Sleep Wake Research Articles

The Kir channel in the nucleus tractus solitarius integrates the chemosensory system with REM sleep executive machinery for homeostatic balance

The locus coeruleus (LC), nucleus tractus solitarius (NTS), and retrotrapezoid nucleus (RTN) are critical chemosensory regions in the brainstem. In the LC, acid-sensing ion channels and proton pumps serve as H+ sensors and facilitate the transition from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep. Interestingly, the potassium inward rectifier (KIR) channels in the LC, NTS, and RTN also act as H+-sensors and are a primary target for improving sleep in obstructive sleep apnea and Rett syndrome patients. However, the role of Kir channels in NREM to REM sleep transition for H+ homeostasis is not known. Male Wistar rats were surgically prepared for chronic sleep–wake recording and drug delivery into the LC, NTS, and RTN. In different animal cohorts, microinjections of the Kir channel inhibitor, barium chloride (BaCl2), at concentrations of 1 mM (low dose) and 2 mM (high dose) in the LC and RTN significantly increased wakefulness and decreased NREM sleep. However, BaCl2 microinjection into the LC notably reduced REM sleep, whereas it didn’t change in the RTN-injected group. Interestingly, BaCl2 microinjections into the NTS significantly decreased wakefulness and increased the percent amount of NREM and REM sleep. Additionally, with the infusion of BaCl2 into the NTS, the mean REM sleep episode numbers significantly increased, but the length of the REM sleep episode didn’t change. These findings suggest that the Kir channels in the NTS, but not in the LC and RTN, modulate state transition from NREM to REM sleep.

The effects of alternate-day fasting on sleep and physical activity in poor sleeping adults: A randomized control trial.

Utilizing a randomized control design, 42 healthy adults (22.5 ± 2.8 years) participated in alternate-day modified fasting over a 12-day treatment period. Assessments of sleep included sleep time, efficiency, latency and wake after sleep onset, and assessments of physical activity included steps, energy expenditure, sedentary time, time spent in light physical activity and time spent in moderate-to-vigorous activity. Additional measurements included body composition and mood. The alternate-day modified fasting group consumed 25.8% ± 0.3% fewer calories compared with the control group (p = 0.03). There were no differences between groups for change in body mass index (p = 0.87), total fat mass (p = 0.91) or total lean mass (p = 0.88). Daily energy expenditure did not differ between groups (p = 0.11). On fast days, participants spent 34.5 ± 12.7 more minutes sedentary (p = 0.01), took 1100 ± 362 fewer steps (p < 0.01), and engaged in 27.2 ± 8.4 fewer minutes of moderate-to-vigorous physical activity (p = 0.00) compared with non-fasting days. Sleep duration, efficiency, latency or wake after sleep onset were not different between conditions (p = 0.92, p = 0.10, p = 0.09 and p = 0.66, respectively). We conclude that alternate-day modified fasting does not alter sleep time, efficiency, latency or wake after sleep onset in people reporting poor sleep quality, and does not alter overall physical activity. Although average daily physical activity is not altered, fasting in this manner does tend to result in more sedentary time and less physical activity with compensation on non-fasting days.

P-tau217 and other blood biomarkers of dementia: variation with time of day

Plasma biomarkers of dementia, including phosphorylated tau (p-tau217), offer promise as tools for diagnosis, stratification for clinical trials, monitoring disease progression, and assessing the success of interventions in those living with Alzheimer’s disease. However, currently, it is unknown whether these dementia biomarker levels vary with the time of day, which could have implications for their clinical value. In two protocols, we studied 38 participants (70.8 ± 7.6 years; mean ± SD) in a 27-h laboratory protocol with either two samples taken 12 h apart or 3-hourly blood sampling for 24 h in the presence of a sleep–wake cycle. The study population comprised people living with mild Alzheimer’s disease (PLWA, n = 8), partners/caregivers of PLWA (n = 6) and cognitively intact older adults (n = 24). Single-molecule array technology was used to measure phosphorylated tau (p-tau217) (ALZpath), amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), glial fibrillary acidic protein, and neurofilament light (NfL) (Neuro 4-Plex E). Analysis with a linear mixed model (SAS, PROC MIXED) revealed a significant effect of time of day for p-tau217, Aβ40, Aβ42, and NfL, and a significant effect of participant group for p-tau217. For p-tau217, the lowest levels were observed in the morning upon waking and the highest values in the afternoon/early evening. The magnitude of the diurnal variation for p-tau217 was similar to the reported increase in p-tau217 over one year in amyloid-β-positive mild cognitively impaired people. Currently, the factors driving this diurnal variation are unknown and could be related to sleep, circadian mechanisms, activity, posture, or meals. Overall, this work implies that the time of day of sample collection may be relevant in the implementation and interpretation of plasma biomarkers in dementia research and care.

