scholarly journals NMDAR activation regulates the daily rhythms of sleep and mood

SLEEP ◽  
2019 ◽  
Vol 42 (10) ◽  
Author(s):  
Jeffrey S Burgdorf ◽  
Martha H Vitaterna ◽  
Christopher J Olker ◽  
Eun Joo Song ◽  
Edward P Christian ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Rem Sleep ◽  
Behavioral Plasticity ◽  
Activity Rhythm ◽  
Drug Effects ◽  
Symptom Burden ◽  
Nrem Sleep ◽  
Learning Task ◽  
Delta Power ◽  
Nmdar Activation

Abstract Study Objectives The present studies examine the effects of NMDAR activation by NYX-2925 diurnal rhythmicity of both sleep and wake as well as emotion. Methods Twenty-four-hour sleep EEG recordings were obtained in sleep-deprived and non-sleep-deprived rats. In addition, the day–night cycle of both activity and mood was measured using home cage ultrasonic-vocalization recordings. Results NYX-2925 significantly facilitated non-REM (NREM) sleep during the lights-on (sleep) period, and this effect persisted for 3 days following a single dose in sleep-deprived rats. Sleep-bout duration and REM latencies were increased without affecting total REM sleep, suggesting better sleep quality. In addition, delta power during wake was decreased, suggesting less drowsiness. NYX-2925 also rescued learning and memory deficits induced by sleep deprivation, measured using an NMDAR-dependent learning task. Additionally, NYX-2925 increased positive affect and decreased negative affect, primarily by facilitating the transitions from sleep to rough-and-tumble play and back to sleep. In contrast to NYX-2925, the NMDAR antagonist ketamine acutely (1–4 hours post-dosing) suppressed REM and non-REM sleep, increased delta power during wake, and blunted the amplitude of the sleep-wake activity rhythm. Discussion These data suggest that NYX-2925 could enhance behavioral plasticity via improved sleep quality as well as vigilance during wake. As such, the facilitation of sleep by NYX-2925 has the potential to both reduce symptom burden on neurological and psychiatric disorders as well as serve as a biomarker for drug effects through restoration of sleep architecture.

scholarly journals 317 Sleep-wake survival dynamics in people with insomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A127-A127
Author(s):  
Lieke Hermans ◽  
Marta Regis ◽  
Pedro Fonseca ◽  
Bertram Hoondert ◽  
Tim Leufkens ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Sleep Quality ◽  
Rem Sleep ◽  
Scale Parameter ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Sleep Fragmentation ◽  
Healthy Controls ◽  
Shape Parameters ◽  
Impaired Sleep

Abstract Introduction Assessing objective measures of sleep fragmentation could yield important features reflecting impaired sleep quality in people with insomnia. Survival analysis allows the specific examination of the stability of NREM sleep, REM sleep and wake. The objective of this study was to assess the differences between survival dynamics of NREM sleep, REM sleep and wake between people with insomnia and healthy controls. Methods We analyzed polysomnography recordings from 88 people with insomnia and 92 healthy controls. For each participant, survival dynamics of REM sleep, NREM sleep and wake were represented using Weibull distributions. We used lasso penalized linear regression to analyze the difference between participant groups with respect to the Weibull scale and shape parameters, while correcting for age, sex, total sleep time and relevant interaction effects. Because comparisons were done for scale and shape parameters of REM sleep, NREM sleep and wake, a Bonferroni correction was applied, resulting in an alpha value of 0.05/6 = 0.0083. Results Significant effects of group were found for the NREM scale parameter (unstandardized model coefficient B=-0.79, t=-3.0, p=0.0035), and for the scale and shape parameters of wake (scale parameter B=7.6, t=2.8, p=0.0065; shape parameter B=0.20, t=2.9, p=0.0048). Results indicated that people with insomnia had less stable NREM sleep and more stable wake after sleep onset compared to healthy controls. Additionally, the altered distribution of wake segment lengths indicated an increased difficulty to fall asleep after longer awakenings in the insomnia group. However, these differences were mainly observed in younger participants. Significant effects of group for the survival parameters of REM sleep were not found. Conclusion As illustrated by our results, survival analysis can be very useful for disentangling different types of sleep fragmentation in people with insomnia. For instance, the current findings suggest that people with insomnia have an increased fragmentation of NREM sleep, but not necessarily of REM sleep. Additional research into the underlying mechanisms of NREM sleep fragmentation could possibly lead to a better understanding of impaired sleep quality in people with insomnia, and consequently to improved treatment. Support (if any):

scholarly journals Multicomponent Analysis of Sleep Using Electrocortical, Respiratory, Autonomic and Hemodynamic Signals Reveals Distinct Features of Stable and Unstable NREM and REM Sleep

