SLEEP

Horwitz, Avel; Bar-Shachar, Yael; Ran-Peled, Dar; Finkelstein, Omer; Ben-Zion, Hamutal; Bar-Kalifa, Eran; Meiri, Gal; Tikotzky, Liat

doi: 10.1093/sleep/zsad029pmid: 36788476

Study ObjectivesThis study assessed and compared mothers’ and fathers’ sleep trajectories from pregnancy and throughout the first year of the infant’s life. We also examined associations between maternal, paternal, and infant sleep.MethodsTwo hundred and thirty-two couples were recruited for the study during pregnancy. Data were collected during pregnancy and at 4, 8, and 12 months postpartum. Maternal, paternal, and infant sleep were monitored at home for seven nights, using actigraphy, sleep diaries, and the Insomnia Severity Index (ISI).ResultsMothers showed more impaired sleep quality than fathers, at all assessments, whereas fathers had shorter sleep duration. Based on the ISI, about 70% of mothers and 50% of fathers showed at least subclinical insomnia at the different assessments. Trajectory analyses (controlling for feeding method and sleeping arrangements) demonstrated a significant deterioration in diary-based and actigraphy sleep quality for both parents, from pregnancy to 4 months. Both parents and infants had an increase in sleep quality from 4 to 12 months, though some parental sleep variables showed a quadratic pattern with a decrease in sleep quality at 8 months. Statistically significant triadic associations at the different assessments were found between mothers’, fathers’, and infants’ sleep. Maternal and infant sleep measures were more strongly correlated than paternal and infant sleep.ConclusionsThe findings highlight the importance of considering the family context of sleep, by demonstrating similarities and differences in the changes that sleep undergoes in new mothers and fathers and by showing how sleep is interrelated between all family members.

Every, James D; Mackay, Stuart G; Sideris, Anders W; Do, Timothy Q; Jones, Andrew; Weaver, Edward M

doi: 10.1093/sleep/zsad176pmid: 37395677

Study ObjectivesPolysomnography parameters measure treatment efficacy for obstructive sleep apnea (OSA), such as reduction in apnea–hypopnea index (AHI). However, for continuous positive airway pressure (CPAP) therapy, polysomnography measures do not factor in adherence and thus do not measure effectiveness. Mean disease alleviation (MDA) corrects polysomnography measures for CPAP adherence and was used to compare treatment effectiveness between CPAP and multilevel upper airway surgery.MethodsThis retrospective cohort study consisted of a consecutive sample of 331 patients with OSA managed with multilevel airway surgery as second-line treatment (N = 97) or CPAP (N = 234). Therapeutic effectiveness (MDA as % change or as corrected change in AHI) was calculated as the product of therapeutic efficacy (% or absolute change in AHI) and adherence (% time on CPAP of average nightly sleep). Cardinality and propensity score matching was utilized to manage confounding variables.ResultsSurgery patients achieved greater MDA % than CPAP users (67 ± 30% vs. 60 ± 28%, p = 0.04, difference 7 ± 3%, 95% confidence interval 4% to 14%) in an unmatched comparison, despite a lower therapeutic efficacy seen with surgery. Cardinality matching demonstrated comparable MDA % in surgery (64%) and CPAP (57%) groups (p = 0.14, difference 8 ± 5%, 95% confidence interval −18% to 3%). MDA measured as corrected change in AHI showed similar results.ConclusionsIn adult patients with OSA, multilevel upper airway surgery and CPAP provide comparable therapeutic effectiveness on polysomnography. For patients with inadequate CPAP use, surgery should be considered.

Wu, Ming-Fung; Thannickal, Thomas C; Li, Songlin; McGregor, Ronald; Lai, Yuan-Yang; Siegel, Jerome M

doi: 10.1093/sleep/zsad135pmid: 37155728

Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB’s mechanism of action on narcolepsy.

Tsunematsu, Tomomi; Matsumoto, Sumire; Merkler, Mirna; Sakata, Shuzo

doi: 10.1093/sleep/zsad193pmid: 37478470

Ponto-geniculo-occipital or pontine (P) waves have long been recognized as an electrophysiological signature of rapid eye movement (REM) sleep. However, P-waves can be observed not just during REM sleep, but also during non-REM (NREM) sleep. Recent studies have uncovered that P-waves are functionally coupled with hippocampal sharp wave ripples (SWRs) during NREM sleep. However, it remains unclear to what extent P-waves during NREM sleep share their characteristics with P-waves during REM sleep and how the functional coupling to P-waves modulates SWRs. Here, we address these issues by performing multiple types of electrophysiological recordings and fiber photometry in both sexes of mice. P-waves during NREM sleep share their waveform shapes and local neural ensemble dynamics at a short (~100 milliseconds) timescale with their REM sleep counterparts. However, the dynamics of mesopontine cholinergic neurons are distinct at a longer (~10 seconds) timescale: although P-waves are accompanied by cholinergic transients, the cholinergic tone gradually reduces before P-wave genesis during NREM sleep. While P-waves are coupled to hippocampal theta rhythms during REM sleep, P-waves during NREM sleep are accompanied by a rapid reduction in hippocampal ripple power. SWRs coupled with P-waves are short-lived and hippocampal neural firing is also reduced after P-waves. These results demonstrate that P-waves are part of coordinated sleep-related activity by functionally coupling with hippocampal ensembles in a state-dependent manner.

