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

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.

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

Frontiers in Physiology ◽

10.3389/fphys.2020.592978 ◽

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.

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

SLEEP ◽

10.1093/sleep/zsz207 ◽

2019 ◽

Vol 43 (1) ◽

Cited By ~ 7

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.

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Diaphragm long-term facilitation following acute intermittent hypoxia during wakefulness and sleep

Journal of Applied Physiology ◽

10.1152/japplphysiol.00055.2011 ◽

2011 ◽

Vol 110 (5) ◽

pp. 1299-1310 ◽

Cited By ~ 21

Author(s):

J. Terada ◽

G. S. Mitchell

Keyword(s):

Rem Sleep ◽

Intermittent Hypoxia ◽

Neural Control ◽

Nrem Sleep ◽

Emg Activity ◽

Natural Sleep ◽

Time Control ◽

Respiratory Plasticity ◽

Long Term Facilitation

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Here, we tested four hypotheses in unanesthetized, spontaneously breathing rats using radiotelemetry for EEG and diaphragm electromyography (Dia EMG) activity: 1) AIH induces LTF in Dia EMG activity; 2) diaphragm LTF (Dia LTF) is more robust during sleep vs. wakefulness; 3) AIH (or repetitive AIH) disrupts natural sleep-wake architecture; and 4) preconditioning with daily AIH (dAIH) for 7 days enhances Dia LTF. Sleep-wake states and Dia EMG were monitored before (60 min), during, and after (60 min) AIH (10, 5-min hypoxic episodes, 5-min normoxic intervals; n = 9), time control (continuous normoxia, n = 8), and AIH following dAIH preconditioning for 7 days (n = 7). Dia EMG activities during quiet wakefulness (QW), rapid eye movement (REM), and non-REM (NREM) sleep were analyzed and normalized to pre-AIH values in the same state. During NREM sleep, diaphragm amplitude (25.1 ± 4.6%), frequency (16.4 ± 4.7%), and minute diaphragm activity (amplitude × frequency; 45.2 ± 6.6%) increased above baseline 0–60 min post-AIH (all P < 0.05). This Dia LTF was less robust during QW and insignificant during REM sleep. dAIH preconditioning had no effect on LTF ( P > 0.05). We conclude that 1) AIH induces Dia LTF during NREM sleep and wakefulness; 2) Dia LTF is greater in NREM sleep vs. QW and is abolished during REM sleep; 3) AIH and repetitive AIH disrupt natural sleep patterns; and 4) Dia LTF is unaffected by dAIH. The capacity for plasticity in spinal pump muscles during sleep and wakefulness suggests an important role in the neural control of breathing.

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

European Journal of Neuroscience ◽

10.1111/ejn.15267 ◽

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

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

npj Parkinson s Disease ◽

10.1038/s41531-021-00211-9 ◽

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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Shining a Light on the Mechanisms of Sleep for Memory Consolidation

Current Sleep Medicine Reports ◽

10.1007/s40675-021-00204-3 ◽

2021 ◽

Author(s):

Michelle A. Frazer ◽

Yesenia Cabrera ◽

Rockelle S. Guthrie ◽

Gina R. Poe

Keyword(s):

Rem Sleep ◽

Neural Activity ◽

Memory Consolidation ◽

Strong Support ◽

Nrem Sleep ◽

Future Research ◽

Sleep Spindles ◽

Slow Oscillations ◽

Theta Waves ◽

Learning Tasks

Abstract Purpose of review This paper reviews all optogenetic studies that directly test various sleep states, traits, and circuit-level activity profiles for the consolidation of different learning tasks. Recent findings Inhibiting or exciting neurons involved either in the production of sleep states or in the encoding and consolidation of memories reveals sleep states and traits that are essential for memory. REM sleep, NREM sleep, and the N2 transition to REM (characterized by sleep spindles) are integral to memory consolidation. Neural activity during sharp-wave ripples, slow oscillations, theta waves, and spindles are the mediators of this process. Summary These studies lend strong support to the hypothesis that sleep is essential to the consolidation of memories from the hippocampus and the consolidation of motor learning which does not necessarily involve the hippocampus. Future research can further probe the types of memory dependent on sleep-related traits and on the neurotransmitters and neuromodulators required.

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The relationship between fasting-induced torpor, sleep and waking in laboratory mice

SLEEP ◽

10.1093/sleep/zsab093 ◽

2021 ◽

Author(s):

Yi-Ge Huang ◽

Sarah J Flaherty ◽

Carina A Pothecary ◽

Russell G Foster ◽

Stuart N Peirson ◽

...

Keyword(s):

Body Temperature ◽

Rem Sleep ◽

Brain Activity ◽

Mammalian Species ◽

Nrem Sleep ◽

Laboratory Mice ◽

State Classification ◽

Metabolic Suppression ◽

The Relationship ◽

Electroencephalogram Eeg

Abstract Study objectives Torpor is a regulated and reversible state of metabolic suppression used by many mammalian species to conserve energy. Whereas the relationship between torpor and sleep has been well-studied in seasonal hibernators, less is known about the effects of fasting-induced torpor on states of vigilance and brain activity in laboratory mice. Methods Continuous monitoring of electroencephalogram (EEG), electromyogram (EMG) and surface body temperature was undertaken in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding. Results All animals showed bouts of hypothermia that became progressively deeper and longer as fasting progressed. EEG and EMG were markedly affected by hypothermia, although the typical electrophysiological signatures of NREM sleep, REM sleep and wakefulness enabled us to perform vigilance-state classification in all cases. Consistent with previous studies, hypothermic bouts were initiated from a state indistinguishable from NREM sleep, with EEG power decreasing gradually in parallel with decreasing surface body temperature. During deep hypothermia, REM sleep was largely abolished, and we observed shivering-associated intense bursts of muscle activity. Conclusions Our study highlights important similarities between EEG signatures of fasting-induced torpor in mice, daily torpor in Djungarian hamsters and hibernation in seasonally-hibernating species. Future studies are necessary to clarify the effects on fasting-induced torpor on subsequent sleep.

