Neural drive to human genioglossus in obstructive sleep apnoea

Abstract

One postulated mechanism for obstructive sleep apnoea (OSA) is insufficient drive to the upper-airway musculature during sleep, with increased (compensatory) drive during wakefulness. This generates more electromyographic activity in upper airway muscles including genioglossus. To understand drives to upper airway muscles, we recorded single motor unit activity from genioglossus in male groups of control (n = 7, 7 +/- 2 events h(-1)) and severe OSA (n = 9, 54 +/- 4 events h(-1)) subjects. One hundred and seventy-eight genioglossus units were recorded using monopolar electrodes. Subjects were awake, supine and breathing through a nasal mask. The distribution of the six types of motor unit activity in genioglossus (Inspiratory Phasic, Inspiratory Tonic, Expiratory Phasic, Expiratory Tonic, Tonic and Tonic Other) was identical in both groups. Single unit action potentials in OSA were larger in area (by 34%, P < 0.05) and longer in duration (by 23%, P < 0.05). Inspiratory units were recruited earlier in OSA than control subjects. In control subjects, Inspiratory Tonic units peaked earlier than Inspiratory Phasic units, while in OSA subjects, Inspiratory Tonic and Phasic units peaked simultaneously. Onset frequencies did not differ between groups, but the peak discharge frequency for Inspiratory Phasic units was higher in OSA (22 +/- 1 Hz) than control subjects (19 +/- 1 Hz, P = 0.003), but conversely, the peak discharge frequency of Inspiratory Tonic units was higher in control subjects (28 +/- 1 Hz versus 25 +/- 1 Hz, P < 0.05). Increased motor unit action potential area indicates that neurogenic changes have occurred in OSA. In addition, the differences in the timing and firing frequency of the inspiratory classes of genioglossus motor units indicate that the output of the hypoglossal nucleus may have changed.

Figure 1

Recording of single motor unit activity in the genioglossus A, experimental set-up showing subject lying supine. The monopolar electrode was positioned 10 mm posterior to the genial tubercle of the mandible and 3 mm from the midline with the reference electrode over the left mandible and a ground electrode above the right clavicle. Subjects breathed through a nasal mask that was connected to a pneumotachograph. The dotted rectangle under the chin indicates where the ultrasound transducer was positioned. B, an image recorded in the sagittal plane using ultrasonography to show the location and depth of geniohyoid and genioglossus muscles and the site of insertion of the monopolar electrode. C, from bottom to top traces, the raw EMG, rectified and integrated EMG (time constant, 50 ms, calibration 0–40 μV), flow, volume, instantaneous frequency plots for 2 units, and the superimposed motor unit potentials for each unit (inset). Two simultaneously recorded units increase their discharge in phase with inspiration. Unit 1 was classed as Inspiratory Tonic and Unit 2 as Inspiratory Phasic. Inset calibrations 400 μV and 2 ms. D, a typical example of an averaged motor unit potential (∼50 sweeps). The shaded modulus indicates the area measured; duration and peak to peak amplitude were also measured.

Figure 3

Classification of single motor unit units in genioglossus based on their firing frequency–volume coefficient of determination A (obstructive sleep apnoea subjects) and B (control subjects) plot the strength (coefficient, r²) and the time of the peak cross-correlations for each unit. The correlations were calculated between volume (inspiratory or expiratory) and the discharge frequency (smoothed over 200 ms) of the motor unit by computing all possible x-axis phase differences between the two signals (see Methods). Time zero represents the end of inspiration. Units were classified into Inspiratory Phasic (filled circles), Inspiratory Tonic (half-filled circles), Expiratory Phasic (filled squares), Expiratory Tonic (half-filled squares), and Tonic and Tonic Other units (crosses). In general, Tonic units showed low r² values (< 0.4), while units with a clear respiratory modulation had high r² values (> 0.4). Inspiratory units had a peak r² before the end of inspiration (negative times) and expiratory units had a peak r² after the end of inspiration during expiration (positive times).

Figure 2

Motor unit action potential (MUAP) parameters for genioglossus in control and obstructive sleep apnoea subjects A, mean peak-to-peak amplitude of motor unit action potentials in the control (triangles) and OSA subjects (circles). B, mean motor unit potential duration. In OSA subjects potential duration was significantly longer compared to control subjects (P < 0.05). C, in OSA subjects, the mean area of motor unit potentials was larger than in the control subjects (P < 0.05). Individual values as well as the mean ± s.e.m. are shown in all panels.

Figure 4

Time-and-frequency Plots of firing of single motor units in the human genioglossus muscle in control subjects and obstructive sleep apnoea subjects during quiet breathing The motor units were sampled during the respiratory cycle and their discharge times are normalized to inspiratory time (0–100% horizontal axis label). A, firing time for control subjects (n = 79 single motor units). B, firing time for each single motor unit for the genioglossus muscle in OSA subjects (n = 99 units). The vertical darkest lines in each panel represent the onset (0%) and end (100%) of inspiration measured from the flow signal. For units which discharged throughout both phases of the respiratory cycle, a continuous horizontal line indicates tonic firing. The time of the peak firing frequency is indicated by a black circle and the mean peak frequency is indicated by the colour of the thick horizontal line. The firing frequencies corresponding to each colour are shown in the inset. The initial and final frequencies are also added as coloured circles. The units are ordered within each category (phasic or tonic) according to their onset discharge time. The percentages for each type of unit were similar for the control and OSA subjects and the onset time of Inspiratory Phasic and Inspiratory Tonic units was earlier in the OSA subjects (see text).

Figure 5

Onset and peak discharge frequencies of genioglossus motor units A (OSA subjects) and B (control subjects) depict mean onset (open circles) and peak discharge frequencies (open triangles) for each motor unit recorded during normal breathing. The overall mean onset (± s.e.m.; filled circles) and peak discharge frequencies (filled triangle) are shown for each of the 5 types of genioglossus units modulated by respiration. The mean onset and peak frequencies are joined by a line. Only the peak frequency is shown for Tonic units.