Chung, Joon; Goodman, Matthew; Huang, Tianyi; Wallace, Meredith L; Lutsey, Pamela L; Chen, Jarvis T; Castro-Diehl, Cecilia; Bertisch, Suzanne; Redline, Susan

doi: 10.1093/sleep/zsad048pmid: 37523657

Study ObjectivesMultiple sleep characteristics are informative of health, sleep characteristics cluster, and sleep health can be described as a composite of positive sleep attributes. We assessed the association between a sleep score reflecting multiple sleep dimensions, and mortality. We tested the hypothesis that more favorable sleep (higher sleep scores) is associated with lower mortality.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a racially and ethnically-diverse multi-site, prospective cohort study of US adults. Sleep was measured using unattended polysomnography, 7-day wrist actigraphy, and validated questionnaires (2010–2013). 1726 participants were followed for a median of 6.9 years (Q1–Q3, 6.4–7.4 years) until death (171 deaths) or last contact. Survival models were used to estimate the association between the exposure of sleep scores and the outcome of all-cause mortality, adjusting for socio-demographics, lifestyle, and medical comorbidities; follow-up analyses examined associations between individual metrics and mortality. The exposure, a sleep score, was constructed by an empirically-based Principal Components Analysis on 13 sleep metrics, selected a priori.ResultsAfter adjusting for multiple confounders, a 1 standard deviation (sd) higher sleep score was associated with 25% lower hazard of mortality (Hazard Ratio [HR]: 0.75; 95% Confidence interval: [0.65, 0.87]). The largest drivers of this association were: night-to-night sleep regularity, total sleep time, and the Apnea-Hypopnea Index.ConclusionMore favorable sleep across multiple characteristics, operationalized by a sleep score, is associated with lower risk of death in a diverse US cohort of adults. Results suggest that interventions that address multiple dimensions may provide novel approaches for improving health.

Song, Yun Min; Choi, Su Jung; Park, Se Ho; Lee, Soo Jin; Joo, Eun Yeon; Kim, Jae Kyoung

doi: 10.1093/sleep/zsad179pmid: 37422720

The prevalence of artificial light exposure has enabled us to be active any time of the day or night, leading to the need for high alertness outside of traditional daytime hours. To address this need, we developed a personalized sleep intervention framework that analyzes real-world sleep–wake patterns obtained from wearable devices to maximize alertness during specific target periods. Our framework utilizes a mathematical model that tracks the dynamic sleep pressure and circadian rhythm based on the user’s sleep history. In this way, the model accurately predicts real-time alertness, even for shift workers with complex sleep and work schedules (N = 71, t = 13~21 days). This allowed us to discover a new sleep–wake pattern called the adaptive circadian split sleep, which incorporates a main sleep period and a late nap to enable high alertness during both work and non-work periods of shift workers. We further developed a mobile application that integrates this framework to recommend practical, personalized sleep schedules for individual users to maximize their alertness during a targeted activity time based on their desired sleep onset and available sleep duration. This can reduce the risk of errors for those who require high alertness during nontraditional activity times and improve the health and quality of life for those leading shift work-like lifestyles.

Piilgaard, Louise; Rose, Laura; Justinussen, Jessica L; Hviid, Camille Gylling; Lemcke, René; Wellendorph, Petrine; Kornum, Birgitte Rahbek

doi: 10.1093/sleep/zsad144pmid: 37210587

Narcolepsy type 1 (NT1) is a neurological disorder caused by disruption of hypocretin (HCRT; or orexin) neurotransmission leading to fragmented sleep/wake states, excessive daytime sleepiness, and cataplexy (abrupt muscle atonia during wakefulness). Electroencephalography and electromyography (EEG/EMG) monitoring is the gold standard to assess NT1 phenotypical features in both humans and mice. Here, we evaluated the digital ventilated home-cage (DVC®) activity system as an alternative to detect NT1 features in two NT1 mouse models: the genetic HCRT-knockout (-KO) model, and the inducible HCRT neuron-ablation hcrt-tTA;TetO-DTA (DTA) model, including both sexes. NT1 mice exhibited an altered dark phase activity profile and increased state transitions, compared to the wild-type (WT) phenotype. An inability to sustain activity periods >40 min represented a robust activity-based NT1 biomarker. These features were observable within the first weeks of HCRT neuron degeneration in DTA mice. We also created a nest-identification algorithm to differentiate between inactivity and activity, inside and outside the nest as a sleep and wake proxy, respectively, showing significant correlations with EEG/EMG-assessed sleep/wake behavior. Lastly, we tested the sensitivity of the activity system to detect behavioral changes in response to interventions such as repeated saline injection and chocolate. Surprisingly, daily consecutive saline injections significantly reduced activity and increased nest time of HCRT-WT mice. Chocolate increased total activity in all mice, and increased the frequency of short out-of-nest inactivity episodes in HCRT-KO mice. We conclude that the DVC® system provides a useful tool for non-invasive monitoring of NT1 phenotypical features, and has the potential to monitor drug effects in NT1 mice.

Kiss, Orsolya; Goldstone, Aimée; de Zambotti, Massimiliano; Yüksel, Dilara; Hasler, Brant P; Franzen, Peter L; Brown, Sandra A; De Bellis, Michael D; Nagel, Bonnie J; Nooner, Kate B; Tapert, Susan F; Colrain, Ian M; Clark, Duncan B; Baker, Fiona C

Perger, Elisa; Arzt, Michael

doi: 10.1093/sleep/zsad189pmid: 37436100

L Mandel, Hannah; Colleen, Gunnar; Abedian, Sajjad; Ammar, Nariman; Charles Bailey, L; Bennett, Tellen D; Daniel Brannock, M; Brosnahan, Shari B; Chen, Yu; Chute, Christopher G; Divers, Jasmin; Evans, Michael D; Haendel, Melissa; Hall, Margaret A;