2020 ◽  
Vol 11 ◽  
Author(s):  
Christopher Wood ◽  
Matt Travis Bianchi ◽  
Chang-Ho Yun ◽  
Chol Shin ◽  
Robert Joseph Thomas
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Slow Oscillation ◽  
Rapid Eye Movement ◽  
Sinus Arrhythmia ◽  
Delta Power ◽  
High Loop

A new concept of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep is proposed, that of multi-component integrative states that define stable and unstable sleep, respectively, NREMS, NREMUS REMS, and REMUS. Three complementary data sets are used: obstructive sleep apnea (20), healthy subjects (11), and high loop gain sleep apnea (50). We use polysomnography (PSG) with beat-to-beat blood pressure monitoring, and electrocardiogram (ECG)-derived cardiopulmonary coupling (CPC) analysis to demonstrate a bimodal, rather than graded, characteristic of NREM sleep. Stable NREM (NREMS) is characterized by high probability of occurrence of the <1 Hz slow oscillation, high delta power, stable breathing, blood pressure dipping, strong sinus arrhythmia and vagal dominance, and high frequency CPC. Conversely, unstable NREM (NREMUS) has the opposite features: a fragmented and discontinuous <1 Hz slow oscillation, non-dipping of blood pressure, unstable respiration, cyclic variation in heart rate, and low frequency CPC. The dimension of NREM stability raises the possibility of a comprehensive integrated multicomponent network model of NREM sleep which captures sleep onset (e.g., ventrolateral preoptic area-based sleep switch) processes, synaptic homeostatic delta power kinetics, and the interaction of global and local sleep processes as reflected in the spatiotemporal evolution of cortical “UP” and “DOWN” states, while incorporating the complex dynamics of autonomic-respiratory-hemodynamic systems during sleep. Bimodality of REM sleep is harder to discern in health. However, individuals with combined obstructive and central sleep apnea allows ready recognition of REMS and REMUS (stable and unstable REM sleep, respectively), especially when there is a discordance of respiratory patterns in relation to conventional stage of sleep.

076 Bright light during wakefulness improves objective and subjective sleep quality: a forced desynchrony study

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A32-A32
Author(s):  
Renske Lok ◽  
Tom Woelders ◽  
Marijke Gordijn ◽  
Minke van Koningsveld ◽  
Klaske Oberman ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Light Exposure ◽  
Circadian Variation ◽  
Bright Light ◽  
Nrem Sleep ◽  
Subjective Sleep Quality ◽  
Subjective Sleep ◽  
Delta Power ◽  
Dim Light ◽  
Time Awake

Abstract Introduction Under real life conditions, increased light exposure during wakefulness seems associated with improved sleep quality, quantified as reduced time awake during bed time, increased time spent in non-REM (NREM) sleep or increased power in the EEG delta band (0.5–4 Hz). The causality of these important relationships and their dependency on circadian clock phase and/or time awake has not been studied in depth. To establish causality of light effects during wake time on subsequent sleep, and to disentangle possible circadian and homeostatic interactions, we employed a forced desynchrony (FD) protocol under dim light (6.5 lux) and bright light (1307 lux) during wakefulness. Methods The protocol consisted of a fast cycling sleep-wake schedule (13h wakefulness – 5h sleep; 4 cycles), followed by 3h recovery sleep in a within subject cross-over design. Individuals (7 men) were equipped with 10 polysomnography electrodes. Subjective sleep quality was measured immediately after wakening. Results Results indicated that circadian variation in delta power was only detected under dim light. Circadian variation in time in rapid eye movement (REM) sleep and wakefulness were uninfluenced by light. Prior light exposure increased accumulation of delta power and time in NREM sleep, while decreasing wakefulness, especially during the circadian wake phase. Subjective sleep quality scores showed that participants were only able to assess light induced improvement of sleep quality correctly when the circadian system promoted wakefulness. Conclusion This study presents significant effects of bright light exposure on sleep architecture, leading to sleep pressure related changes in objective sleep quality. At the end of the scheduled sleep phase after increased light exposure, more delta power and NREM sleep were detected, especially when sleep occurred outside the normal sleep phase. Subjective sleep quality scores showed light-induced improvements coinciding with increased delta power and time spend in NREM sleep, suggesting that light during wakefulness may improve subsequent sleep quality. These findings may have important implications for insomnia treatment and clinical applications of light therapy. Support (if any) This research was funded by the University of Groningen Campus Fryslân (Grant No. 01110939; co-financed by Philips Drachten and Provincie Fryslân). Additional financial support was obtained from a NWO-STW Program Grant “OnTime” (project 12185).

