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[Display omitted] • Fentanyl was administered at dark onset and sleep-wakefulness (S-W) was examined. • Fentanyl administration significantly increased wakefulness for the first 6 h. • This initial increase in wakefulness was followed by a rebound sleep for next 6 h. • Sulpiride was injected in the accumbal core before fentanyl and S-W was examined. • D2R blockade by sulpiride in the core attenuated the effects of fentanyl on S-W. Fentanyl, a potent analgesic and addictive substance, significantly impacts sleep-wakefulness (S-W). Acutely, it promotes wake, whereas chronic abuse leads to severe sleep disruptions, including insomnia, which contributes to opioid use disorders (OUD), a chronic brain disease characterized by compulsive opioid use and harmful consequences. Although the critical association between sleep disruptions and fentanyl addiction is acknowledged, the precise mechanisms through which fentanyl influences sleep remain elusive. Recent studies highlight the role of the dopaminergic system of the nucleus accumbens (NAc) in S-W regulation, but its specific involvement in mediating fentanyl's effects on S-W remains unexplored. We hypothesized that dopamine D2 receptors mediate fentanyl-induced effects on S-W. To test this hypothesis, male C57BL/6J mice, instrumented with sleep recording electrodes and bilateral guide cannulas above the accumbal core region (NAcC), were utilized in this study. At dark onset, animals were bilaterally administered sulpiride (D2 receptors antagonist; 250 ng/side) in the NAcC followed by an intraperitoneal injection of fentanyl (1.2 mg/Kg). S-W was examined for the next 12 h. We found that systemic administration of fentanyl significantly increased wakefulness during the first 6 h of the dark which was followed by a significant increase in NREM and REM sleep during the second 6 h of the dark period. D2-receptor blockade significantly reduced this effect as evidenced by a significant reduction in fentanyl-induced wakefulness during first 6 h of dark period and sleep rebound during the second 6 h. Our findings suggest that D2 receptors in the NAcC plays a vital role in mediating the fentanyl-induced changes in S-W. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both. Method: Data presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the default mode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits—one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography. Results: Slow wave sleep duration influenced working memory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = −0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = −0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = −0.001, p = 0.017) and marginally predicted by slow wave sleep duration (B = 0.002, p = 0.081) and sleep efficiency (B = 0.006, p = 0.090). Conclusions: Findings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period. Clinical trial registration: This study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona&country=United%20States&state=Arizona&cond=insomnia&intr=tms%20&rank=1 [ABSTRACT FROM AUTHOR]

Summary The transition from non‐rapid eye movement (NREM) to rapid eye movement (REM) sleep is considered a transitional or intermediate stage (IS), characterised by high amplitude spindles in the frontal cortex and theta activity in the occipital cortex. Early reports in rats showed an IS lasting from 1 to 5 s, but recent studies suggested a longer duration of this stage of up to 20 s. To further characterise the IS, we analysed its spectral characteristics on electrocorticogram (ECoG) recordings of the olfactory bulb (OB), primary motor (M1), primary somatosensory (S1), and secondary visual cortex (V2) in 12 Wistar male adult rats. By comparing the IS with consolidated NREM/REM epochs, our results reveal that the IS has specific power spectral patterns that fall out of the NREM and REM sleep state power distribution. Specifically, the main findings were that sigma (11–16 Hz) power in OB, M1, S1, and V2 increased during the IS compared with NREM and REM sleep, which started first in the frontal part of the brain (OB −54 s, M1 −53 s) prior to the last spindle occurrence. The beta band (17–30 Hz) power showed a similar pattern to that of the sigma band, starting −54 s before the last spindle occurrence in the M1 cortex. Notably, sigma infraslow coupling (~0.02 Hz) increased during the IS but occurred at a slower frequency (~0.01 Hz) compared with NREM sleep. Thus, we argue that the NREM to REM transition contains its own local spectral profile, in accordance with previous reports, and is more extended than described previously. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess seasonal and age-related variations in sleep quality using Fitbit data and offer lifestyle recommendations for enhancing winter sleep quality. Methods: Fitbit sleep and activity data of 51 participants randomly recruited from members of the Association for Research in Supporting System of Chronic Disease, a nonprofit organization in the Yamanashi Prefecture of Japan, were collected and retrospectively analyzed from July to December 2022. Sleep stage targets were set at 10% to 25% for deep sleep, 50% to 60% for shallow sleep, and 20% to 25% for REM sleep. Participants were categorized into improved, unchanged, and worsened groups based on sleep stage unit changes between August and December. Results: The median (interquartile range) age was 71 (68–74) years old. There were eight participants in the improved group, 23 in the unchanged group, and nine in the worsened group. The improved group showed significantly more steps (990 ± 1,102 steps/day, p =.039) in December than in August, while the worsened group showed fewer steps (−507 ± 1,638 steps/day, p =.38). Conclusion: Increasing step count in winter may improve sleep quality, as assessed by sleep stage. Further research considering potential confounders and factors affecting winter sleep is needed to support and extend these findings. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Idiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α‐synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post‐mortem LTS.To assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post‐mortem presence of LTS in a broader, less‐selected, volunteer elderly population.We studied 652 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders, which were evaluated for PRBD, had completed annual movement and cognitive assessments, and had at least one the University of Pennsylvania Smell Identification Test (UPSIT) olfactory test.Histological evidence of LTS was significantly more frequent in those who had PRBD (112/152: 73.7%) than those without (177/494: 35.8%) (P < 0.001). LTS was more frequent in cases with PRBD and a low UPSIT score (90.8%) compared to cases with PRBD only (73.7%) (P < 0.001) or cases with a low UPSIT score only (69.4%) (P < 0.001). Sensitivity of PRBD diagnosis for predicting LTS was 38.8% and specificity 88.8%, whereas sensitivity of a low UPSIT score was 74.4% and specificity 73.4% (Youden's index = 0.276 for PRBD, 0.478 for UPSIT). When combining both measures, sensitivity was 34.3% and specificity increased to 97.2%.PRBD, diagnosed without sleep study confirmation, combined with a reduced olfactory performance is highly specific for predicting post‐mortem presence of LTS. The combination of both measures may provide a cost‐effective means of predicting LTS in a broader community. [ABSTRACT FROM AUTHOR]

Aim: To assess self‐reported parasomnias in patients with sleep disorders and explore relationships with psychiatric illness, comorbidities, subjective sleep assessments, and polysomnographic study results. Methods: Results from intake questionnaires and polysomnographic assessments, collected from 240 sleep centers across 30 US states between 2004 and 2019, were analyzed retrospectively. Of 540,000 total patients, 371,889 who answered parasomnia‐specific questions were included. Patients responding "often" or "always" to parasomnia‐specific questions were considered "symptom‐positive," whereas a "few times" or "never" were considered "symptom‐negative" (controls). Results: The study sample was 54.5% male with mean age 54 years (range, 2–107 years). Frequencies for the different parasomnias were 16.0% for any parasomnia, 8.8% for somniloquy, 6.0% for hypnagogic hallucinations, 4.8% for sleep‐related eating disorder, 2.1% for sleep paralysis, and 1.7% for somnambulism. Frequent parasomnias were highly associated with diagnosed depression (odds ratio = 2.72). All parasomnias were associated with being younger and female and with symptoms of depression, anxiety, insomnia, restless legs, pain, medical conditions, fatigue, and sleepiness. Associations with objective sleep metrics showed characteristics of consolidated sleep and differentiated weakly between nonrapid eye movement sleep and rapid eye movement sleep parasomnias. Machine learning accurately classified patients with parasomnia versus controls (balanced accuracies between 71% and 79%). Benzodiazepines, antipsychotics, and opioids increased the odds of experiencing parasomnias, while antihistamines and melatonin reduced the odds. Z‐drugs were found to increase the likelihood of a sleep‐related eating disorder. Conclusion: Our findings suggest that parasomnias may be clinically relevant, yet understudied, symptoms of depression and anxiety. Further investigation is needed to quantify the nature of multimorbidity, including causality and implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