Dopamine D2 receptors in the accumbal core region mediates the effects of fentanyl on sleep-wakefulness

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.

A - 139 A Neuropsychological Case Study of an Individual Diagnosed with Langerhans Cell Histiocytosis

Abstract Objective Langerhans cell histiocytosis (LCH) is a rare, idiopathic, cancer-like condition resulting from an overproduction of Langerhans cells. Disseminated LCH can spread across various anatomical systems, and prognosis is mainly dependent on organ involvement. Due to the rarity of this condition, potential neuropsychological effects are not fully understood. However, current research suggests that individuals with LCH are prone to develop various comorbid neuropsychiatric problems such as depression, anxiety, and impaired intellectual functioning. Method The current case is an 18-year-old, right-handed, Hispanic female who was diagnosed with LCH (brain and bone) in 2020. Cognitive symptoms began in 2016 at age 11. She was initially diagnosed with a low-grade glioma after a biopsy of a supracellular mass in 2017 but has developed various comorbid conditions since then. These include panhypopituitarism, NMDA encephalitis with behavioral disturbance, encephalomalacia, and epilepsy. She has undergone two 9-month rounds of chemotherapy and has been followed for neuroimaging with MRI and CT since 2017. Results Neuropsychological test findings from January 2024 indicated global deficits in intellectual functioning. Severe disruptions in sleep–wake cycle were also evident during testing. Although language abilities were relatively well preserved, abstract reasoning and executive functioning were greatly impaired. Psychological screeners also suggested anxiety and depression. Conclusions This case provides evidence of neurocognitive and psychiatric symptoms that can occur as a result of LCH and frequent comorbid health conditions. Neuropsychological testing can help monitor these effects on individuals with LCH across the lifespan.

Improvement in self-reported, but not actigraphic, sleep measures with suvorexant in people with well-controlled Restless Legs Syndrome and persistent insomnia

BackgroundSleep disturbance remains common in people with Restless Legs Syndrome (RLS), even after RLS symptoms are sufficiently controlled with medication. We conducted a placebo-controlled crossover trial to examine the efficacy of suvorexant in improving sleep quality and quantity in people with well-controlled RLS and persistent insomnia. MethodsIn this double-blind, randomized, placebo-controlled crossover trial, 34 participants (70.6 % female, mean age = 62.7) with well-controlled RLS were randomized to placebo or suvorexant (10–20 mg) for 6 weeks, followed by a 2-week washout and then the opposite treatment. Study inclusion required an IRLS score <15, insomnia diagnosis per DSM-5, and a diary-reported combined Sleep Onset Latency (SOL) and Wake After Sleep Onset (WASO) > 45 min and a Total Sleep Time (TST) < 7 h on 7/14 baseline nights. The primary outcome was actigraphically-derived TST, and secondary outcomes were Insomnia Severity Index (ISI) score and actigraphically-derived WASO. Data for all sleep metrics were collected at baseline and for the last two weeks of each treatment period. ResultsThere were no significant improvements in actigraphically-derived TST (p = 0.58) or WASO (p = 0.99) while taking suvorexant compared to placebo. However, there were significant reductions in insomnia symptoms, measured by the ISI, as well as increases in diary-reported TST (p = 0.01) while taking suvorexant compared to placebo. The most commonly reported side effect of suvorexant was fatigue (29.4 %). ConclusionsWe observed no significant differences between treatments in actigraphically-derived sleep measures, but support for suvorexant's benefit for overall insomnia and self-reported quantity of sleep in people with well-controlled RLS who continue to suffer from insomnia. Clinical trials registration numberNCT04706091.

