Supraspinal fatigue in human inspiratory muscles with repeated sustained maximal efforts.

To investigate the involvement of supraspinal fatigue in the loss of maximal inspiratory pressure (Pimax), we fatigued the inspiratory muscles. Six participants performed 5 sustained maximal isometric inspiratory efforts (15-s contractions, duty cycle ∼75%) which reduced Pimax, as measured from esophageal and mouth pressure, to around half of their initial maximums. Transcranial magnetic stimulation (TMS) delivered over the motor cortex near the beginning and end of each maximal effort evoked superimposed twitch-like increments in the ongoing Pimax, increasing from ∼1.0% of Pimax in the unfatigued contractions to ≥40% of ongoing Pimax for esophageal and mouth pressures. The rate of increase in the superimposed twitch as Pimax decreased with fatigue was not significantly different between the esophageal and mouth pressure measures. The inverse relationship between superimposed twitch pressure and Pimax indicates a progressive decline in the ability of motor cortical output to drive the inspiratory muscles maximally, leading to the development of supraspinal fatigue. TMS also evoked silent periods in the electromyographic recordings of diaphragm, scalenes, and parasternal intercostal. The duration of the silent period increased with fatigue in all three muscles, which suggests greater intracortical inhibition, with the largest change observed in the diaphragm. The peak rate of relaxation in pressure during the silent period slowed as fatigue developed, indicating peripheral contractile changes in the active inspiratory muscles. These changes in the markers of fatigue show that both central and peripheral fatigue contribute to the loss in Pimax when inspiratory muscles are fatigued with repeated sustained maximal efforts.NEW & NOTEWORTHY When the inspiratory muscles are fatigued with repeated sustained maximal efforts, supraspinal fatigue, a component of central fatigue, contributes to the loss in maximal inspiratory pressure. The presence of supraspinal fatigue was confirmed by the increase in amplitude of twitch-like increments in pressure evoked by motor cortical stimulation during maximal efforts, indicating that motor cortical output was not maximal as extra muscle force could be generated to increase inspiratory pressure.

Genioglossus motor unit activity in supine and upright postures in obstructive sleep apnea.

This study investigated whether a change in posture affected the activity of the upper-airway dilator muscle genioglossus in participants with and without obstructive sleep apnea (OSA). During wakefulness, a monopolar needle electrode was used to record single motor unit activity in genioglossus in supine and upright positions to alter the gravitational load that causes narrowing of the upper airway. Activity from 472 motor units was recorded during quiet breathing in 17 males, nine of whom had OSA. The mean number of motor units for each participant was 11.8 (SD 3.4) in the upright and 16.0 (SD 4.2) in the supine posture. For respiratory-modulated motor units, there were no significant differences in discharge frequencies between healthy controls and participants with OSA. Within each breath, genioglossus activity increased through the recruitment of phasic motor units and an increase in firing rate, with an overall increase of ~6 Hz (50%) across both postures and participant groups. However, the supine posture did not lead to compensatory increases in the peak discharge frequencies of inspiratory and expiratory motor units, despite the increase in gravitational load on the upper airway. Posture also had no significant effect on the discharge frequency of motor units that showed no respiratory modulation during quiet breathing. We postulate that, in wakefulness, any increase in genioglossus activity to compensate for the gravitational effects on the upper airway is achieved primarily through the recruitment of additional motor units in both healthy controls and participants with OSA.

Motor unit territories in human genioglossus estimated with multichannel intramuscular electrodes.

