Sleep Stages Research Articles

Breathtaking dreams: reduced REM phenotype in REM-related sleep apnea

PurposeThe expression of the respiratory events in OSA is influenced by different mechanisms. In particular, REM sleep can highly increase the occurrence of events in a subset of OSA patients, a condition dubbed REM-OSA (often defined as an AHI 2 times higher in REM than NREM sleep). However, a proper characterization of REM-OSA and its pathological sequelae is still inadequate, partly because of limitations in the current definitions.MethodsWe propose a new interpretation of the REM-OSA definition, extending it from a AHI-ratio to a two-dimensional space, considering both time and events ratios in REM over NREM separately. Within this space, we analyzed current definitions of REM-OSA in three large clinical dataset and identified the underlying sources of heterogeneity.ResultsWe observed that REM-OSA and REM-independent-OSA subgroups exist. Some subgroups exhibited abnormal REM characteristics (e.g., REM-OSA with reduced time in REM). Others had OSA features that are intermediate between REM-independent-OSA participants and those with a clear disproportion of REM events.ConclusionWe found that a time and events’ ratio of REM and NREM allow a more precise characterization of REM-OSA subgroups. Our new interpretation can be used to bolster new research into REM-OSA pathophysiological mechanisms.

Lateralized differences in power spectra across different frequency bands during NREM sleep in patients with primary insomnia

Lateralized differences in power spectra across different frequency bands during NREM sleep in patients with primary insomnia

Multimodal Neural Network Analysis of Single-Night Sleep Stages for Screening Obstructive Sleep Apnea

Multimodal Neural Network Analysis of Single-Night Sleep Stages for Screening Obstructive Sleep Apnea

Evening Alpha-Lactalbumin Supplementation Alters Sleep Architecture and Reduces Morning Reaction Time in an Athletically Trained Population With Sleep Difficulties.

Evening consumption of a whey protein rich in the amino acid tryptophan, alpha-lactalbumin (ALAC), has previously shown to benefit sleep-particularly among poor sleepers. Given trained populations often experience sleep difficulty, this study investigated whether evening supplementation of ALAC would influence sleep outcomes, mood, and next-day cognitive performance within a trained population with sleep difficulties. Nineteen trained participants (females, n = 11) with sleep difficulties (Athlete Sleep Screening Questionnaire: 8.1 ± 3.1; Pittsburgh Sleep Quality Index: 10.5 ± 4.1) completed this double-blinded, counterbalanced, randomized, crossover trial. Forty grams of ALAC or control were supplemented 2hr presleep for three consecutive nights in a controlled environment, with sleep measured using dry electroencephalography. Blood samples were taken on the first evening of each experimental trial, with mood, sleepiness, and recovery assessed across the evening and morning. A cognitive testing battery was also completed each morning. During the ALAC condition, the primary findings were that participants had raised plasma tryptophan levels (p < .01), increased nonrapid eye movement Stage 2 sleep duration (CON: 205.9 ± 33.3; ALAC: 216.5 ± 33.1min), reduced rapid eye movement duration (CON: 110.8 ± 27.9; ALAC: 99.7 ± 23.1min), and improved reaction time in cognitive tests involving sensory motor speed, spatial orientation, and vigilant attention (p < .05). Data suggestevening supplementation of 40g ALAC alters sleep architecture and improves next-morning reaction time in trained populations with sleep difficulties. Therefore, trained individuals experiencing sleep difficulty may benefit from acute ALAC supplementation to assist next-day performance. Future research should investigate this effect within habitual environments, outside of a tightly controlled setting.

Self-Similarity Analysis of Heartbeat Fluctuations in Sleep Among Female Shift Workers

Cardiovascular signals exhibit self-similarity characteristics, which are influenced by changes in autonomic nervous system (ANS) regulation caused by shift work. This study aims to assess the self-similarity properties of inter-beat interval (IBI) in healthy female shift workers and non-shift workers in different sleep stages to detect alterations in heartbeat fluctuations due to shift work. Short- and long-term self-similarity properties of the IBI signal ([Formula: see text] and [Formula: see text] scaling exponents, respectively) were analyzed using Detrended Fluctuation Analysis. Time and frequency indices were also calculated. In addition, Principal Component Analysis (PCA) was employed to reduce dimensionality and evaluate group separability based on the obtained features. Most indices showed similar values in the different sleep stages for both groups, but [Formula: see text] during light sleep and sympathovagal balance during REM sleep showed a significant decrease in shift workers compared to non-shift workers ([Formula: see text]). In addition, PCA was able to separate shift workers from non-shift workers and differentiate between nighttime and daytime sleep of workers. This analysis aids in identifying cardiovascular impairment associated with shift work and suggests a loss of ANS self-similarity in shift workers, indicating reduced adaptive capacity. Such alterations in ANS behavior could lead to serious health consequences related to cardiovascular disease.