For decades the greatest goal of Parkinson's disease (PD) research has often been distilled to the discovery of treatments that prevent the disease or its progression. However, until recently only the latter has been realistically pursued through randomized clinical trials of candidate disease-modifying therapy (DMT) conducted on individuals after they received traditional clinical diagnosis of PD (i.e., tertiary prevention trials). Now, in light of major advances in our understanding of the prodromal stages of PD, as well as its genetics and biomarkers, the first secondary prevention trials for PD are beginning. In this review, we take stock of DMT trials to date, summarize the breakthroughs that allow the identification of cohorts at high risk of developing a traditional diagnosis of PD, and describe key design elements of secondary prevention trials and how they depend on the prodromal stage being targeted. These elements address whom to enroll, what interventions to test, and how to measure secondary prevention (i.e., slowed progression during the prodromal stages of PD). Although these design strategies, along with the biological definition, subtype classification, and staging of the disease are evolving, all are driven by continued progress in the underlying science and integrated by a broad motivated community of stakeholders. While considerable methodological challenges remain, opportunities to move clinical trials of DMT to earlier points in the disease process than ever before have begun to unfold, and the prospects for PD prevention are nowtangible. [ABSTRACT FROM AUTHOR]

Synucleinopathies are disorders characterized by the aggregation and deposition of pathological α-synuclein conformers. The underlying neurodegenerative processes begin years or decades before the onset of cardinal motor symptoms. This prodromal phase may manifest with various signs or symptoms. However, there are no current standardized laboratory tests to ascertain the progression and conversion of prodromal conditions such as mild cognitive impairment, isolated REM sleep behavior disorder or pure autonomic failure. The aim of this systematic review was to evaluate the diagnostic possibilities using human biofluids as source material to detect pathological α-synuclein in the prodromal phase of synucleinopathies. Our review identified eight eligible studies, that investigated pathological α-synuclein conformers using cerebrospinal fluid from patients with prodromal signs of synulceinopathies to differentiate this patient group from non-synucleinopathies, while only one study investigated this aspect using blood as medium. While previous studies clearly demonstrated a high diagnostic performance of α-synuclein seed amplification assays for differentiating synucleinopathies with Lewy bodies from healthy controls, only few analyses were performed focussing on individuals with prodromal disease. Nevertheless, results for the early detection of α-synuclein seeds using α-synuclein seed amplification assays were promising and may be of particular relevance for future clinical trials and clinical practice. [ABSTRACT FROM AUTHOR]

The recent development of new methods to detect misfolded α-synuclein (αSyn) aggregates in biofluids and tissue biopsies in the earliest Parkinson's disease (PD) phases is dramatically challenging the biological definition of PD. The αSyn seed amplification methods in cerebrospinal fluid (CSF) showed high sensitivity and specificity for early diagnosis of PD and Lewy bodies disorders. Several studies in isolated REM sleep behavior disorders and other at-risk populations also demonstrated a high prevalence of CSF αSyn positivity and its potential value in predicting the phenoconversion to clinically manifested diseases. Growing evidence exists for αSyn aggregates in olfactory mucosa, skin, and other tissues in subjects with PD or at-risk subjects. DOPA decarboxylase and numerous other candidates have been additionally proposed for either diagnostic or prognostic purposes in earliest PD phases. The newly described αSyn detection in blood, through its quantification in neuronally-derived exosome vesicles, represents a technical challenge that could open a new scenario for the biological diagnosis of PD. Despite this growing evidence in the field, most of method of αSyn detection and markers still need to be validated in ongoing longitudinal studies through an accurate assessment of different prodromal disease subtypes and scenarios before being definitively implemented in clinical settings. [ABSTRACT FROM AUTHOR]

The ability to identify individuals in the prodromal phase of Parkinson's disease has improved in recent years, raising the question of whether and how those affected should be informed about the risk of future disease. Several studies investigated prognostic counselling for individuals with isolated REM sleep behavior disorder and have shown that most patients want to receive information about prognosis, but autonomy and individual preferences must be respected. However, there are still many unanswered questions about risk disclosure or early diagnosis of PD, including the impact on personal circumstances, cultural preferences and specific challenges associated with different profiles of prodromal symptoms, genetic testing or biomarker assessments. This narrative review aims to summarize the current literature on prognostic counselling and risk disclosure in PD, as well as highlight future perspectives that may emerge with the development of new biomarkers and their anticipated impact on the definition of PD. Plain Language Summary: An important goal of Parkinson's disease research is to diagnose the disease at an earlier stage, even before the typical motor symptoms appear, in the so-called 'prodromal phase'. Currently, there are no treatments available that can slow down or prevent disease progression in this early phase, even though many of the early symptoms are treatable. This raises ethical questions about whether people want to know their future risk of Parkinson's and, if so, how this information should be given. This article summarizes the current state of knowledge, but also open questions about risk disclosure in the prodromal phase of Parkinson's. Previous studies have shown that many people with early symptoms of Parkinson's would like to know their risk, but that the individual's wish to know (or not to know) must first be ascertained and respected. Future studies need to find out whether very early diagnosis of Parkinson's might have an impact on people affected, for example in terms of psychological stress or anxiety, and whether cultural background might influence attitudes to risk disclosure. Furthermore, it is expected that in the future it will be possible to make an early diagnosis of Parkinson's using specific new techniques, e.g., by testing spinal fluid. It is of utmost importance to find out if and how test results of these new techniques should be communicated to patients, even if they do not lead to direct medical treatment. [ABSTRACT FROM AUTHOR]

During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The most important among them are REM sleep behavior disorder (RBD) and olfactory dysfunction. RBD is a parasomnia characterized by the loss of REM sleep muscle atonia and dream-enacting behaviors. Olfactory dysfunction in individuals with prodromal PD is usually described as hyposmia (reduced sense of smell) or anosmia (complete loss of olfactory function). These symptoms can precede the full expression of motor symptoms by decades. A close comprehension of these symptoms and the underlying mechanisms may enable early screening as well as interventions to improve patients' quality of life. Therefore, these symptoms have unmatched potential for identifying PD patients in prodromal stages, not only allowing early diagnosis but potentially opening a window for early, possibly disease-modifying intervention. However, they come with certain challenges. This review addresses some of the key opportunities and pitfalls of both RBD and olfactory dysfunction as early markers of PD. [ABSTRACT FROM AUTHOR]

The article "To Home-Routine-Sleep, or Not to Home-Routine-Sleep: That Is the Intensive Care Question" discusses the impact of sleep disruptions on critically ill children in the Pediatric Intensive Care Unit (PICU). Factors such as chaotic surroundings, pain, medications, and caregiving can disrupt circadian rhythms and inhibit melatonin production, leading to cognitive impairment. The study highlights the importance of maintaining consistent sleep routines and identifies modifiable factors like sound pollution and nutrition timing that can impact sleep quality in the PICU. While the study provides valuable insights, methodological weaknesses limit the robustness of its conclusions, emphasizing the need for further research to develop effective sleep-promoting interventions for critically ill children. [Extracted from the article]

