Sleep Stages Research Articles

Monocytes migrate to the brain after MI to promote deep sleep to aid cardiac healing.

Monocytes migrate to the brain after MI to promote deep sleep to aid cardiac healing.

Gender-specific associations between slow wave sleep and cardiovascular risk factors: too early to tell?

Gender-specific associations between slow wave sleep and cardiovascular risk factors: too early to tell?

Influence of sleep on seizures and interictal epileptiform discharges in epilepsy.

Sleep significantly influences seizure occurrence and interictal epileptiform discharges (IEDs) in patients with epilepsy. Sleep-related epilepsy, where seizures occur exclusively or predominantly during sleep, has been observed in various epilepsy syndromes. Understanding the influence of sleep on seizures and IEDs is crucial in the diagnosis, classification, and management of epilepsy. Although there is a bidirectional relationship between sleep and epilepsy, this review focuses on the influence of sleep on seizures and IEDs in epilepsy. Seizures are more common during non-rapid eye movement (NREM) sleep, particularly during stage N2, and are suppressed during rapid eye movement (REM) sleep. Sleep also activates IEDs, increasing the diagnostic yield of EEG recordings. The rate of IEDs increases during NREM sleep, reaches its maximum during stage N3, and decreases during REM sleep. Sleep affects the electrical field of IEDs, with an increase of spiking fields during NREM sleep and a decrease during REM sleep. In the localization of epileptogenic foci, REM sleep is less sensitive but more specific than NREM sleep. Thalamocortical EEG synchronization during NREM sleep and desynchronization during REM sleep underlie their opposing effects on seizures and IEDs. Accumulating evidence has suggested an antiseizure effect of orexinergic antagonism in animal studies. Interventions that promote REM sleep, including orexinergic antagonists, should be studied in the future as novel treatment strategies for epilepsy.

A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats.

Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization. Cannabinol (CBN) is a minor cannabinoid used in the community in "isolate' products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures. The effects of CBN on sleep in rats using polysomnography were therefore examined. CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep. Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB1 receptors with comparable potency and efficacy to Δ9-THC, however, CBN had much lower activity. We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself. This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action.

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

Abstract Background Cytokines, 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. Results Mice 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. Conclusion The 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.

Based -evidence, an intervention study to improve sleep quality in awake adult ICU patients: a prospective, single-blind, clustered controlled trial.

Evidence-based guidelines advocate promoting sleep in intensive care unit (ICU) patients, yet many patients experience poor sleep quality. We sought to develop a collaborative evidence-based intervention with healthcare providers and assess whether evidence-based sleep interventions could improve sleep quality in awake adult ICU patients. We conducted a prospective, nonrandomized cluster control trial in two intensive care units (ICUs) at a tertiary general teaching hospital in China. Patients aged 18years or older who stayed in the ICU for one night or more and were conscious were eligible for enrollment. We only blinded the patients, not the outcome assessors. On the basis of evidence-based practice and clinical reality, we developed intervention measures for the intervention group, which mainly included four aspects: reducing environmental noise in the ICU, adjusting nursing actions, modifying nighttime lighting, and other measures. The assessment tools used were wearable actigraphy sleep monitoring devices and the Richards-Campbell Sleep Questionnaire (RCSQ). The primary outcomes were patient sleep quality, including total sleep time, deep sleep time, light sleep time, rapid eye movement (REM) time, number of awakenings, overall sleep score, and patients' self-assessment of their sleep quality that night. The data collected were analyzed via SPSS and Mplus statistical software for between-group analysis, pre-post comparison, profile analysis, and calculation of the intervention effect size. From September 1, 2023, to January 31, 2024, 713 patients underwent eligibility assessment, and ultimately 246 patients were included in the analysis, with 125 in the intervention group and 121 in the control group. Comparative analysis revealed no statistically significant differences in sleep quality between the two groups when the duration in the ICU = 1 night (P > 0.05), with a small intervention effect size. However, the intervention group had higher sleep quality scores (sleep monitoring wristband: 57.74 ± 22.55 > 57.72 ± 19.39; RCSQ questionnaire: 60.58 ± 22.14 > 57.61 ± 24.4) and total sleep time (440.42 ± 262.11 > 420.31 ± 236.89), a lower awakening frequency (3.98 ± 2.69 < 6.09 ± 4.66) and a lower awakening frequency (3.976 ± 2.693 < 6.09 ± 4.664) than did the control group. The sleep quality of patients who stayed in the ICU for > 1 night significantly improved in all the parameters except rapid eye movement time (min) according to the pre-post-test analyses (P < 0.05), with a medium to large intervention effect size and favorable intervention effects. Evidence-based interventions significantly improve sleep quality in ICU patients hospitalized for more than one day. However, our results do not support the improvement of sleep quality in patients admitted to the ICU for one day. ChiCTR2300075763, Registered 14 September 2023-Retrospectively registered, https://www.chictr.org.cn/bin/userProject.

