Drive versus Pressure Contributions to Genioglossus Activity in Obstructive Sleep Apnea.

Rationale: Loss of pharyngeal dilator muscle activity is a key determinant of respiratory events in obstructive sleep apnea (OSA). After the withdrawal of wakefulness stimuli to the genioglossus at sleep onset, mechanoreceptor negative pressure and chemoreceptor ventilatory drive feedback govern genioglossus activation during sleep, but the relative contributions of drive and pressure stimuli to genioglossus activity across progressive obstructive events remain unclear. We recently showed that drive typically falls during events, whereas negative pressures increase, providing a means to assess their individual contributions to the time course of genioglossus activity. Objectives: For the first time, we critically test whether the loss of drive could explain the loss of genioglossus activity observed within events in OSA. Methods: We examined the time course of genioglossus activity (EMGgg; intramuscular electromyography), ventilatory drive (intraesophageal diaphragm electromyography), and esophageal pressure during spontaneous respiratory events (using the ensemble-average method) in 42 patients with OSA (apnea-hypopnea index 5-91 events/h). Results: Multivariable regression demonstrated that the falling-then-rising time course of EMGgg may be well explained by falling-then-rising drive and rising negative pressure stimuli (model R = 0.91 [0.88-0.98] [95% confidence interval]). Overall, EMGgg was 2.9-fold (0.47-∞) more closely associated with drive than pressure stimuli (ratio of standardized coefficients, ßdrive:ßpressure; ∞ denotes absent pressure contribution). However, individual patient results were heterogeneous: approximately one-half (n = 22 of 42) exhibited drive-dominant responses (i.e., ßdrive:ßpressure > 2:1), and one-quarter (n = 11 of 42) exhibited pressure-dominant EMGgg responses (i.e., ßdrive:ßpressure < 1:2). Patients exhibiting more drive-dominant EMGgg responses experienced greater event-related EMGgg declines (12.9 [4.8-21.0] %baseline/standard deviation of ßdrive:ßpressure; P = 0.004, adjusted analysis). Conclusions: Loss of genioglossus activity precipitating events in patients with OSA is strongly associated with a contemporaneous loss of drive and is greatest in those whose activity tracks drive rather than pressure stimuli. These findings were upheld for events without prior arousal. Responding to falling drive rather than rising negative pressure during events may be deleterious; future therapeutic strategies whose aim is to sustain genioglossus activity by preferentially enhancing responses to rising pressure rather than falling drive are of interest.

Surface electromyographic activity of submental muscles during different types of swallow-specific tasks: A comparative study.

BACKGROUND: Repetitive performance of a motor task has been proposed to increase the ability to perform that motor task. Therefore, exercise training including swallow-specific task may be an optimal training to improve swallowing function. OBJECTIVES: To determine the submental muscles activity during different types of swallow-specific tasks (effortful swallow, ES; tongue-hold swallow, THS; swallow with Kinesio taping, SwKT; and head extension swallowing exercise, HESE) compared to normal swallow (NS), and also compare these tasks within themselves. METHODS: Thirty-five healthy adults participated in this prospective experimental study with one participant group. The surface electromyography (sEMG) was used to evaluate submental muscles activity while performing swallow-specific tasks. RESULTS: While the greatest submental muscles activity was revealed during the ES, HESE, NS and THS tasks, respectively, the lowest was obtained during SwKT. When compared to NS, ES caused a statistically greater submental muscles activity (p1  = .000 and p2  = .000), although SwKT revealed a lower submental muscles activity (p1  = .002 and p2  = .000). When swallow-specific tasks were compared within themselves, ES caused the highest muscles activity (p < .005) than all other tasks, and HESE caused higher muscles activity than THS and SwKT (p < .005). CONCLUSION: Different swallow-specific tasks can cause increased or decreased submental muscles activity compared to NS task. Since ES and HESE are superior in selective submental muscles, they appear to be more promising in terms of submental muscles gains in long-term exercise training.

