmM CRH neurons are selectively activated during REM sleep and recruited during P-waves, and opto- and chemogenetic experiments revealed that this population promotes REM sleep. Chemogenetic manipulation also induced prolonged changes in P-wave frequency, while brief optogenetic activation reliably triggered P-waves along with transiently accelerated theta oscillations in the electroencephalogram (EEG). Together, these findings anatomically and functionally delineate a common medullary hub for the regulation of both REM sleep and P-waves.

The temporal structure of REM sleep shows minute-scale fluctuations across brain and body in mice and humans

Abstract: Significance Rapid eye movement sleep (REM) was originally identified in relation to dreaming and has various functions in neurodevelopment, synaptogenesis, and memory consolidation. REM is traditionally defined by stereotypical neurophysiology, including wake-like brain electrical activity, muscle atonia, and rapid eye movements. In this study, we identify a temporal pattern defining REM physiology consisting of brain activity and respiratory rate fluctuating at the timescale of approximately minutes, with the frequency of such fluctuations matching the incidence of classical rapid eye movements. With these findings, we identify a metric with which to study the timing of REM-dependent processes.

Considering REM Sleep Behavior Disorder in the Management of Parkinson’s Disease

Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) is the result of the loss of physiological inhibition of muscle tone during REM sleep, characterized by dream-enacting behavior and widely recognized as a prodromal manifestation of alpha-synucleinopathies. Indeed, patients with isolated RBD (iRBD) have an extremely high estimated risk to develop a neurodegenerative disease after a long follow up. Nevertheless, in comparison with PD patients without RBD (PDnoRBD), the occurrence of RBD in the context of PD (PDRBD) seems to identify a unique, more malignant phenotype, characterized by a more severe burden of disease in terms of both motor and non-motor symptoms and increased risk for cognitive decline. However, while some medications (eg, melatonin, clonazepam, etc.) and non-pharmacological options have been found to have some therapeutic benefits on RBD there is no available treatment able to modify the disease course or, at least, slow down the neurodegenerative process underlying phenoconversion. In this scenario, the long prodromal phase may allow an early therapeutic window and, therefore, the identification of multimodal biomarkers of disease onset and progression is becoming increasingly crucial. To date, several clinical (motor, cognitive, olfactory, visual, and autonomic features) neurophysiological, neuroimaging, biological (biofluids or tissue biopsy), and genetic biomarkers have been identified and proposed, also in combination, as possible diagnostic or prognostic markers, along with a potential role for some of them as outcome measures and index of treatment response. In this review, we provide an insight into the present knowledge on both existing and future biomarkers of iRBD and highlight the difference with PDRBD and PDnoRBD, including currently available treatment options.

Comparison of sleep deprivation and a low dose of ketamine on sleep and the electroencephalogram in Brown Norway rats.

Abstract: Ketamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid, suggesting a different mode of action. A rapid antidepressant effect is also observed following sleep deprivation (SD). In the present study, we aimed to evaluate the effect of a 6-h SD and acute ketamine treatment on vigilance states, locomotor activity, and electroencephalogram (EEG) power density spectra in Brown Norway rats under constant condition over 2 recording days. After SD and after the initial waking period induced by ketamine, both treatments induced a similar increase in non-rapid eye movement (NREM) sleep and EEG slow-wave activity (SWA) in NREM sleep. Rapid eye movement (REM) sleep was reduced immediately after both treatments but was recovered later only after the SD. The effects on the waking EEG differed between the treatments, with a faster theta peak during and after SD, and no change in the waking spectrum after ketamine. In conclusion, SD and ketamine both lead to an acute increment in NREM sleep SWA as well as in a reduction in REM sleep. The results suggest that selective suppression of REM sleep, combined with enhancement of SWA during NREM may be effective in the treatment of depression.