Sleep characteristics during the first year postpartum in a cohort of Black and White women

Study objectivesThe postpartum period is a unique time when sleep deficiency often occurs. Black and White adults are reported to have differences in sleep characteristics, but little is known if these differences exist in the postpartum period. Therefore, the purpose of this study was to examine sleep characteristics in a cohort of Black and White women from 6-8 weeks to 12 months postpartum. MethodsParticipants were 49 Black and 85 White women who gave birth to an infant at ≥37 weeks gestation. Participants were instructed to wear an Actiwatch for 7 days at 6-8 weeks, 4, 6, 9, and 12 months postpartum. Mixed-effects linear models with a race by time interaction were used to examine if characteristics differed between races over time. ResultsOnly bedtime varied by race. White women had a later bedtime at 6-8 weeks compared to 6 months, but no significant change occurred for Black women. For the entire sample, average nighttime sleep duration increased from 385 min at 6-8 weeks to 404 min at 4 months postpartum. Percent sleep during the sleep interval and wake after sleep onset (WASO) improved by 6 and 9 months, respectively. However, average WASO remained >45 min and sleep efficiency <85 % at all timepoints for both Black and White women. Compared to White women, Black women had significantly shorter sleep duration (range: 40.6-59.9 min shorter across all timepoints, p < 0.0001) and time in bed (range: 17.5-67.6 minutes shorter, p = 0.0046), and lower percent sleep (range: 0.7-1.2 % lower, p = 0.0407) and sleep efficiency (range: 2.6-5.7 % lower, p = 0.0005). Sociodemographic factors were associated with sleep outcomes in Black and White women while behavioral factors were associated with sleep outcomes in White women only. ConclusionWhile there were improvements in nighttime sleep duration and quality, sleep duration remained suboptimal, and quality remained poor throughout the first year postpartum. In this sample, differences existed in factors associated with sleep outcomes between Black and White women.

Оценка эффективности нового лекарственного препарата Курс Успокоин таблетки для коррекции возрастных когнитивных нарушений у кошек

The treatment by Kurs Uspokoin tablets in a minimum initial daily dose of 7 mg/kg for the first three days, with a further increase to 14 mg/kg, showed a positive effect in correcting the behavior of older cats with progressive simptoms of cognitive disfunction. During the treatment were registered a statistically and clinically significant decrease in idiopathic vocalization, restoration of sleep cycles and wakefulness, elimination of house-soiling behavior, disorientation, increased activity, and improvement of social behavior. During the treatment by Kurs Uspokoin tablets and after its discontinuation no adverse reactions were registered.

Variations in objectively measured sleep parameters in patients with different premature ejaculation syndromes.