The discharge patterns of genioglossus motor units during breathing have been well-characterized in previous studies, but their localization and territories are not known. In this study, we used two newly developed intramuscular multichannel electrodes to estimate the territories of genioglossus motor units in the anterior and posterior regions of the muscle. Seven healthy men participated. Each electrode contained fifteen bipolar channels, separated by 1 mm, and was inserted percutaneously below the chin, perpendicular to the skin, to a depth of 36 mm. Single motor unit activity was recorded with subjects awake, supine, and breathing quietly through a nasal mask for 180 s. Motor unit territories were estimated from the spike-triggered averages of the electromyographic signal from each channel. A total of 30 motor units were identified: 22 expiratory tonic, 1 expiratory phasic, 2 tonic, 3 inspiratory tonic, and 2 inspiratory phasic. Motor units appeared to be clustered based on unit type, with peak activities for expiratory units predominantly located in the anterior and superficial fibers of genioglossus and inspiratory units in the posterior region. Of these motor unit types, expiratory tonic units had the largest estimated territory, a mean 11.3 mm (SD 1.9). Estimated territories of inspiratory motor units ranged from 3 to 6 mm. In accordance with the distribution of motor unit types, the estimated territory of genioglossus motor units varied along the sagittal plane, decreasing from anterior to posterior. Our findings suggest that genioglossus motor units have large territories relative to the cross-sectional size of the muscle. NEW & NOTEWORTHY In this study, we used a new multichannel intramuscular electrode to address a fundamental property of human genioglossus motor units. We describe the territory of genioglossus motor units in the anterior and posterior regions of the muscle and show a decrease in territory size from anterior to posterior and that expiratory-related motor units have larger estimated territories than inspiratory-related motor units.

Correction: Effects of Aging on Genioglossus Motor Units in Humans.

[This corrects the article DOI: 10.1371/journal.pone.0104572.].

TMS-evoked silent periods in scalene and parasternal intercostal muscles during voluntary breathing.

Transcranial magnetic stimulation (TMS) during voluntary muscle contraction causes a period of reduced electromyographic (EMG) activity (EMG). This is attributed to cortical inhibition and is known as the 'silent period'. Silent periods were compared in inspiratory muscles following TMS during voluntary inspiratory efforts during normocapnia, hypercapnia, and hypocapnia. TMS was delivered during isometric and dynamic contractions of scalenes and parasternal intercostals at 25% maximum inspiratory pressure. Changing end-tidal CO2 did not affect the duration of the silent period nor suppression of EMG activity during the silent period. In scalenes, silent periods were shorter for dynamic compared to isometric contractions (p<0.05); but contraction type did not alter the degree of suppression of EMG during the silent period. In parasternal intercostal, no significant differences in silent period parameters occurred for the different contraction types. The lack of effect of end-tidal CO2 suggests that descending drive from the medullary respiratory centres does not independently activate the inspiratory muscles during voluntary inspiratory efforts.

Mechanisms contributing to the response of upper-airway muscles to changes in airway pressure.

This study assessed the effects of inhaled lignocaine to reduce upper airway surface mechanoreceptor activity on 1) basal genioglossus and tensor palatini EMG, 2) genioglossus reflex responses to large pulses (∼10 cmH2O) of negative airway pressure, and 3) upper airway collapsibility in 15 awake individuals. Genioglossus and tensor palatini muscle EMG and airway pressures were recorded during quiet nasal breathing and during brief pulses (250 ms) of negative upper-airway pressure. Lignocaine reduced peak inspiratory (5.6 ± 1.5 vs. 3.8 ± 1.1% maximum; mean ± SE, P < 0.01) and tonic (2.8 ± 0.8 vs. 2.1 ± 0.7% maximum; P < 0.05) genioglossus EMG during quiet breathing but had no effect on tensor palatini EMG (5.0 ± 0.8 vs. 5.0 ± 0.5% maximum; P = 0.97). Genioglossus reflex excitation to negative pressure pulses decreased after anesthesia (60.9 ± 20.7 vs. 23.6 ± 5.2 µV; P < 0.05), but not when expressed as a percentage of the immediate prestimulus baseline. Reflex excitation was closely related to the change in baseline EMG following lignocaine (r(2) = 0.98). A short-latency genioglossus reflex to rapid increases from negative to atmospheric pressure was also observed. The upper airway collapsibility index (%difference) between nadir choanal and epiglottic pressure increased after lignocaine (17.8 ± 3.7 vs. 28.8 ± 7.5%; P < 0.05). These findings indicate that surface receptors modulate genioglossus but not tensor palatini activity during quiet breathing. However, removal of input from surface mechanoreceptors has minimal effect on genioglossus reflex responses to large (∼10 cmH2O), sudden changes in airway pressure. Changes in pressure rather than negative pressure per se can elicit genioglossus reflex responses. These findings challenge previous views and have important implications for upper airway muscle control.

