Sensorimotor function of the upper-airway muscles and respiratory sensory processing in untreated obstructive sleep apnea

Abstract

Numerous studies have demonstrated upper-airway neuromuscular abnormalities during wakefulness in snorers and obstructive sleep apnea (OSA) patients. However, the functional role of sensorimotor impairment in OSA pathogenesis/disease progression and its potential effects on protective upper-airway reflexes, measures of respiratory sensory processing, and force characteristics remain unclear. This study aimed to gain physiological insight into the potential role of sensorimotor impairment in OSA pathogenesis/disease progression by comparing sensory processing properties (respiratory-related evoked potentials; RREP), functionally important protective reflexes (genioglossus and tensor palatini) across a range of negative pressures (brief pulses and entrained iron lung ventilation), and tongue force and time to task failure characteristics between 12 untreated OSA patients and 13 controls. We hypothesized that abnormalities in these measures would be present in OSA patients. Upper-airway reflexes (e.g., genioglossus onset latency, 20 ± 1 vs. 19 ± 2 ms, P = 0.82), early RREP components (e.g., P1 latency 25 ± 2 vs. 25 ± 1 ms, P = 0.78), and the slope of epiglottic pressure vs. genioglossus activity during iron lung ventilation (-0.68 ± 1.0 vs. -0.80 ± 2.0 cmH(2)O/%max, P = 0.59) were not different between patients and controls. Maximal tongue protrusion force was greater in OSA patients vs. controls (35 ± 2 vs. 27 ± 2 N, P < 0.01), but task failure occurred more rapidly (149 ± 24 vs. 254 ± 23 s, P < 0.01). Upper-airway protective reflexes across a range of negative pressures as measured by electromyography and the early P1 component of the RREP are preserved in OSA patients during wakefulness. Consistent with an adaptive training effect, tongue protrusion force is increased, not decreased, in untreated OSA patients. However, OSA patients may be vulnerable to fatigue of upper-airway dilator muscles, which could contribute to disease progression.

Figures

Fig. 1.

Schematic of the timeline for the experimental protocol. Pulses: brief pulses of negative upper-airway pressure were delivered to elicit upper airway reflex responses and respiratory-related evoked potential waveforms. Iron Lung: entrained iron lung ventilation was performed to examine the response of the genioglossus muscle to negative upper-airway pressure and any potential differences in responsiveness in the evening (PM) compared with the morning (AM). 8 h standard PSG: polysomnography was performed to document the presence or absence of sleep-disordered breathing (the epiglottic pressure catheter was removed). Force/Task Failure: maximal tongue protrusion force and time to task failure protocols were performed. Refer to the text for further details.

Fig. 2.

Example of the ensemble-average of the rectified raw genioglossus EMG and the corresponding mask pressure in one individual subject. The key components used to quantify reflex responses and stimulus characteristics are highlighted, including stimulus onset (vertical line), stimulus magnitude (nadir pressure), baseline genioglossus EMG (horizontal line), reflex excitation onset, excitation peak, suppression onset/excitation cessation, suppression nadir, and suppression cessation. Refer to the text for further details.

Fig. 3.

Respiratory-related evoked potential (RREP) group average waveforms at Cz and stimulus characteristics (epiglottic pressure). *Significant difference in the latency of this RREP waveform component between groups (P < 0.01).

Fig. 4.

Tracings of the parameters that were measured during basal breathing and entrained iron lung ventilation in one individual subject. DI EMG, surface rectified electromyogram overlaying the chest wall (diaphragm); GG EMG, raw intramuscular genioglossus muscle activity; PetCO2, end-tidal CO2 measured at the nares; Pmask, pressure at the mask; Plung, pressure inside the iron lung; Pepi, pressure at the level of the epiglottis; VT, tidal volume; Airflow, flow measured via nasal mask and pneumotachograph.

Fig. 5.

A: representative example during the maximal tongue protrusion force task. In this case, the maximum force achieved by the subject was ∼35 N. B: an example of the repetitive isometric contraction task that was used to examine time to task failure and the criteria used to define task failure. In this instance, time to task failure occurred after ∼2.5 min.

Fig. 6.

Relationship between genioglossus activity and epiglottic pressure during entrained iron lung ventilation before and after an 8-h sleep opportunity. The slope of peak genioglossus activity vs. negative epiglottic pressure during entrained iron lung ventilation was not different between groups (patients vs. controls) or in the evening vs. the morning. Similarly, there were no statistically significant differences in the y-intercept of this relationship although there was a tendency for a decrease in the morning compared with the evening in the controls but not in the OSA patients. Refer to the text for further details.

Fig. 7.

Maximal voluntary tongue protrusion force (A) and time to task failure (B). *Significant difference between groups (P < 0.01).