Selected Contribution: Regulation of sleep-wake states in response to intermittent hypoxic stimuli applied only in sleep

2001 ◽  
Vol 90 (6) ◽  
pp. 2490-2501 ◽  
Author(s):  
Hedieh Hamrahi ◽  
Richard Stephenson ◽  
Safraaz Mahamed ◽  
Kiong Sen Liao ◽  
Richard L. Horner
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Intermittent Hypoxia ◽  
Recovery Period ◽  
Rapid Eye Movement ◽  
Sleep Regulation ◽  
Recovery Sleep ◽  
Obstructive Sleep ◽  
Independent Effects ◽  
Rebound Increase

Recurrent sleep-related hypoxia occurs in common disorders such as obstructive sleep apnea (OSA). The marked changes in sleep after treatment suggest that stimuli associated with OSA (e.g., intermittent hypoxia) may significantly modulate sleep regulation. However, no studies have investigated the independent effects of intermittent sleep-related hypoxia on sleep regulation and recovery sleep after removal of intermittent hypoxia. Ten rats were implanted with telemetry units to record the electroencephalogram (EEG), neck electromyogram, and body temperature. After >7 days recovery, a computer algorithm detected sleep-wake states and triggered hypoxic stimuli (10% O2) or room air stimuli only during sleep for a 3-h period. Sleep-wake states were also recorded for a 3-h recovery period after the stimuli. Each rat received an average of 69.0 ± 6.9 hypoxic stimuli during sleep. The non-rapid eye movement (non-REM) and rapid-eye-movement (REM) sleep episodes averaged 50.1 ± 3.2 and 58.9 ± 6.6 s, respectively, with the hypoxic stimuli, with 32.3 ± 3.2 and 58.6 ± 4.8 s of these periods being spent in hypoxia. Compared with results for room air controls, hypoxic stimuli led to increased wakefulness ( P < 0.005), nonsignificant changes in non-REM sleep, and reduced REM sleep ( P < 0.001). With hypoxic stimuli, wakefulness episodes were longer and more frequent, non-REM periods were shorter and more frequent, and REM episodes were shorter and less frequent ( P < 0.015). Hypoxic stimuli also increased faster frequencies in the EEG ( P < 0.005). These effects of hypoxic stimuli were reversed on return to room air. There was a rebound increase in REM sleep, increased slower non-REM EEG frequencies, and decreased wakefulness ( P < 0.001). The results show that sleep-specific hypoxia leads to significant modulation of sleep-wake regulation both during and after application of the intermittent hypoxic stimuli. This study is the first to determine the independent effects of sleep-related hypoxia on sleep regulation that approximates OSA before and after treatment.

Effect of sleep deprivation on responses to airway obstruction in the sleeping dog

1994 ◽  
Vol 77 (4) ◽  
pp. 1811-1818 ◽  
Author(s):  
C. P. O'Donnell ◽  
E. D. King ◽  
A. R. Schwartz ◽  
P. L. Smith ◽  
J. L. Robotham
Keyword(s):  
Sleep Deprivation ◽  
Airway Obstruction ◽  
Eye Movement ◽  
Rem Sleep ◽  
Recovery Period ◽  
Sleep Time ◽  
Inspiratory Effort ◽  
Sleep Architecture ◽  
Rapid Eye Movement ◽  
Obstructive Sleep

The effect of sleep deprivation on sleep architecture and respiratory responses to repetitive airway obstruction during sleep was investigated in four chronically instrumented tracheostomized dogs during 12-h nocturnal experiments. A 24-h period of prior sleep deprivation increased (P < 0.05) the rate at which airway obstruction could be induced from 20 +/- 3 (SE) to 37 +/- 10 times/h compared with non-sleep-deprived dogs. During non-rapid-eye-movement sleep the duration of obstruction, minimum arterial hemoglobin saturation, and peak negative inspiratory effort at arousal were 20.5 +/- 1.0 s, 91.7 +/- 0.5%, and 28.4 +/- 1.8 mmHg, respectively, in non-sleep-deprived dogs. Sleep deprivation increased (P < 0.01) the duration of obstruction to 28.0 +/- 0.9 s, worsened (P < 0.05) the minimal arterial hemoglobin desaturation to 85.4 + 3.1%, and increased (P < 0.025) the peak negative inspiratory effort at arousal to 36.1 +/- 1.6 mmHg. Sleep deprivation also caused increases (P < 0.025) in total sleep time, rapid-eye-movement (REM) sleep time, and percentage of time in REM sleep in a 2-h recovery period without airway obstruction at the end of the study. We conclude that airway obstruction in the sleeping dog can reproduce the disturbances in sleep architecture and respiration that occur in obstructive sleep apnea and that prior sleep deprivation will increase apnea severity, degree of somnolence, and REM sleep rebound independent of change in upper airway collapsibility.