Introduction: Sleep disturbances are being increasingly recognized in association with autoimmune encephalitis (AIE). We investigated the prevalence of sleep-related symptoms and polysomnographic features of patients with AIE and the long-term outcomes in these patients in a multi-center, prospective study from Turkey. Methods: We prospectively evaluated patients with definite AIE in a common database including demographics, AIE-related and sleep-related symptomatology. Maximum and latest modified Rankin scores (mRS) and Liverpool Outcome Score (LOS) were noted. Results: Of 142 patients, 87 patients (61.3%) fulfilled the criteria for definite AIE (mean age, 46.8+18.8 years; 51.7% women; mean disease duration, 21.0+38.4 months). 78.9% of patients had at least one or more new onset or worsened sleep-related symptomatology: insomnia (55.3%), excessive daytime sleepiness (EDS, 28.0%), sleep apnea (18.7%), REM sleep behavior disorder (RBD, 17.3%), restless legs syndrome (10.7%) and oneiric stupor (9.3%). Sleep efficiency, N3 and REM sleep were decreased and N1 sleep was increased in patients with Ab[+] AIE. LOS points were highest in those with insomnia and sleep apnea, and lowest in those with EDS, RBD and oneiric stupor. RBD and sleep apnea were more common in anti-LG1 Ab[+] group than anti-NMDAR Ab[+] group. Index of periodic leg movements was highest in anti-LG1 Ab[+] group. Patients with EDS and oneiric stupor had more common memory problems. Maximum and latest mRS scores were positively correlated with EDS and oneiric stupor. EDS, RBD and oneiric stupor were negatively correlated with LOS points. Conclusion: Our study emphasizes the presence and importance of early diagnosis of sleep disturbances in AIE in regard to their deteriorative influences on disease prognosis. [ABSTRACT FROM AUTHOR]

Identifying biomarkers that predict substance use disorder propensity may better strategize antiaddiction treatment. Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus critically mediate interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Surface EEG signals and real-time calcium (Ca2+) activities of lateral hypothalamus MCH neurons (Ca2+ MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+ MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+ MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. An EEG waveform derivative—a modified theta-delta-theta peak ratio (EEG TDT ratio)—accurately tracked real-time Ca2+ MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through vigilance states, sleep manipulations, and circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG TDT ratio, suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG TDT ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG TDT ratio also exhibited advantages over conventional REMS measures for the predictions. The identified EEG TDT ratio may serve as a noninvasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker for predicting drug use propensity. [ABSTRACT FROM AUTHOR]

Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp + neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp + neurons, neurons expressing nitric oxide synthase 1 (Nos1 + neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1 + neurons also project to areas that control wide forebrain activity. Ablating Crhbp + neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease. [Display omitted] • Crhbp + SubLDT→Gi neurons promote REM sleep and muscle atonia • Nos1 + DPGi,Pr neurons promote REM sleep and project to areas regulating forebrain activity • The above 2 neuronal populations constitute a pontine-medullary loop circuit • CRHBP+ SubLDT neurons are lost in human patients with Parkinson's disease and RBD A neuronal circuit originating in the brainstem pons and medulla strongly induces REM sleep, even in awake mice. Moreover, a subpopulation of neurons within this circuit is lost in patients with Parkinson's disease, a neurodegenerative disease characterized by severe REM sleep abnormalities. [ABSTRACT FROM AUTHOR]

Background: Insomnia is more prevalent in individuals with Autism Spectrum Disorder (ASD), can worsen core-symptoms and reduces quality of life of both individuals and caregivers. Although ASD is four times more prevalent in males than females, less is known about sex specific sleep differences in autistic individuals. Recent ASD studies suggest that sleep problems may be more severe in females, which aligns with the sex bias seen in insomnia for the general population. We have previously shown that male mice with a mutation in the high confidence ASD gene Shank3, Shank3∆C, recapitulate most aspects of the ASD insomnia phenotype. The objective of the present study was to leverage the Shank3∆C model to investigate sex-specific effects in sleep using polysomnography. Methods: Adult male and female Shank3∆C and wildtype (WT) littermates were first recorded for 24 h of baseline recordings. Subsequently, they were sleep deprived (SD) for five hours via gentle handling and allowed 19 h of recovery sleep to characterize the homeostatic response to SD. Vigilance states (rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wake) were assigned by manual inspection using SleepSign. Data processing, statistical analysis and visualization were conducted using MATLAB. Results: Sex and genotype effects were found during baseline sleep and after SD. At baseline, male Shank3∆C mice sleep less during the dark period (active phase) while female Shank3∆C mice sleep less during the light period (rest phase) and sleep more during the dark period. Both male and female Shank3∆C mice show reduced spectral power in NREM sleep. We detect a significant effect of sex and genotype in sleep onset latency and homeostatic sleep pressure (sleepiness). In addition, while male Shank3∆C mice fail to increase sleep time following SD as seen in WT, female Shank3∆C mice decrease sleep time. Conclusions: Overall, our study demonstrates sex differences in sleep architecture and homeostatic response to SD in adult Shank3∆C mice. Thus, our study demonstrates an interaction between sex and genotype in Shank3∆C mice and supports the use of the Shank3∆C model to better understand mechanisms contributing to the sex differences in insomnia in ASD in clinical populations. Plain language summary: Sleep problems are common in people with Autism Spectrum Disorder (ASD) and can make their condition worse, impacting both their lives and those of their caregivers. Historically ASD has been diagnosed more often in males and much less is known about the female phenotype. However, recent studies suggest that sleep problems may be more severe in autistic females. We previously shown that the ASD mouse model, Shank3∆C, display an autism like sleep phenotype. Using this model, we examine sex specific deficits in sleep. We investigated canonical measures of sleep during undisturbed conditions (sleep architecture) and after sleep deprivation (sleep homeostasis). Our findings revealed that male Shank3∆C mice slept less during their active period while female Shank3∆C mice slept less during their rest period and more during their active period. In addition, both male and female Shank3∆C mice displayed lower sleep quality. After sleep deprivation, both male and female Shank3∆C mice took longer to fall asleep despite accumulation of sleep pressure, however, differences in sleep time after sleep deprivation differed based on sex. In healthy controls, sleep time increases after sleep deprivation. Male Shank3∆C mice showed no such increase in sleep time, while female Shank3∆C mice slept even less. Our results suggest sex specific differences in two hallmark measures of sleep, architecture and sleep homeostasis in this ASD model. These results highlight the importance of awareness of sex specific differences when studying sleep in ASD as well as eventual treatment or interventions. Highlights: At baseline, Shank3∆C mice have a time-of-day dependent reduction in sleep time. Male Shank3∆C mice had reduced sleep during the active phase, while female mice had reduced sleep during the rest phase but increased sleep during the active phase. Shank3∆C mice have a reduction of EEG spectral power during non-rapid eye movement sleep, suggesting reduced sleep synchrony or quality. Both male and female Shank3∆C mice show an impaired response to sleep deprivation. While male Shank3∆C mice fail to increase sleep time after sleep deprivation, female Shank3∆C mice decrease sleep time after sleep deprivation. After sleep deprivation, both male and female Shank3∆C mutant mice have a delayed sleep onset despite accumulation of sleep pressure similar to wildtype animals. [ABSTRACT FROM AUTHOR]

Introduction: Little was known about the relationship between sleep disturbances and depressive and anxiety disorders, as well as the efficacy of treatment regimens. Methods: During 2021 to 2023, a total of 417 participants were screened by Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA-14) for psychological status, and Pittsburgh sleep quality index (PSQI) assessment. 409 participants were finally enrolled, of which 188 (45.97%) were suffered from sleep disorders. All participants were received polysomnography (PSG) followed by six-week pharmacological treatment of escitalopram and zopiclone, and finally assessed by HAMD-17 and HAMA-14 for treatment efficacy. Result: PSG monitoring indicated that participants with depression experienced prolonged rapid eye movement sleep latency (REMSL) and increased wakefulness after sleep onset (WASO) (P=0.030 and P=0.002, respectively). Those with anxiety disorders demonstrated a significantly higher percentage of non-rapid eye movement sleep (NREM%) and reduced WASO (P=0.013 and P=0.001, respectively). After six-weeks pharmacological treatment, participants with or without sleep disorders exhibited with similar efficacy outcomes of depression and anxiety disorders (P>0.05). However, every point of PSQI increment at baseline would decrease 0.78 and 0.85 times of probability of effective pharmacological treatment of depression and anxiety disorders. Moreover, participants with both effective outcomes of depression and anxiety disorders were found significant shorter sleep onset latency (SOL) (P<0.001). Discussion: The insights gained underscore the necessity of considering sleep disturbances in enhancing the overall effectiveness of pharmacological treatments for depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

