Sleep-wake Cycle Research Articles

Fractal motor activity during wakefulness and sleep: a window into depression recency and symptom recurrence

Abstract Background Motor activity fluctuations in healthy adults exhibit fractal patterns characterized by consistent temporal correlations across wide-ranging time scales. However, these patterns are disrupted by aging and psychiatric conditions. This study aims to investigate how fractal patterns vary across the sleep–wake cycle, differ based on individuals' recency of depression diagnosis, and change before and after a depressive episode. Methods Using actigraphy from two cohorts (n = 378), we examined fractal motor activity patterns both between individuals without depression and with varying recencies of depression and within individuals before and after depressive symptom recurrence. To evaluate fractal patterns, we quantified temporal correlations in motor activity fluctuations across different time scales using a scaling exponent, α. Linear mixed models were utilized to assess the influence of the sleep–wake cycle, (recency of) depression, and their interaction on α. Results Fractal activity patterns in all individuals varied across the sleep–wake cycle, showing stronger temporal correlations during wakefulness (larger α = 1.035 ± 0.003) and more random activity fluctuations during sleep (smaller α = 0.784 ± 0.004, p < 0.001). This sleep–wake difference was reduced in recently depressed individuals (1–6 months), leading to larger α during sleep (0.836 ± 0.017), compared to currently depressed (0.781 ± 0.018, p = 0.006), remitted (0.776 ± 0.014, p < 0.001), and never-depressed individuals (0.773 ± 0.016, p < 0.001). Moreover, remitted individuals who experienced depressive symptom recurrence during antidepressant tapering exhibited a larger α during sleep after the symptom onset as compared to before (after: α = 0.703 ± 0.022; before: α = 0.680 ± 0.022; p < 0.001). Conclusions These findings suggest a link between fractal motor activity patterns during sleep and depressive symptom recurrence in remitted individuals and those with recent depression.

Orexants, Orexin Receptor Antagonists: Novel Therapeutic Agents for Insomnia Disorder

Insomnia is when a person feels difficulty falling asleep or staying asleep, often associated with complications, such as fatigue, sleepiness, etc. Insomnia may cause disruptions in daytime physical and mental abilities. Orexins or hypocretins are the neuropeptides secreted from the lateral hypothalamus and play a major role in the sleep-wake cycle through a complex interplay between wake-promoting and sleep-promoting neuronal systems. Orexin receptor antagonists (Orexants) are the new treatment options for insomnia disorder, narcolepsy, and other sleep disturbances. There are two classes of Orexants, namely those that bind selectively to a specific orexin receptor are selective orexin receptor antagonists (SORA), and the others that bind to both the orexin receptors are dual orexin receptor antagonists (DORA). The first DORA was almorexant but restricted in use and the other three approved DORAs, such as suvorexant, lemborexant, and daridorexant were approved by the FDA, and several other DORAs and SORAs are under various stages of discovery and clinical investigation. Among the labeled limitations, the currently approved Orexants are contraindicated in people with narcolepsy and are controlled substances owing to their misuse liability. The present review discussed the sleep-wake cycle, phases of a sleep cycle, orexins, and Orexants, and summarized the pharmacology of the three approved DORAs, a type of Orexants and their potential advantages and limitations of their use in pharmacotherapy of insomnia disorder.

Rhythmic astrocytic GABA production synchronizes neuronal circadian timekeeping in the suprachiasmatic nucleus

AbstractAstrocytes of the suprachiasmatic nucleus (SCN) can regulate sleep-wake cycles in mammals. However, the nature of the information provided by astrocytes to control circadian patterns of behavior is unclear. Neuronal circadian activity across the SCN is organized into spatiotemporal waves that govern seasonal adaptations and timely engagement of behavioral outputs. Here, we show that astrocytes across the mouse SCN exhibit instead a highly uniform, pulse-like nighttime activity. We find that rhythmic astrocytic GABA production via polyamine degradation provides an inhibitory nighttime tone required for SCN circuit synchrony, thereby acting as an internal astrocyte zeitgeber (or “astrozeit”). We further identify synaptic GABA and astrocytic GABA as two key players underpinning coherent spatiotemporal circadian patterns of SCN neuronal activity. In describing a new mechanism by which astrocytes contribute to circadian timekeeping, our work provides a general blueprint for understanding how astrocytes encode temporal information underlying complex behaviors in mammals.