scholarly journals Computational model of brain-stem circuit for state-dependent control of hypoglossal motoneurons

2018 ◽  
Vol 120 (1) ◽  
pp. 296-305 ◽  
Author(s):  
Mohsen Naji ◽  
Maxim Komarov ◽  
Giri P. Krishnan ◽  
Atul Malhotra ◽  
Frank L. Powell ◽  
...  
Keyword(s):  
Eye Movement ◽  
Neuronal Network ◽  
Rem Sleep ◽  
Rapid Eye Movement ◽  
Hypoglossal Motoneurons ◽  
State Dependent ◽  
Obstructive Sleep ◽  
Pharyngeal Muscles ◽  
Serotonergic Drugs

In patients with obstructive sleep apnea (OSA), the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Experimental studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contributes to depression of hypoglossal motoneurons and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. In this new study, we developed a biophysical network model to test the hypothesis that, to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons needs to include excitatory and inhibitory perihypoglossal interneurons that mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. In the model, the state-dependent activation of the hypoglossal motoneurons was in qualitative agreement with in vivo data during simulated rapid eye movement (REM) and non-REM sleep. The model was applied to test the mechanisms of action of noradrenergic and serotonergic drugs during REM sleep as observed in vivo. We conclude that the proposed minimal neuronal circuit is sufficient to explain in vivo data and supports the hypothesis that perihypoglossal interneurons may mediate state-dependent monoaminergic drive to hypoglossal motoneurons. The population of the hypothesized perihypoglossal interneurons may serve as novel targets for pharmacological treatment of OSA. NEW & NOTEWORTHY In vivo studies suggest that during rapid eye movement sleep, withdrawal of noradrenergic and serotonergic drives critically contributes to depression of hypoglossal motoneurons (HMs), which innervate the tongue muscles. By means of a biophysical model, which is consistent with a broad range of empirical data, we demonstrate that the neuronal network controlling the excitability of HMs needs to include excitatory and inhibitory interneurons that mediate noradrenergic and serotonergic drives to HMs.

scholarly journals 0559 Association of Rapid Eye Movement Sleep with Insulin Resistance in Han Chinese Patients With Obstructive Sleep Apnea

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A214-A215
Author(s):  
C Zhang ◽  
H Xu ◽  
J Zou ◽  
J Guan ◽  
H Yi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Eye Movement ◽  
Sleep Duration ◽  
Rem Sleep ◽  
Han Chinese ◽  
Sensitivity Index ◽  
Rapid Eye Movement ◽  
Obstructive Sleep

Abstract Introduction Obstructive sleep apnea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but rapid eye movement (REM) sleep has been hypothesized to play a key role. To investigate the associations of insulin resistance with respiratory events and sleep duration during REM sleep, 4,062 Han Chinese individuals with suspected OSA were screened and 2,899 were analyzed. Methods We screened 4,062 participants with suspected OSA who underwent polysomnography in our sleep center from 2009 to 2016. Polysomnographic variables, biochemical indicators, and physical measurements were collected. Logistic regression analyses were conducted to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for insulin resistance as assessed by hyperinsulinemia, the homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin resistance index (FIRI), and Bennet’s insulin sensitivity index (ISI). Results The final analyses included 2,899 participants. After adjusting for age, gender, body mass index, waist circumference, mean arterial pressure, smoking status, alcohol consumption, and the apnea and hypopnea index during non-REM sleep (AHINREM), the results revealed that AHI during REM sleep (AHIREM) was independently associated with insulin resistance; across higher AHIREM quartiles, the ORs (95% CIs) for hyperinsulinemia were 1.340 (1.022, 1.757), 1.210 (0.882, 1.660), and 1.632 (1.103, 2.416); those for abnormal HOMA-IR were 1.287 (0.998, 1.661), 1.263 (0.933, 1.711), and 1.556 (1.056, 2.293); those for abnormal FIRI were 1.386 (1.048, 1.835), 1.317 (0.954, 1.818), and 1.888 (1.269, 2.807); and those for abnormal Bennet’s ISI were 1.297 (1.003, 1.678), 1.287 (0.949, 1.747), and 1.663 (1.127, 2.452) (P &lt; 0.01 for all linear trends). Additionally, the results showed that for every 1-h increase in REM duration, the risk of hyperinsulinemia decreased by 22.3% (P &lt; 0.05). Conclusion The present study demonstrated that AHIREM was independently associated with hyperinsulinemia and abnormal HOMA-IR, FIRI, and Bennet’s ISI. Additionally, REM sleep duration was independently associated with hyperinsulinemia. Support This study was supported by Grants-in-aid from Shanghai Municipal Commission of Science and Technology (No.18DZ2260200).

scholarly journals An Asymmetrical Hypothesis for the NREM-REM Sleep Alternation—What Is the NREM-REM Cycle?