Objective: Multiple system atrophy (MSA) is commonly associated with rapid eye movement sleep behavior disorder (RBD). Research on the prevalence of RBD in MSA and its effects on MSA patients has yielded inconsistent results. Currently, there is only one meta-analysis discussing the prevalence of RBD in MSA, but no meta-analysis discussing the impact of RBD on MSA. Methods: A systematic review and meta-analysis was conducted by searching studies related to MSA and RBD in PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate prevalence of RBD, odds ratio (OR), weighted mean differences (WMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. Results: The prevalence of polysomnography confirmed-RBD in MSA was 79.9% (95% CI, 68.8-89.3%) in a pooled sample of 598 subjects. Patients with MSA who had RBD were notably younger at examination than those without RBD (WMD -3.26 years, 95% CI -4.99 to -1.53), and the age of disease onset in MSA patients with RBD was significantly lower than in those without RBD (WMD -3.27, 95% CI -5.06 to -1.48). Additionally, RBD was more common among male patients with MSA compared to female patients (OR 2.11, 95% CI 1.31 to 3.39). MSA patients with RBD also exhibited significantly higher Unified Multiple System Atrophy Rating Scale (UMSARS) I and IV scores than those without RBD (WMD 2.99, 95% CI 0.10 to 4.88, and WMD 0.23, 95% CI 0.03 to 0.43). Conclusion: The prevalence of polysomnography-confirmed RBD in MSA is 79.9%. The prevalence in Asian population was lower than in Europe and America, which might be related to an underestimation in Asian populations. Additionally, patients with MSA and RBD tend to be younger at examination, have an earlier age of onset, and exhibit more severe disease manifestations compared to MSA patients without RBD. [ABSTRACT FROM AUTHOR]

Summary The ‘first night effect’ (FNE) is a well‐known phenomenon in polysomnographic (PSG) sleep studies, resulting in significant variations in the macrostructure of wakefulness and sleep states, particularly between the initial and subsequent sleep recording sessions. The FNE phenomenon during sleep has been studied in various species, revealing complex variations between several sessions of sleep recording. The present study used a non‐invasive PSG method to examine differences between various vigilance states in four adult female dromedary camels during 4 consecutive nights and days of sleep recording. The results indicate the presence of a FNE in the architecture of the dromedary camel's vigilance states. On the first night, the proportions of wakefulness and light non‐rapid eye movment (NREM) sleep (drowsiness) were higher, at a mean (standard error of the mean [SEM]) of 40.92% (0.88%) and 14.93% (0.37%), respectively; while the proportion of rumination (mean [SEM] 29.55% [0.92%]) was lower compared to consecutive nights. No FNE was found on deep NREM sleep, while night‐time REM sleep had a shorter proportion during the first night compared to subsequent consecutive nights. A significantly lower REM/total sleep time (TST) ratio was observed on the first night. Daytime comparisons did not show any significant differences for the different vigilance states. The increase in wakefulness and light NREM sleep and the reduction in REM sleep and REM/TST sleep on the first night indicate a decline in sleep quality in the dromedary camel due to the FNE. Thus, we recommend excluding from a PSG sleep study at least the first session/night of the recordings to ensure accurate results. [ABSTRACT FROM AUTHOR]

During paradoxical sleep (PS, aka REM sleep) the cerebral cortex displays rapid electroencephalographic activity similar to that of wakefulness, whereas in the posterior associative thalamus, rapid activity is interrupted by frequent periods of slow‐wave (delta) oscillations at 2–3 Hz, thereby dissociating the intrinsic frequency in thalamus and cortex. Here we studied the functional consequences of such a dissociation using intrathalamic and intracortical recordings in 21 epileptic patients, applying coherence analysis to examine changes in functional connectivity between the posterior thalamus (mainly medial pulvinar) and six cortical functional networks, and also between each cortical network with respect to the others. Periods of slow‐wave thalamic activity ('delta PS') were more prevalent than phases of 'rapid PS,' and the delta/rapid thalamic alternance did not overlap with the classical tonic/phasic dichotomy based on rapid eye movements. Thalamo‐cortical and cortico‐cortical functional connectivity significantly decreased during delta PS, relative to both rapid PS periods and to wakefulness. The fact that delta thalamic activity and low thalamo‐cortical binding coincided with a suppression of cortico‐cortical connectivity supports a crucial role for the posterior associative thalamus, and particularly the medial pulvinar, in ensuring trans‐thalamic communication between distant cortical areas. Disruption of such a trans‐thalamic communication during delta PS compromises the functional binding between cortical areas, and consequently might contribute to the alteration of perceptual experiences commonly reported during dreams. Key points: During paradoxical, or REM, sleep (PS), rapid thalamic activity is interrupted by frequent periods of slow delta waves at 2–3 Hz.During these periods of thalamic delta activity there was a drastic drop of functional connectivity between associative thalamus and cortex, and also among different cortical networks.The delta/rapid alternance did not overlap with the classically defined 'tonic/phasic' periods and therefore suggests a distinct dichotomy of functional states in PS.Recurrent decrease in thalamo‐cortical and cortico‐cortical functional connectivity during PS may compromise the spatio‐temporal binding between cortical areas, which in turn could hinder the formation of coherent mental content during dreams. [ABSTRACT FROM AUTHOR]

Delirium is a heterogeneous syndrome primarily characterized by fluctuations in attention and awareness. Sleep–wake disturbances are a common and significant feature of delirium and can manifest as circadian rhythm inversion, sleep fragmentation, and reduced rapid eye movement (REM) and slow‐wave sleep. Some literature suggests that the relationship between sleep disruption and delirium is reciprocal wherein the two reinforce one another and may share an underlying etiology. As there are no FDA‐approved medications for delirium or delirium‐related sleep disturbances, management is primarily focused on addressing underlying medical concerns and promoting physiologic circadian patterns with non‐pharmacological behavioral interventions. In practice, however, medications are often used, albeit with limited evidence to support their use. This literature review explores the pharmacology and pharmacokinetics of several medications with literature investigating their use in delirium: melatonin, ramelteon, dual orexin receptor antagonists (DORAs), and dexmedetomidine. Current evidence suggests a possible benefit of ramelteon or melatonin, dexmedetomidine for patients in the ICU setting, and DORAs as therapeutic options for the re‐regulation of sleep–wake cycle disruption in delirium. We discuss pertinent pharmacokinetic and pharmacodynamic factors that may influence clinical decision‐making regarding these interventions. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Rapid eye movement sleep behavior disorder (RBD) is linked to the diffuse‐malignant subtype and higher cognitive burden in Lewy body disease (LBD).This study explores brain β‐amyloid deposition and its association with cognitive decline across the RBD–LBD continuum.Patients with isolated RBD (iRBD), Parkinson's disease with probable RBD (PDRBD), and dementia with Lewy bodies with probable RBD (DLBRBD) underwent 18F‐florbetaben positron emission tomography, 3T magnetic resonance imaging scans, and comprehensive neuropsychological assessments. Subjects were categorized as cognitively normal (NC), mild cognitive impairment (MCI), or dementia. Global and regional standardized uptake value ratios (SUVR) were estimated in predefined cognitive volumes of interest (VOI) derived from voxel‐wise comparison analysis among the cognitive groups, namely the prefrontal, parietal, precentral cortices, lingual gyrus, and supplementary motor area. Generalized linear models assessed the relationship between 18F‐florbetaben SUVRs and neuropsychological testing, adjusting for age and sex. Subgroup analysis focused on the polysomnography‐confirmed iRBD‐continuum subset (n = 41) encompassing phenoconverters and nonconverters in our prospective iRBD cohort.Eighty‐six subjects were classified as follows: 14 NC, 54 MCI, and 18 dementia. The proportion of positive β‐amyloid scans increased with advanced cognitive stages (P = 0.038). β‐Amyloid signals in cognitive VOIs were elevated in subgroups showing impairment in Trail‐Making Test B (TMT‐B). A linear association between TMT‐B z score and global cortical β‐amyloid levels was observed in the iRBD‐continuum subset (P = 0.013).Cortical β‐amyloid accumulates with declines in executive function within the RBD–LBD continuum. TMT‐B performance may be a useful marker associating with β‐amyloid load, particularly in the iRBD population. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