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0327 NREM Sleep EEG in Typically Developing and Drug-Naïve ADHD Adolescents: Data from a Longitudinal Study

SLEEP ◽

10.1093/sleep/zsaa056.324 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A124-A124

Author(s):

T Basishvili ◽

M Eliozishvili ◽

T Oniani ◽

T Tchintcharauli ◽

I Sakhelashvili ◽

...

Keyword(s):

Longitudinal Study ◽

Nrem Sleep ◽

Sleep Eeg ◽

Brain Maturation ◽

Adhd Group ◽

Typically Developing ◽

Eeg Activity ◽

Theta Power ◽

Delta Power ◽

Drug Naïve

Abstract Introduction Structural MRI studies suggest delayed brain maturation in children with attention deficit hyperactivity disorder (ADHD). The steep adolescent decline in sleep slow wave EEG activity provides an opportunity to investigate brain electrophysiological evidence for this maturational delay. Most ADHD sleep EEG studies have been cross-sectional. Here we present data from an ongoing longitudinal study of the maturational trajectories of sleep EEG in drug-naïve ADHD and typically developing adolescents. Methods Nine children diagnosed with ADHD (combined subtype, DSM-V criteria, mean age 12.39±0.61 years), and nine typically developing controls (12.07±0.35 years) were recruited. Subjects underwent an adaptation night and all night polysomnography twice yearly at the Laboratory. Sleep EEG was analyzed using fast Fourier transform. NREM delta and theta EEG activity were compared across first two recordings. Results Group effects (ADHD vs. control) on all night delta and theta energy, and delta power were not significant (p>0.2 for all). All night theta power was lower (p=0.035) for the ADHD group, and all night NREM sleep duration trended (p=0.060) toward being lower for the ADHD group. Controlling for sleep duration differences by examining only the first 5 h of NREM sleep showed no group effect on delta power (p=0.77) and a trend toward lower theta power (p=0.057) for the ADHD group. Conclusion At age 12 to 13 years, NREM sleep delta EEG did not differ between ADHD and control subjects. Theta power, which declines at a younger age than delta, was lower in control subjects. The two recordings thus far differ only by 6 months. The entire study will provide 5 semiannual recordings and allow us to determine if the higher theta power in the ADHD group will hold and if delta power will be greater as well, and thus provide electrophysiological support for the delayed brain maturation suggested by MRI findings. Support Shota Rustaveli National Science Foundation Grant FR17_94; Subjects Recruitment Support - Mental Health Service in Tbilisi “Kamara”.

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Heterogeneous activity level of jaw-closing and -opening muscles and its association with arousal levels during sleep in the guinea pig

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00205.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. R34-R42 ◽

Cited By ~ 10

Author(s):

Takafumi Kato ◽

Yuji Masuda ◽

Hayato Kanayama ◽

Norimasa Nakamura ◽

Atsushi Yoshida ◽

...

Keyword(s):

Heart Rate ◽

Eye Movement ◽

Rem Sleep ◽

Muscle Activity ◽

Guinea Pigs ◽

Nrem Sleep ◽

Activity Level ◽

Jaw Muscles ◽

High Activity Level ◽

Motor Activities

Exaggerated jaw motor activities during sleep are associated with muscle symptoms in the jaw-closing rather than the jaw-opening muscles. The intrinsic activity of antagonistic jaw muscles during sleep remains unknown. This study aims to assess the balance of muscle activity between masseter (MA) and digastric (DG) muscles during sleep in guinea pigs. Electroencephalogram (EEG), electroocculogram, and electromyograms (EMGs) of dorsal neck, MA, and DG muscles were recorded with video during sleep-wake cycles. These variables were quantified for each 10-s epoch. The magnitude of muscle activity during sleep in relation to mean EMG activity of total wakefulness was up to three times higher for MA muscle than for DG muscle for nonrapid eye movement (NREM) and rapid-eye-movement (REM) sleep. Although the activity level of the two jaw muscles fluctuated during sleep, the ratio of activity level for each epoch was not proportional. Epochs with a high activity level for each muscle were associated with a decrease in δEEG power and/or an increase in heart rate in NREM sleep. However, this association with heart rate and activity levels was not observed in REM sleep. These results suggest that in guinea pigs, the magnitude of muscle activity for antagonistic jaw muscles is heterogeneously modulated during sleep, characterized by a high activity level in the jaw-closing muscle. Fluctuations in the activity are influenced by transient arousal levels in NREM sleep but, in REM sleep, the distinct controls may contribute to the fluctuation. The above intrinsic characteristics could underlie the exaggeration of jaw motor activities during sleep (e.g., sleep bruxism).

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