Poor sleep quality is now a cause of sexual dysfunction. To investigate variations in sleep quality among patients with different types of premature ejaculation (PE) and a control group. Patients with PE were categorized into groups according to 4 types: lifelong (LPE), acquired (APE), variable (VPE), and subjective (SPE). Basic demographic information about the participants was first collected, and then clinical data were obtained. Outcomes included the 5-item International Index of Erectile Function, Premature Ejaculation Diagnostic Tool, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pittsburgh Sleep Quality Index, self-estimated intravaginal ejaculation latency time (minutes), and sleep monitoring parameters obtained from a wearable device (Fitbit Charge 2). A total of 215 participants were enrolled in the study, of which 136 patients with PE were distributed as follows: LPE (31.62%), APE (42.65%), VPE (10.29%), and SPE (15.44%). Subjective scales showed that patients with APE were accompanied by a higher prevalence of erectile dysfunction, anxiety, and depression, as well as poorer sleep quality (assessed by the Pittsburgh Sleep Quality Index). The results of objective sleep parameters revealed that average durations of sleep onset latency (minutes) and wake after sleep onset (minutes) in patients with APE (mean ± SD; 20.03 ± 9.14, 55 ± 23.15) were significantly higher than those with LPE (15.07 ± 5.19, 45.09 ± 20.14), VPE (13.64 ± 3.73, 38.14 ± 11.53), and SPE (14.81 ± 4.33, 42.86 ± 13.14) and the control group (12.48 ± 3.45, 37.14 ± 15.01; P < .05). The average duration of rapid eye movement (REM; minutes) in patients with APE (71.34 ± 23.18) was significantly lower than that in patients with LPE (79.67 ± 21.53), VPE (85.93 ± 6.93), and SPE (80.86 ± 13.04) and the control group (86.56 ± 11.93; P < .05). Similarly, when compared with the control group, patients with LPE had significantly longer durations of sleep onset latency and wake after sleep onset and a significantly shorter duration of REM sleep. Our study suggests that clinicians should pay attention not only to male physical assessment but also to mental health and sleep quality. This study suggests that changes in sleep structure occur in patients with PE, which may provide some direction for future research. However, the cross-sectional study design does not allow us to conclude that sleep is a risk factor for PE. After controlling for traditional parameters such as age, erectile dysfunction, anxiety, and depression, sleep parameters are independently associated with PE. Patients with APE and LPE show significant alterations in sleep parameters, with patients with APE having notably poorer sleep quality, whereas patients with VPE and SPE have sleep parameters similar to controls.

Metadata recommendations for light logging and dosimetry datasets

BackgroundLight exposure significantly impacts human health, regulating our circadian clock, sleep–wake cycle and other physiological processes. With the emergence of wearable light loggers and dosimeters, research on real-world light exposure effects is growing. There is a critical need to standardize data collection and documentation across studies.ResultsThis article proposes a new metadata descriptor designed to capture crucial information within personalized light exposure datasets collected with wearable light loggers and dosimeters. The descriptor, developed collaboratively by international experts, has a modular structure for future expansion and customization. It covers four key domains: study design, participant characteristics, dataset details, and device specifications. Each domain includes specific metadata fields for comprehensive documentation. The user-friendly descriptor is available in JSON format. A web interface simplifies generating compliant JSON files for broad accessibility. Version control allows for future improvements.ConclusionsOur metadata descriptor empowers researchers to enhance the quality and value of their light dosimetry datasets by making them FAIR (findable, accessible, interoperable and reusable). Ultimately, its adoption will advance our understanding of how light exposure affects human physiology and behaviour in real-world settings.

GBA-AAV mitigates sleep disruptions and motor deficits in mice with REM sleep behavior disorder

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Feasibility and usability of three consecutive nights with self-applied, home polysomnography.

In-laboratory polysomnography, the gold-standard for diagnosing sleep disorders, is resource-demanding and not conducive to multiple night evaluations. Ambulatory polysomnography, especially when self-applied, could be a viable alternative. This study aimed to assess the feasibility and reliability of self-applied polysomnography over three consecutive nights in untrained participants, assessing: technical success rate; comparing sleep diagnostic variables from single and multiple nights; and evaluating participants' subjective experience. Data were collected from 78 participants (55.1% females) invited to test a self-applicable polysomnography device for three consecutive nights at home. The technical success rate for valid sleep recordings was 82.5% out of 234 planned study nights, with 87.2% of participants obtaining at least two valid nights. Misclassification of obstructive sleep apnea severity was higher in participants with mild OSA (21.4%) compared with those with moderate-to-severe obstructive sleep apnea or no obstructive sleep apnea. Sleep efficiency and wake after sleep onset showed improvement from Night 1 to Night 3 (p < 0.001), and the mean polysomnography set-up time decreased significantly over this period. Participants reported moderate-to-high satisfaction with the device (System Usability Scale score 71.2 ± 12.4). The findings suggest that self-applied polysomnography is a feasible diagnostic method for untrained individuals at risk for sleep disorders, and that multiple night assessments can improve diagnostic precision for mild obstructive sleep apnea cases.