Evaluation of morphological features of palatopharyngeus insertion into the thyroid cartilage.

The attachment of the palatopharyngeus extended from the posterior end of the thyroid cartilage to the posterior margin of the inferior constrictor attachment that might contribute to successive swallowing movements. Laryngeal elevation is essential for proper swallowing and breathing. Recently, clinical research has demonstrated that the palatopharyngeus, a longitudinal muscle of the pharynx, is involved in the elevation of the larynx. However, the morphological relationship between the larynx and palatopharyngeus remains unclear. In the present study, we analyzed the attachment site and characteristics of the palatopharyngeus in the thyroid cartilage. We evaluated 14 halves of seven heads from Japanese cadavers (average age: 76.4 years); 12 halves, anatomically and two halves histologically. A part of the palatopharyngeus, which originated from the inferior aspect of the palatine aponeurosis, was attached to the inner and outer surfaces of the thyroid cartilage through collagen fibers. The attachment area extends from the posterior end of the thyroid cartilage to the posterior margin of the attachment site of the inferior constrictor. The palatopharyngeus may elevate the larynx with the suprahyoid muscles and contribute to successive movements of swallowing with surrounding muscles. Based on our findings and previous studies, palatopharyngeus with various muscle bundle directions may be essential for the coordination of continuous swallowing events.

Growth in fetuses of the constrictor pharyngis superior with special reference to its meeting with the buccinator: an embryological basis of adult variations in palatopharyngeal anatomy.

PURPOSE: The constrictor pharyngis superior (CPS) initially develops along the posterior wall of the pharyngeal mucosal tube, whereas, during the early phase, the buccinators (BC) are far anterolateral to the CPS. The process and timing of their meeting during fetal growth have not been determined. METHODS: The topographical relationship between the growing BC and CPS was assessed in histological sections from 22 early- and mid-term fetuses of approximate gestational age (GA) 8-16 weeks, and eight late-term fetuses of approximate GA 31-39 weeks. RESULTS: At 8-9 weeks, the palatopharyngeus appeared to pull the CPS up and forward. Until 11 weeks, the CPS was attached to the hamulus of the pterygoid (pterygopharyngeal part). Until 13 weeks, the CPS extended anterolaterally beyond the hamulus to meet the BC. Some BC muscle fibers originated from the oral mucosa. Notably, by 30 weeks, the CPS-BC interface had become covered by or attached to the palatopharyngeus. Muscle fibers of the palatopharyngeus, however, were thinner than those of the CPS and BC. At and near the interface, BC muscle fibers tended to run along the left-right axis, whereas those of the CPS ran anteroposteriorly. A definite fascia (i.e., a future pterygomandibular raphe) was usually absent between these muscles in fetuses. CONCLUSIONS: The excess anterior growth of the CPS with its subsequent degeneration might cause individual anatomical variations in composite muscle bundles of the palatopharyngeus-CPS complex or palatopharyngeal sphincter. A tensile transduction from the BC to the CPS through the raphe seemed unnecessary for cooperative suckling and swallowing after birth.

Impaired pharyngeal reflex responses to negative pressure: a novel cause of sleep apnea in multiple sclerosis.