Misalignment Between Circadian Preference and Accelerometer-Derived Sleep-Wake Cycle With Increased Risk of Cardiometabolic Diseases

BackgroundThe relationship of circadian misalignment, sleep-wake cycle, and cardiometabolic diseases (CMDs) remains unclear. ObjectivesThis prospective study investigated the associations between circadian misalignment and CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke, and explored potential mechanisms. MethodsData from 60,965 participants without pre-existing CMDs from the UK Biobank study and followed for an average of 7.9 years were analyzed. Circadian misalignment was determined by comparing self-reported chronotype and accelerometer-derived sleep timing. Incident CMDs were documented via multiple medical registries and self-reported information. Cox proportional hazards models were applied to estimate HRs and 95% CIs for these associations. ResultsA U-shaped relationship between circadian misalignment and both T2D and CHD was observed. Compared to individuals with aligned midsleep and circadian preferences (the third quintile, Q3), those with advanced and delayed circadian misalignment had higher risks of T2D (HR: 1.22 [95% CI: 1.03-1.45] for Q1 and 1.39 [95% CI: 1.18-1.62] for Q5). Delayed circadian misalignment also associated with higher CHD risk (HR: 1.15 [95% CI: 1.01-1.31] for Q4 and 1.16 [95% CI: 1.02-1.33] for Q5). The association between delayed circadian misalignment and CMDs was greater in women (T2D, Pinteraction = 0.03) and younger adults (CHD, Pinteraction = 0.02). Early (HR: 1.19 [95% CI: 1.06-1.34]), rather than late, chronotype was associated with an increased T2D risk. ConclusionsBoth advanced and delayed circadian misalignment were associated with an increased CMD risk, highlighting the potential health benefits of aligning sleep-wake cycles with individual circadian preferences.

Samelisant (SUVN-G3031), A Histamine 3 Receptor Inverse Agonist: Results from The Phase 2 Double-Blind Randomized Placebo-Controlled Study for The Treatment of Excessive Daytime Sleepiness in Adult Patients with Narcolepsy

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5% patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

Impacts of circadian disruptions on behavioral rhythms in mice.

Circadian rhythms are fundamental biological processes that recur approximately every 24 h, with the sleep-wake cycle or circadian behavior being a well-known example. In the field of chronobiology, mice serve as valuable model animals for studying mammalian circadian rhythms due to their genetic similarity to humans and the availability of various genetic tools for manipulation. Monitoring locomotor activity in mice provides valuable insights into the impact of various conditions or disturbances on circadian behavior. In this review, we summarized the effects of disturbance of biological rhythms on circadian behavior in mice. External factors, especially light exert a significant impact on circadian behavior. Additionally, feeding timing, food composition, ambient temperature, and physical exercise contribute to variations in the behavior of the mouse. Internal factors, including gender, age, genetic background, and clock gene mutation or deletion, are effective as well. Understanding the effects of circadian disturbances on murine behavior is essential for gaining insights into the underlying mechanisms of circadian regulation and developing potential therapeutic interventions for circadian-related disorders in humans.

Long-term exposure to excessive norepinephrine in the brain induces tau aggregation, neuronal death, and cognitive deficits in early tau transgenic mice.

Alzheimer's disease (AD) is marked by the presence of intraneuronal neurofibrillary tangles (NFTs), which are primarily composed of hyperphosphorylated tau protein. The locus coeruleus (LC), the brain's main source of norepinephrine (NE), is one of the earliest regions to develop NFTs and experience neurodegeneration in AD. While LC-derived NE plays beneficial roles in cognition, emotion, locomotion, and the sleep-wake cycle, its impact on tau pathology is unclear. To explore this relationship, we administered intraperitoneal injections of either N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), a selective neurotoxin for noradrenergic neurons, or reboxetine (RBX), a norepinephrine reuptake inhibitor, to decrease or increase NE levels, respectively, in early tau transgenic mice expressing mutant human P301L tau (ADLPTau) for two months. Only the RBX-treated mice exhibited cognitive deficits, as evidenced by their performance in the Y-maze, novel object recognition, and contextual fear conditioning tests. Immunohistochemical analysis revealed increased hyperphosphorylated tau aggregates in the LC and hippocampus of the RBX-treated mice. Furthermore, neuronal apoptosis was observed in the hippocampal CA1 region of these mice. Western blotting showed that RBX injections led to the overactivation of tau kinases PKA and GSK3β, resulting in hyperphosphorylated tau, neuronal loss, and cognitive impairments. Consistent with these findings, human brain organoids exposed to higher NE concentrations also displayed elevated hyperphosphorylated tau and increased activity of the same tau kinases. These findings suggest that excessive NE exposure accelerates tau pathology by overactivating the tau kinases. Thus, modulating NE levels in the brain via the LC-NE system could be a potential therapeutic strategy for tau-related AD.