Neurogenic changes in the upper airway of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is linked to local neural injury that evokes airway muscle remodelling. The upper airway muscles of patients with OSA are exposed to intermittent hypoxia as well as vibration induced by snoring. A range of electrophysiological and other studies have established altered motor and sensory function of the airway in OSA. The extent to which these changes impair upper airway muscle function and their relationship to the progression of OSA remains undefined. This review will collate the evidence for upper airway remodelling in OSA, particularly the electromyographic changes in upper airway muscles of patients with OSA.

Effects of tongue position and lung volume on voluntary maximal tongue protrusion force in humans.

Maximal voluntary protrusion force of the human tongue has not been examined in positions beyond the incisors or at different lung volumes. Tongue force was recorded with the tongue tip at eight positions relative to the incisors (12 and 4mm protrusion, neutral and 4, 12, 16, 24 and 32mm retraction) at functional residual capacity (FRC), total lung capacity (TLC) and residual volume (RV) in 15 healthy subjects. Maximal force occurred between 12mm and 32mm retraction (median 16mm). Maximum force at FRC was reproducible at the optimal tongue position across sessions (P=0.68). Across all positions at FRC the average force was highest at 24mm retraction (28.3±5.3N, mean±95% CI) and lowest at 12mm protrusion (49.1±4.6% maximum; P<0.05). Across all tongue positions, maximal force was on average 9.3% lower at FRC than TLC and RV (range: 4.5-12.7% maximum, P<0.05). Retracted positions produce higher-force protrusions with a small effect of lung volume.

Effects of aging on genioglossus motor units in humans.

The genioglossus is a major upper airway dilator muscle thought to be important in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive sleep apnea although the mechanisms are unclear and the effects of aging on motor unit remodeled in the genioglossus remains unknown. To assess possible changes associated with aging we compared quantitative parameters related to motor unit potential morphology derived from EMG signals in a sample of older (n = 11; >55 years) versus younger (n = 29; <55 years) adults. All data were recorded during quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which estimated a MUP template from each extracted motor unit potential train (MUPT) for both the selective concentric needle and concentric needle macro (CNMACRO) recorded EMG signals. 2074 MUPTs from 40 subjects (mean±95% CI; older AHI 19.6±9.9 events/hr versus younger AHI 30.1±6.1 events/hr) were extracted. MUPs detected in older adults were 32% longer in duration (14.7±0.5 ms versus 11.1±0.2 ms; P  =  0.05), with similar amplitudes (395.2±25.1 µV versus 394.6±13.7 µV). Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7±6.5 µV versus 51.3±3.0 µV; P<0.05), with areas 24% larger (160.6±18.6 µV.ms versus 130.0±7.4 µV.ms; P<0.05) than those detected in younger adults. These results confirm that remodeled motor units are present in the genioglossus muscle of individuals above 55 years, which may have implications for OSA pathogenesis and aging related upper airway collapsibility.

Physiological mechanisms of upper airway hypotonia during REM sleep.

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.

A mechanism for upper airway stability during slow wave sleep.