Obstructive sleep apnea (OSA) is common in people with multiple sclerosis (MS). However, people with MS often do not have "typical" anatomical risk factors (i.e., nonobese and female predominance). Accordingly, nonanatomical factors such as impaired upper-airway muscle function may be particularly important for OSA pathogenesis in MS. Therefore, this study aimed to investigate genioglossus (largest upper-airway dilator muscle) reflex responses to brief pulses of upper-airway negative pressure in people with OSA and MS. Eleven people with MS and OSA and 10 OSA controls without MS matched for age, sex, and OSA severity were fitted with a nasal mask, pneumotachograph, choanal and epiglottic pressure sensors, and intramuscular electrodes into genioglossus. Approximately 60 brief (250 ms) negative pressure pulses (approximately -12 cmH2O mask pressure) were delivered every 2-6 breaths at random during quiet nasal breathing during wakefulness to determine genioglossus electromyogram (EMGgg) reflex responses (timing, amplitude, and morphology). Where available, recent clinical MRI brain scans were evaluated for the number, size, and location of brainstem lesions in the group with MS. When present, genioglossus reflex excitation responses were similar between MS participants and controls (e.g., peak excitation amplitude = 229 ± 85% vs. 282 ± 98% baseline, P = 0.17). However, ∼30% of people with MS had either an abnormal (predominantly inhibition) or no protective excitation reflex. Participants with MS without a reflex had multiple brainstem lesions including in the hypoglossal motor nucleus which may impair sensory processing and/or efferent output. Impaired pharyngeal reflex function may be an important contributor to OSA pathogenesis for a proportion of people with MS.NEW & NOTEWORTHY This study investigated the function of an important reflex that helps protect the upper airway from closing during negative (suction) pressure in people with and without multiple sclerosis (MS) and obstructive sleep apnea (OSA). We found that ∼30% of people with MS had either no protective reflex or an abnormal reflex response. These findings indicate that impaired upper-airway reflex function may be an important contributor to OSA for a substantial proportion of people with MS.

Three-Dimensional Anatomy of the Palatopharyngeus and Its Relation to the Levator Veli Palatini Based on Micro-Computed Tomography.

BACKGROUND: Although multiple studies have been reported on the palatopharyngeus and levator veli palatini, their subtle anatomy and functions remain unclear. The authors elucidated the relationship between these muscles and their functional implications based on three-dimensional digital techniques. METHODS: Cadaveric specimens were stained with iodine-potassium iodide and scanned using micro-computed tomography. The muscle fibers were drawn on the exported Imaging and Communications in Medicine images to reconstruct a three-dimensional model and further simplified. RESULTS: In the soft palate, the palatopharyngeus was divided into three bundles. The largest inferior head was found to attach to the palatine aponeurosis, soft palate, and the hard palate on the oral side, which occupied approximately the anterior 28.4 to 36.2 percent of the soft palate in the midline. The superior head was thin and attached to the palatine aponeurosis and the surrounding mucosa on the nasal side. The posterior head was located posterior to the levator veli palatini with fibers attaching to the levator veli palatini and the median portion of the uvula. The levator veli palatini was clasped by the three heads of the palatopharyngeus. The fasciculi of the palatopharyngeus converged into a bundle of muscles at the pharynx and inserted into the lateral and posterior pharyngeal wall. CONCLUSIONS: The palatopharyngeus is the largest muscle that connects the soft palate and pharyngeal wall; it closely coordinates with the levator veli palatini to control levator veli palatini overlifting, narrow the velopharyngeal port with the help of the superior constrictor, and elevate the pharynx. The palatopharyngeus and levator veli palatini help each other in velopharyngeal closure through coordination from other muscles.

The combination of intermittent electrical stimulation with acute intermittent hypoxia strengthens genioglossus muscle discharge in chronic intermittent hypoxia-pretreated rats.

OBJECTIVE: Exploring whether the genioglossus discharge in chronic intermittent hypoxia(CIH) - pretreated rats could be enhanced by intermittent electrical stimulation combined with acute intermittent hypoxia(AIH). METHODS: Rats were pretreated with CIH for 4 weeks and then were randomly divided into 6 groups: time control, intermittent electric stimulation, AIH, intermittent electric stimulation + AIH, continuous electric stimulation and continuous hypoxia exposure. The genioglossus discharges were recorded and compared before and after stimulation. Normoxic-treated rats were grouped and treated with the same stimulation protocols. RESULTS: Intermittent electrical stimulation or AIH temporarily increased the activity of the genioglossus discharge, in which the degree of the increase was significantly higher in CIH-pretreated rats than in normoxic rats.After intermittent electrical stimulation, AIH evoked a sustained elevation of genioglossus discharge activities in CIH-pretreated rats, in which the degree of the increase was significantly higher than in rats induced by a single intermittent electric stimulation. CONCLUSION: Intermittent electrical stimulation combined with AIH strengthens the genioglossus plasticity in CIH-pretreated rats.