Harnessing the Power of Light Laser Technology in Medicine, Industry, and Defense

There is much more to light than just our ability to see. It is an essential component of human life and has a significant physiological, psychological, and social impact on us. Light has influenced our lives in many ways, from the beginning of time, when our ancestors worshipped the sun, to our current dependence on artificial lighting. It helps us navigate and understand the world, controls our sleepwake cycles, and affects our moods. The many benefits of light will be examined in this introduction, along with its critical role in our general evolution as a species and in our health and well-being. At the same time, light is a profound energy source, with applications ranging from everyday illumination to high-tech uses in medical, industrial, and defense sectors. One of the most potent ways lights are harnessed is through laser technology, which focuses light on an intense, coherent beam. This article explores how lasers, as a light-driven power, are revolutionizing areas such as healthcare (e.g., LASIK and surgical applications), industrial manufacturing, and military operations.

Super-resolution imaging of fast morphological dynamics of neurons in behaving animals.

Neurons are best studied in their native states in which their functional and morphological dynamics support animals' natural behaviors. Super-resolution microscopy can potentially reveal these dynamics in higher details but has been challenging in behaving animals due to severe motion artifacts. Here we report multiplexed, line-scanning, structured illumination microscopy, which can tolerate motion of up to 50 μm s-1 while achieving 150-nm and 100-nm lateral resolutions in its linear and nonlinear forms, respectively. We continuously imaged the dynamics of spinules in dendritic spines and axonal boutons volumetrically over thousands of frames and tens of minutes in head-fixed mouse brains during sleep-wake cycles. Super-resolution imaging of axonal boutons revealed spinule dynamics on a scale of seconds. Simultaneous two-color imaging further enabled analyses of the spatial distributions of diverse PSD-95 clusters and opened up possibilities to study their correlations with the structural dynamics of dendrites in the brains of head-fixed awake mice.

A biological rhythm in the hypothalamic system links sleep-wake cycles with feeding-fasting cycles

The hypothalamus senses the appetite-regulating hormones and also coordinates the metabolic function in alignment with the circadian rhythm. This alignment is essential to maintain the physiological conditions that prevent clinically important comorbidities, such as obesity or type-2 diabetes. However, a complete model of the hypothalamus that relates food intake with circadian rhythms and appetite hormones has not yet been developed. In this work, we present a computational model that accurately allows interpreting neural activity in terms of hormone regulation and sleep-wake cycles. We used a conductance-based model, which consists of a system of four differential equations that considers the ionotropic and metabotropic receptors, and the input currents from homeostatic hormones. We proposed a logistic function that fits available experimental data of insulin hormone concentration and added it into a short-term ghrelin model that served as an input to our dynamical system. Our results show a double oscillatory system, one synchronized by light-regulated sleep-wake cycles and the other by food-regulated feeding-fasting cycles. We have also found that meal timing frequency is highly relevant for the regulation of the hypothalamus neurons. We therefore present a mathematical model to explore the plausible link between the circadian rhythm and the endogenous food clock.

Management of Sleep Disorders in the Elderly

Healthy elderly can adapt to physiological changes in their sleep. The prevalence of sleep disorders and insomnia in particular is high in the elderly. They are often associated with one or more somatic and/or psychiatric conditions that they aggravate. In clinical practice, it is important to assess whether the sleep complaint fits into the framework of: 1) Physiological changes in the sleep-wake cycle during the day or circadian rhythms related to aging. 2) Defective lifestyle habits. 3) A specific sleep disorder, 4) A somatic or psychiatric condition that requires specific treatment; The management of sleep disorders in elderly should not be minimized and requires rigorous and multidisciplinary management. Psychotherapies are preferred as first-line treatment. In the case where therapeutic prescription is necessary, low doses must be given, and adjusted according to the terrain and the evolution. Through this article, we will try, through the latest recommendations, to make an update on the management of these disorders in the elderly, who are a weakened terrain associating psychiatric and somatic comorbidities.