Statistical Complexity Analysis of Sleep Stages.

Studying sleep stages is crucial for understanding sleep architecture, which can help identify various health conditions, including insomnia, sleep apnea, and neurodegenerative diseases, allowing for better diagnosis and treatment interventions. In this paper, we explore the effectiveness of generalized weighted permutation entropy (GWPE) in distinguishing between different sleep stages from EEG signals. Using classification algorithms, we evaluate feature sets derived from both standard permutation entropy (PE) and GWPE to determine which set performs better in classifying sleep stages, demonstrating that GWPE significantly enhances sleep stage differentiation, particularly in identifying the transition between N1 and REM sleep. The results highlight the potential of GWPE as a valuable tool for understanding sleep neurophysiology and improving the diagnosis of sleep disorders.

OLFACTORY INTERVENTIONS FOR SLEEP ENHANCEMENT: A REVIEW

Sleep is essential for cognitive function, emotional balance, and overall well-being. Disruptions like insomnia or poor sleep quality can have negative consequences. Various methods, including bedtime perfumes, have been studied to improve sleep. This review examines the scientific basis of scent-based sleep enhancement, focusing on the olfactory system and the effects of specific aromatic compounds on sleep. The olfactory system plays a crucial role in how scents influence sleep. Odor molecules bind to receptors in the nasal cavity, sending signals to the olfactory bulb, which processes these signals and relays them to the limbic system. This connection allows scents to evoke emotional responses and impact sleep. Historically, scent therapy has been used across cultures. The effectiveness of bedtime perfumes depends on their delivery methods. Diffusers, sprays and roll-on oils are common ways to disperse essential oils. Incorporating these perfumes into comprehensive sleep hygiene routine, including a consistent sleep schedule and a calming environment, maximizes their benefits. Future research should identify specific scent compounds that induce sleep, explore the interaction between olfactory stimuli and sleep stages and investigate the long-term safety and efficacy of bedtime perfumes. In conclusion, bedtime perfumes can improve sleep quality through the power of scent. Understanding olfactory pathways, calming scents and the historical context of scent therapy helps individuals make informed choices about using these fragrances. Peer Review History: Received 2 October 2024; Reviewed 11 November; Accepted 20 December; Available online 15 January 2025 Academic Editor: Dr. Gehan Fawzy Abdel Raoof Kandeel, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt, gehankandeel9@yahoo.com Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.0/10

An Interpretable Single-Channel EEG Sleep Staging Model Based on Prototype Matching and Multitask Learning

An Interpretable Single-Channel EEG Sleep Staging Model Based on Prototype Matching and Multitask Learning

Sleep-wake patterns of fencing athletes: a long-term wearable device study.

Sleep is the most efficient means of recovery for athletes, guaranteeing optimal athletic performance. However, many athletes frequently experience sleep problems. Our study aims to describe the sleep-wake patterns of fencing athletes and determine whether factors, such as sex, competitive level and training schedules, could affect the sleep-wake rhythm. Sleep data from 23 fencing athletes were collected using the Huawei Band 6, monitoring key sleep parameters such as bedtime, wake time, duration of deep and light sleep, wake periods, REM sleep duration, and nap duration. During this period, athletes were required to wear the band continuously for 24 hours daily, except bathing, charging, and competition times. Athletes averaged 7.97 hours of sleep per night, with significant differences observed in wake time (p=0.015) and midpoint of sleep (p=0.048) between high-level and low-level athletes, as well as a higher frequency of naps among high-level (χ2=11.97, p=0.001) and female (χ2=3.88, p=0.049) athletes. Nap duration was negatively correlated with night sleep duration (r=-0.270, p<0.001). Athletes were observed for changes in sleep-wake patterns from Monday to Sunday. On Mondays, Wednesdays, and Fridays, when there was no morning training, the athletes' wake-up time and the midpoint of sleep were shifted significantly backward, and there were significant differences in sleep parameters between training days and rest days. The sleep patterns of athletes differ according to level and gender. The sleep-wake patterns of athletes are influenced by training schedules, indicating the presence of sleep rhythm disruption.

