Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

Abstract

Several studies have shown that obstructive sleep apnoea (OSA) improves during slow wave sleep (SWS) for reasons that remain unclear. Recent studies have identified forms of neural memory such as short-term potentiation or after-discharge that can occur in response to upper airway obstruction. Neural memory may play a role in the development of stable breathing during SWS by increasing upper airway muscles activity in this sleep stage. We hypothesize that the after-discharge of the genioglossus muscle following upper airway obstruction is enhanced during SWS compared to non-rapid eye movement stage 2 (N2). During sleep, we performed five-breath drops in continuous positive airway pressure (CPAP-drop) to simulate obstructive events and reflexively activate the genioglossus. Immediately afterwards, CPAP was returned to an optimal level. Once the post-drop ventilation returned to eupnoea, the genioglossus after-discharge was measured as the time it took for genioglossus activity to return to baseline levels. In total, 171 CPAP-drops were analysed from a group of 16 healthy subjects and 19 OSA patients. A mixed-model analysis showed that after-discharge duration during SWS was 208% (95% confidence interval = 112% to 387%, P = 0.022) greater than during N2 after adjusting for covariates (ventilatory drive, CPAP levels). There was also a non-significant trend for a -35% reduction in after-discharge duration following an arousal vs. no-arousal from sleep (95% confidence interval = -59.5% to 5%, P = 0.08). Genioglossus after-discharge is two-fold greater in SWS vs. N2, which could partly explain the breathing stabilization described in OSA patients during this sleep stage.

Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature

“…Moreover, the drugs tested to date were unable to increase the arousal threshold by more than 20–30% (see below for a detailed description). Ideally, a drug that mimics the effects of slow wave sleep (a state in which the arousal threshold is elevated) would be ideal for reducing OSA severity, given that this is a relatively protected stage of sleep in regards to OSA [111,112,113,114].…”

Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options

“…After-discharge in the genioglossus muscle has been recently proposed to be a protective factor for OSA, as it prevents periods of low genioglossus muscle activity following a period of increased respiratory drive, such as at the termination of respiratory events, after the arousals. Although multiunit genioglossus after-discharge (inspiratory and expiratory) was not found to differ between patients with OSA and healthy individuals following reversal of upper airway obstruction [42], enhancement of after discharge may still have a role in OSA treatment. Our group in Boston has recently shown that greater and longer after discharge is associated with slow wave sleep [42], a protected sleep state in which OSA patients experience less obstructive events and more stable breathing on average.…”

“…Although multiunit genioglossus after-discharge (inspiratory and expiratory) was not found to differ between patients with OSA and healthy individuals following reversal of upper airway obstruction [42], enhancement of after discharge may still have a role in OSA treatment. Our group in Boston has recently shown that greater and longer after discharge is associated with slow wave sleep [42], a protected sleep state in which OSA patients experience less obstructive events and more stable breathing on average. Other characteristics of deep sleep that may help upper airway muscle recruitment and reduced respiratory events are the higher arousal threshold and ventilatory drive measured during this stage.…”

What short‐term potentiation is and why it may be relevant to obstructive sleep apnoea

“…In an article in this issue of The Journal of Physiology , Taranto‐Montemurro et al . () explore the possibility that the improved UA stability in SWS may result from a more potent AD in this stage. They indeed found this to be true both in healthy controls and in OSA patients; the duration of AD increased as the same subjects entered SWS.…”

“…The exact mechanism for this was not known although it was suspected that higher arousal threshold in SWS contributed by delaying arousal and allowing the normal compensatory mechanisms to progress to the required level. In an article in this issue of The Journal of Physiology, Taranto-Montemurro et al (2018) explore the possibility that the improved UA stability in SWS may result from a more potent AD in this stage. They indeed found this to be true both in healthy controls and in OSA patients; the duration of AD increased as the same subjects entered SWS.…”