The Physiological and Pharmacological Roles of Melatonin and Pregabalin

Melatonin and pregabalin are two important compounds that are broadly used in the fields of physiological and medicinal sciences. Melatonin is a primary hormone mainly secreted by the pineal gland and plays an important role in regulating circadian rhythms, sleep-wake cycles, and neuroimmune processes. Its strong antioxidant anti-inflammatory and anti-apoptotic properties have protected it against a wide range of diseases, from cancer to neurological disorders. In this study, the synthesis of melatonin will be widely studied, mainly regarding its role in regulating circadian rhythms and sleep, and its possible therapeutic use in treating neurological diseases and inflammation-related disorders. Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid (GABA), with anticonvulsant, analgesic, and anxiolytic actions. Clinical practice has widely utilized it because studies indicate that it is useful in treating a variety of conditions: fibromyalgia, epilepsy, neuropathic pain, and generalized anxiety disorder. This article reviews aspects of the pharmacokinetics of pregabalin, its useful functions in pain treatment, and its impact on calcium channel regulation. The review also discusses indications of pregabalin in therapy, along with its possible side effects. This review article aims to consider the molecular processes underlying the activities of melatonin and pregabalin and their therapeutic potential for the management of sleep disorders, inflammation, and neurological diseases to future use of these compounds clinically.

Interleukin-12 modulates sleep–wake activity and improves performance in a memory task

BackgroundCytokines, known for their pro- and anti-inflammatory roles, are also key regulators of sleep–wake cycles. Classical pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), are associated with increased sleep, particularly slow-wave sleep (SWS), while anti-inflammatory cytokines, like interleukin-10 (IL-10), generally reduce sleep duration. Given the essential role of sleep in memory consolidation, this study aimed to investigate whether interleukin-12 (IL-12), a pro-inflammatory cytokine, could increase sleep duration following a memory acquisition task and subsequently improve memory performance. Male Swiss mice were surgically implanted with electrodes for electrocorticogram (ECoG) and electromyogram (EMG) recordings to track their sleep–wake cycles. After a recovery period, baseline sleep–wake activity was recorded. The mice were then randomly assigned to two groups and treated with either IL-12 (0.5 µg, i.p.) or a phosphate-buffered saline (PBS, i.p.) control, administered immediately before the multiple-trial inhibitory avoidance (MTIA) task, a behavioral test used to assess memory performance. Following the memory acquisition session, sleep–wake activity was immediately recorded for a continuous 24-h period.ResultsMice treated with IL-12 exhibited longer latency to cross into the dark compartment during the MTIA test, indicating improved memory retention compared to the control group. Interestingly, this improved performance was associated with prolonged wakefulness, particularly in the first three hours after task acquisition.ConclusionThe study shows that IL-12 can improve memory retention through prolonged wake episodes rather than increased sleep. This finding challenges the conventional understanding that sleep is the primary state for memory consolidation, suggesting that under specific conditions, wakefulness may also play a key role in supporting memory processes. Further research is needed to explore the underlying mechanisms of IL-12's cognitive effects.

Are the Sleep-Wake Cycle and Sleep Duration Ethnically Determined? A Comparison of Tibetan and Japanese Children's Sleep.

Several environmental factors affect sleep. We investigated the sleep and sleep-related habits of preschool children living in Tibet and conducted an international comparison with those in Japan. We conducted a community-based cross-sectional study using the Chinese version of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P-C) and compared the results with previous data on Japanese children. The sleep status of 3113 children aged 3-6 years old in Qinghai province was evaluated. The average wake time and bedtime of the Tibetan children were 7:20 ± 0:31 and 21:16 ± 0:43, respectively. Their mean nocturnal sleep duration was 10.0 ± 0.7 h. In comparing 3-year-old children, the time for which they viewed TV in Tibet was shorter (65.5 ± 44.6 min) than that in Japan (149.7 ± 76.6 min), and the mother's bedtime was earlier in Tibet (21:28 ± 2:14) than in Japan (23:20 ± 1:05). However, the bedtime and sleep duration of the Tibetan children (21:17 ± 0:37 and 10.0 ± 0.7 h) were fairly similar to those of the Japanese children (21:24 ± 1:57 and 9.8 ± 0.8 h). The late bedtime and short nocturnal sleep duration of Tibetan toddlers were the same as those of Japanese toddlers despite considerable differences in their lifestyle and environment.