Exploration of an intrinsically explainable self-attention based model for prototype generation on single-channel EEG sleep stage classification.

Prototype-based methods in deep learning offer interpretable explanations for decisions by comparing inputs to typical representatives in the data. This study explores the adaptation of SESM, a self-attention-based prototype method successful in electrocardiogram (ECG) tasks, for electroencephalogram (EEG) signals. The architecture is evaluated on sleep stage classification, exploring its efficacy in predicting stages with single-channel EEG. The model achieves comparable test accuracy compared to EEGNet, a state-of-the-art black-box architecture for EEG classification. The generated prototypical components are exaimed qualitatively and using the area over the perterbation curve (AOPC) indicate some alignment with expected bio-markers for different sleep stages such as alpha spindles and slow waves in non-REM sleep, but the results are severely limited by the model's ability to only extract and present information in the time-domain. Ablation studies are used to explore the impact of kernel size, number of heads, and diversity threshold on model performance and explainability. This study represents the first application of a self-attention based prototype method to EEG data and provides a step forward in explainable AI for EEG data analysis.

Changes to human sleep architecture during long-duration spaceflight.

Both rapid eye movement and non-rapid eye movement sleep are important for cognitive function and well-being, yet few studies have examined whether human sleep architecture is affected by long-duration spaceflight. We recorded 256 nights of sleep from five crew members before (n = 112 nights), during (n = 83 nights) and after (n = 61 nights) ~6-month missions aboard the Mir space station, using the Nightcap sleep monitor. We compared sleep outcomes (including total sleep time, efficiency, latency, rapid eye movement and non-rapid eye movement) during spaceflight with those on Earth. We also evaluated longitudinal changes over time in space. We found that wakefulness increased by 1 hr in space compared with on Earth. Over time in space, rapid eye movement was initially reduced and then recovered to near preflight levels at the expense of non-rapid eye movement sleep. Upon return to Earth, sleep architecture returned to preflight distribution. Our findings suggest that spaceflight may alter sleep architecture and should be explored further.

The effect of restricted and free-living conditions on light exposure and sleep in older adults

ABSTRACT During the COVID-19 pandemic, studies reported that restricted living conditions were associated with worse subjective sleep quality. This effect might have been caused by reduced light exposure during lockdowns. We investigated light exposure levels, subjective and objective sleep and physical activity levels in older adults during restricted and free-living conditions after the pandemic. Ninety-one participants (62.7 ± 8.4 years) recruited from the community using social media with 44 participants (63.4 ± 8.9 years) completed follow-up during free-living conditions. Participants wore an actigraphy device and completed sleep diaries for 7 days during each condition. Light values were extracted in hourly bins across the 24-h period and objective and subjective sleep were compared between the conditions. There was an increase in mean 24-h light exposure during restricted-living (1103.7 ± 1024.8 lux) compared to free-living (803.0 ± 803.6 lux; p < 0.001). This was partially related to participants spending 18 min more in bright light conditions (>1,000 lux) during wakefulness in restricted living (2.6 ± 1.9 h) compared to free-living (2.3 ± 2.0 h; p = 0.036). Despite differences in light exposure, there were no significant differences in objective and subjective sleep parameters between the two conditions. More research is required to better understand behaviours related to light exposure and how this may impact on sleep.

Characterising the power spectrum dynamics of the non-REM to REM sleep transition.

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

Combination Drug Therapy with Acetazolamide, Eszopiclone +/- Venlafaxine for Obstructive Sleep Apnea (RESCUE-Combo): A Randomized, Double-blind, Placebo-controlled Trial.

Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially improve OSA severity in select patients. We tested whether acetazolamide+eszopiclone (DualRx) improves OSA severity. We further explored whether addition of venlafaxine (TripleRx) improves OSA in patients who do not fully respond to DualRx. In this double-blind, crossover trial, twenty OSA patients underwent a baseline polysomnography followed by DualRx/Placebo phases in random order. Subsequently, 18 patients underwent an open-label TripleRx phase. Each phase lasted 3 days and concluded with polysomnography. The primary outcome was the placebo-adjusted change in apnea-hypopnea index during supine, non-rapid eye movement sleep (AHINREM,supine) from baseline to DualRx. Secondary outcomes included other OSA metrics, sleep parameters, and select clinical outcomes (blood pressure, symptoms, vigilance). Participants were on average middle-aged, overweight and relatively diverse (20% women, 60% non-white) with severe OSA (median [IQR] AHINREM,supine 32.8 [20-48.8] events/h). Compared with placebo, DualRx was well tolerated, improved the AHINREM,supine (-13.8 [-24.1 to -5.2] events/h or -45 [-77 to -14] %, PWilcoxon=0.003), AHIOverall, hypoxic burden and sleep architecture (P<0.05), but not the selected clinical outcomes. TripleRx did not provide a clear benefit relative to DualRx, although some measures of OSA-related hypoxemia improved more substantially. There were no serious side effects. Short-term use of dual-drug therapy with acetazolamide+eszopiclone substantially improved OSA severity. Adding venlafaxine did not generally improve OSA severity but may be beneficial for some patients. Longer term studies are needed to assess effects on clinically important outcomes. Clinical trial registration available at www. gov, ID: NCT04639193.

IntelliSleepScorer, a Software Package with a Graphic User Interface for Mice Automated Sleep Stage Scoring

IntelliSleepScorer, a Software Package with a Graphic User Interface for Mice Automated Sleep Stage Scoring

Tetrodotoxin-mediated Inactivation of Medial Prefrontal Cortex Decreases Wakefulness and Rapid Eye Movement Sleep, and Increases Slow-Wave Sleep in Rat.

Tetrodotoxin-mediated Inactivation of Medial Prefrontal Cortex Decreases Wakefulness and Rapid Eye Movement Sleep, and Increases Slow-Wave Sleep in Rat.

Evaluation of a new single-channel EEG-based approach for automated identification of sleep stages

Evaluation of a new single-channel EEG-based approach for automated identification of sleep stages

Mouth Leak is Associated with Sleep Fragmentation During Nasal CPAP Treatment of OSA and May Be Detected by Leak Waveform Analysis.

Mouth air leak is a major cause of low adherence to nasal CPAP in patients with obstructive sleep apnea (OSA). However, CPAP reports do not distinguish mouth from mask leak. We hypothesized that mouth air leak is terminated abruptly by an arousal from sleep and mouth closing that can be detected by CPAP leak waveform analysis. Describe patterns of mouth air leak waveform during polysomnography (PSG) in patients with OSA treated with well-fitted nasal CPAP. PSG recordings with a jaw motion sensor to detect mouth opening were performed in OSA patients treated with nasal CPAP with suspected mouth air leak. Careful mask fitting and visual inspection excluded mask leak. Mouth leak episodes were characterized by an increase (≥ 20%) above the intentional leak. Leak episodes were classified as intermittent (< 5 minutes) or continuous (≥ 5 minutes). Twenty patients (80% men; age: 63±11 years; body mass index: 29.9±6 kg/m2; baseline apnea hypopnea index: 46.9±19 events/h) treated with nasal CPAP and documented mouth leak completed the study. All but one patient experienced an overlap of intermittent and continuous mouth leak. Most mouth leak episodes ended with mouth closure (97.7%) and an arousal (52.7%) or awakening (38.6%). Only 34.9% of the leak episodes were associated with respiratory events. Intermittent mouth air leak was more common in sleep stages N1+ N2 (P<0.01), while continuous leak was more common in sleep stage N3 (P<0.01). Continuous episodes of air leak were associated with a higher amplitude of mouth opening. CPAP report waveform was able to detect only 29.6% of the leak episodes detected by PSG. Only 10 patients (50%) had a high unintentional leak according to the criterion adopted by ResMed and only 2 patients (10%) presented large leak according to the Philips criterion. Intermittent and continuous mouth leak during nasal CPAP frequently co-exist and contribute to sleep fragmentation. Identification of leak waveform patterns may help detect mouth air leak which in turn is an important cause of poor CPAP adherence.

