Genioglossus Reflex Research Articles

P033 Assessment of Upper Airway Dilator Muscle Function and Collapsibility in People with Multiple Sclerosis with Versus without Sleep Apnea

Abstract Introduction Upper airway reflex responses to negative pressure are important to prevent upper airway narrowing and closure. Recent evidence indicates ~30% of people with multiple sclerosis (MS) have an impaired upper airway dilator reflex response. Thus, the aims of this study were to compare genioglossus muscle reflex responses and upper airway collapsibility in non-obese people with MS, with and without OSA. Methods Non-obese adults with MS and OSA vs MS without OSA were instrumented with pressure sensors at the choanae and epiglottis. Bipolar fine wires were inserted into the genioglossus. A nasal mask and pneumotachograph were attached to a breathing circuit to deliver brief (~250ms) suction pressure (~-12cmH2O) during early inspiration every 2-10 breaths while awake. Genioglossus reflex onset latency, peak latency and peak amplitude were quantified. The upper airway collapsibility index was the percent difference between choanal and epiglottic airway pressures during negative pressure. Results 15 people with MS (6 males), aged 48±13years, BMI=25±3kg/m-2 and AHI=13±17events/h (mean±SD) were studied. 47% had OSA (AHI>10events/h). Genioglossus reflex excitation onset latency (22±2 vs. 24±19ms), peak excitation latency (37±11 vs. 38±23ms) and peak amplitude (258±125 vs. 205±95%) were not different between OSA vs. non-OSA. The upper airway was more collapsible in people with OSA (49±32 vs. 17±16%, p=0.04). Conclusions There is a high prevalence of OSA among non-obese people with MS. There was no systematic difference in upper airway dilator muscle function. However, the upper airway is ~65% more collapsible in people with MS and OSA despite absence of obesity.

Regional genioglossus reflex responses to negative pressure pulses in people with obstructive sleep apnea.

Tongue and upper airway dilator muscle movement patterns during quiet breathing vary in people with obstructive sleep apnea (OSA). Many patients have inadequate or counterproductive responses to inspiratory negative airway pressure that likely contributes to their OSA. This may be due, at least in part, to inadequate or nonhomogeneous reflex drive to different regions of the largest upper airway dilator, genioglossus. To investigate potential regional heterogeneity of genioglossus reflex responses in OSA, brief suction pulses were applied via a nasal breathing mask and an electromyogram (EMG) was recorded in four regions (anterior oblique, anterior horizontal, posterior oblique, and posterior horizontal) using intramuscular fine wire electrodes in 15 people with OSA. Genioglossus short-latency reflex excitation amplitude had regional heterogeneity (horizontal vs. oblique regions) when expressed in absolute units but homogeneity when normalized as a percentage of the immediate (100 ms) prestimulus EMG. Regional variability in reflex morphology (excitation and inhibition) was present in one-third of the participants. The minimum cross-sectional area (CSA) of the pharyngeal airway was quantified using MRI and may be related to the amplitude of the short-latency reflex response to negative pressure as we found that people with a smaller CSA tended to have a greater reflex amplitude (e.g., horizontal region r2=0.41, P = 0.01). These findings highlight the complexity of genioglossus reflex control, the potential for regional heterogeneity, and the functional importance of upper airway anatomy in mediating genioglossus reflex responses to rapid changes in negative pressure in OSA.NEW & NOTEWORTHY Our findings indicate that 30% of participants had regional heterogeneity in reflex morphology (excitation/inhibition) to brief pulses of negative upper-airway pressure across anterior oblique, anterior horizontal, posterior oblique, and posterior horizontal regions of the genioglossus muscle. Reflex excitation amplitude was proportional to prestimulus drive, with increased activation in oblique compared with horizontal regions of the posterior tongue. People with narrower upper-airway anatomy tended to have increased genioglossus reflex amplitude to negative pressure pulses during wakefulness.

Changes in pharyngeal collapsibility and genioglossus reflex responses to negative pressure during the respiratory cycle in obstructive sleep apnoea.