A randomized, crossover trial of one night of oxygen therapy for obstructive sleep apnea in patients with fibrotic interstitial lung disease.

There is no satisfactory treatment for obstructive sleep apnea (OSA) in patients with interstitial lung disease (ILD) because of poor tolerance of positive airway pressure (PAP) therapy. Supplemental oxygen therapy has been shown to reduce hypoxemia and is well tolerated in patients with ILD. However, little is known about the effect of nocturnal oxygen supplementation (NOS) on OSA in patients with ILD. In this study, we evaluated one night of oxygen therapy in ILD patients with OSA. Forty-one patients with fibrotic ILD and OSA were randomized to receive supplemental oxygen or air for one night each in a crossover design separated by a washout period of one week. Polysomnography was performed, and sleep-disordered breathing, nocturnal desaturation, sleep architecture, and cardiovascular reactions were monitored. During nights with sham oxygen, the median (interquartile range) apnea-hypopnea index (AHI) was 14.1/h (10.4/h-24.1/h). The percentage of patients in the N3 sleep stage (N3%) was 19.5% (14.0-31.2%). NOS significantly decreased the AHI by a median of 9.3/h (95% CI, 7.6/h-14.4/h; P < 0.001), increased N3% by 4.4% (95% CI, 0.3-10.1%; P = 0.049), and lowered the sleep stage change index by 1.6/h (95% CI, 0.0/h-4.8/h; P = 0.036). NOS improved the oxygen desaturation index (ODI) by -8.8/h (95% CI, -13.4/h to -5.9/h; P < 0.001) and the mean SpO2 by 3.0% (95% CI, 2.6-4.5%; P < 0.001). The mean heart rate during sleep was reduced with the NOS; however, total sleep time and nocturnal blood pressure did not change. In patients with OSA and ILD, one night of oxygen therapy significantly improved sleep-disordered breathing, sleep architecture, nocturnal oxygenation, and heart rate. NOS may be a therapeutic option for ILD patients with OSA.

The Influence of Serotonergic Signaling on Quality of Life, Depression, Insomnia, and Hypoxia in Obstructive Sleep Apnea Patients: Cross-Sectional Study.

Background/Objectives: Serotonin and the serotonin transporter (SERT) may have a multifaceted, but not fully understood, role in obstructive sleep apnea (OSA) and its impact on mental health in this group of patients. This study aimed to investigate changes in serotonin and the serotonin transporter (SERT) and their association with depressive and insomnia symptoms. Methods: This study included 76 participants (OSA group: n = 36, control group (CG): n = 40) who underwent polysomnography, while venous blood samples (evening and morning) were analyzed for serotonin and the SERT using ELISA. SERT mRNA expression in peripheral leukocytes was measured via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Participants were evaluated for depression, insomnia, and quality of life (QoL). Results: This study found no significant differences in SERT mRNA or serotonin between the OSA group and CG. In the CG, individuals without mood disorders had higher baseline SERT levels and evening/morning SERT ratios than those with depression. Among the OSA participants, those with good QoL had elevated serotonin levels in the evening (p = 0.028) and morning (p = 0.043) compared to those with poor QoL. Baseline SERT protein levels were higher in the CG than in the OSA group for insomnia, while SERT mRNA expression was higher in the OSA group. Linear regression models showed 13.3% and 13.1% for non-rapid eye movement sleep (NREM) apnea/hypopnea index (AHI) and AHI variability, respectively, which was accounted for by the morning SERT level, while 30.8% of the arousal index variability was explained by the morning serotonin level. Conclusions: Serotonergic signaling may influence quality of life, depression, and insomnia in OSA, as well as the severity of the disease itself. Stratifying patients by clinical and laboratory phenotypes could enable more personalized treatment.

Phasic dopamine release in the nucleus accumbens influences REM sleep timing.