Efferent pathways from the suprachiasmatic nucleus to the horizontal limbs of diagonal band promote NREM sleep during the dark phase in mice

The regulation of circadian rhythms and the sleep–wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep–wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN–HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non–rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN–HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep–wake states regulation.

Global Prevalence of Sleep Bruxism and Awake Bruxism in Pediatric and Adult Populations: A Systematic Review and Meta-Analysis.

Background/Objectives: The purpose of this systematic review was to assess the global prevalence of sleep bruxism and awake bruxism in pediatric and adult populations. Methods: This systematic review was conducted by analyzing studies published from 2003 to 2023. The following keyword combination was utilized: prevalence, epidemiology, population, and bruxism. The PubMed database was analyzed, supplemented by manual searches using the Google search. Additionally, the snowballing procedure method was applied. A double assessment of the quality of publications was carried out to preserve the highest possible quality of evidence (e.g., Joanna Briggs Institute critical appraisal checklist). Analyses were conducted using the R statistical language. Results: The global bruxism (sleep and awake) prevalence is 22.22%. The global sleep bruxism prevalence is 21% and awake prevalence is 23%. The occurrence of sleep bruxism, based on polysomnography, was estimated at 43%. The highest prevalence of sleep bruxism was observed in North America at 31%, followed by South America at 23%, Europe at 21%, and Asia at 19%. The prevalence of awake bruxism was highest in South America at 30%, followed by Asia at 25% and Europe at 18%. Conclusions: One in four individuals may experience awake bruxism. Bruxism is a significant factor among women. It was observed that age is a significant factor for the occurrence of sleep bruxism in women. Among the limitations of the study is the lack of analysis of the prevalence of bruxism in Africa and Australia due to not collecting an adequate sample for analysis. The study was registered in the Open Science Framework (10.17605/OSF.IO/ZE786).

Narcolepsy and pediatric acute-onset neuropsychiatric syndrome: A case report that suggests a putative link between the two disorders

Narcolepsy with cataplexy (NT1) is a rare hypothalamic disorder that presents with a dysregulation of the sleep–wake cycle (i.e., excessive daytime sleepiness and sleep and cataplectic attacks) and other motor, cognitive, psychiatric, metabolic, and autonomic disturbances, with putative autoimmune pathogenesis. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder that presents with acute-onset obsessive–compulsive symptoms and/or a severe eating restriction, with concomitant cognitive, behavioral, or affective symptoms caused by infections and other environmental triggers provoking an inflammatory brain response, which evolves into a chronic or progressive neuroimmune disorder. In this study, we present the case of a 13-year-old boy with vocal tics and syncopal-like episodes, eventually diagnosed as NT1 and PANS, and from this we discuss the hypothesis that both NT1 and PANS might belong to the same immunological spectrum, resulting in comparable imbalances in key neurotransmitter axes (i.e., orexinergic and dopaminergic), with conceptual and operational implications, especially with regards to the pharmacological tretament

Menstrual variations of sleep–wake rhythms in healthy women

Menstrual variations of sleep–wake rhythms in healthy women

Sleep benefits perceptual but not movement-based learning of locomotor sequences

Practicing complex locomotor skills, such as those involving a step sequence engages distinct perceptual and motor mechanisms that support the recall of learning under new conditions (i.e., skill transfer). While sleep has been shown to enhance learning of sequences of fine movements (i.e., sleep-dependent consolidation), here we examined whether this benefit extends to learning of a locomotor pattern. Specifically, we tested the perceptual and motor learning of a locomotor sequence following sleep compared to wake. We hypothesized that post-practice sleep would increase locomotor sequence learning in the perceptual, but not in the motor domain. In this study, healthy young adult participants (n = 48; 18–33 years) practiced a step length sequence on a treadmill cued by visual stimuli displayed on a screen during training. Participants were then tested in a perceptual condition (backward walking with the same visual stimuli), or a motor condition (forward walking but with an inverted screen). Skill was assessed immediately, and again after a 12-h delay following overnight sleep or daytime wake (n = 12 for each interval/condition). Off-line learning improved following sleep compared to wake, but only for the perceptual condition. Our results suggest that perceptual and motor sequence learning are processed separately after locomotor training, and further points to a benefit of sleep that is rooted in the perceptual as opposed to the motor aspects of motor learning.