0716 Quality of Life in Idiopathic REM Sleep Behavior Disorder and Isolated REM Sleep Without Atonia

Abstract: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) can affect quality of life (QOL) for both patient and bed partner; isolated REM sleep without atonia (iRSWA) has been less well-studied. We aimed to investigate whether QOL changes over time in those with either iRBD or iRSWA, as well as compare these changes to one another. Additionally, we attempted to demonstrate whether certain QOL changes were associated with phenoconversion to neurodegenerative illness. We prospectively analyzed data from the “REM Sleep Behavior Disorder Associations with Parkinson’s Disease Study (RAPiDS)” cohort both at baseline and then at follow-up evaluations. We utilized the Neuro-QOL self-reported questionnaire to ascertain subjects’ level of QOL. There were 6 with iRSWA and 33 with iRBD, with an average age of 61.9 ± 13.0 years, with 13 women and 26 men. Significant QOL changes were found in both iRSWA and iRBD group. Among those who phenoconverted, fatigue and social functioning were the main QOL issues that that worsened over time. This is the first time the Neuro-QOL has been studied in iRBD and iRSWA. QOL can be affected in both conditions; fatigue and social functioning seem to be of particular importance as they may be associated with phenoconversion. Grant from a private individual

Empirical Evidence of the Effects of Parkinson's Disease and Rapid Eye Movement Sleep Behavior Disorder on Reading and Speech Ability

Abstract: This study used UPDRS III scale, scale B and scale C to investigate 30 cases of PD patients, 50 cases of RBD patients and 50 cases of normal people, and analyzed the difference of barrier scores between PD patients and RBD patients. The differences in reading ability and monologue ability among the three groups of research subjects were analyzed. The three scales are subjected to exploratory factor analysis to verify whether the structure of the three scales is good or not. The analysis results show that the impairment score of PD patients is higher than that of RBD patients, that is, the severity of impairment in PD patients is higher than that of RBD patients; Statistical differences exist in reading ability among the three groups, suggesting that the reading ability of the three groups is different; Statistical differences in the monologue ability among the three groups of people indicate the monologue ability of the three groups of people is different. In the analysis, 7, 4 and 4 common factors were extracted from UPDRS III scale, scale B and scale C respectively, which explained 68.955% and 68.955% of the total variation of UPDRS III scale, scale B and scale C. 73.589% and 72.298% respectively. It shows that the structure of the three scales is good and reasonable, and the collected data can be used, and the data are representative.

Validation of the relationship between rapid eye movement sleep and sleep-related erections in healthy adults by a feasible instrument fitbit charge 2TM.

Abstract: BACKGROUND Sleep, particularly rapid eye movement (REM) sleep, has been found to be associated with Sleep-related erections (SREs). While Rigiscan is currently a more accurate method for monitoring nocturnal erectile events, the Fitbit, a smart wearable device, shows great potential for sleep monitoring. OBJECTIVES To analyze the relationship between SREs and sleep by recruiting sexually active, healthy men for simultaneous monitoring of sleep and nocturnal penile tumescence and rigidity (NPTR). PATIENTS AND METHODS Using Fitbit Charge2TM and Rigiscan, we simultaneously monitored nocturnal sleep and erections in 43 healthy male volunteers, and analyzed the relationship between sleep periods and erectile events with the Statistical Package for Social Sciences. RESULTS Among all erectile events, 89.8% were related to REM, and 79.2% of all REM periods were associated with erectile events. Moreover, a statistical correlation was shown between the duration of REM and the time of total erectile events (first night: 𝜌 = 0.316, p = 0.039; second night: 𝜌 = 0.370, p = 0.015). DISCUSSION AND CONCLUSION Our study shows a potential link between SREs and REM sleep, which has implications for the current examination of SREs and further research into the mechanisms of erectile function. Meanwhile, the wearable device Fitbit has shown a potential promise for sleep monitoring in patients with erectile dysfunction. The results provide an alternative approach for further research on the relationship between erectile function and sleep with large sample sizes in the future. This article is protected by copyright. All rights reserved.

Quantitative measurement of motor activity during sleep in isolated REM sleep behavior disorder patients using actigraphy before and after treatment with clonazepam.

Abstract: STUDY OBJECTIVES We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures. RESULTS Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered "much or very much improved" on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman's rho=0.78, p<0.001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho=0.47, p=0.030 for proximal movements, rho=0.47, p=0.032 for axial movements). CONCLUSIONS Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.

Reduction in the propensity of rapid eye movement sleep and phasic-to-tonic ratio in patients with refractory epilepsy.