2021 ◽  
Vol 15 ◽  
Author(s):  
Olivier Le Bon
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Refractory Period ◽  
High Variability ◽  
Oscillator Model ◽  
Rapid Eye Movement ◽  
Sleep Regulation ◽  
Short Term ◽  
Sleep Episode ◽  
Sleep Homeostasis

Since the discovery of rapid eye movement (REM) sleep (Aserinsky and Kleitman, 1953), sleep has been described as a succession of cycles of non-REM (NREM) and REM sleep episodes. The hypothesis of short-term REM sleep homeostasis, which is currently the basis of most credible theories on sleep regulation, is built upon a positive correlation between the duration of a REM sleep episode and the duration of the interval until the next REM sleep episode (inter-REM interval): the duration of REM sleep would therefore predict the duration of this interval. However, the high variability of inter-REM intervals, especially in polyphasic sleep, argues against a simple oscillator model. A new “asymmetrical” hypothesis is presented here, where REM sleep episodes only determine the duration of a proportional post-REM refractory period (PRRP), during which REM sleep is forbidden and the only remaining options are isolated NREM episodes or waking. After the PRRP, all three options are available again (NREM, REM, and Wake). I will explain why I think this hypothesis also calls into question the notion of NREM-REM sleep cycles.

The Regulation of Sleep

2021 ◽  
Author(s):  
Craig Heller
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Control Mechanisms ◽  
Rapid Eye Movement ◽  
Sleep Regulation ◽  
Short Article ◽  
Feedback Information ◽  
State Changes ◽  
And Control

The words “regulation” and “control” have different meanings. A rich literature exists on the control mechanisms of sleep—the genomic, molecular, cellular, and circuit processes responsible for arousal state changes and characteristics. The regulation of sleep refers to functions and homeostatic maintenance of those functions. Much less is known about sleep regulation than sleep control, largely because functions of sleep are still unknown. Regulation requires information about the regulated variable that can be used as feedback information to achieve optimal levels. The circadian timing of sleep is regulated, and the feedback information is entraining stimuli such as the light–dark cycle. Sleep itself is homeostatically regulated, as evidenced by sleep deprivation experiments. Eletroenceophalography (EEG) slow-wave activity (SWA) is regulated, and it appears that adenosine is the major source of feedback information, and that fact indicates an energetic function for sleep. The last aspect of sleep regulation discussed in this short article is the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep cycling. Evidence is discussed that supports the argument that NREM sleep is in a homeostatic relationship with wake, and REM sleep is in a homeostatic relationship with NREM sleep.

Upper airway closing pressures in obstructive sleep apnea

1984 ◽  
Vol 57 (2) ◽  
pp. 520-527 ◽  
Author(s):  
F. G. Issa ◽  
C. E. Sullivan
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Eye Movement ◽  
Rem Sleep ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Stage I ◽  
Stage Iii ◽  
Rapid Eye Movement ◽  
Obstructive Sleep

We studied 18 patients with obstructive sleep apnea (OSA). Each subject slept while breathing through the nose with a specially designed valveless breathing circuit. Low levels of continuous positive airway pressure (CPAP) applied through the nose (2.5–15.0 cmH2O) prevented OSA and allowed long periods of stable stage III/IV sleep and rapid-eye-movement (REM) sleep. Externally applied complete nasal occlusion while the upper airway was patent resulted in upper airway closure during inspiration which was identified by a sudden deviation of nasal pressure from tracheal or esophageal pressure. The level of upper airway closing pressure (UACP) did not change throughout the occlusion test, suggesting that upper airway dilator muscles do not respond to asphyxia during sleep. The upper airway was more collapsible during stage I/II non-rapid-eye-movement (NREM) and REM sleep compared with stage III/IV NREM sleep. The pooled mean UACP was 3.1 +/- 0.4 cmH2O in stage I/II NREM, 4.2 +/- 0.2 cmH2O in stage III/IV NREM, and 2.4 +/- 0.2 cmH2O in REM sleep. Nasal occlusion at successively higher levels of CPAP did not alter the level of UACP in stage I/II NREM and REM sleep but resulted in the upper airway becoming more stable in stage III/IV NREM sleep, suggesting a reflex which augments the tone of upper airway dilator muscles.

