Modulation Of Sleep Research Articles

Targeted single cell expression profiling identifies integrators of sleep and metabolic state.

Animals modulate sleep in accordance with their internal and external environments. Metabolic cues are particularly potent regulators of sleep, allowing animals to alter their sleep timing and amount depending on food availability and foraging duration. The fruit fly, Drosophila melanogaster , suppresses sleep in response to acute food deprivation, presumably to forage for food. This process is dependent on a single pair of Lateral Horn Leucokinin (LHLK) neurons, that secrete the neuropeptide Leucokinin. These neurons signal to insulin producing cells and suppress sleep under periods of starvation. The identification of individual neurons that modulate sleep-metabolism interactions provides the opportunity to examine the cellular changes associated with sleep modulation. Here, we use single-cell sequencing of LHLK neurons to examine the transcriptional responses to starvation. We validate that a Patch-seq approach selectively isolates RNA from individual LHLK neurons. Single-cell CEL-Seq comparisons of LHLK neurons between fed and 24-hr starved flies identified 24 genes that are differentially expressed in accordance with starvation state. In total, 12 upregulated genes and 12 downregulated genes were identified. Gene-ontology analysis showed an enrichment for Attacins , a family of anti-microbial peptides, along with several transcripts with diverse roles in regulating cellular function. Targeted knockdown of differentially expressed genes identified multiple genes that function within LHLK neurons to regulate sleep-metabolism interactions. Functionally validated genes include an essential role for the E3 ubiquitin Ligase insomniac, the sorbitol dehydrogenase Sodh1, as well as AttacinC and AttacinB in starvation-induced sleep suppression. Taken together, these findings provide a pipeline for identifying novel regulators of sleep-metabolism interactions within individual neurons.

Sleep-wake behavior and responses to sleep deprivation and immune challenge of protein kinase RNA-activated knockout mice

Protein Kinase RNA-activated (PKR) is an enzyme that plays a role in many systemic processes, including modulation of inflammation, and is implicated in neurodegenerative diseases, such as Alzheimer’s disease (AD). PKR phosphorylation results in the production of several cytokines involved in the regulation / modulation of sleep, including interleukin-1β, tumor necrosis factor-α and interferon-γ. We hypothesized targeting PKR would alter spontaneous sleep of mice, attenuate responses to sleep deprivation, and inhibit responses to immune challenge. To test these hypotheses, we determined the sleep-wake phenotype of mice lacking PKR (knockout; PKR-/-) during undisturbed baseline conditions; in responses to six hours of sleep deprivation; and after immune challenge with lipopolysaccharide (LPS). Adult male mice (C57BL/6J, n = 7; PKR-/-, n = 7) were surgically instrumented with EEG recording electrodes and an intraperitoneal microchip to record core body temperature. During undisturbed baseline conditions, PKR -/- mice spent more time in non-rapid eye movement sleep (NREMS) and rapid-eye movement sleep (REMS), and less time awake at the beginning of the dark period of the light:dark cycle. Delta power during NREMS, a measure of sleep depth, was less in PKR-/- mice during the dark period, and core body temperatures were lower during the light period. Both mouse strains responded to sleep deprivation with increased NREMS and REMS, although these changes did not differ substantively between strains. The initial increase in delta power during NREMS after sleep deprivation was greater in PKR-/- mice, suggesting a faster buildup of sleep pressure with prolonged waking. Immune challenge with LPS increased NREMS and inhibited REMS to the same extent in both mouse strains, whereas the initial LPS-induced suppression of delta power during NREMS was greater in PKR-/- mice. Because sleep regulatory and immune responsive systems in brain are redundant and overlapping, other mediators and signaling pathways in addition to PKR are involved in the responses to acute sleep deprivation and LPS immune challenge.

Early-life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions.

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiologicaland cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early-life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para-chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10-20, followed by sleep deprivation-induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain-derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.