Electromyographic activation patterns during swallowing in older adults.

Age-related weakness due to atrophy and fatty infiltration in oropharyngeal muscles may be related to dysphagia in older adults. However, little is known about changes in the oropharyngeal muscle activation pattern in older adults. This was a prospective and experimental study. Forty healthy participants (20 older [> 60 years] and 20 young [< 60 years] adults) were enrolled. Six channel surface electrodes were placed over the bilateral suprahyoid (SH), bilateral retrohyoid (RH), thyrohyoid (TH), and sternothyroid (StH) muscles. Electromyography signals were then recorded twice for each patient during swallowing of 2 cc of water, 5 cc of water, and 5 cc of a highly viscous fluid. Latency, duration, and peak amplitude were measured. The activation patterns were the same, in the order of SH, TH, and StH, in both groups. The muscle activation patterns were classified as type I and II; the type I pattern was characterized by a monophasic shape, and the type II comprised a pre-reflex phase and a main phase. The oropharyngeal muscles and SH muscles were found to develop a pre-reflex phase specifically with increasing volume and viscosity of the swallowed fluid. Type I showed a different response to the highly viscous fluid in the older group compared to that in the younger group. However, type II showed concordant changes in the groups. Therefore, healthy older people were found to compensate for swallowing with a pre-reflex phase of muscle activation in response to increased liquid volume and viscosity, to adjust for age-related muscle weakness.

Pharyngeal and upper esophageal sphincter motor dynamics during swallow in children.

BACKGROUND: Motor abnormalities of pharyngeal contraction or upper esophageal sphincter (UES) relaxation can lead to swallowing problems. METHODS: We reviewed high-resolution esophageal manometry of children ≤18 years and classified into two groups based on the results of videofluoroscopic study of swallow (VFSS), as normal or abnormal. The UES metrics (integrated relaxation pressure [IRP], resting pressure [URP], and nadir pressure [UNP]), as well as peak pharyngeal pressure (velopharyngeal and meso-hypopharyngeal), were analyzed. RESULTS: UES metrics: There were 142 and 19 subjects in the normal and abnormal groups, respectively. In the normal group, the median UES-IRP at 0.2, 0.4, 0.6, 0.8 seconds, URP, and UNP were 1.0, 4.0, 11.0, 18.0, 53.5, and -1.0 mm Hg while in the abnormal group were 10.0, 13.0, 21.0, 25.5, 47.0, and 8.0 mm Hg. The UES-IRP at 0.2, 0.4, 0.6 seconds, and UNP was significantly higher in the abnormal group. Pharyngeal metrics: We included 58 subjects in normal and 10 subjects in the abnormal group. The median of peak velopharyngeal and meso-hypopharyngeal pressures were lower in the abnormal group; 188.50 vs 210.50, P = .185 and 110.00 vs 144.75 mm Hg, P = .065. CONCLUSIONS AND INFERENCES: The UES-IRP was lower than adults, URP was higher than preterm but less than adults, and UNP was lower than neonates but similar to adults. The pharyngeal pressures were higher than those reported for neonates and adults. Our data indicate that motor dynamics of swallowing may change from neonates to adulthood and reflect a maturational process. The subjects with abnormal VFSS had significantly higher UES-IRP and UNP compared to normal VFSS.

Nerve fiber analysis of the lingual branch of the glossopharyngeal nerve in human adult subjects.