STUDY OBJECTIVES: The severity of obstructive sleep apnea is diminished (sometimes markedly) during slow wave sleep (SWS). We sought to understand why SWS stabilizes the upper airway. Increased single motor unit (SMU) activity of the major upper airway dilating muscle (genioglossus) should improve upper airway stability. Therefore, we hypothesized that genioglossus SMUs would increase their activity during SWS in comparison with Stage N2 sleep. DESIGN: The activity of genioglossus SMUs was studied on both sides of the transition between Stage N2 sleep and SWS. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-nine subjects (age 38 ± 13 yr, 17 males) were studied. INTERVENTION: SWS. MEASUREMENT AND RESULTS: Subjects slept overnight with fine-wire electrodes in their genioglossus muscles and with full polysomnographic and end tidal carbon dioxide monitors. Fifteen inspiratory phasic (IP) and 11 inspiratory tonic (IT) units were identified from seven subjects and these units exhibited significantly increased inspiratory discharge frequencies during SWS compared with Stage N2 sleep. The peak discharge frequency of the inspiratory units (IP and IT) was 22.7 ± 4.1 Hz in SWS versus 20.3 ± 4.5 Hz in Stage N2 (P < 0.001). The IP units also fired for a longer duration (expressed as a percentage of inspiratory time) during SWS (104.6 ± 39.5 %TI) versus Stage N2 sleep (82.6 ± 39.5 %TI, P < 0.001). The IT units fired faster during expiration in SWS (14.2 ± 1.8 Hz) versus Stage N2 sleep (12.6 ± 3.1 Hz, P = 0.035). There was minimal recruitment or derecruitment of units between SWS and Stage N2 sleep. CONCLUSION: Increased genioglossus SMU activity likely makes the airway more stable and resistant to collapse throughout the respiratory cycle during SWS.

Functional role of neural injury in obstructive sleep apnea.

The causes of obstructive sleep apnea (OSA) are multifactorial. Neural injury affecting the upper airway muscles due to repetitive exposure to intermittent hypoxia and/or mechanical strain resulting from snoring and recurrent upper airway closure have been proposed to contribute to OSA disease progression. Multiple studies have demonstrated altered sensory and motor function in patients with OSA using a variety of neurophysiological and histological approaches. However, the extent to which the alterations contribute to impairments in upper airway muscle function, and thus OSA disease progression, remains uncertain. This brief review, primarily focused on data in humans, summarizes: (1) the evidence for upper airway sensorimotor injury in OSA and (2) current understanding of how these changes affect upper airway function and their potential to change OSA progression. Some unresolved questions including possible treatment targets are noted.

Discharge patterns of human tensor palatini motor units during sleep onset.

STUDY OBJECTIVES: Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. DESIGN: The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. SETTING: Sleep laboratory. PARTICIPANTS: Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. INTERVENTION: Sleep onset. MEASUREMENTS AND RESULTS: Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. CONCLUSIONS: TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP.

Neurogenic changes in the upper airway of patients with obstructive sleep apnea.

RATIONALE: Controversy persists regarding the presence and importance of hypoglossal nerve dysfunction in obstructive sleep apnea (OSA). OBJECTIVES: We assessed quantitative parameters related to motor unit potential (MUP) morphology derived from electromyographic (EMG) signals in patients with OSA versus control subjects and hypothesized that signs of neurogenic remodeling would be present in the patients with OSA. METHODS: Participants underwent diagnostic sleep studies to obtain apnea-hypopnea indices. Muscle activity was detected with 50-mm concentric needle electrodes. The concentric needle was positioned at more than 10 independent sites per subject, after the local anatomy of the upper airway musculature was examined by ultrasonography. All activity was quantified with subjects awake, during supine eupneic breathing while wearing a nasal mask connected to a pneumotachograph. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which extracted motor unit potential trains (MUPTs) contributed by individual motor units from the composite EMG signals. Quantitative measurements of MUP templates, including duration, peak-to-peak amplitude, area, area-to-amplitude ratio, and size index, were compared between the untreated patients with OSA and healthy control subjects. MEASUREMENTS AND MAIN RESULTS: A total of 1,655 MUPTs from patients with OSA (n = 17; AHI, 55 ± 6/h) and control subjects (n = 14; AHI, 4 ± 1/h) were extracted from the genioglossus muscle EMG signals. MUP peak-to-peak amplitudes in the patients with OSA were not different compared with the control subjects (397.5 ± 9.0 vs. 382.5 ± 10.0 µV). However, the MUPs of the patients with OSA were longer in duration (11.5 ± 0.1 vs. 10.3 ± 0.1 ms; P < 0.001) and had a larger size index (4.09 ± 0.02 vs. 3.92 ± 0.02; P < 0.001) compared with control subjects. CONCLUSIONS: These results confirm and quantify the extent and existence of structural neural remodeling in OSA.