Cardiovascular changes associated with obstructive sleep apnea syndrome

1992 ◽  
Vol 72 (2) ◽  
pp. 583-589 ◽  
Author(s):  
R. Stoohs ◽  
C. Guilleminault
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Eye Movement ◽  
Rem Sleep ◽  
Sleep Apnea Syndrome ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Significant Drop ◽  
Obstructive Sleep ◽  
The Impact

Five men free of lung or cardiovascular diseases and with severe obstructive sleep apnea participated in a study on the impact of sleep states on cardiovascular variables during sleep apneas. A total of 128 obstructive apneas [72 from stage 2 non-rapid-eye-movement (NREM) sleep and 56 from rapid-eye-movement (REM) sleep] were analyzed. Each apnea was comprised of an obstructive period (OP) followed by a hyperventilation period, which was normally associated with an arousal. Heart rate (HR), stroke volume (SV), cardiac output (CO) (determined with an electrical impedance system), radial artery blood pressures (BP), esophageal pressure nadir, and arterial O2 saturation during each OP and hyperventilation period were calculated for NREM and REM sleep. During stage 2 NREM sleep, the lowest HR always occurred during the first third of the OP, and the highest was always seen during the last third. In contrast, during REM sleep the lowest HR was always noted during the last third of the OP. There was an inverse correlation when the percentage of change in HR over the percentage of change in SV during an OP was considered. The HR and SV changes during NREM sleep allowed maintenance of a near-stable CO during OPs. During REM sleep, absence of a compensatory change in SV led to a significant drop in CO. Systolic, diastolic, and mean BP always increased during the studied OPs.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Apnoea–Hypopnoea Index during Rapid Eye Movement and Non-Rapid Eye Movement Sleep in Obstructive Sleep Apnoea

2008 ◽  
Vol 36 (5) ◽  
pp. 906-913 ◽  
Author(s):  
M Muraki ◽  
S Kitaguchi ◽  
H Ichihashi ◽  
R Haraguchi ◽  
T Iwanaga ◽  
...  
Keyword(s):  
Eye Movement ◽  
Obstructive Sleep Apnoea ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Sleep Apnoea ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Multivariate Logistic Regression ◽  
Obstructive Sleep ◽  
Nocturnal Polysomnography

This study investigated the differences in apnoea-hypopnoea index (AHI) during rapid eye movement (REM) sleep (AHI-REM) and AHI during non-REM (NREM) sleep (AHI-NREM) in patients with obstructive sleep apnoea (OSA). Nocturnal polysomnography was performed in 102 Japanese OSA patients and their AHI along with a variety of other factors were retrospectively evaluated. Regardless of the severity of AHI, mean apnoea duration was longer and patients' lowest recorded oxygen saturation measured by pulse oximetry was lower during REM sleep than during NREM sleep. Approximately half of the patients ( n = 50) had a higher AHI-NREM than AHI-REM. In subjects with AHI ≤ 60 events/h, AHI-NREM was significantly higher than AHI-REM. On multivariate logistic regression, severe AHI ≤ 30 events/h was the only predictor of a higher AHI-NREM than AHI-REM. This may indicate that important, but unknown, factors related to the mechanism responsible for the severity of OSA are operative during NREM sleep.

Vasopressin regulates human sleep by reducing rapid-eye-movement sleep

1992 ◽  
Vol 262 (3) ◽  
pp. E295-E300 ◽  
Author(s):  
J. Born ◽  
C. Kellner ◽  
D. Uthgenannt ◽  
W. Kern ◽  
H. L. Fehm
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Double Blind ◽  
Physiological Conditions ◽  
Upper Limit ◽  
Stage 2 Sleep ◽  
Time Awake

In two double-blind experiments, effects of intravenous infusion of arginine vasopressin (AVP) on sleep were evaluated in 2 groups of 10 men (20-35 yr). In experiment I, subjects were tested on two occasions, during which they received either placebo or 0.33 IU/h AVP. In experiment II, on three different occasions, subjects received either placebo or 0.66 or 0.99 IU/h AVP. Infusions were administered between 2200 and 0700 h. Nocturnal plasma AVP concentrations were close to the upper limit of the normal physiological range during 0.66 IU/h AVP (16.6 +/- 2.2 pg/ml) but markedly exceeded this range during 0.99 IU/h AVP (25.0 +/- 1.6 pg/ml). Results indicate primary effects of AVP on rapid-eye-movement (REM) sleep, with moderate reductions in REM sleep during 0.33 IU/h AVP (averaging -10.5%) and with substantial reductions in REM sleep (-24.0%) during 0.66 IU/h AVP. During 0.99 IU/h AVP the effect did not further increase (-24.4%). Less consistent effects of AVP were an increase in stage 2 sleep and in time awake. Effects of AVP were not mediated by changes in cortisol or blood pressure. Results suggest AVP to participate in REM sleep regulation under normal physiological conditions.

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