PURPOSE: Fibers of the glossopharyngeal part of the superior constrictor muscle are connected with fibers of the transverse lingual muscle, forming a ring of muscle at the base of the tongue. This group of muscles constrict the midpharyngeal cavity during retrusive movement of the tongue. The purpose of this study is to identify the contribution of the lingual branch of the glossopharyngeal nerve to the neuro-motor control of three muscles: the glossopharyngeal part of the superior pharyngeal constrictor muscle, the palatopharyngeal and the palatoglossus muscles. METHODS: Six en bloc samples (9 sides), including the tissue from the skull base to the hyoid bone were obtained from adult human cadavers. Nerve fiber of the lingual branch of the glossopharyngeal nerve (main root of the glossopharyngeal nerve) was examined by the use of a binocular stereomicroscope. RESULTS: We observed that, after branching to the stylopharyngeal muscle, the lingual branch of the glossopharyngeal nerve branched to the glossopharyngeal part of the superior pharyngeal constrictor muscle, the palatopharyngeal and the palatoglossus muscles before inserting into the space between the muscle layers of the superior and middle pharyngeal constrictors. CONCLUSION: These neuromuscular arrangements may suggest the presence of specialized constrictive movements of the midpharygeal cavity at the level of the base of the tongue with the retrusive movement of the tongue. The simultaneous contraction of the palatopharyngeal and palatoglossus muscles on the pharyngeal stage of deglutition may aid in the passage of bolus from the oral cavity to the midpharyngeal cavity by increasing pharyngeal pressure.

Evaluation of Swallowing Related Muscle Activity by Means of Concentric Ring Electrodes.

Surface electromyography (sEMG) can be helpful for evaluating swallowing related muscle activity. Conventional recordings with disc electrodes suffer from significant crosstalk from adjacent muscles and electrode-to-muscle fiber orientation problems, while concentric ring electrodes (CREs) offer enhanced spatial selectivity and axial isotropy. The aim of this work was to evaluate CRE performance in sEMG recordings of the swallowing muscles. Bipolar recordings were taken from 21 healthy young volunteers when swallowing saliva, water and yogurt, first with a conventional disc and then with a CRE. The signals were characterized by the root-mean-square amplitude, signal-to-noise ratio, myopulse, zero-crossings, median frequency, bandwidth and bilateral muscle cross-correlations. The results showed that CREs have advantages in the sEMG analysis of swallowing muscles, including enhanced spatial selectivity and the associated reduction in crosstalk, the ability to pick up a wider range of EMG frequency components and easier electrode placement thanks to its radial symmetry. However, technical changes are recommended in the future to ensure that the lower CRE signal amplitude does not significantly affect its quality. CREs show great potential for improving the clinical monitoring and evaluation of swallowing muscle activity. Future work on pathological subjects will assess the possible advantages of CREs in dysphagia monitoring and diagnosis.

The key role of the mandible in modulating airflow amplitude during sleep.

RATIONALE: Mandibular position and motion during sleep rely on the balance between mandibular elevators and depressors. We hypothesized that vertical mandibular position (VMP) modulates airflow amplitude during sleep. METHODS: VMP, tidal nasal flow pressure (NFP) and concurrent surface electromyographic activity of the masseters (sEMG-m) were recorded and processed by a customized algorithm from 100 polysomnographic fragments including a micro-arousal (25 obstructive sleep apnea patients). The relationship between mandibular position and changes in airflow was analysed. RESULT: Concurrent VMP and sEMG-m activity changes routinely occurred before a new steady state of airflow documented by NFP. Vertical mandible depression was associated with a median (95% CI) reduction in NFP of 40.9% (14.6%-71.3%, p = 0.007) while vertical mandible elevation and mouth closure were associated with a median (95% CI) relative increase in NFP after arousal of 52.6% (17.9%-56.2%, p = 0.001). CONCLUSION: Elevation and lowering of the mandible were associated with changes in masseteric EMG activity modulating airflow amplitude during sleep.

A Novel Method Using Kinesiology Taping for the Activation of Suprahyoid Muscles in Healthy Adults: A Preliminary Research.