A mobile app providing individually-tailored psychoeducation about sleep for older adults with chronic health conditions and low health literacy.

This paper reports on a study of a mobile app that provides tailored information about sleep to individuals aged 40 and older who have chronic health conditions and low health literacy. The sleep module was a part of a multitopic app focused on chronic disease self-management. Participants were randomly assigned to receive sleep psychoeducation at reading levels equivalent to 3rd, 6th or 8th grade. The primary outcome measure was the Pittsburgh Sleep Quality Index (PSQI), which was completed at baseline, after the intervention, and again three months later. Outcomes were assessed using repeated measures mixed effects models. Most participants were Black, Indigenous, or Other Persons of Color (BIPOC; 87%); they had average reading level at the 7th grade. Health literacy, socioeconomic status, and number of health conditions were related to the PSQI. The PSQI score decreased over the course of the three study visits for all groups, consistent with a small to medium effect size (d = 0.40). No effect of treatment group was observed. Participants were positive about the usefulness and helpfulness of the app. Results suggest that a brief tailored information intervention may be beneficial for individuals aged 40 and older who have low health literacy and chronic health conditions. Further development of the intervention may enhance its clinical effectiveness.

Retrospective examination of cannabis vs. other substance misuse: Associations with 30-day readmission and global assessment of functioning in hospitalized patients with serious mental illness

Substance misuse in individuals with psychiatric disorders is associated with worsening symptoms and hospitalization. The present retrospective, observational study analyzed inpatient psychiatry hospital EHR data from 2013 to 2020 (N = 12,742) in patients with co-occurring psychiatric disorders and substance misuse. Substance use was categorized as cannabis-only, alcohol-only, or illicit/poly-substance. Two outcome variables were evaluated using multiple-regression: (1) Global Assessment of Functioning (GAF) Score at admission, and (2) 30-day readmission rate. Covariates included primary Axis I disorder, living situation, Race/Ethnicity, education, sex, age, and total same-hospital readmissions (>30 days). Controlling for all covariates, the cannabis-only group had (1) significantly higher GAF score at admission (less severity) vs. both other groups; and (2) lower 30-day readmission rates vs. the illicit/poly-substance use group only. Post-hoc analyses revealed the results for the cannabis-only group vs. other drug use groups were robust, holding across all primary psychiatric diagnoses. Study limitations included lack of formal SUD diagnosis, lack of information in the EHR to quantify substance use patterns, retrospective study design, and lack of data to examine an appropriate psychiatric inpatient group free of substance misuse. Results are discussed in terms of the putative therapeutic efficacy of THC and cannabidiol on modulation of sleep, anxiety, and agitation.

Human Prosocial Preferences Are Related to Slow-Wave Activity in Sleep.

Prosocial behavior is crucial for the smooth functioning of the society. Yet, individuals differ vastly in the propensity to behave prosocially. Here, we try to explain these individual differences under normal sleep conditions without any experimental modulation of sleep. Using a portable high-density EEG, we measured the sleep data in 54 healthy adults (28 females) during a normal night's sleep at the participants' homes. To capture prosocial preferences, participants played an incentivized public goods game in which they faced real monetary consequences. The whole-brain analyses showed that a higher relative slow-wave activity (SWA, an indicator of sleep depth) in a cluster of electrodes over the right temporoparietal junction (TPJ) was associated with increased prosocial preferences. Source localization and current source density analyses further support these findings. Recent sleep deprivation studies imply that sleeping enough makes us more prosocial; the present findings suggest that it is not only sleep duration, but particularly sufficient sleep depth in the TPJ that is positively related to prosociality. Because the TPJ plays a central role in social cognitive functions, we speculate that sleep depth in the TPJ, as reflected by relative SWA, might serve as a dispositional indicator of social cognition ability, which is reflected in prosocial preferences. These findings contribute to the emerging framework explaining the link between sleep and prosocial behavior by shedding light on the underlying mechanisms.

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.

Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia

Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potency in addressing this particular issue remains to be determined. Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both in vitro and in vivo. Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity. CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.

Auditory closed-loop modulation of slow wave sleep to treat major depressive disorder

Auditory closed-loop modulation of slow wave sleep to treat major depressive disorder

Semi-Automatic Analysis of Specific Electroencephalographic Patterns during NREM2 Sleep in a Pediatric Population after SARS-CoV-2 Infection.

The post-COVID-19 condition is defined by the World Health Organization as the persistence of symptoms or development of new symptoms three months after the initial SARS-CoV-2 infection, lasting for at least two months without a clear explanation. Neuropsychiatric disorders associated with this condition include asthenia, memory and concentration problems, and sleep disturbances. Our study aims to investigate sleep patterns following SARS-CoV-2 infection using EEG findings and a sleep quality questionnaire completed by parents (Sleep Disturbance Scale for Children-SDSC). Notably, our investigation is based on a convenience sample. The patients in our sample, aged 1 to 14 years, are not currently taking any medications; rather, they are undergoing follow-up assessments at the Child Neuropsychiatry department of the University Hospital of Messina for neurodevelopmental evaluations. Specifically, we are analyzing amplitude and power spectrum data in the first five minutes of NREM2 sleep, calculated from EEG recordings obtained via bipolar leads within three months after the onset of the disease. These results will be compared with controls performed on the same subjects in the six months preceding the infection. The focus of the study was sleep spindles, which are generated by the thalamocortical systems and play a role in sleep modulation, memory, and learning. Preliminary analysis suggests a predominant increase in the slow component of the spindles in the right-frontal lead.

Neurophysiological and behavioral synchronization in group-living and sleeping mice

Social interactions profoundly influence animal development, physiology, and behavior. Yet, how sleep-a central behavioral and neurophysiological process-is modulated by social interactions is poorly understood. Here, we characterized sleep behavior and neurophysiology in freely moving and co-living mice under different social conditions. We utilized wireless neurophysiological devices to simultaneously record multiple individuals within a group for 24 h, alongside video acquisition. We first demonstrated that mice seek physical contact before sleep initiation and sleep while in close proximity to each other (hereafter, "huddling"). To determine whether huddling during sleep is a motivated behavior, we devised a novel behavioral apparatus allowing mice to choose whether to sleep in close proximity to a conspecific or in solitude, under different environmental conditions. We also applied a deep-learning-based approach to classify huddling behavior. We demonstrate that mice are willing to forgo their preferred sleep location, even under thermoneutral conditions, to gain access to social contact during sleep. This strongly suggests that the motivation for prolonged physical contact-which we term somatolonging-drives huddling behavior. We then characterized sleep architecture under different social conditions and uncovered a social-dependent modulation of sleep. We also revealed coordination in multiple neurophysiological features among co-sleeping individuals, including in the timing of falling asleep and waking up and non-rapid eye movement sleep (NREMS) intensity. Notably, the timing of rapid eye movement sleep (REMS) was synchronized among co-sleeping male siblings but not co-sleeping female or unfamiliar mice. Our findings provide novel insights into the motivation for physical contact and the extent of social-dependent plasticity in sleep.

