Physiological mechanisms of upper airway hypotonia during REM sleep

Abstract

Study objectives: Rapid eye movement (REM)-induced hypotonia of the major upper airway dilating muscle (genioglossus) potentially contributes to the worsening of obstructive sleep apnea that occurs during this stage. No prior human single motor unit (SMU) study of genioglossus has examined this possibility to our knowledge. We hypothesized that genioglossus SMUs would reduce their activity during stable breathing in both tonic and phasic REM compared to stage N2 sleep. Further, we hypothesized that hypopneas occurring in REM would be associated with coincident reductions in genioglossus SMU activity.

Design: The activity of genioglossus SMUs was studied in (1) neighboring epochs of stage N2, and tonic and phasic REM; and (2) during hypopneas occurring in REM.

Setting: Sleep laboratory.

Participants: 29 subjects (38 ± 13 y) (17 male).

Intervention: Natural sleep, including REM sleep and REM hypopneas.

Measurement and results: Subjects slept overnight with genioglossus fine-wire intramuscular electrodes and full polysomnography. Forty-two SMUs firing during one or more of stage N2, tonic REM, or phasic REM were sorted. Twenty inspiratory phasic (IP), 17 inspiratory tonic (IT), and five expiratory tonic (ET) SMUs were characterized. Fewer units were active during phasic REM (23) compared to tonic REM (30) and stage N2 (33). During phasic REM sleep, genioglossus IP and IT SMUs discharged at slower rates and for shorter durations than during stage N2. For example, the SMU peak frequency during phasic REM 5.7 ± 6.6 Hz (mean ± standard deviation) was less than both tonic REM 12.3 ± 9.7 Hz and stage N2 16.1 ± 10.0 Hz (P < 0.001). The peak firing frequencies of IP/IT SMUs decreased from the last breath before to the first breath of a REM hypopnea (11.8 ± 10.9 Hz versus 5.7 ± 9.4 Hz; P = 0.001).

Conclusion: Genioglossus single motor unit activity is significantly reduced in REM sleep, particularly phasic REM. Single motor unit activity decreases abruptly at the onset of REM hypopneas.

Keywords: Obstructive sleep apnea; genioglossus; rapid eye movement sleep; single motor unit; upper airway hypotonia.

Figure 1

The genioglossus EMG data chosen for analysis in this example was chosen as follows. As per our protocol, stage N2 data were analyzed from the penultimate epoch before REM (first shaded area going from left to right). The existence of an arousal (A) at the end of the first and beginning of the second tonic REM epoch meant we could not simply chose the second tonic REM epoch to analyze. Therefore as per protocol, tonic REM data was analyzed from > 10 seconds after this arousal (A). A full 30 sec (i.e., one epoch) of consecutive tonic REM was analyzed (see second shaded area). Finally, the phasic REM used for analysis required three separate periods of data so as to make up a 30-sec epoch. The phasic REM segements chosen had sustained rapid eye movements (see final three shaded areas coinciding with REMs). A, arousal; EMG, electromyography;. EOG, electrooculography; GG, genioglossus.

Figure 2

Example of raw data from stage N2. This figure shows the instantaneous discharge frequency plots of the three SMUs, which were sorted and extracted from the raw genioglossus EMG signals. The overlaid detailed morphologies for each SMU are seen in the inset. The baseline tonic frequency is measured as the tonic expiratory discharge frequency averaged over 500 ms. The onset time of inspiratory tonic units refers to the time that the units start firing faster than the baseline/tonic expiratory discharge frequency. The end time of inspiratory tonic units refers to the time that the units resume firing at the baseline/tonic expiratory discharge frequency.

Figure 3

A global outline of the 42 single motor units showing the stage(s) in which they were active. IP, inspiratory phasic; IT, inspiratory tonic; ET, expiratory tonic.

Figure 4

Raw data from a single subject encapsulate the key findings of our study. Our study shows that the activity of the genioglossus is greatly diminished in phasic rapid eye movement (REM). Also, during REM-related hypopneas genioglossus (GG), single motor unit (SMU) activity decreases and is coincident with the onset of the hypopnea. In this example, REM heralds an immediate reduction in GG SMU activity and with it a hypopnea.