Impaired pharyngeal anatomy and increased airway collapsibility is a major cause of obstructive sleep apnoea (OSA) and a mediator of its severity. Upper airway reflexes to changes in airway pressure provide important protection against airway closure. This study shows increased pharyngeal collapsibility and attenuated genioglossus reflex responses during expiration in people with OSA. Upper airway collapse contributes to obstructive sleep apnoea (OSA) pathogenesis. Pharyngeal dilator muscle activity varies throughout the respiratory cycle and may contribute to dynamic changes in pharyngeal collapsibility. However, whether upper airway collapsibility and reflex responses to changes in airway pressure vary throughout the respiratory cycle in OSA is unclear. Thus, this study quantified differences in upper airway collapsibility and genioglossus electromyographic (EMG) activity and reflex responses during different phases of the respiratory cycle. Twelve middle-aged people with OSA (2 female) were fitted with standard polysomnography equipment: a nasal mask, pneumotachograph, two fine-wire intramuscular electrodes into the genioglossus, and a pressure catheter positioned at the epiglottis and a second at the choanae (the collapsible portion of the upper airway). At least 20 brief (∼250ms) pressure pulses (∼-11cmH2 O at the mask) were delivered every 2-10 breaths during four conditions: (1) early inspiration, (2) mid-inspiration, (3) early expiration, and (4) mid-expiration. Mean baseline genioglossus EMG activity 100ms prior to pulse delivery and genioglossus reflex responses were quantified for each condition. The upper airway collapsibility index (UACI), quantified as 100×(nadir choanal - epiglottic pressure)/nadir choanal pressure during negative pressure pulses, varied throughout the respiratory cycle (early inspiration=43±25%, mid-inspiration=29±19%, early expiration=83±19% and mid-expiration=95±11% (mean±SD) P<0.01). Genioglossus EMG activity was lower during expiration (e.g. mid-expiration vs. mid-inspiration=76±23vs. 127±41% of early-inspiration, P<0.001). Similarly, genioglossus reflex excitation was delayed (39±11vs. 23±7ms, P<0.001) and reflex excitation amplitude attenuated during mid-expiration versus early inspiration (209±36vs. 286±80%, P=0.009). These findings may provide insight into the physiological mechanisms of pharyngeal collapse in OSA.

Genioglossus reflex responses to brief pulses of negative pharyngeal pressure in people with multiple sclerosis

Genioglossus reflex responses to brief pulses of negative pharyngeal pressure in people with multiple sclerosis

Genioglossus reflex responses to negative upper airway pressure are altered in people with tetraplegia and obstructive sleep apnoea.

Protective reflexes in the throat area (upper airway) are crucial for breathing. Impairment of these reflexes can cause breathing problems during sleep such as obstructive sleep apnoea (OSA). OSA is very common in people with spinal cord injury for unknown reasons. This study shows major changes in protective reflexes that serve to keep the upper airway open in response to suction pressures in people with tetraplegia and OSA. These results help us understand why OSA is so common in people with tetraplegia and provide new insight into how protective upper airway reflexes work more broadly. More than 60% of people with tetraplegia have obstructive sleep apnoea (OSA). However, the specific causes are unknown. Genioglossus, the largest upper-airway dilator muscle, is important in maintaining upper-airway patency. Impaired genioglossus muscle function following spinal cord injury may contribute to OSA. This study aimed to determine if genioglossus reflex responses to negative upper-airway pressure are altered in people with OSA and tetraplegia compared to non-neurologically impaired able-bodied individuals with OSA. Genioglossus reflex responses measured via intramuscular electrodes to ∼60 brief (250ms) pulses of negative upper-airway pressure (∼-15cmH2 O at the mask) were compared between 13 participants (2 females) with tetraplegia plus OSA and 9 able-bodied controls (2 females) matched for age and OSA severity. The initial short-latency excitatory reflex response was absent in 6/13 people with tetraplegia and 1/9 controls. Genioglossus reflex inhibition in the absence of excitation was observed in three people with tetraplegia and none of the controls. When the excitatory response was present, it was significantly delayed in the tetraplegia group compared to able-bodied controls: excitation onset latency (mean±SD) was 32±16vs. 18±9ms, P=0.045; peak excitation latency was 48±17vs. 33±8ms, P=0.038. However, when present, amplitude of the excitation response was not different between groups, 195±26vs. 219±98% at baseline, P=0.55. There are major differences in genioglossus reflex morphology and timing in response to rapid changes in airway pressure in people with tetraplegia and OSA. Altered genioglossus function may contribute to the increased risk of OSA in people with tetraplegia. The precise mechanisms mediating these differences are unknown.

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.

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.