Circadian desynchrony in early life leads to enduring autistic-like behavioral changes in adulthood

Circadian rhythm regulates a variety of biological processes in almost all living organisms. Modern lifestyles, e.g. transmeridian travel, night shift, light at night, etc., frequently disrupt people’s regular sleep-wake cycles and create a misalignment (circadian desynchrony) between the natural environment and the endogenous body clock, and between different circadian oscillators within the body. The long-term consequences of circadian desynchrony on neurodevelopment and adult behavior remain elusive. Increasing clinical evidence supports a correlation between the disruption of the circadian system and neurodevelopmental disorders, such as autism spectrum disorders. Despite clinical correlations, experimental evidence is yet to establish a link between circadian disturbance in early life and adult behavioral changes. Here, using a “short day” (SD) mouse model, in which mice were exposed to an 8 h/8 h light/dark (LD) cycle mimicking a “shift work” schedule from gestation day 1 to postnatal day 21, we performed a battery of behavioral tests to assess changes in adult behaviors, including sociability, affective behaviors, stereotypy, cognition and locomotor functions. In contrast to the control mice kept in a 12 h/12 h LD cycle, the adult SD mice entrained to the 8 h/8 h LD cycle, but their free running rhythms remained normal in constant darkness. Interestingly, however, the SD mice displayed diminished sociability, a reduced preference for social novelty, excessive repetitive behaviors, and compromised cognitive functions, all of which resemble characteristics of autism-like behavioral alterations. In addition, the SD mice exhibited significant anxiety- and depressive-like behaviors and impaired motor functions. By western blotting and immunostaining analyses, hyperactivation of the mTORC1/S6K1 pathway was detected in multiple forebrain regions of SD mice. These findings underscore the enduring impact of early-life circadian disruption on neurochemical signaling and behavioral patterns into adulthood, highlighting a pivotal role for circadian regulation in neurodevelopment.

Research progress on melatonin, 5-HT, and orexin in sleep disorders of children with autism spectrum disorder.

Sleep disorders are among the common comorbidities of autism spectrum disorder (ASD), which not only affect the daily life and learning ability of children but may also exacerbate other symptoms of ASD, seriously impacting the quality of life of children and their families. Given this, understanding the neurobiological mechanisms of sleep disorders in children with ASD has significant research value for developing effective intervention strategies. Melatonin, 5-HT, and orexin are key neurotransmitters that regulate the sleep-wake cycle. Through in-depth analysis of the biological functions and regulatory pathways of these neurotransmitters, new perspectives may be provided for personalized treatment of sleep disorders in children with ASD. This article reviews the research progress on melatonin, 5-HT, and orexin in sleep disorders among children with autism spectrum disorder, focusing on exploring the mechanisms of these key neurotransmitters in sleep disorders of children with ASD and how they affect the sleep-wake cycle, providing a theoretical basis for improving the sleep quality of children with ASD.

Postsynaptic competition between calcineurin and PKA regulates mammalian sleep-wake cycles.

The phosphorylation of synaptic proteins is a significant biochemical reaction that controls the sleep-wake cycle in mammals1-3. Protein phosphorylation in vivo is reversibly regulated by kinases and phosphatases. In this study, we investigate a pair of kinases and phosphatases that reciprocally regulate sleep duration. First, we perform a comprehensive screen of protein kinase A (PKA) and phosphoprotein phosphatase (PPP) family genes by generating 40 gene knockout mouse lines using prenatal and postnatal CRISPR targeting. We identify a regulatory subunit of PKA (Prkar2b), a regulatory subunit of protein phosphatase 1 (PP1; Pppr1r9b) and catalytic and regulatory subunits of calcineurin (also known as PP2B) (Ppp3ca and Ppp3r1) as sleep control genes. Using adeno-associated virus (AAV)-mediated stimulation of PKA and PP1-calcineurin activities, we show that PKA is a wake-promoting kinase, whereas PP1 and calcineurin function as sleep-promoting phosphatases. The importance of these phosphatases in sleep regulation is supported by the marked changes in sleep duration associated with their increased and decreased activities, ranging from approximately 17.3 h per day (PP1 expression) to 4.3 h per day (postnatal CRISPR targeting of calcineurin). Localization signals to the excitatory post-synapse are necessary for these phosphatases to exert their sleep-promoting effects. Furthermore, the wake-promoting effect of PKA localized to the excitatory post-synapse negated the sleep-promoting effect of PP1-calcineurin. These findings indicate that PKA and PP1-calcineurin have competing functions in sleep regulation at excitatory post-synapses.