Abstract: STUDY OBJECTIVES Patients with epilepsy exhibit disturbed sleep architecture and shorter rapid eye movement (REM) sleep compared with healthy controls. REM sleep consists of two microstates, phasic and tonic REM. Studies suggest that epileptic activity is suppressed in phasic but not in tonic REM. However, changes in the REM microstructure in patients with epilepsy are still unknown. Therefore, this study evaluated the differences in REM microstructure between patients with refractory and medically controlled epilepsy. METHODS This retrospective case-control study included patients with refractory and medically controlled epilepsy. Sleep parameters of the patients were recorded by standard polysomnography. In addition, the microstructures of sleep and REM sleep were compared between the two epilepsy groups. RESULTS Forty-two patients with refractory epilepsy and 106 with medically controlled epilepsy were evaluated. The refractory group showed significantly decreased REM sleep (p = 0.0062), particularly in the first and second sleep cycles (p = 0.0028 and 0.00482, respectively), as well as longer REM latency (p = 0.0056). Eighteen and 28 subjects in the refractory and medically controlled epilepsy groups, respectively, with comparable REM sleep percentages, underwent REM microstructure examination. Phasic REM sleep was significantly lower in the refractory group (4.5% ± 2.1% vs. 8.0% ± 4.1%; p = 0.002). In addition, the phasic-to-tonic ratio was significantly decreased (4.8 ± 2.3 vs. 8.9 ± 4.9; p = 0.002) and negatively associated with refractory epilepsy (coefficient = -0.308, p = 0.0079). CONCLUSION Patients with refractory epilepsy exhibited REM sleep disturbance at both macro and microstructure levels.

Subjectively intense odor does not affect dream emotions during rapid eye movement sleep

Abstract: Dreams experienced during rapid eye movement (REM) sleep have emotional features. Intervention methods for dream affectivity have recently garnered interest; we previously demonstrated that negative dreams were induced during REM sleep by exposure to favorable or familiar odors. However, the underlying mechanisms behind this phenomenon remain unclear. Thus, to address this gap, we investigated whether more intense odors could induce negative dreams, as odors tend to be perceived as more intense when they are preferred or familiar. Contrary to our hypothesis, the results of our study indicated that subjective intense odors did not induce negative dreams. We initially anticipated stronger odors to have a greater impact on dream emotionality, as they stimulate the brain more intensely. Notably, during arousal, weak odors tended to evoke a more potent olfactory response, while strong odors tended to produce a weaker response. To investigate whether this difference influenced the effects on dreams, we compared the respiratory activities of the strongly and weakly perceived odor groups; however, no significant differences were observed. Our findings suggest that subjectively perceived strong odors are unlikely to affect dream emotionality and may be processed differently than favorable or familiar odors.

Is REM Density a Measure of Arousal during Sleep?

Abstract: Rapid eye movements (REMs), an expression of REM sleep phasic activity, occur against a stable background of cortical desynchronization and the absence of axial tone. The significance of REMs during the sleep period was initially attributed to the mental content of dreams, linking the REMs to the dream scenario. Although fascinating, the so-called “scanning hypothesis” has not been supported by consistent evidence, and thus an alternative hypothesis is necessary to understand REMs significance during sleep. Some data suggest that the frequency of REMs during the REM sleep period, known as REM density, might be related to sleep depth or arousal during sleep. REM density increases across the night concomitantly with the progressive reduction in sleep pressure, and consistently it is higher at the circadian time when arousal appears to be higher, and it is decreased in those conditions, such as after sleep deprivation, which produce increased sleep pressure. REM density is also increased in major affective disorders, and it has been suggested either as a risk factor to develop the illness or as a predictive index of response to drug treatment. Disfunction of the neurotransmitter systems involved in arousal mechanisms and wake/sleep control might underlie the altered REM density described in depression. Understanding of the REM density mechanisms could help to untangle functional significance and regulation of REM sleep. Following the seminal idea of Aserinsky that REM density is an index of sleep satiety, it may also provide a sensitive measure of sleep homeostasis in addition to, or even as an alternative to, the consolidated analysis of slow wave activity. REM density can also be utilized to explore those mechanisms which end sleep, and considered a physiological marker which indicate during sleep the “time to wake”.

The Views of Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder on Risk Disclosure.