Hypothesis on the potential of repetitive transcranial magnetic stimulation to modulate neurochemical pathways and circadian rhythm in ADHD

Disturbances in the circadian rhythms are generally present in adults subjects with Attention Deficit Hyperactivity Disorder. However, may present in children with the same clinical condition. Poor sleep quality interferes with neural inputs and outputs in areas that are fundamental in neurobiological aspects, such as the dorsolateral prefrontal cortex, which can affect circadian rhythm, cognition, emotional and social control. The dorsolateral prefrontal cortex is an area involved in executive functions and sleep–wake regulation and is underactivated in subjects Attention Deficit Hyperactivity Disorder, which may be one of the main causes of alterations in the circadian cycle. Currently, studies with non-invasive therapeutic methods for adult populations and children with these disorders remain scarce, revealing a significant gap in understanding and treatment. In this context, the aim is investigate the potential effectiveness of repetitive transcranial magnetic stimulation as alternative non-invasive treatment of these disorders. In the present study, it is suggested that use excitatory currents from 10 Hz to 20 Hz in the right dorsolateral prefrontal cortex leads to an improvement in the circadian rhythm mechanism. This is because the excitatory current will promote an increase in dopamine (a neurotransmitter that regulates the circadian cycle) and an increase in glutamate and glutamine concentrations to restore homeostasis in brain regions linked to the sleep–wake cycle.

Efficient Sleep–Wake Cycle Staging via Phase–Amplitude Coupling Pattern Classification

The objective and automatic detection of the sleep–wake cycle (SWC) stages is essential for the investigation of its physiology and dysfunction. Here, we propose a machine learning model for the classification of SWC stages based on the measurement of synchronization between neural oscillations of different frequencies. Publicly available electrophysiological recordings of mice were analyzed for the computation of phase–amplitude couplings, which were then supplied to a multilayer perceptron (MLP). Firstly, we assessed the performance of several architectures, varying among different input choices and numbers of neurons in the hidden layer. The top performing architecture was then tested using distinct extrapolation strategies that would simulate applications in a real lab setting. Although all the different choices of input data displayed high AUC values (&gt;0.85) for all the stages, the ones using larger input datasets performed significantly better. The top performing architecture displayed high AUC values (&gt;0.95) for all the extrapolation strategies, even in the worst-case scenario in which the training with a single day and single animal was used to classify the rest of the data. Overall, the results using multiple performance metrics indicate that the usage of a basic MLP fed with highly descriptive features such as neural synchronization is enough to efficiently classify SWC stages.

Sleep–wake changes and incident depressive symptoms in midlife women

Our study aimed to investigate the relationship between sleep–wake changes and depressive symptoms events among midlife women. We enrolled 1579 women aged 44–56 years who had no clinically relevant depressive symptoms at baseline. Depressive symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression scale. At the third and fourth follow-up visits, women reported their sleep habits. The sleep midpoint was defined as the time to fall asleep plus one-half of the sleep duration. Sleep–wake changes were determined by the difference in the midpoint of sleep between the third and fourth visits, which were 1 year apart. The median follow-up time was 7 years (range 1–7 years). Cox proportional hazard models were fitted to calculate hazard ratios and 95% confidence intervals for the incidence of depressive symptoms associated with sleep–wake changes. After adjusting for potential confounding factors, the hazard ratio (95% confidence interval) of depressive symptoms for severe sleep midpoint changes was 1.51 (1.12, 2.05) compared with mild sleep midpoint changes. This relationship remained statistically significant and changed little when additionally controlling for sleep duration, sleep quality, insomnia symptoms, use of sleep medications, use of nervous medications, glucose, insulin, lipids, dietary energy intake, and C-reactive protein. Our findings indicate that exposure to long-term severe sleep–wake changes increases the risk of depressive symptoms in midlife women.