Adenosine-Dependent Arousal Induced by Astrocytes in a Brainstem Circuit.

Astrocytes play a crucial role in regulating sleep-wake behavior. However, how astrocytes govern a specific sleep-arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep-wake cycles with state-differential Ca2+ activity, peaking during transitions from sleep to wakefulness. Using chemogenetic and optogenetic approaches, they find that activating PZ astrocytes elicited and sustained wakefulness by prolonging arousal episodes while impeding transitions from wakefulness to non-rapid eye movement (NREM) sleep. Activation of PZ astrocytes specially induced the elevation of extracellular adenosine through the ATP hydrolysis pathway but not equilibrative nucleoside transporter (ENT) mediated transportation. Strikingly, the rise in adenosine levels induced arousal by activating A1 receptors, suggesting a distinct role for adenosine in the PZ beyond its conventional sleep homeostasis modulation observed in the basal forebrain (BF) and cortex. Moreover, at the circuit level, PZ astrocyte activation induced arousal by suppressing the GABA release from the PZGABA neurons, which promote NREM sleep and project to the parabrachial nucleus (PB). Thus, their study unveils a distinctive arousal-promoting effect of astrocytes within the PZ through extracellular adenosine and elucidates the underlying mechanism at the neural circuit level.

Sleep Management: The Use of Continuous Physiological Monitoring to Support Patient Self-Care

Circadian misalignment (CM) is a sleep disruption where an individual’s circadian rhythm and actual sleep-wake cycle are unsynchronized. CM is frequently misdiagnosed and difficult to treat but can adversely impact short-term and long-term health outcomes. CM often interacts bidirectionally with chronic conditions affecting cognitive and physical functionality. Continuous physiological monitoring (CPM) of the hormone melatonin would support real-time, patient-driven interventions to address CM. However, patient-driven self-care tasks involve complex information processing and decision-making. Effective CPM use requires situation awareness regarding current circadian health and projected future status, sufficient background knowledge to identify circadian intervention alternatives, and selection of appropriate alternatives given their current state. Melatonin data has characteristics distinct from biomarkers previously subject to CPM, introducing further challenges around data presentation. Task analysis efforts can identify the cognitive processes involved in five different tasks associated with a continuous melatonin monitor to identify necessary informational elements to include in interface design.

Heart rate variability in chronic ischemic stroke: analysis during the sleep-wake cycle.

Alterations of the autonomic nervous system (ANS) in the chronic stage of ischemic stroke (IS) are not well understood. Heart rate variability (HRV) provides a noninvasive approach to assess autonomic function. To compare the HRV parameters during the sleep-wake cycle between patients with IS in the chronic stage and healthy subjects. We conducted a retrospective transversal study based on clinical records and 24-hour electrocardiogram (EKG) monitoring registries of 179 patients with a confirmed IS diagnosis and 184 age- and sex-matched healthy subjects. Circadian variation was calculated according to the variation of the total autonomic activity (VTAI) and the parasympathetic activity (VPAI) indexes. Comparisons were performed using nonparametric tests. Multivariable analyses were performed with canonical discriminant analysis (CDA) and a three-way analysis of variance (ANOVA). Statistical significance was established with a confidence level of 95%. During waking hours, the healthy group exhibited higher variability in the time domain and frequency domain parameters: standard deviation of NN intervals (SDNN, p < 0.001) and of the average NN intervals (SDANN, p < 0.001), as well as low-frequency (LF) band (p < 0.001). During sleep, the difference was higher in the high-frequency (HF) band (p < 0.001), and lower in the low-/high-frequency ratio (LF/HF, p < 0.001). Both VPAI and VTAI showed less significant difference in IS patients (p < 0.001). There was diminished heart vagal activity among IS patients, as measured through HRV. During sleep, this is likely caused by an imbalance in the sympathetic and parasympathetic systems shifting through the sleep phases. These imbalances could persist over time in patients with IS, lasting months after the initial injury.