The human genioglossus response to negative airway pressure: stimulus timing and route of delivery

The genioglossus reflex response to sudden onset pulses of negative airway pressure (NAP) in humans is reported to occur more commonly at end rather than onset of expiration when delivered via a mouthpiece. We examined whether this response was modulated by the route of stimulus delivery throughout the respiratory cycle. The genioglossus surface EMG (GGsEMG) response to NAP delivered randomly throughout the respiratory cycle was measured in a set of experiments: (i) 40 stimuli of NAP at -5, -7.5 and -10 cmH2O applied to eight healthy, awake, supine males via nose-mask; and (ii) 60 stimuli of -7.5 cmH2O NAP applied to 15 subjects via both nose-mask and mouthpiece in random order. Despite similar pressure changes being detected in the epiglottis during both routes of stimulus delivery, far lower pressure changes were measured at the nasal choanae during mouthpiece compared with nose-mask delivery. There were no significant differences between the responses during any phase of respiration, nor when NAP was delivered via nose-mask or mouthpiece. We conclude that the sensitivity of the GGsEMG response to NAP in humans does not vary significantly with phase of respiration or route of breathing.

Genioglossus reflex inhibition to upper-airway negative-pressure stimuli during wakefulness and sleep in healthy males.

During wakefulness, obstructive sleep apnoea patients appear to compensate for an anatomically narrow upper airway by increasing upper airway dilator muscle activity, e.g. genioglossus, at least partly via a negative-pressure reflex that may be diminished in sleep. Previous studies have assessed the negative-pressure reflex using multi-unit, rectified, moving-time-average EMG recordings during brief pulses of negative upper-airway pressure. However, moving-time averaging probably obscures the true time-related reflex morphology, potentially masking transient excitatory and inhibitory components. This study aimed to re-examine the genioglossus negative-pressure reflex in detail, without moving-time averaging. Bipolar fine-wire electrodes were inserted per orally into the genioglossus muscle in 17 healthy subjects. Two upper airway pressure catheters were inserted per nasally. Genioglossus EMG reflex responses were generated via negative-pressure stimuli (approximately -10 cmH2O at the choanae, 250 ms duration) delivered during wakefulness and sleep. Ensemble-averaged, rectified, genioglossus EMG recordings demonstrated reflex activation (onset latency 26+/-1 ms; peak amplitude 231+/-29% of baseline) followed by a previously unreported suppression (peak latency 71+/-4 ms; 67+/-8% of baseline). Single-motor-unit activity, clearly identifiable in approximately 10% of trials in six subjects, showed a concomitant increase in the interspike interval from baseline (26+/-9 ms, P=0.01). Genioglossus negative-pressure reflex morphology and amplitude of the initial peak were maintained in non-rapid eye movement (NREM) sleep but suppression amplitude was more pronounced during NREM and declined further during REM sleep compared to wakefulness. These data indicate there are both excitatory and inhibitory components to the genioglossus negative-pressure reflex which are differentially affected by state.

Changes in reflex responses of the genioglossus muscle during sleep in rabbits

Changes in reflex responses in the genioglossus (GG) muscle evoked by electrical stimulation of the inferior alveolar nerve and GG muscle tone (background activity, BGA) were investigated during sleep–wakefulness stages in rabbits. The GG muscle showed two types of electromyographic activity patterns: a respiration-related phasic activity and non-respiration-related activity. GG reflex responses and BGA exhibited a stage-dependent decrease as they were constantly suppressed from quiet wakefulness to non-rapid eye movement sleep to rapid eye movement sleep (REMS). Degree of suppression of reflexes was much larger than that of BGA regardless of GG activity patterns. When amplitude of reflex responses was compared between with and without rapid eye movements during REMS, no difference between the conditions was noted. These results suggest that excitability of the GG muscle is affected by sleep stages by not only a modulation of excitability in motoneurons but also in interneurons involved in the reflex arc.

Mandibular joint control of genioglossus muscle activity in the cat ( Felis domesticus) and monkey ( Macaca irus)

Jaw position had a profound influence on genioglossus (GG) muscle activity, the amount of activity varying with the amount of jaw opening. Mandibular rotations of 21 from tooth contact position increased the GG activity which was maintained as long as the jaw was opened. The response could be abolished by bilateral local anaesthesia of the mandibular joint (MJ). Bipolar stimulation of the small branches of the auriculotemporal nerve which supply the joint elicited a reproducible reflex response in the ipsilateral GG muscle with a latency of approximately 10 ms. The reflex could be abolished by administering a muscle relaxant or by severing or anaesthetizing the branches of the auriculotemporal nerve central to the stimulating electrode. Anaesthetizing or severing the nerves supplying the masseter or temporalis muscles did not abolish the GG reflex response to the nerve stimulus or the response to jaw opening. A prior threshold glossopharyngeal (IX) or superior laryngeal (SL) nerve stimulus produced an early facilitation of the GG reflex elicited by threshold MJ stimulation. In contrast, a supra-threshold lingual, IX or SL nerve stimulus resulted in a long-lasting inhibition of the GG reflex. A number of functional relationships may explain the significance of these excitatory and inhibitory responses in the GG muscle.