Based on the activity of dopamine (DA) neurons during behavioral states, the DA system has long been thought to be foundational in regulating sleep-wake behavior; over the past decade advances in circuit manipulation and recording techniques have strengthened this perspective. Recently, several studies have demonstrated that DA release in regions of the limbic system is important in the promotion of REM sleep. Yet how DA dynamics change within bouts of sleep, how these changes are regulated, and whether they influence future state changes remains unclear. To address these questions, in mice of both sexes we used in vivo fiber photometry and inhibitory optogenetics to identify a specific role of DA transients in the nucleus accumbens (NAcc) in state transitions from NREM sleep. We found that DA transients increase their frequency and amplitude over the duration of NREM sleep and that this increase is more pronounced during NREM bouts that transition into REM sleep. Next, we found that DA transients in NREM sleep are influenced by changes in REM sleep pressure. Finally, we show that transient DA release in the NAcc plays a functional role in regulating the timing of REM sleep entrances, as inhibition of midbrain DA neuron terminals in the NAcc prolonged bouts of NREM sleep and decreased the frequency of bouts of REM sleep. These findings demonstrate that DA release in the NAcc is dynamically regulated by sleep pressure and has a functional role in transitions from NREM sleep, particularly those into REM sleep.Significance Statement Sleep is a central component of daily life and is heavily influenced by midbrain dopamine neurons. Dopamine release in limbic regions, such as the nucleus accumbens, has been implicated in the promotion of REM sleep. However, dopamine release dynamics during sleep and how these influence future changes in state remain unclear. We used a fluorescence-based dopamine biosensor to elucidate the pattern of dopamine release during sleep and inhibitory optogenetics to disrupt dopamine release. Dopamine release increases across the duration of NREM sleep bouts and is sensitive to REM sleep need. Inhibition of dopamine terminals in the nucleus accumbens decreases the frequency of REM sleep. This suggests that phasic dopamine release during NREM sleep functionally influences REM sleep timing.

Royal jelly reduced non-rapid eye movement sleep fragmentation and restored sleep stability in diet-induced obese mice.

Royal jelly (RJ) is recognized due to its high nutritional value and potential health benefits. Previous research showed that RJ supplementation decreased fat accumulation, resulting in weight loss and improvements in hyperglycemia and insulin resistance in high-fat diet (HFD)-induced obese mice. To expand the weight-reducing properties of RJ, this study aimed to investigate the effects of RJ supplementation on HFD-induced obese mice with impaired sleep stabilization. Over a 20-week period, the C57BL/6J mice were divided into the following dietary groups: normal diet (ND), ND supplemented with 5% lyophilized RJ powder (ND + RJ), HFD, and HFD supplemented with 5% lyophilized RJ powder (HFD + RJ) groups. Compared with the HFD group, the HFD + RJ group exhibited a significant reduction in body weight via a decrease in fat mass. Moreover, much like the ND group, the HFD + RJ group demonstrated improvements in the fragmentation of non-rapid eye movement (NREM) sleep and wakefulness. These processes contributed to the reestablishment of sleep/wake continuity and restored the overall stability of sleep. In contrast, the ND + RJ and ND groups exhibited a similar sleep/wake architecture. Thus, RJ supplementation in the ND demonstrated no substantial effect on sleep/wake. According to these findings, dietary RJ improves the sleep/wake architecture and restores sleep stability. Hence, RJ is a promising dietary component for addressing obesity and restoring sleep stability.

Fractal cycles of sleep, a new aperiodic activity-based definition of sleep cycles.

Sleep cycles are defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. Fractal or aperiodic neural activity is a well-established marker of arousal and sleep stages measured using electroencephalography. We introduce a new concept of 'fractal cycles' of sleep, defined as a time interval during which time series of fractal activity descend to their local minimum and ascend to the next local maximum. We assess correlations between fractal and classical (i.e. non-REM - REM) sleep cycle durations and study cycles with skipped REM sleep. The sample comprised 205 healthy adults, 21 children and adolescents and 111 patients with depression. We found that fractal and classical cycle durations (89±34 vs 90±25 min) correlated positively (r=0.5, p<0.001). Children and adolescents had shorter fractal cycles than young adults (76±34 vs 94±32 min). The fractal cycle algorithm detected cycles with skipped REM sleep in 91-98% of cases. Medicated patients with depression showed longer fractal cycles compared to their unmedicated state (107±51 vs 92±38 min) and age-matched controls (104±49 vs 88±31 min). In conclusion, fractal cycles are an objective, quantifiable, continuous and biologically plausible way to display sleep neural activity and its cycles.