POOR SLEEP HEALTH MAY BUILD THE ONSET OF A FEAR OF FALLING AMONG COMMUNITY-DWELLING OLDER ADULTS

Abstract A greater fear of falling (FOF) predicts activity restrictions, falls, disability, and increases the risk of mortality among older adults. Although poor sleep has been identified as a relevant factor for FOF among older adults, evidence is primarily shown in cross-sectional studies using isolated sleep characteristics. Whether multidimensional sleep health contributes to increase in FOF among older adults who are particularly vulnerable to falls is less well understood. We investigated the longitudinal relationship between sleep health and the incidence of FOF among community-dwelling older adults and how the association differed between those with or without prior falls experiences. Data were from individuals who completed the sleep module in the National Health and Aging Trends Study (2013-2014; n=695). FOF was assessed with a single item. Multidimensional sleep health was measured with self-reported sleep items based on the SATED model (i.e., sleep satisfaction, daytime alertness, timing, efficiency, and duration). Covariates included sociodemographics, assistive device usage, health, and sleep medications. Multiple logistic regression was used to analyze the data. Poor sleep health was associated with the onset of FOF at 1-year follow-up (OR=1.20, 95%CI=1.02-1.41). Moreover, poor sleep health increased the odds of having FOF among individuals without prior falls experiences and elevated the already heightened risks of developing FOF among those who fell at baseline. Improving sleep health may potentially prevent older adults from developing FOF.

Poor sleep health predicts the onset of a fear of falling among community-dwelling older adults

IntroductionA greater fear of falling predicts disability, falls, and mortality among older adults. Although poor sleep has been identified as a relevant risk factor for fear of falling among older adults, evidence is primarily shown in cross-sectional studies using isolated sleep characteristics. Less is known about whether prior fall experiences change the sleep health-fear of falling link among older adults. We investigated the longitudinal relationship between sleep health and the incidence of fear of falling among community-dwelling older adults and how the association differed between those with or without prior fall experiences. MethodsData were from individuals who completed the sleep module in the National Health and Aging Trends Study (2013-2014; n = 686). Fear of falling was assessed with a single item. Multidimensional sleep health was measured with self-reported sleep items based on the SATED model (ie, sleep satisfaction, daytime alertness, timing, efficiency, and duration). Covariates included sociodemographics, assistive device usage, health, risky behavior, and sleep medications. Multiple logistic regression was used to analyze the data. ResultsPoor sleep health was associated with the onset of fear of falling at 1-year follow-up (odds ratios=1.20, 95% confidence interval=1.02-1.41). Moreover, poor sleep health increased the odds of having fear of falling among individuals without prior falls experiences and elevated the already heightened risks of developing fear of falling among those who fell at baseline. ConclusionsGiven that fear of falling and experiencing a fall each increase the risk of the other occurring in the future, improving sleep health may prevent older adults from stepping into the vicious cycle of fear of falling and falls.

Disturbed laterality of non-rapid eye movement sleep oscillations in post-stroke human sleep: a pilot study.

Sleep is known to promote recovery post-stroke. However, there is a paucity of data profiling sleep oscillations in the post-stroke human brain. Recent rodent work showed that resurgence of physiologic spindles coupled to sleep slow oscillations (SOs) and concomitant decrease in pathological delta (δ) waves is associated with sustained motor performance gains during stroke recovery. The goal of this study was to evaluate bilaterality of non-rapid eye movement (NREM) sleep-oscillations (namely SOs, δ-waves, spindles, and their nesting) in post-stroke patients vs. healthy control subjects. We analyzed NREM-marked electroencephalography (EEG) data in hospitalized stroke-patients (n = 5) and healthy subjects (n = 3). We used a laterality index to evaluate symmetry of NREM oscillations across hemispheres. We found that stroke subjects had pronounced asymmetry in the oscillations, with a predominance of SOs, δ-waves, spindles, and nested spindles in affected hemisphere, when compared to the healthy subjects. Recent preclinical work classified SO-nested spindles as restorative post-stroke and δ-wave-nested spindles as pathological. We found that the ratio of SO-nested spindles laterality index to δ-wave-nested spindles laterality index was lower in stroke subjects. Using linear mixed models (which included random effects of concurrent pharmacologic drugs), we found large and medium effect size for δ-wave nested spindle and SO-nested spindle, respectively. Our results in this pilot study indicate that considering laterality index of NREM oscillations might be a useful metric for assessing recovery post-stroke and that factoring in pharmacologic drugs may be important when targeting sleep modulation for neurorehabilitation post-stroke.

Loneliness and Marital Quality as Predictors of Older Adults' Insomnia Symptoms.