• AD is the most common neurodegenerative disease and associated with sleep problems. • Abnormal accumulation of Aβ and hyperphosphorylated tau are key contributors to AD. • Circadian rhythm and neuronal oscillation disorders is associated with AD pathology. • Sleep disorders worsen Aβ and tau pathology and cause severe neuroinflammation. Alzheimer's disease (AD) is the most prevalent dementia, pathologically featuring abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, while sleep, divided into rapid eye movement sleep (REM) and nonrapid eye movement sleep (NREM), plays a key role in consolidating social and spatial memory. Emerging evidence has revealed that sleep disorders such as circadian disturbances and disruption of neuronal rhythm activity are considered as both candidate risks and consequence of AD, suggesting a bidirectional relationship between sleep and AD. This review will firstly grasp basic knowledge of AD pathogenesis, then highlight macrostructural and microstructural alteration of sleep along with AD progression, explain the interaction between accumulation of Aβ and hyperphosphorylated tau, which are two critical neuropathological processes of AD, as well as neuroinflammation and sleep, and finally introduce several methods of sleep enhancement as strategies to reduce AD-associated neuropathology. Although theories about the bidirectional relationship and relevant therapeutic methods in mice have been well developed in recent years, the knowledge in human is still limited. More studies on how to effectively ameliorate AD pathology in patients by sleep enhancement and what specific roles of sleep play in AD are needed. [ABSTRACT FROM AUTHOR]

We used numerical methods to define the normative structure of the different stages of sleep and wake (W) in a pilot study of 19 participants without pathology (18–64 years old) using a double-banana bipolar montage. Artefact-free 120–240 s epoch lengths were visually identified and divided into 1 s windows with a 10% overlap. Differential channels were grouped into frontal, parieto-occipital, and temporal lobes. For every channel, the power spectrum (PS) was calculated via fast Fourier transform and used to compute the areas for the delta (0–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) bands, which were log-transformed. Furthermore, Pearson's correlation coefficient and coherence by bands were computed. Differences in logPS and synchronization from the whole scalp were observed between the sexes for specific stages. However, these differences vanished when specific lobes were considered. Considering the location and stages, the logPS and synchronization vary highly and specifically in a complex manner. Furthermore, the average spectra for every channel and stage were very well defined, with phase-specific features (e.g., the sigma band during N2 and N3, or the occipital alpha component during wakefulness), although the slow alpha component (8.0–8.5 Hz) persisted during NREM and REM sleep. The average spectra were symmetric between hemispheres. The properties of K-complexes and the sigma band (mainly due to sleep spindles—SSs) were deeply analyzed during the NREM N2 stage. The properties of the sigma band are directly related to the density of SSs. The average frequency of SSs in the frontal lobe was lower than that in the occipital lobe. In approximately 30% of the participants, SSs showed bimodal components in the anterior regions. qEEG can be easily and reliably used to study sleep in healthy participants and patients. [ABSTRACT FROM AUTHOR]

Objective: Levodopa‐induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. Method s : We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non‐DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six‐channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. Results: Compared with the non‐DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole‐night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5–2 Hz, 0.5–4 Hz, and 2–4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low‐frequency (0.5–2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. Conclusion: PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low‐frequency (0.5–2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD. [ABSTRACT FROM AUTHOR]

Sleep, constituting approximately one‐third of the human lifespan, is a crucial physiological process essential for physical and mental well‐being. Normal sleep consists of an orderly progression through wakefulness, non‐rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the "hormone of sleep," plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high‐affinity G‐protein coupled receptors known as MT1 and MT2. Selective modulation of these receptors presents a promising therapeutic avenue for sleep disorders. This review examines research on the multifaceted role of melatonin in sleep regulation, focusing on selective ligands targeting MT1 and MT2 receptors, as well as studies involving MT1 and MT2 knockout mice. Contrary to common beliefs, growing evidence suggests that melatonin, through MT1 and MT2 receptors, might not only influence circadian aspects of sleep but likely, also modulate the homeostatic process of sleep and sleep architecture, or could be the molecule linking the homeostatic and circadian regulation of sleep. Furthermore, the distinct brain localization of MT1 and MT2 receptors, with MT1 receptors primarily regulating REM sleep and MT2 receptors regulating NREM sleep, is discussed. Collectively, sleep regulation extends beyond the circulating levels and circadian peak of melatonin; it also critically involves the expression, molecular activation, and regulatory functions of MT1 and MT2 receptors across various brain regions and nuclei involved in the regulation of sleep. This research underscores the importance of ongoing investigation into the selective roles of MT1 and MT2 receptors in sleep. Such research efforts are expected to pave the way for the development of targeted MT1 or MT2 receptors ligands, thereby optimizing therapeutic interventions for sleep disorders. [ABSTRACT FROM AUTHOR]

Introduction: Strong indications support the notion that idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) acts as a precursor to multiple α‐synucleinopathies, including Parkinson's disease and dementia with Lewy bodies. Despite numerous investigations into the alterations in cortical thickness and the volume of subcortical areas associated with this condition, comprehensive studies on the cortical surface morphology, focusing on gyrification and sulcal depth changes, are scarce. The purpose of this research was to explore the cortical surface morphology in individuals with probable iRBD (piRBD), to pinpoint early‐phase diagnostic markers. Methods: This study included 30 piRBD patients confirmed using the RBD Screening Questionnaire (RBDSQ) and 33 control individuals selected from the Parkinson's Progression Markers Initiative (PPMI) database. They underwent neurophysiological tests and MRI scans. The FreeSurfer software was utilized to estimate cortical thickness (CTH), cortical and subcortical volumetry, local gyrification index (LGI), and sulcus depth (SD). Subsequently, these parameters were compared between the two groups. Additionally, linear correlation analysis was employed to estimate the relationship between brain morphological parameters and clinical parameters. Results: Compared to the healthy control (HC), piRBD patients exhibited a significant reduction in CTH, LGI, and cortical volume in the bilateral superior parietal, lateral occipital, orbitofrontal, temporo‐occipital, bilateral rostral middle frontal, inferior parietal, and precentral brain regions. Moreover, a significant and notable correlation was observed between CTH and Geriatric Depression Scale (GDS), letter–number sequencing (LTNS), the Benton Judgment of Line Orientation (BJLO) test, and the symbol digit modalities test (SDMT) in several brain regions encompassing the motor cortex. Conclusion: Patients with piRBD displayed widespread atrophy in various brain regions, predominantly covering the motor and sensory cortex. Furthermore, LGI could serve as a prognostic biomarker of disease's progression in piRBD. [ABSTRACT FROM AUTHOR]