Day-to-day variability in sleep and activity predict the onset of a hypomanic episode in patients with bipolar disorder.

Detecting transitions in bipolar disorder (BD) is essential for implementing early interventions. Our aim was to identify the earliest indicator(s) of the onset of a hypomanic episode in BD. We hypothesized that objective changes in sleep would be the earliest indicator of a new hypomanic or manic episode. In this prospective, observational, contactless study, participants used wearable technology continuously to monitor their daily activity and sleep parameters. They also completed weekly self-ratings using the Altman Self-Rating Mania Scale (ASRM). Using time-frequency spectral derivative spike detection, we assessed the sensitivity, specificity, and balanced accuracy of wearable data to identify a hypomanic episode, defined as at least one or more weeks with consecutive ASRM scores ≥10. Of 164 participants followed for a median (IQR) of 495.0 (410.0) days, 50 experienced one or more hypomanic episodes. Within-night variability in sleep stages was the earliest indicator identifying the onset of a hypomanic episode (mean ± SD) sensitivity: 0.94 ± 0.19; specificity: 0.80 ± 0.19; balanced accuracy: 0.87 ± 0.13), followed by within-day variability in activity levels: sensitivity: 0.93 ± 0.18; specificity: 0.84 ± 0.13; balanced accuracy: 0.89 ± 0.11. Limitations of our study includes a small sample size. Strengths include the use of densely sampled data in a well-characterized cohort followed for over a year, as well as the use of a novel approach using time-frequency analysis to dynamically assess behavioral features at a granular level. Detecting and predicting the onset of hypomanic (or manic) episodes in BD is paramount to implement individualized early interventions.

Obstructive sleep apnea and polysomnographic predictors of neuropsychological performance two years after injury in a prospective cohort of adults with traumatic brain injury

Objective: Obstructive sleep apnea (OSA) has been associated with structural and functional brain changes and cognitive impairment in sleep clinic samples. Persons with traumatic brain injury (TBI) are at increased risk of OSA compared to community samples, and many experience chronic cognitive disability. However, the impact of OSA on cognitive outcome after TBI is unknown. The purpose of this study was to examine the relationship between polysomnographic sleep parameters on neuropsychological performance 2 years following TBI. We hypothesized that oxygen desaturation, sleep fragmentation, and sleep depth would predict neuropsychological performance. Method: Participants (N = 123) were persons with moderate-to-severe TBI who underwent Type 1 Polysomnography during acute neurorehabilitation. At 2 years post-TBI, participants completed telephone-based neuropsychological testing (the Brief Test of Adult Cognition by Telephone). General linear models were fit to investigate the relationship between sleep parameters and neuropsychological performance, controlling for demographics and posttraumatic amnesia. Results: When controlling for demographics, injury characteristics, and other sleep parameters, greater percent of Stage 1 sleep time predicted poorer cognitive performance (Overall BTACT composite, p = 0.0078, ηp2 = 6.6%; Verbal Memory composite, p = 0.0407, ηp2 = 3.9%; Executive Function composite, p = 0.0215, ηp2 = 4.9%). Oxygen desaturation, cortical arousals, Stage 3 sleep, and the obstructive apnea-hypopnea index were not significantly associated with cognitive outcome. Conclusions: Reduced sleep depth was associated with cognitive outcome in persons with TBI; these findings require replication. Future research should examine whether improving sleep (e.g. increasing deep sleep) during acute recovery can improve cognitive recovery following TBI.

Clinical validation of a wireless patch-based polysomnography system.

Onera Health has developed the first wireless, patch-based, type-II PSG system, the Onera Sleep Test System (STS), to allow studies to be performed unattended at the patient's home or in any bed at a medical facility. The goal of this multicenter study was to validate data collected from the patch-based PSG to a traditional PSG for sleep staging and AHI. Simultaneous traditional PSG and patch-based PSG study data were obtained in a sleep laboratory from 206 participants with a suspected sleep disorder recruited from 7 clinical sites. Blinded, randomized scoring of the traditional PSG and patch-based PSG recordings was completed according to The AASM Manual for the Scoring of Sleep and Associated Events, version 2.6 criteria by three independent scorers. Concordance correlation coefficients were high between the patch-based device and traditional PSG across essential sleep and respiratory variables - TST (0.87); Wake (0.84); NREM (0.80); N1 (0.72); N2 (0.71); N3 (0.64); REM (0.80) and AHI (0.94). There was substantial agreement between epoch sleep staging scored on the patch-based device and traditional PSG (average Cohen's kappa of 0.62 ± 0.13 across all scorers). The patch-based type-II PSG had a similar performance on sleep staging and respiratory variables when compared to Traditional PSG, thus making it possible to use the patch-based PSG for a routine PSG study. These results open the possibility of performing unattended PSG studies efficiently and accurately outside the sleep laboratory improving access to high quality sleep assessments for patients with sleep disorders. Registry: ClinicalTrials.gov; Identifier: NCT05310708.