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

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.

Posterolateral surface electrical stimulation of abdominal expiratory muscles to enhance cough in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) patients have respiratory complications because of abdominal muscle weakness and paralysis, which impair the ability to cough. OBJECTIVE: This study aims to enhance cough in high-level SCI subjects (n = 11, SCI at or above T6) using surface electrical stimulation of the abdominal muscles via 2 pairs of posterolaterally placed electrodes. METHODS: From total lung capacity, subjects performed maximum expiratory pressure (MEP) efforts against a closed airway and voluntary cough efforts. Both efforts were performed with and without superimposed trains of electrical stimulation (50 Hz, 1 second) at a submaximal intensity set to evoke a gastric pressure (P(ga)) of 40 cm H(2)O at functional residual capacity. RESULTS: In the MEP effort, stimulation increased the maximal P(ga) (from 21.4 ± 7.0 to 59.0 ± 5.7 cm H(2)O) and esophageal pressure (P(es); 47.2 ± 11.7 to 65.6 ± 13.6 cm H(2)O). During the cough efforts, stimulation increased P(ga) (19.5 ± 6.0 to 57.9 ± 7.0 cm H(2)O) and P(es) (31.2 ± 8.7 to 56.6 ± 10.5 cm H(2)O). The increased expiratory pressures during cough efforts with stimulation increased peak expiratory flow (PEF, by 36% ± 5%), mean expiratory flow (by 80% ± 8%), and expired lung volume (by 41% ± 16%). In every subject, superimposed electrical stimulation improved peak expiratory flow during cough efforts (by 0.99 ± 0.12 L/s; range, 0.41-1.80 L/s). Wearing an abdominal binder did not improve stimulated cough flows or pressures. CONCLUSIONS: The increases in P(ga) and PEF with electrical stimulation using the novel posterolateral electrode placement are 2 to 3 times greater than improvements reported in other studies. This suggests that posterolateral electrical stimulation of abdominal muscles is a simple noninvasive way to enhance cough in individuals with SCI.

Motor unit recruitment in human genioglossus muscle in response to hypercapnia.

STUDY OBJECTIVES: single motor unit recordings of the genioglossus (GG) muscle indicate that GG motor units have a variety of discharge patterns, including units that have higher discharge rates during inspiration (inspiratory phasic and inspiratory tonic), or expiration (expiratory phasic and expiratory tonic), or do not modify their rate with respiration (tonic). Previous studies have shown that an increase in GG muscle activity is a consequence of increased activity in inspiratory units. However, there are differences between studies as to whether this increase is primarily due to recruitment of new motor units (motor unit recruitment) or to increased discharge rate of already active units (rate coding). Sleep-wake state studies in humans have suggested the former, while hypercapnia experiments in rats have suggested the latter. In this study, we investigated the effect of hypercapnia on GG motor unit activity in humans during wakefulness. SETTING: sleep research laboratory. PARTICIPANTS: sixteen healthy men. MEASUREMENTS AND RESULTS: each participant was administered at least 6 trials with P(et)CO(2) being elevated 8.4 (SD = 1.96) mm Hg over 2 min following a 30-s baseline. Subjects were instrumented for GG EMG and respiratory measurements with 4 fine wire electrodes inserted subcutaneously into the muscle. One hundred forty-one motor units were identified during the baseline: 47% were inspiratory modulated, 29% expiratory modulated, and 24% showed no respiratory related modulation. Sixty-two new units were recruited during hypercapnia. The distribution of recruited units was significantly different from the baseline distribution, with 84% being inspiratory modulated (P < 0.001). Neither units active during baseline, nor new units recruited during hypercapnia, increased their discharge rate as P(et)CO(2) increased (P > 0.05 for all comparisons). CONCLUSIONS: increased GG muscle activity in humans occurs because of recruitment of previously inactive inspiratory modulated units.