Background: SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility. While sleep disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients. Methods: Here, we assessed sleep disturbances in patients through caregiver reported surveys and in a transgenic mouse model of SLC13A5 deficiency. A total of 26 patients were evaluated with the Sleep Disturbance Scale for Children three times over a one-year span. Sleep and wake activities were assessed in the SLC13A5 knock-out (KO) mice using wireless telemetry devices. Results: A high burden of clinically significant sleep disturbances were reported in the patients, with heterogeneous symptoms that remained stable across time. While sleep disturbances were common, less than 30% of patients were prescribed medications for sleep. Comparatively, in SLC13A5 KO mice using EEG recordings, significant alterations were found during light cycles, when rodents typically sleep. During the sleep period, SLC13A5 mice had increased activity, decreased paradoxical sleep, and changes in absolute power spectral density, indicating altered sleep architecture in the mouse model. Conclusions: Our results demonstrate a significant component of sleep disturbances in SLC13A5 patients and mice, highlighting a potential gap in patient care. Further investigation of sleep dysfunction and the underlying etiologies of sleep disturbances in SLC13A5 citrate transporter disorder is warranted. [ABSTRACT FROM AUTHOR]

The influence of brain atrophy on sleep microstructure in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. The objective of the study is to explore the relationship between sleep microstructure and brain atrophy in SCA2 and its role in the clinical phenotype. Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI, and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. The sleep spindle activity exhibited a negative correlation with the number of trials required to complete the verbal memory test (VMT), and a positive correlation with the cerebellar volume, but the significance of the latter correlation did not survive multiple testing corrections. However, the causal mediation analyses unveiled that sleep spindle activity significantly mediates the association between cerebellar atrophy and VMT performance. Regarding REM sleep, both phasic EMG activity and REM sleep without atonia exhibited significant associations with pontine atrophy and disease severity measures. However, they did not demonstrate a causal mediation effect between the atrophy measures and disease severity. Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindle activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as disease biomarkers. Clinical trial registration number (TRN): No applicable. [ABSTRACT FROM AUTHOR]

Summary: Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full‐night in‐laboratory polysomnography from 100 patients with Down syndrome, and 100 age‐ and sex‐matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.4 years); 84 were younger than 12 years, and 54 were male. From each electroencephalogram, we extracted relative power in six frequency bands or rhythms (delta, theta, alpha, slow sigma, fast sigma, and beta) from six channels (frontal F3 and F4, central C3 and C4, and occipital O1 and O2) during five sleep stages (N3, N2, N1, R and W)—180 features in all. We examined differences in relative power between Down syndrome and control electroencephalograms for each feature separately. During wake and N1 sleep stages, alpha rhythms (8.0–10.5 Hz) had significantly lower power in patients with Down syndrome than controls. Moreover, the rate of increase in alpha power with age during rapid eye movement sleep was significantly slower in Down syndrome than control subjects. During wake and N1 sleep, delta rhythms (0.25–4.5 Hz) had higher power in patients with Down syndrome than controls. During N2 sleep, slow sigma rhythms (10.5–12.5 Hz) had lower power in patients with DS than controls. These findings extend previous research from routine electroencephalogram studies demonstrating that patients with Down syndrome had reduced circadian amplitude—the difference between wake alpha power and deep sleep delta power was smaller in Down syndrome than control subjects. We envision that these brain oscillatory activities may be used as surrogate markers for clinical trials for patients with Down syndrome. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to reveal the pathophysiology of isolated rapid eye movement sleep behaviour disorder (RBD) in patients using multilayer network analysis. Participants eligible for isolated RBD were included and verified via polysomnography. Both iRBD patients and healthy controls underwent brain MRI, including T1‐weighted imaging and diffusion tensor imaging. Grey matter matrix was derived from T1‐weighted images using a morphometric similarity network. White matter matrix was formed from diffusion tensor imaging‐based structural connectivity. Multilayer network analysis of grey and white matter was performed using graph theory. We studied 29 isolated RBD patients and 30 healthy controls. Patients exhibited a higher average overlap degree (27.921 vs. 23.734, p = 0.002) and average multilayer clustering coefficient (0.474 vs. 0.413, p = 0.002) compared with controls. Additionally, several regions showed significant differences in the degree of overlap and multilayer clustering coefficient between patients with isolated RBD and healthy controls at the nodal level. The degree of overlap in the left medial orbitofrontal, left posterior cingulate, and right paracentral nodes and the multilayer clustering coefficients in the left lateral occipital, left rostral middle frontal, right fusiform, right inferior posterior parietal, and right parahippocampal nodes were higher in patients with isolated RBD than in healthy controls. We found alterations in the multilayer network at the global and nodal levels in patients with isolated RBD, and these changes may be associated with the pathophysiology of isolated RBD. Multilayer network analysis can be used widely to explore the mechanisms underlying various neurological disorders. [ABSTRACT FROM AUTHOR]

Summary: How memory representations are shaped during and after their encoding is a central question in the study of human memory. Recognition responses to stimuli that are similar to those observed previously can hint at the fidelity of the memories or point to processes of generalization at the expense of precise memory representations. Experimental studies utilizing this approach showed that emotions and sleep both influence these responses. Sleep, and more specifically rapid eye movement sleep, is assumed to facilitate the generalization of emotional memories. We studied mnemonic discrimination by the emotional variant of the Mnemonic Separation Task in participants (N = 113) who spent a daytime nap between learning and testing compared with another group that spent an equivalent time awake between the two sessions. Our findings indicate that the discrimination of similar but previously not seen items from previously seen ones is enhanced in case of negative compared with neutral and positive stimuli. Moreover, whereas the sleep and the wake groups did not differ in memory performance, participants entering rapid eye movement sleep exhibited increased generalization of emotional memories. Our findings indicate that entering into rapid eye movement sleep during a daytime nap shapes emotional memories in a way that enhances recognition at the expense of detailed memory representations. [ABSTRACT FROM AUTHOR]

Summary: Sleep‐disordered breathing is highly prevalent in individuals with high‐level spinal cord injury. In addition, chest mechanics are known to be altered, leading to paradoxical breathing. Here we investigated the interaction between paradoxical breathing and sleep quality in these patients, and its association with measurements of respiratory function, hypercapnic ventilatory response and peak exercise ventilation. Home‐based polysomnography was performed in 13 patients with spinal cord injury (C4 to T4) untreated for sleep‐disordered breathing. We defined paradoxical breathing as counterphase between thoracic and abdominal movements during slow‐wave and rapid eye movement sleep. Sleep quality, pulmonary function, hypercapnic ventilatory responses and peak exercise ventilation were compared between those with and without paradoxical breathing. Half of individuals presented with nocturnal paradoxical breathing. Despite similar age, body mass index, injury level, time since injury, and respiratory function, those with paradoxical breathing had higher apnea–hypopnea index (13 ± 8 versus 5 ± 3 events per hr) and average sleep heart rate (67 ± 12 versus 54 ± 4 bpm; p < 0.05). Moreover, paradoxical breathing was associated with lower hypercapnic ventilatory response (slope: 0.35 ± 0.17 versus 0.96 ± 0.38) and lower peak exercise ventilation (33 ± 4 versus 48 ± 12 L min−1; p < 0.05). Nocturnal respiratory muscle desynchronization could play a role in the pathophysiology of sleep apnea, and could relate to low ventilatory responses to both hypercapnia and exercise in high‐level spinal cord injury. Polysomnography may be an important diagnostic tool for these patients for whom therapeutic approaches should be considered to treat this abnormality. [ABSTRACT FROM AUTHOR]

Summary: The circuitry underlying the initiation, maintenance, and coordination of wakefulness, rapid eye movement sleep, and non‐rapid eye movement sleep is not thoroughly understood. Sleep is thought to arise due to decreased activity in the ascending reticular arousal system, which originates in the brainstem and awakens the thalamus and cortex during wakefulness. Despite the conventional association of sleep–wake states with hippocampal rhythms, the mutual influence of the hippocampal formation in regulating vigilance states has been largely neglected. Here, we focus on the subiculum, the main output region of the hippocampal formation. The subiculum, particulary the ventral part, sends extensive monosynaptic projections to crucial regions implicated in sleep–wake regulation, including the thalamus, lateral hypothalamus, tuberomammillary nucleus, basal forebrain, ventrolateral preoptic nucleus, ventrolateral tegmental area, and suprachiasmatic nucleus. Additionally, second‐order projections from the subiculum are received by the laterodorsal tegmental nucleus, locus coeruleus, and median raphe nucleus, suggesting the potential involvement of the subiculum in the regulation of the sleep–wake cycle. We also discuss alterations in the subiculum observed in individuals with sleep disorders and in sleep‐deprived mice, underscoring the significance of investigating neuronal communication between the subiculum and pathways promoting both sleep and wakefulness. [ABSTRACT FROM AUTHOR]