The suprahyoid muscles play a major role in safe swallowing in the pharyngeal phase. Therefore, it is clinically important to design a therapeutic approach for strengthening the suprahyoid muscles for safe and normal swallowing. This study aimed to investigate the activation of suprahyoid muscles by resistance training using kinesiology taping (KT). We enrolled 23 healthy adults. All participants performed saliva swallowing five times at 5 s intervals in three conditions (without KT, 50% stretch with KT, and 80% stretch with KT). KT in the I and reverse V shapes was pulled vertically from the hyolaryngeal complex to the sternum and medially from the superior surface of the clavicle, respectively. Another KT horizontally covered the hyolaryngeal complex to enhance the movement restriction of the hyolaryngeal complex during swallowing. Activation of the suprahyoid muscles during swallowing in the two conditions was measured using surface electromyography. In addition, a 0-10 numerical rating self-report scale was used to evaluate the required effort and the resistance felt during swallowing. Both KT 50% and 80% were significantly higher in surface electromyography (sEMG) mean value, peak value, required effort, and resistance felt during swallowing compared to normal swallowing (p < 0.05). In addition, KT 80% was significantly higher in sEMG value, peak value, required effort, and resistance felt during swallowing than KT 50% (p < 0.05). This study demonstrated that KT applied to the area under the hyolaryngeal complex improves activation of the suprahyoid muscle during swallowing. Therefore, KT applied as resistance during swallowing is considered to have therapeutic potential in dysphagia rehabilitation.

Sole-ground contact and sitting leg position influence suprahyoid and sternocleidomastoid muscle activity during swallowing of liquids.

Clinically, the stable sole-ground contact in the diet is considered as important for achieving safe swallows in the dysphagic patients. However, the effects of varied sole-ground contacts on swallow-related muscles activities remain unclear. The aim of this study was to investigate the effects of sole-ground contacts on the muscle activities during swallow for various materials; 26 healthy adult subjects participated in this study. Three different sole-ground contact conditions were investigated; sole-ground contact with knees bent to 90° (KB 90°), sole-ground contact with knees bent to 135° (KB 135°), and sole-ground off the floor (Off). Participants swallowed four bolus materials (saliva, 5-ml water, 10-ml water, and 5-ml yogurt) in each sole-ground contact condition. The muscular activities of the suprahyoid (SH) muscle and the sternocleidomastoid muscle during swallowing were detected and recorded using surface electromyography. The sole-ground contact pressure was evaluated using the data acquisition system. Duration of SH during 10-ml water swallow for Off was significantly longer than that for KB 90°. Duration of SH during 5-ml yogurt swallow for Off was significantly longer than that for KB 90°. Integration of SH during 10-ml water swallow for Off was significantly greater than that for KB 135°. Integration of SH during 5-ml yogurt swallow for Off was significantly greater than that for KB 90°. No significant differences were found in peak of SH. Sole-ground contact conditions had significant effect on swallow-related muscles activities. The stable sitting positions might be more advantageous for performing effective swallows compared with less stable sitting positions.

Effects of oral neuromuscular training on swallowing dysfunction among older people in intermediate care-a cluster randomised, controlled trial.

OBJECTIVES: this prospective, cluster randomised, controlled trial investigated the effect of oral neuromuscular training among older people in intermediate care with impaired swallowing. METHODS: older people (≥65 years) with swallowing dysfunction were cluster randomised according to care units for 5 weeks of neuromuscular training of the orofacial and pharyngeal muscles or usual care. The primary endpoint was the change in swallowing rate (assessed with a timed water swallow test) from baseline to the end-of-treatment and 6 months post-treatment. The secondary endpoints were changes in signs of aspiration during the water swallow test, and swallowing-related quality of life (QOL). An intention-to-treat principle was followed, and mixed-effects models were used for data analysis with the clustered study design as a random factor. RESULTS: in total, 385 participants from 36 intermediate care units were screened, and 116 participants were randomly assigned to oral neuromuscular training (intervention; n = 49) or usual care (controls; n = 67). At the end of treatment, the geometric mean of the swallowing rate in the intervention group had significantly improved 60% more than that of controls (P = 0.007). At 6 months post-treatment, the swallowing rate of the intervention group remained significantly better (P = 0.031). Signs of aspiration also significantly reduced in the intervention group compared with controls (P = 0.01). No significant between-group differences were found for swallowing-related QOL. CONCLUSIONS: oral neuromuscular training is a new promising swallowing rehabilitation method among older people in intermediate care with impaired swallowing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02825927.