Sleep structure of short-term insomnia disorder with mild cognitive impairment in older adults and their correlation with cognitive function: a case-control study.

This study seeks to delineate the sleep architecture characteristics in older adults with short-term insomnia and mild cognitive impairment (MCI) and to explore their association with cognitive performance. Ninety elderly individuals with short-term insomnia were enrolled and stratified into two cohorts based on their Montreal Cognitive Assessment (MoCA) scores: the Short-Term Insomnia Group (STID) comprising 35 participants and the Short-Term Insomnia with Cognitive Impairment Group (STID-MCI) with 55 participants. Demographic data, Pittsburgh Sleep Quality Index (PSQI), MoCA, Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and polysomnography (PSG) parameters were compared between groups. Correlations between MoCA scores and PSG metrics were also analyzed. No significant disparities were noted between groups in terms of HAMD-17, HAMA, and PSQI scores (p > 0.05). However, marked differences were identified in MoCA scores and its subdomains (p < 0.05). Significant variations were also observed in the duration and proportion of slow-wave sleep (N3) between groups (p < 0.05). In STID-MCI patients, memory scores correlated positively with N3 duration and percentage (p < 0.05), while verbal functions and attention were positively associated with rapid eye movement (REM) sleep duration. This study highlights the potential of PSG in the clinical assessment of cognitive function and underscores the need for targeted interventions to improve sleep quality in this vulnerable population.

Transcriptional regulation of daily sleep amount by TCF4–HDAC4–CREB complex in mice

Abstract Histone deacetylase HDAC4/5 cooperates with cAMP response element-binding protein (CREB) in the transcriptional regulation of daily sleep amount downstream of LKB1-SIK3 kinase cascade in mice. Here, we report a significant enrichment of the E-box motifs for the basic loop–helix–loop (bHLH) proteins near the CREB- and HDAC4-binding sites in the mouse genome. Adeno-associated virus-mediated expression of class I bHLH transcription factors, such as TCF4, TCF3, or TCF12, across the mouse brain neurons reduces the duration of rapid eye movement sleep (REMS) and non-REMS (NREMS). TCF4 requires its bHLH domain to regulate REMS or NREMS amount, of which the latter is mostly independent of the E-box-binding activity. Consistent with that TCF4 interacts with CREB and HDAC4 via the bHLH domain, TCF4 relies on CREB and partly on HDAC4 to regulate NREMS/REMS amount. Conversely, the ability of CREB to regulate sleep duration also requires its binding to TCF4 and HDAC4. Together, these results indicate that TCF4, HDAC4, and CREB could function cooperatively in the transcriptional regulation of daily sleep amount in mice.

Anything but small: Microarousals stand at the crossroad between noradrenaline signaling and key sleep functions.

Continuous sleep restores the brain and body, whereas fragmented sleep harms cognition and health. Microarousals (MAs), brief (3- to 15-s-long) wake intrusions into sleep, are clinical markers for various sleep disorders. Recent rodent studies show that MAs during healthy non-rapid eye movement (NREM) sleep are driven by infraslow fluctuations of noradrenaline (NA) in coordination with electrophysiological rhythms, vasomotor activity, cerebral blood volume, and glymphatic flow. MAs are hence part of healthy sleep dynamics, raising questions about their biological roles. We propose that MAs bolster NREM sleep's benefits associated with NA fluctuations, according to an inverted U-shaped curve. Weakened noradrenergic fluctuations, as may occur in neurodegenerative diseases or with sleep aids, reduce MAs, whereas exacerbated fluctuations caused by stress fragment NREM sleep and collapse NA signaling. We suggest that MAs are crucial for the restorative and plasticity-promoting functions of sleep and advance our insight into normal and pathological arousal dynamics from sleep.