Abstract: BACKGROUND Isolated rapid eye movement sleep behavior disorder (iRBD) is associated with an increased risk of Parkinson's disease and other synucleinopathies. There is no consensus about disclosure of this risk to patients with iRBD. OBJECTIVE The objective of our study was to assess the experiences of risk disclosure in a group of patients with iRBD and their views on what, when, and how this should be done. METHODS A survey was administered to patients with iRBD to explore their experiences and views on risk disclosure. RESULTS Thirty-one patients with iRBD (28 males; mean age, 70 [SD 8.7] years; mean disease duration, 8.7 [SD 6.4] years) were included. A third reported they had not been informed about the link between iRBD and other conditions by clinicians at diagnosis, but 90% would have liked to have received prognostic information, and 60% indicated that this should happen at the point that iRBD was diagnosed. Most participants wanted this information to come from the clinician diagnosing and treating iRBD (90.3%). Almost three-quarters (72.2%) had searched for this information online. CONCLUSIONS Patients with iRBD mostly wished to have received information regarding the potential implications of iRBD when the diagnosis was made. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dermal Real‐Time Quaking‐Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α‐Synucleinopathy

Abstract: Skin biopsy is a potential tool for the premortem confirmation of an α‐synucleinopathy.

Eye movements during phasic vs. tonic REM sleep are biomarkers of dissociable EEG processes for the consolidation of novel problem-solving skills.

Abstract: The hallmark eye movement (EM) bursts that occur during Rapid Eye Movement (REM) sleep are markers of consolidation for procedural memory involving novel cognitive strategies and problem-solving skills. Examination of the brain activity associated with EMs during REM sleep might elucidate the processes involved in memory consolidation, and may uncover the functional significance of REM sleep and EMs themselves. Participants performed a REM-dependent, novel procedural problem-solving task (i.e., the Tower of Hanoi; ToH) before and after intervals of either overnight sleep (n=20) or a daytime 8-hour wake period (n=20). In addition, event-related spectral perturbation (ERSP) of the electroencephalogram (EEG) time-locked to EMs occurring either in bursts (i.e., phasic REM), or in isolation (i.e., tonic REM), were compared to sleep on a non-learning control night. ToH improvement was greater following sleep compared to wakefulness. During sleep, frontal-central theta (~2-8 Hz) and central-parietal-occipital sensorimotor rhythm (SMR) activity (~8-16 Hz) time-locked to EMs, were greater on the ToH night vs. control night, and during phasic REM sleep, were both positively correlated with overnight memory improvements. Furthermore, SMR power during tonic REM increased significantly from the control night to ToH night, but was relatively stable from night-to-night during phasic REM. These results suggest that EMs are markers of learning-related increases in theta and SMR during phasic and tonic REM sleep. Phasic and tonic REM sleep may be functionally distinct in terms of their contribution to procedural memory consolidation.

Ketamine affects homeostatic sleep regulation in the absence of the circadian sleep-regulating component in freely moving rats

Abstract: Pharmacological effects of ketamine may affect homeostatic sleep regulation via slow wave related mechanisms. In the present study effects of ketamine applied at anesthetic dose (80 mg/kg) were tested on neocortical electric activity for 24 h in freely moving rats. Ketamine effects were compared to changes during control (saline) injections and after 6 h gentle handling sleep deprivation (SD). As circadian factors may mask drug effects, an illumination protocol consisting of short light-dark cycles was applied. Ketamine application induced a short hypnotic stage with characteristic slow cortical rhythm followed by a long-lasting hyperactive waking resulting pharmacological SD. Coherence analysis indicated an increased level of local synchronization in broad local field potential frequency ranges during hyperactive waking but not during natural- or SD-evoked waking. Both slow wave sleep and rapid eye movement sleep were replaced after the termination of the ketamine effect. Our results show that both ketamine-induced hypnotic state and hyperactive waking can induce homeostatic sleep pressure with comparable intensity as 6 h SD, but ketamine-induced waking was different compared to the SD-evoked one. Both types of waking stages were different compared to spontaneous waking but all three types of wakefulness can engage the homeostatic sleep regulating machinery to generate sleep pressure dissipated by subsequent sleep. Current-source density analysis of the slow waves showed that cortical transmembrane currents were stronger during ketamine-induced hypnotic stage compared to both sleep replacement after SD and ketamine application, but intracortical activation patterns showed only quantitative differences. These findings may hold some translational value for human medical ketamine applications aiming the treatment of depression-associated sleep problems, which can be alleviated by the homeostatic sleep effect of the drug without the need for an intact circadian regulation.