Recruitment and rate-coding strategies of the human genioglossus muscle.

Single motor unit (SMU) analysis provides a means to examine the motor control of a muscle. SMUs in the genioglossus show considerable complexity, with several different firing patterns. Two of the primary stimuli that contribute to genioglossal activation are carbon dioxide (CO(2)) and negative pressure, which act through chemoreceptor and mechanoreceptor activation, respectively. We sought to determine how these stimuli affect the behavior of genioglossus SMUs. We quantified genioglossus SMU discharge activity during periods of quiet breathing, elevated CO(2) (facilitation), and continuous positive airway pressure (CPAP) administration (inhibition). CPAP was applied in 2-cmH(2)O increments until 10 cmH(2)O during hypercapnia. Five hundred ninety-one periods (each ∼ 3 breaths) of genioglossus SMU data were recorded using wire electrodes(n = 96 units) from 15 awake, supine subjects. Overall hypercapnic stimulation increased the discharge rate of genioglossus units (20.9 ± 1.0 vs. 22.7 ± 0.9 Hz). Inspiratory units were activated ∼ 13% earlier in the inspiratory cycle, and the units fired for a longer duration (80.6 ± 5.1 vs. 105.3 ± 4.2% inspiratory time; P < 0.05). Compared with baseline, an additional 32% of distinguishable SMUs within the selective electrode recording area were recruited with hypercapnia. CPAP led to progressive SMU inhibition; at ∼ 6 cmH(2)O, there were similar numbers of SMUs active compared with baseline, with peak frequencies of inspiratory units close to baseline, despite elevated CO(2) levels. At 10 cmH(2)O, the number of units was 36% less than baseline. Genioglossus inspiratory phasic SMUs respond to hypercapnic stimulation with changes in recruitment and rate coding. The SMUs respond to CPAP with derecruitment as a homogeneous population, and inspiratory phasic units show slower discharge rates. Understanding upper airway muscle recruitment/derecruitment may yield therapeutic targets for maintenance of pharyngeal patency.

A secondary reflex suppression phase is present in genioglossus but not tensor palatini in response to negative upper airway pressure.

On the basis of recent reports, the genioglossus (GG) negative-pressure reflex consists initially of excitation followed by a secondary state-dependent suppression phase. The mechanistic origin and functional role of GG suppression is unknown but has been hypothesized to arise from transient inhibition of respiratory active neurons as a protective reflex to prevent aspiration, as observed in other respiratory muscles (e.g., diaphragm) during airway occlusion. Unlike GG, tensor palatini (TP) is a tonic muscle with minimal respiratory phasic activation during relaxed breathing, although both muscles are important in preserving pharyngeal patency. This study aimed to compare GG vs. TP reflex responses to the same negative-pressure stimulus. We hypothesized that reflex suppression would be present in GG, but not TP. Intramuscular GG and TP EMGs were recorded in 12 awake, healthy subjects (6 female). Reflex responses were generated via 250-ms pulses of negative upper airway pressure (approximately -16 cmH2O mask pressure) delivered in early inspiration. GG and TP demonstrated reflex activation in response to negative pressure (peak latency 31+/-4 vs. 31+/-6 ms and peak amplitude 318+/-55 vs. 314+/-26% baseline, respectively). A secondary suppression phase was present in 8 of 12 subjects for GG (nadir latency 54+/-7 ms, nadir amplitude 64+/-6% baseline), but not in any subject for TP. These data provide further support for the presence of excitatory and inhibitory components of GG (phasic muscle) in response to brief upper airway negative-pressure pulses. Conversely, no reflex suppression below baseline was present in TP (tonic muscle) in response to the same stimuli. These differential responses support the hypothesis that GG reflex suppression may be mediated via inhibition of respiratory-related premotor input.