Genioglossal response to mechanical vibrations of the mandible and the submandibular muscles.

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to dilate the airways as needed during breathing. The genioglossus (GG) activity is known to be modulated by several reflexes evoked via the mechanoreceptors of the upper airways. The primary objective of this paper was to investigate the effectiveness of activating these reflex pathways using mechanical stimulation of the mandible or the submandibular muscles. In eight healthy subjects, 3-s long, 5-mm vertical mechanical vibrations were delivered at 8 and 12 Hz to the lower jaw in a seated position, while the GG EMG was recorded using a custom-made sublingual electrode, along with the activity of the masseter (MS) and mylohyoid (MH). All three muscle activities were significantly higher during stimulation compared with the baseline (P < 0.02), and the increase was larger at 12 Hz versus 8 Hz (P < 0.02). All three muscle responses had components that synchronized with the mechanical stimuli, but those of MS were much more strongly phase-locked to the vibrational cycle. In 10 healthy subjects, we also applied mechanical vibrations to the submandibular muscles at three different stimulation intensities, while subjects were lying in a supine position. The GG activity increased significantly above the baseline (P = 0.026) in 9 out of 10 subjects, and the elevated activity persisted after termination of the stimulus for a few seconds. The results demonstrate that GG muscle responses can be evoked with mechanical vibrations applied to the lower jaw or the submandibular muscles in healthy subjects during wakefulness. NEW & NOTEWORTHY The evoked responses observed in the genioglossus (GG) activity during mechanical vibrations of the lower jaw or the submandibular muscles may lead to therapeutic applications for improving the patency of airways during sleep. The presence of these GG reflexes may also explain a mechanism by which the vibrations produced during snoring can help the airways stay open in individuals who may otherwise have obstructed airways in sleep.

Dose-dependent effects of mandibular advancement on upper airway collapsibility and muscle function in obstructive sleep apnea.

STUDY OBJECTIVES: Mandibular advancement splints (MAS) are the leading treatment alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). However, not all patients experience clinical benefit and treatment prediction remains challenging. Understanding the effects of mandibular advancement on pharyngeal collapsibility and muscle function may provide valuable information on the mechanisms of MAS, and thereby help to develop novel approaches for patient selection. Thus, we aimed to determine dose-dependent effects of mandibular advancement on pharyngeal collapsibility and muscle function concurrently in OSA patients undergoing MAS therapy. METHODS: Twelve (11 male) MAS-naïve patients underwent a detailed physiology sleep study (polysomnography) to quantify pharyngeal collapsibility (PCRIT), pharyngeal muscle responsiveness to negative pharyngeal pressure (via genioglossus intramuscular electromyography and an epiglottic pressure sensor) and effectiveness to restore airflow and minute ventilation (Vi) after 1-minute transient CPAP reductions (induced airflow-limitation) at three mandibular advancement positions: 0% (habitual bite), 50% and 100% of the maximum comfortable mandibular advancement. Standard clinical polysomnography after MAS therapy optimization was performed to determine treatment outcome. RESULTS: Overall, participants were obese with severe OSA (mean ± SD: BMI = 31 ± 4 kg/m2, apnea-hypopnea index [AHI] = 33 ± 14 events/hour). PCRIT decreased with mandibular advancement in a dose-dependent manner (1.8 ± 3.9 vs. -0.9 ± 2.9 vs. -4.0 ± 3.6 cmH2O; p < 0.001). There was no systematic change in genioglossus muscle responsiveness (p = 0.09) or effectiveness to restore peak airflow (p = 0.4) or Vi (p = 0.7) with mandibular advancement. CONCLUSIONS: Mandibular advancement reduces pharyngeal collapsibility in a dose-dependent manner without systematically changing genioglossus muscle function in a predominantly obese and severe OSA population. This indicates that the primary mode of action of MAS therapy is via improvement in passive pharyngeal anatomy.