Medical Textiles of Self-Inflating On Air Mattress Bed and Belt for Nursing Physical Therapy Education and Training Performing a Healing Process

Medical textiles of a self-inflating air mattress bed and belt include an air chamber and a foam panel therein. The air chamber is defined by top and bottom sheet panels and a valve allowing air passage into and out of the air chamber. The foam panel includes the field of airflow passage there through, and the top and bottom sheet panels are mechanically coupled directly together via the apertures in the foam panel of the air mattress conducted to improve sleep quality. This study investigated the effect of variations in the surface characteristics of mattress beds and belts on pelvic fracture patients’ sleep quality. The present study developed a mattress bed and belt whose rigidity can be varied by controlling the amount of air in its air cells. To investigate the effect of the variable rigidity of the air mattress bed and belt on pelvic fracture patients’ sleep quality, participants (women, ages 13-45) were instructed to sleep on the air mattress bed and belt under different conditions, and their sleep quality was subjectively and objectively investigated. Subjectively, sleep quality is assessed based on the participants’ evaluations of the depth and length of their sleep. Objectively, medical textiles for pelvic fracture patients and mattress bed and belt specifications are estimated using the sleep stage information obtained by analyzing the movements and brain waves of the participants during their sleep. A subjective assessment of the sleep quality demonstrates that the participants’ sleep was worse with the adjustment of the air mattress bed and belt.

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.

Temporal and sleep stage-dependent agreement in manual scoring of respiratory events.

Obstructive sleep apnea diagnosis is based on the manual scoring of respiratory events. The agreement in the manual scoring of the respiratory events lacks an in-depth investigation as most of the previous studies reported only the apnea-hypopnea index or overall agreement, and not temporal, second-by-second or event subtype agreement. We hypothesized the temporal and subtype agreement to be low because the event duration or subtypes are not generally considered in current clinical practice. The data comprised 50 polysomnography recordings scored by 10 experts. The respiratory event agreement between the scorers was calculated using kappa statistics in a second-by-second manner. Obstructive sleep apnea severity categories (no obstructive sleep apnea/mild/moderate/severe) were compared between scorers. The Fleiss' kappa value for binary (event/no event) respiratory event scorings was 0.32. When calculated separately within N1, N2, N3 and R, the Fleiss' kappa values were 0.12, 0.23, 0.22 and 0.23, respectively. Binary analysis conducted separately for the event subtypes showed the highest Fleiss' kappa for hypopneas to be 0.26. In 34% of the participants, the obstructive sleep apnea severity category was the same regardless of the scorer, whereas in the rest of the participants the category changed depending on the scorer. Our findings indicate that the agreement of manual scoring of respiratory events depends on the event type and sleep stage. The manual scoring has discrepancies, and these differences affect the obstructive sleep apnea diagnosis. This is an alarming finding, as ultimately these differences in the scorings affect treatment decisions.

Difficulty in artificial word learning impacts targeted memory reactivation and its underlying neural signatures.

Sleep associated memory consolidation and reactivation play an important role in language acquisition and learning of new words. However, it is unclear to what extent properties of word learning difficulty impact sleep associated memory reactivation. To address this gap, we investigated in 22 young healthy adults the effectiveness of auditory targeted memory reactivation (TMR) during non-rapid eye movement sleep of artificial words with easy and difficult to learn phonotactical properties. Here, we found that TMR of the easy words improved their overnight memory performance, whereas TMR of the difficult words had no effect. By comparing EEG activities after TMR presentations, we found an increase in slow wave density independent of word difficulty, whereas the spindle-band power nested during the slow wave up-states - as an assumed underlying activity of memory reactivation - was significantly higher in the easy/effective compared to the difficult/ineffective condition. Our findings indicate that word learning difficulty by phonotactics impacts the effectiveness of TMR and further emphasize the critical role of prior encoding depth in sleep associated memory reactivation.

Difficulty in artificial word learning impacts targeted memory reactivation and its underlying neural signatures

Sleep associated memory consolidation and reactivation play an important role in language acquisition and learning of new words. However, it is unclear to what extent properties of word learning difficulty impact sleep associated memory reactivation. To address this gap, we investigated in 22 young healthy adults the effectiveness of auditory targeted memory reactivation (TMR) during non-rapid eye movement sleep of artificial words with easy and difficult to learn phonotactical properties. Here, we found that TMR of the easy words improved their overnight memory performance, whereas TMR of the difficult words had no effect. By comparing EEG activities after TMR presentations, we found an increase in slow wave density independent of word difficulty, whereas the spindle-band power nested during the slow wave up-states – as an assumed underlying activity of memory reactivation – was significantly higher in the easy/effective compared to the difficult/ineffective condition. Our findings indicate that word learning difficulty by phonotactics impacts the effectiveness of TMR and further emphasize the critical role of prior encoding depth in sleep associated memory reactivation.