The current study examined associations between marital quality, loneliness, and sleep within a nationally representative sample of older adults who participated in Wave 2 of the National Social Life, Health, and Aging Project (NSHAP). Participants (N = 559) had a spouse or partner and completed a novel sleep module that included subjective (i.e., insomnia symptoms) and objective (i.e., wake after sleep onset;WASO) markers of sleep. Upon controlling for demographics and markers of mental and physical health, a distinct pattern of findings emerged for subjective versus objective markers of sleep. Regarding subjective sleep, older adults who experienced greater loneliness reported more insomnia symptoms, but only when spousal emotional support was low-moderate. Regarding objective sleep, older adults who reported more affectionate touch from their spouse experienced less WASO. Collectively, these findings identify specific aspects of marital quality that may have unique implications for partnered older adults' subjective and objective sleep quality.

Effects of sleep deprivation on sleep and sleep electroencephalogram in secretin-receptor knockout mice

Recent studies has consistently demonstrated a relationship between secretin and autism-like behavior in mice. Therefore, secretin-receptor knockout (SCTR-KO) mice are used to study autism. However, with respect to humans, some studies have reported that secretin administration could improve autistic symptoms in contrast to other studies. A consistent finding revealed that several patients with autism spectrum disorders (ASD) experience comorbid sleep disorders. To examine the relationship between secretin and sleep, we recorded the core body temperature and locomotor activity of SCTR-KO (-/-) and wild-type (WT) (+/+) mice in the baseline condition and after 4 h of sleep deprivation. No significant differences were observed between the SCTR-KO and control mice in the baseline condition. However, during the first dark period following sleep deprivation, we observed an increase in non-rapid eye movement sleep in the SCTR-KO group, which demonstrated that the absence of secretin induces fragmentation making it difficult for the SCTR-KO mice to maintain sleep and wakefulness. Our results follow previous reports that a large proportion of patients with ASD complain of drowsiness and decreased focus during the day. Secretin functions as an intestinal peptide that neutralizes gastric acid and as a neuropeptide in the brain; it also affects social cognitive behavior and acts as a neurotrophic factor. We have proposed that secretin might be a contributing factor to the modulation of sleep.

Examining sleep modulation by Drosophila ellipsoid body neurons.

Recent work in Drosophila has uncovered several neighboring classes of sleep-regulatory neurons within the central complex. However, the logic of connectivity and network motifs remains limited by the incomplete examination of relevant cell types. Using a recent genetic-anatomical classification of ellipsoid body ring neurons, we conducted a thermogenetic screen in female flies to assess sleep/wake behavior and identified two wake-promoting drivers that label ER3d neurons and two sleep-promoting drivers that express in ER3m cells. We then used intersectional genetics to refine driver expression patterns. Activation of ER3d cells shortened sleep bouts, suggesting a key role in sleep maintenance. While sleep-promoting drivers from our miniscreen label overlapping ER3m neurons, intersectional strategies cannot rule out sleep regulatory roles for additional neurons in their expression patterns. Suppressing GABA synthesis in ER3m neurons prevents post-injury sleep, and GABAergic ER3d cells are required for thermogenetically induced wakefulness. Finally, we use an activity-dependent fluorescent reporter for putative synaptic contacts to embed these neurons within the known sleep-regulatory network. ER3m and ER3d neurons may receive connections from wake-active Helicon/ExR1 cells, and ER3m neurons likely inhibit ER3d neurons. Together, these data suggest a neural mechanism by which previously uncharacterized circuit elements stabilize sleep-wake states.Significance StatementNeural circuits that control sleep must be stable to ensure therapeutic rest but readily adaptable to a variety of experiences. The Drosophila ellipsoid body (EB) regulates many cognitive processes, and recent studies show that certain EB neurons can intensify sleepiness, but the contributions of other EB neuron subclasses in sleep regulation remain unclear. Thus, we searched for sleep-regulatory neurons across the EB to better understand sleep control. Our studies indicate that ER3d neurons promote wakefulness by reducing the persistence of sleep episodes and suggest that ER3m neuron activity may increase sleep. Understanding the stability and flexibility of sleep, then, may emerge from investigating the connectivity and conductivity of sleep-regulatory neurons in the EB.

Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite.

Orexin plays a significant role in the modulation of REM sleep, as well as in the regulation of appetite and feeding. This review explores, first, the current evidence on the role of orexin in the modulation of sleep and wakefulness and highlights that orexin should be considered essentially as a neurotransmitter inhibiting REM sleep and, to a much lesser extent, a wake promoting agent. Subsequently, the relationship between orexin, REM sleep, and appetite regulation is examined in detail, shedding light on their interconnected nature in both physiological conditions and diseases (such as narcolepsy, sleep-related eating disorder, idiopathic hypersomnia, and night eating syndrome). Understanding the intricate relationship between orexin, REM sleep, and appetite regulation is vital for unraveling the complex mechanisms underlying sleep-wake patterns and metabolic control. Further research in this field is encouraged in order to pave the way for novel therapeutic approaches to sleep disorders and metabolic conditions associated with orexin dysregulation.

Micro SleepNet: efficient deep learning model for mobile terminal real-time sleep staging.

The real-time sleep staging algorithm that can perform inference on mobile devices without burden is a prerequisite for closed-loop sleep modulation. However, current deep learning sleep staging models have poor real-time efficiency and redundant parameters. We propose a lightweight and high-performance sleep staging model named Micro SleepNet, which takes a 30-s electroencephalography (EEG) epoch as input, without relying on contextual signals. The model features a one-dimensional group convolution with a kernel size of 1 × 3 and an Efficient Channel and Spatial Attention (ECSA) module for feature extraction and adaptive recalibration. Moreover, the model efficiently performs feature fusion using dilated convolution module and replaces the conventional fully connected layer with Global Average Pooling (GAP). These design choices significantly reduce the total number of model parameters to 48,226, with only approximately 48.95 Million Floating-point Operations per Second (MFLOPs) computation. The proposed model is conducted subject-independent cross-validation on three publicly available datasets, achieving an overall accuracy of up to 83.3%, and the Cohen Kappa is 0.77. Additionally, we introduce Class Activation Mapping (CAM) to visualize the model's attention to EEG waveforms, which demonstrate the model's ability to accurately capture feature waveforms of EEG at different sleep stages. This provides a strong interpretability foundation for practical applications. Furthermore, the Micro SleepNet model occupies approximately 100 KB of memory on the Android smartphone and takes only 2.8 ms to infer one EEG epoch, meeting the real-time requirements of sleep staging tasks on mobile devices. Consequently, our proposed model has the potential to serve as a foundation for accurate closed-loop sleep modulation.

Modulation of sleep using noninvasive stimulations during sleep.

Among the various sleep modulation methods for improving sleep, three methods using noninvasive stimulation during sleep have been reviewed and summarized. The first method involves noninvasive direct brain stimulation to induce a current directly in the brain cortex. Electrically or magnetically applied stimulations trigger electrical events such as slow oscillations or sleep spindles, which can also be recorded by an electroencephalogram. The second method involves sensory stimulation during sleep, which provides stimulation through the sensory pathway to invoke equivalent brain activity like direct brain stimulation. Olfactory, vestibular, and auditory stimulation methods have been used, resulting in several sleep-modulating effects, which are characteristic and depend on the experimental paradigm. The third method is to modulate sleep by shifting the autonomic balance affecting sleep homeostasis. To strengthen parasympathetic dominance, stimulation was applied to decrease heart rate by synchronizing the heart rhythm. These noninvasive stimulation methods can strengthen slow-wave sleep, consolidate declarative or procedural memory, and modify sleep macrostructure. These stimulation methods provide evidence and possibility for sleep modulation in our daily life as an alternative method for the treatment of disturbed sleep and enhancing sleep quality and performance beyond the average level.