The effects of Le Fort I osteotomy on velopharyngeal function in cleft patients.

INTRODUCTION: Maxillary advancement may affect speech in cleft patients. The aim of this study was to evaluate whether preoperative velopharyngeal (VP) function and cleft type can predict VP function after a Le Fort I maxillary osteotomy. MATERIALS AND METHODS: One hundred consecutive nonsyndromic cleft patients (54 females, 64 males) who underwent Le Fort I osteotomies were retrospectively evaluated. Pre- and postoperative VP function was assessed perceptually and instrumentally by a Nasometer. A five-point scale was used to rate velopharyngeal insufficiency symptoms (VPI 0-4). To assess reliability, 30 video recordings were re-evaluated. RESULTS: Preoperatively, 89% of patients had normal or insignificant VPI (0-1), and only 3% had moderate VPI (3). Postoperatively, 77% of patients had VPI values of 0-1 and 14% had moderate to severe VPI values (VPI 3-4). A positive correlation was found between pre- and postoperative VPI scores, whereas the cleft type did not affect speech results. Patients with a preoperatively normal VPI (0) were not at risk for postoperative velopharyngeal incompetence. CONCLUSIONS: There was an overall significant negative change in speech after a Le Fort I osteotomy. At-risk patients presented with borderline (1) or more severe VPI (2 and 3) preoperatively.

Reboxetine and hyoscine butylbromide improve upper airway function during nonrapid eye movement and suppress rapid eye movement sleep in healthy individuals.

STUDY OBJECTIVES: Recent findings indicate that noradrenergic and antimuscarinic processes are crucial for sleep-related reductions in pharyngeal muscle activity. However, there are few human studies. Accordingly, this study aimed to determine if a combined noradrenergic and antimuscarinic intervention increases pharyngeal dilator muscle activity and improves airway function in sleeping humans. METHODS: Genioglossus (GG) and tensor palatini electromyography (EMG), pharyngeal pressure, upper airway resistance, and breathing parameters were acquired in 10 healthy adults (5 female) during two overnight sleep studies after 4 mg of reboxetine (REB) plus 20 mg of hyoscine butylbromide (HBB) or placebo using a double-blind, placebo-controlled, randomized, cross-over design. RESULTS: Compared with placebo, peak and tonic GG EMG were lower (Mean ± SD: 83 ± 73 vs. 130 ± 75, p = 0.021 and 102 ± 102 vs. 147 ± 123 % wakefulness, p = 0.021, respectively) but the sleep-related reduction in tensor palatini was less (Median [25th, 75th centiles]: 53[45, 62] vs. 34[28, 38] % wakefulness, p = 0.008) with the drug combination during nonrapid eye movement (non-REM) sleep. These changes were accompanied by improved upper airway function including reduced pharyngeal pressure swings, airway resistance, respiratory load compensation, and increased breathing frequency during N2. REB and HBB significantly reduced rapid eye movement sleep compared with placebo (0.6 ± 1.1 vs. 14.5 ± 6.8 % total sleep time, p < 0.001). CONCLUSIONS: Contrary to our hypothesis, GG muscle activity (% wakefulness) during non-REM sleep was lower with REB and HBB. However, sleep-related reductions in tensor palatini activity were less and upper airway function improved. These findings provide mechanistic insight into the role of noradrenergic and antimuscarinic processes on upper airway function in humans and have therapeutic potential for obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au, trial ID: ACTRN12616000469415.