Daytime Affect and Sleep EEG Activity: A Data-Driven Exploration

Abstract: It has long been thought that links between affect and sleep are bidirectional. However, few studies have directly assessed the relationships between (1) pre-sleep affect and sleep EEG activity, and (2) sleep EEG activity and post-sleep affect. This study aims to systematically explore the correlations between pre-/post-sleep affect and EEG activity during sleep. In a community sample of adults (n=51), we measured participants’ positive and negative affect in the evening before sleep and in the next morning after sleep. Participants slept at their residence for one night of EEG recording. Using Fourier transforms, the EEG power at each channel was estimated during rapid eye movement (REM) sleep and non-REM (NREM) sleep for the full range of sleep EEG frequencies. We first present heatmaps of the raw correlations between pre-/post-sleep affect and EEG power during REM and NREM sleep. We then thresholded the raw correlations with a medium effect size |r| ≥ 0.3. Using a cluster-based permutation test, we identified a significant cluster indicating a negative correlation between pre-sleep positive affect and EEG power in the alpha frequency range during REM sleep. This result suggests that more positive affect during the daytime may be associated with less fragmented REM sleep that night. Overall, our exploratory results lay the foundation for confirmatory research on the relationship between daytime affect and sleep EEG activity.

Muscle injury induces an increase in total and NREM sleep time.

Abstract: STUDY OBJECTIVES This study describes macro- and micro- sleep responses to a myotoxic skeletal muscle injury and investigates possible mechanisms. METHODS We recorded the electroencephalogram(EEG)/electromyogram(EMG) of 24 wistar rats before and after induction of Tibialis Anterior muscle injury (n=8 per group: control, control +buprenorphine and injured). A top-down analysis of sleep characteristics was processed from total sleep time (TST), sleep stages, sleep stability, spectral-analysis, and spindles. To further investigate the mechanisms involved, we analyzed the protein level of sleep regulatory molecules including TNF-α, IL-1β, IGF-1, BMAL1 in plasma, frontal cortex, hippocampus, and tibialis anterior, collected at Day +2 after injury from non-EEG/EMG implanted rats. RESULTS Muscle injury induces a significant increase in total sleep time at 48 and 72h post-injury, specific to NREM sleep. These increases occur during the dark period and are associated with higher stability of sleep over 24h, without change in the different power/frequency spectral bands of NREM/REM sleep. There was no corresponding sleep increase in slow-wave activity or spindle density, nor were there changes in brain levels of the sleep-regulating proinflammatory cytokine IL-1β, which is otherwise involved in the local response to injury. Conversely, decreased protein levels of brain IGF-1 and muscle BMAL1, a core circadian clock gene, after injury may play a role in increased sleep time. CONCLUSION Muscle injury induces an increase in total sleep time at 48- and 72-hours post-injury, specific to NREM sleep during the dark period in rats and is associated with higher sleep stability over 24 hours.

Sleep structure and related clinical characteristics in drug-naïve Parkinson's disease with subjectively different sleep quality

Abstract: Background Sleep disturbance is a common non-motor symptom of Parkinson's disease (PD). Most polysomnography (PSG) studies are conducted when patients are in their “on medication” state. Our study aimed to investigate changes in the sleep structure in drug-naive PD patients with poor subjective sleep quality based on polysomnography (PSG) and to explore potential correlations between sleep structure and clinical features of the disease. Methods A total of 44 drug-naive PD patients were included. All patients completed a standardized questionnaire to obtain demographic and clinical characteristics and underwent whole-night PSG recording. Patients with PSQI scores >5.5 were considered poor sleepers, and patients with PSQI scores <5.5 were considered to be good sleepers. Results There were 24 (54.5%) PD patients in the good sleeper group and 20 (24.5%) PD patients in the poor sleeper group. We observed that poor sleepers had severe non-motor symptoms (NMS) and worse life quality. The PSG displayed that they had a longer wake-up time after sleep onset (WASO) and lower sleep efficiency (SE). Correlation analysis revealed that the micro-arousal index was positively associated with UPDRS-III, and the N1 sleep percentage was negatively associated with the NMS score in good sleepers. For poor sleepers, rapid eye movement (REM) sleep percentage was negatively related to the Hoehn-Yahr (H-Y) stage, WASO increased with UPDRS-III, periodic limb movement index (PLMI) increased with the NMS score, and N2 sleep percentage was negatively related to the score of life quality. Conclusion Night awakening is the main manifestation of decreased sleep quality in drug-naive PD patients. Poor sleepers have severe non-motor symptoms and poor life quality. Additionally, the increase in nocturnal arousal events may predict the progression of motor dysfunction.