Mechanisms of the deep, slow-wave, sleep-related increase of upper airway muscle tone in healthy humans

Abstract

Upper airway muscle activity is reportedly elevated during slow-wave sleep (SWS) when compared with lighter sleep stages. To uncover the possible mechanisms underlying this elevation, we explored the correlation between different indices of central and reflex inspiratory drive, such as the changes in airway pressure and end-expiratory CO₂ and the changes in the genioglossus (GG) and tensor palatini (TP) muscle activity accompanying transitions from the lighter N2 to the deeper N3 stage of non-rapid eye movement (NREM) sleep in healthy young adult men. Forty-six GG and 38 TP continuous electromyographic recordings were obtained from 16 men [age: 20 ± 2.5 (SD) yr; body mass index: 22.5 ± 1.8 kg/m²] during 32 transitions from NREM stages N2 to N3. GG but not TP activity increased following transition into N3 sleep, and the increase was positively correlated with more negative airway pressure, increased end-tidal CO₂, increased peak inspiratory flow, and increased minute ventilation. None of these correlations was statistically significant for TP. Complementary GG and TP single motor unit analysis revealed a mild recruitment of GG units and derecruitment of TP units during the N2 to N3 transitions. These findings suggest that, in healthy individuals, the increased GG activity during SWS is driven primarily by reflex stimulation of airway mechanoreceptors and central chemoreceptors.NEW & NOTEWORTHY The characteristic increase in the activity of the upper airway dilator muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulation of airway mechanoreceptors and central chemoreceptors. No evidence was found for the presence of a central SWS-specific drive stimulating genioglossus activity in young healthy individuals. However, it remains to be determined whether a central drive exists in obstructive sleep apnea patients.

Keywords: genioglossus; non-rapid eye movement sleep; slow-wave sleep; tensor palatini; upper airway muscles.

Fig. 1.

Top: transition from stage N2 of non-rapid eye movement (NREM) sleep (segment A) to stage N3 (segment B). Bottom: segments A and B enlarged. To allow for visually adequate expansion, the highlighted segments are ~20 s rather than the 30-s-long epochs that were used for analysis in this study. The signals shown are as follows: lead C3 to A2 of the electroencephalogram (EEG), CO₂, epiglottic pressure (P_EPI) – epiglottic pressure, flow – airway air flow, and the raw electromyograms (EMGs) recorded from the genioglossus (GG) and tensor palatini (TP). In this subject, there was evidence of flow limitation whose magnitude was larger than in other subjects enrolled in this study and thus represents a “worst case scenario.”

Fig. 2.

Scatter plots showing the relationship between the change from stage N2 to stage N3 of NREM sleep in the mean GG compound spike density during inspiration and the concurrent changes in the nadir of airway pressure (A) or end-tidal CO₂ ($\mathrm{P}\mathrm{E}{\mathrm{T}}_{\mathrm{C}{\mathrm{O}}_{\mathrm{2}}}$; B). Data points represent paired differences between stage N3 and stage N2 values. Dashed lines indicate the levels of no difference between the 2 stages; straight lines represent the linear regression for all data points in the plots, whereas curvilinear lines indicate the 95% confidence intervals.

Fig. 3.

Scatter plots showing the relationship between the change from stage N2 to stage N3 of NREM sleep in the mean $\mathrm{P}\mathrm{E}{\mathrm{T}}_{\mathrm{C}{\mathrm{O}}_{\mathrm{2}}}$ and the concurrent changes in the nadir of epiglottic pressure (P_EPI; A) and minute ventilation (Vi; B). Data points represent paired differences between stage N3 and stage N2 values. Dashed lines indicate the levels of no difference between the two stages; straight lines represent the linear regression for all data points in the plots, whereas curvilinear lines indicate the 95% confidence intervals.