Background: Little is known about the characteristics and occurrence frequencies of rapid eye movements (REMs) during REM sleep in movement disorders. Objectives: The aim of this study was to detect and characterize REMs during polysomnographically defined REM sleep as recorded by electro‐oculography (EOG) in 12 patients with progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD) and 12 healthy controls. Methods: Using a modified EOG montage, we developed an algorithm that automatically detects and characterizes REMs during REM sleep based on their presumptive saccadic kinematics. Results: Compared to PD and healthy controls, REM densities and REM peak velocities were significantly reduced in PSP. These effects were most pronounced in vertical REMs. Conclusion: Ocular motor dysfunction, one of the cardinal features of PSP, seems to be equally at play during REM sleep and wakefulness. For future studies, we provide a novel tool for the unbiased analysis of REMs during REM sleep in movement disorders. [ABSTRACT FROM AUTHOR]

Aim: To investigate the role of autonomic nervous system in subpopulations of children with enuresis. Methods: We included 35 children with enuresis, divided in children with (17) and without nocturnal polyuria (18) and 43 healthy controls. For all participants hormones and neurotransmitters were measured. Patients and controls wore a sleep tracker device and children with enuresis underwent a 24 h blood pressure monitoring, nocturnal urine output measurement and uroflowmetry. Results: Children with enuresis had lower than controls copeptin and aldosterone, with the latter being more prominent in patients without nocturnal polyuria. Dopamine was lower in patients without nocturnal polyuria compared with patients with nocturnal polyuria. Children without polyuria experienced episodes only during NREM sleep, whereas in children with polyuria episodes occurred in both REM and NREM sleep. Children with enuresis experienced a non‐dipping phenomenon during sleep which was more prominent in the group without polyuria. Conclusion: In patients with nocturnal polyuria, nocturnal enuresis is associated with sympathetic hyperactivity which results in pressure polyuria and significantly lower systolic dipping during sleep. On the contrary, in children without nocturnal polyuria, it is mostly associated with bladder overactivity due to parasympathetic overstimulation as demonstrated by the NREM‐related enuretic episodes and the lower aldosterone and dopamine levels. [ABSTRACT FROM AUTHOR]

Summary Dreaming, a common yet mysterious cognitive phenomenon, is an involuntary process experienced by individuals during sleep. Although the fascination with dreams dates back to ancient times and gained therapeutic significance through psychoanalysis in the early twentieth century, its scientific investigation only gained momentum with the discovery of rapid eye movement (REM) sleep in the 1950s. This review synthesises current research on the neurobiological and psychological aspects of dreaming, including factors influencing dream recall and content, neurophysiological correlates, and experimental models, and discusses the implications for clinical practice. [ABSTRACT FROM AUTHOR]

Background: REM Sleep Behavior Disorder (RBD) is characterized by absence of physiological muscle atonia during REM sleep (REM sleep without atonia, RWA). Nigro-striatal dopaminergic impairment is a feature of Parkinson disease (PD) and can be identified in prodromal stages as well, such as idiopathic RBD (iRBD). Aims of this study are to explore the efficacy of an automatic RWA quantification in identifying RBD patients and the correlation between RWA and nigro-striatal dopaminergic function. Methods: Forty-five iRBD, 46 PD with RBD, 24 PD without RBD patients and 11 healthy controls were enrolled in the Genoa Center (group A) and 25 patients with iRBD (group B) were enrolled in the Danish Center. Group A underwent brain [123I]FP-CIT-SPECT and group B underwent brain [18F]PE2I-PET as measures of nigro-striatal dopaminergic function. Chin muscle activity was recorded in all subjects and analyzed by applying a published automatic algorithm. Correlations between RWA and nigro-striatal dopaminergic function were explored. Results: The automatic quantification of RWA significantly differentiated RBD from non-RBD subjects (AUC = 0.86), although with lower accuracy compared with conventional visual scoring (AUC = 0.99). No significant correlation was found between RWA and nigro-striatal dopaminergic function. Conclusion: The automatic quantification of RWA is a reliable tool to identify subjects with RBD and may be used as a first-line screening tool, but without correlations with nigro-striatal dopaminergic functioning. [ABSTRACT FROM AUTHOR]

• EEG patterns during RBD movements resemble those of voluntary movements during wakefulness. • EEG patterns preceding RBD movements show no differences regarding the presence or absence of PD. • Results suggest a main involvement of the cortex in the generation of the movements during REM sleep. Motor symptoms of Parkinson's disease improve during REM sleep behavior disorder movement episodes. Our aim was to study cortical activity during these movement episodes, in patients with and without Parkinson's disease, in order to investigate the cortical involvement in the generation of its electromyographic activity and its potential relationship with Parkinson's disease. We looked retrospectively in our polysomnography database for patients with REM sleep behavior disorder, analyzing fifteen patients in total, seven with idiopathic REM sleep behavior disorder and eight associated with Parkinson's disease. We selected segments of REM sleep with the presence of movements (evidenced by electromyographic activation), and studied movement-related changes in cortical activity by averaging the electroencephalographic signal (premotor potential) and by means of time/frequency transforms. We found a premotor potential and an energy decrease of alpha–beta oscillatory activity preceding the onset of electromyographic activity, together with an increase of gamma activity for the duration of the movement. All these changes were similarly present in REM sleep behavior disorder patients with and without Parkinson's disease. Movement-related changes in electroencephalographic activity observed in REM sleep behavior disorder are similar to those observed during voluntary movements, regardless of the presence of Parkinson's disease motor symptoms. These results suggest a main involvement of the cortex in the generation of the movements during REM sleep. [ABSTRACT FROM AUTHOR]

• Investigated the characteristics of EEG activity before dream enactment behaviors during REM sleep in patients with iRBD. • Before the behaviors, delta/gamma power increases and wide-range beta-band connectivity increases were observed. • These findings suggest distinct cortical activity patterns during dream enactment in iRBD. This study aimed to identify electroencephalogram correlates of dream enactment behaviors (DEBs) and elucidate their cortical dynamics in patients with isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). This cross-sectional study included 15 patients with iRBD. Two REM sleep periods in routine polysomnography were compared: the 60 s preceding the DEBs ("pre-representative behavior" [preR]), and the 60 s with the least submental electromyogram activity ("background" [BG]). Six EEG frequency bands and electrooculogram were analyzed; power spectra, coherence and phase-locking values in four 15-s periods were examined to assess trends. These indices were also compared between preR and BG. Compared with BG, significantly higher delta power in the F3 channel and gamma power in the F4 and O2 channels were observed during preR. For functional connectivity, the widespread beta-band connectivity was significantly increased during preR than BG. Before notable REM sleep behaviors, uneven distributed higher EEG spectral power in both very low and high frequencies, and increased wide-range beta band functional connectivity, were observed over 60 s, suggesting cortical correlates to subsequent DEBs. This study may shed light on the pathological mechanisms underlies RBD through the routine vPSG analysis, leading to detection of DEBs. [ABSTRACT FROM AUTHOR]