Intermittent hypoxia causes REM sleep deficits and decreases EEG delta power in NREM sleep in the C57BL/6J mouse

2006 ◽  
Vol 7 (1) ◽  
pp. 7-16 ◽  
Author(s):  
V POLOTSKY ◽  
A RUBIN ◽  
A BALBIR ◽  
T DEAN ◽  
P SMITH ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Intermittent Hypoxia ◽  
Nrem Sleep ◽  
Delta Power

scholarly journals Sleep and Diurnal Rest-Activity Rhythm Disturbances in a Mouse Model of Alzheimer’s Disease

2020 ◽  
Author(s):  
Mikolaj J. Filon ◽  
Eli Wallace ◽  
Samantha Wright ◽  
Dylan J. Douglas ◽  
Lauren I. Steinberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rem Sleep ◽  
Activity Rhythm ◽  
Activity Levels ◽  
Wild Type ◽  
Drug Bioavailability ◽  
Activity Rhythms ◽  
Delta Power ◽  
Rest Activity

AbstractStudy ObjectivesAccumulating evidence suggests a strong association between sleep, amyloid-beta (Aβ) deposition, and Alzheimer’s disease (AD). We sought to determine if: (1) deficits in rest-activity rhythms and sleep are significant phenotypes in J20 AD mice, (2) metabotropic glutamate receptor 5 inhibitors (mGluR5) could rescue deficits in rest-activity rhythms and sleep, and (3) Aβ levels are responsive to treatment with mGluR5 inhibitors.MethodsDiurnal rest-activity levels were measured by actigraphy and sleep-wake patterns by electroencephalography (EEG), while animals were chronically treated with mGluR5 inhibitors. Behavioral tests were performed, and Aβ levels measured in brain lysates.ResultsJ20 mice exhibited a 4.5 hour delay in the acrophase of activity levels compared to wild-type littermates, and spent less time in REM sleep during the second half of the light period. J20 mice also exhibited decreased NREM delta power but increased NREM sigma power. The mGluR5 inhibitor CTEP rescued the REM sleep deficit and improved NREM delta and sigma power but did not correct rest-activity rhythms. No statistically significant differences were observed in Aβ levels, rotarod performance or the passive avoidance task following chronic mGluR5 inhibitor treatment.ConclusionsJ20 mice have disruptions in rest-activity rhythms and reduced homeostatic sleep pressure (reduced NREM delta power). NREM delta power was increased following treatment with an mGluR5 inhibitor. Drug bioavailability was poor. Further work is necessary to determine if mGluR5 is a viable target for treating sleep phenotypes in AD.Statement of SignificanceSleep disruption is evolving as an important risk factor as well as phenotype of neurological diseases including Alzheimer’s disease. This study is novel in determining alterations in the rest-activity rhythm and sleep-wake pattern of J20 Alzheimer’s disease mice and wild type littermates. Specifically, there is a delay in acrophase with prolonged hyperactivity during the dark cycle, and reduced sleep pressure that was improved by treatment with mGluR5 inhibitor. Critical remaining knowledge gaps and future directions include testing the effects of Alzheimer’s disease drugs on rescue of sleep and rest-activity patterns in other Alzheimer’s disease models. These studies are relevant to human Alzheimer’s disease as monitoring sleep phenotypes may predict disease risk, and therapies that normalize sleep patterns may slow progression.

scholarly journals The effect of dream report collection and dream incorporation on memory consolidation during sleep

2018 ◽  
Author(s):  
Sarah F. Schoch ◽  
Maren J. Cordi ◽  
Michael Schredl ◽  
Bjöern Rasch
Keyword(s):  
Task Performance ◽  
Rem Sleep ◽  
Memory Consolidation ◽  
Memory Performance ◽  
Nrem Sleep ◽  
Learning Task ◽  
Association Learning ◽  
Dream Report ◽  
Waking Up ◽  
The Relationship

AbstractWaking up during the night to collect dream reports is a commonly used method to study dreams. This method has also been applied in studies on the relationship between dreams and memory consolidation. However, it is unclear if these awakenings influence ongoing memory consolidation processes. Furthermore, only few studies have examined if task incorporation into dreams is related to enhanced performance in the task. Here we compare memory performance in a word-picture association learning task after a night with (up to six awakenings) and without awakenings in 22 young and healthy participants. We then examine if the task is successfully incorporated into the dreams and if this incorporation is related to the task performance the next morning. We show that while the awakenings impair both subjective and objective sleep quality, these awakenings did not impair ongoing memory consolidation during sleep. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. No incorporation occurred in dreams collected only in the morning. Task incorporation into NREM sleep dreams, but not REM sleep dreams showed a relationship with task performance the next morning.We conclude that the method of awakenings to collect dream reports is suitable for dream and memory studies, and is even crucial to uncover task incorporations. Furthermore, our study suggests that dreams in NREM rather than REM sleep might be related to processes of memory consolidation during sleep.