Background and purpose: Migraine and sleep disorders share a bidirectional relationship, but little is known about the specific association between migraine and rapid eye movement (REM) sleep behaviour disorder (RBD). The aim was to assess the prevalence of RBD and associated clinical characteristics in adults with migraine. Methods: This analysis is part of a cross‐sectional survey study conducted at the Headache Centre of the Charité—Universitätsmedizin Berlin between August 2020 and March 2023. At the end of their regular medical consultation, patients with migraine filled out (1) the validated RBD Screening Questionnaire (RBDSQ), (2) a questionnaire on REM sleep intrusions and (3) the Depression, Anxiety and Stress Scale 21. The primary endpoint was the percentage of patients with a positive RBD screening. A multivariate analysis was performed to identify characteristics independently associated with features of RBD. Results: A total of 751 patients (44.1 ± 13.2 years; 87.4% female) with complete RBDSQ were included in this analysis, of which 443 (58.9%) screened positive for RBD. In multivariate analysis, a positive screening for RBD was associated with younger age (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.8–0.9 per 10‐year increase; p = 0.005) and with features suggestive of REM sleep intrusions (OR 4.3, 95% CI 1.8–10.4; p = 0.001). Migraine aura remained in the model without reaching statistical significance (OR 1.3, 95% CI 0.9–1.8; p = 0.079). Discussion: Symptoms of RBD are frequent in adults with migraine. Further studies including polysomnography are required to confirm this association, and to explore potential common pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Chronic pain due to peripheral neuropathy can lead to sleep disorders that significantly worsen the patient's quality of life. Previously, we conducted brain wave measurements in a rat model of neuropathic pain and identified its potential as a model for sleep disorders associated with chronic pain (reported). In this study, we quantified melatonin secretion and assessed its circadian rhythm in a rat model of pain-induced sleep disorder. To create a model of chronic constriction injury (CCI), rats were loosely tied around the sciatic nerve, with approximately 1 mm spacing, 14 days before the experiment. Rats with no ties around the sciatic nerve were used as controls. Electroencephalograms and electromyograms were recorded for 3 days, and the episodes of waking, REM sleep, and non-REM sleep were compared between the groups. The samples for microanalysis were collected every 30 min and used for melatonin analysis. Compared to the control group, the CCI model group exhibited an increase in wake episodes and a decrease in non-REM sleep episodes. Analysis of the area under the curve of melatonin secretion revealed a significant increase in melatonin secretion and a loss of circadian rhythm in the CCI model group. Melatonin secretion markedly increased accompanied by loss of circadian rhythm in a rat model of CCI. Further studies investigating the causal relationship between neuropathic pain and melatonin secretion are warranted. [ABSTRACT FROM AUTHOR]

Background. This study assessed the potential efficacy of donepezil in treating autism spectrum disorder (ASD), a neurodevelopmental condition characterized by social communication difficulties and repetitive behaviors. Donepezil, primarily used to treat Alzheimer’s disease as an acetylcholinesterase inhibitor, has gained attention as a potential treatment for ASD symptoms. Methods. Following PRISMA guidelines, a systematic review was conducted to investigate the effects of donepezil on individuals with ASD. Outcome measures assessed various aspects of ASD, including language skills, executive function, behavior, and core symptoms. Nine studies were identified, including four randomized controlled trials (RCTs), three retrospective studies, one open-label trial, and one case report. Results. One RCT reported significant improvements in expressive and receptive language skills, especially in younger children. Another study combining donepezil with choline supplementation showed enhanced receptive language skills, particularly in younger participants. An open-label trial indicated improved rapid eye movement sleep patterns in autistic children treated with donepezil. Several retrospective studies reported improvements in behavioral symptoms, such as aggression and hyperactivity. However, other RCTs did not find statistically significant improvements in executive functioning. Conclusion. In general, donepezil use in ASD demonstrates promise in specific areas, notably language development and behavioral symptom management. However, the results are contradictory, requiring further research to clarify its role, optimal dosing, long-term effects, and potential side effects in individuals with ASD. Practical Implications. Donepezil can be used to improve the clinical global impression and language skills of people with ASD. [ABSTRACT FROM AUTHOR]

Background: Chronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects. Methods: A total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model. Results: Chronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels. Conclusion: These findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks. [ABSTRACT FROM AUTHOR]

Objective: Non‐invasive biomarkers have recently shown promise for seizure forecasting in people with epilepsy. In this work, we developed a seizure‐day forecasting algorithm based on nocturnal sleep features acquired using a smart shirt. Methods: Seventy‐eight individuals with epilepsy admitted to the Centre hospitalier de l'Université de Montréal epilepsy monitoring unit wore the Hexoskin biometric smart shirt during their stay. The shirt continuously measures electrocardiography, respiratory, and accelerometry activity. Ten sleep features, including sleep efficiency, sleep latency, sleep duration, time spent in non‐rapid eye movement sleep (NREM) and rapid eye movement sleep (REM), wakefulness after sleep onset, average heart and breathing rates, high‐frequency heart rate variability, and the number of position changes, were automatically computed using the Hexoskin sleep algorithm. Each night's features were then normalized using a reference night for each patient. A support vector machine classifier was trained for pseudo‐prospective seizure‐day forecasting, with forecasting horizons of 16‐ and 24‐h to include both diurnal and nocturnal seizures (24‐h) or diurnal seizures only (16‐h). The algorithm's performance was assessed using a nested leave‐one‐patient‐out cross‐validation approach. Results: Improvement over chance (IoC) performances were achieved for 48.7% and 40% of patients with the 16‐ and 24‐h forecasting horizons, respectively. For patients with IoC performances, the proposed algorithm reached mean IoC, sensitivity and time in warning of 34.3%, 86.0%, and 51.7%, respectively for the 16‐h horizon, and 34.2%, 64.4% and 30.2%, respectively, for the 24‐h horizon. Significance: Smart shirt‐based nocturnal sleep analysis holds promise as a non‐invasive approach for seizure‐day forecasting in a subset of people with epilepsy. Further investigations, particularly in a residential setting with long‐term recordings, could pave the way for the development of innovative and practical seizure forecasting devices. Plain Language Summary: Seizure forecasting with wearable devices may improve the quality of life of people living with epilepsy who experience unpredictable, recurrent seizures. In this study, we have developed a seizure forecasting algorithm using sleep characteristics obtained from a smart shirt worn at night by a large number of hospitalized patients with epilepsy (78). A daily seizure forecast was generated following each night using machine learning methods. Our results show that around half of people with epilepsy may benefit from such an approach. [ABSTRACT FROM AUTHOR]

Purpose : The aim of this study was to investigate sleep parameters and architecture in patients admitted to the intensive care unit (ICU) on the day of abdominal surgery. Methods : A total of ten patients who underwent laparotomy under general anesthesia at the hepatopancreatobiliary surgery department of a general hospital in Busan, South Korea participated in this observational study. We measured total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep stages on their first night in the ICU using the WatchPAT300. Furthermore, we used nonparametric statistics to examine differences in postoperative sleep based on sedative administration. Results : The Median (IQR) TST for the participants was 399.50(263.80) minutes; the SE was 75.1 (30.4)%; the WASO rate was 27.8(30.6)%; and the WASO frequency was 5.50(8.50) times. Patients' rapid eye movement (REM) sleep time was 114.31(87.88) minutes, with 55.8(11.9)% of N1, 18.2(5.3)% of N2, and 24.8 (11.7)% of N3 sleep stages. The sedation group had a longer TST (Z=-2.619, p=.008), higher SE (Z=-2.611, p=.008), lower WASO rate (Z=-2.611, p=.008), smaller number of WASOs (Z=-2.627, p=.008), and longer REM sleep (Z=-2.617, p=.008) compared to the non-sedation group. Conclusion : We observed a high rate of light sleep and awakenings during sleep in patients admitted to the ICU after surgery. Moreover, non-sedated patients lacked either deep or REM sleep. Sleep-improving interventions are needed for non-sedated surgical patients who are admitted to the ICU. [ABSTRACT FROM AUTHOR]