scholarly journals An attempt to identify reproducible high-density EEG markers of PTSD during sleep

SLEEP ◽  
2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Chao Wang ◽  
Sridhar Ramakrishnan ◽  
Srinivas Laxminarayan ◽  
Andrey Dovzhenok ◽  
J David Cashmere ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Spectral Power ◽  
Brain Activity ◽  
Nrem Sleep ◽  
High Density ◽  
Post Traumatic Stress ◽  
Significant Group ◽  
Delta Power ◽  
Regional Brain Activity

Abstract Study Objectives We examined electroencephalogram (EEG) spectral power to study abnormalities in regional brain activity in post-traumatic stress disorder (PTSD) during sleep. We aimed to identify sleep EEG markers of PTSD that were reproducible across nights and subsamples of our study population. Methods Seventy-eight combat-exposed veteran men with (n = 31) and without (n = 47) PTSD completed two consecutive nights of high-density EEG recordings in a laboratory. We performed spectral-topographical EEG analyses on data from both nights. To assess reproducibility, we used the first 47 consecutive participants (18 with PTSD) for initial discovery and the remaining 31 participants (13 with PTSD) for replication. Results In the discovery analysis, compared with non-PTSD participants, PTSD participants exhibited (1) reduced delta power (1–4 Hz) in the centro-parietal regions during nonrapid eye movement (NREM) sleep and (2) elevated high-frequency power, most prominent in the gamma band (30–40 Hz), in the antero-frontal regions during both NREM and rapid eye movement (REM) sleep. These findings were consistent across the two study nights, with reproducible trends in the replication analysis. We found no significant group differences in theta power (4–8 Hz) during REM sleep and sigma power (12–15 Hz) during N2 sleep. Conclusions The reduced centro-parietal NREM delta power, indicating reduced sleep depth, and the elevated antero-frontal NREM and REM gamma powers, indicating heightened central arousal, are potential objective sleep markers of PTSD. If independently validated, these putative EEG markers may offer new targets for the development of sleep-specific PTSD diagnostics and interventions.

GABA A receptor β 1 ‐subunit knock‐out mice show increased delta power in NREM sleep and decreased theta power in REM sleep

2021 ◽  
Author(s):  
Maria Elena Klibo Lie ◽  
Christina Birkedahl Falk‐Petersen ◽  
Louise Piilgaard ◽  
Nane Griem‐Krey ◽  
Petrine Wellendorph ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Knock Out ◽  
Gaba A ◽  
Theta Power ◽  
Delta Power ◽  
Knock Out Mice

scholarly journals Toward asleep DBS: cortico-basal ganglia spectral and coherence activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jing Guang ◽  
Halen Baker ◽  
Orilia Ben-Yishay Nizri ◽  
Shimon Firman ◽  
Uri Werner-Reiss ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Rem Sleep ◽  
Standard Procedure ◽  
Low Frequency ◽  
Nrem Sleep ◽  
Sleep Cycle ◽  
Advanced Parkinson’S Disease ◽  
Low Frequency Power ◽  
The Brain ◽  
Frequency Power

AbstractDeep brain stimulation (DBS) is currently a standard procedure for advanced Parkinson’s disease. Many centers employ awake physiological navigation and stimulation assessment to optimize DBS localization and outcome. To enable DBS under sedation, asleep DBS, we characterized the cortico-basal ganglia neuronal network of two nonhuman primates under propofol, ketamine, and interleaved propofol-ketamine (IPK) sedation. Further, we compared these sedation states in the healthy and Parkinsonian condition to those of healthy sleep. Ketamine increases high-frequency power and synchronization while propofol increases low-frequency power and synchronization in polysomnography and neuronal activity recordings. Thus, ketamine does not mask the low-frequency oscillations used for physiological navigation toward the basal ganglia DBS targets. The brain spectral state under ketamine and propofol mimicked rapid eye movement (REM) and Non-REM (NREM) sleep activity, respectively, and the IPK protocol resembles the NREM-REM sleep cycle. These promising results are a meaningful step toward asleep DBS with nondistorted physiological navigation.

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