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Frédéric Sériès - One of the best experts on this subject based on the ideXlab platform.
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Diaphragm and Genioglossus corticomotor excitability in patients with obstructive sleep apnea and control subjects.
Journal of sleep research, 2015Co-Authors: Jean-christian Borel, Eric Rousseau, Simon Gakwaya, César Augusto Melo-silva, Frédéric SérièsAbstract:Corticomotor excitability of peripheral muscles appears to be altered in patients with obstructive sleep apnea. However, there is no evidence of such alteration for upper airway/respiratory muscles that are involved in the pathophysiology of this disease. The aim of this study was to compare the effects of hypercapnic stimulation on diaphragm and Genioglossus corticomotor excitability in awake healthy subjects versus patients with obstructive sleep apnea. Corticomotor excitability was assessed by transcranial magnetic stimulation in 12 untreated apneic men (48 ± 10 years; body mass index = 28.9 ± 4.7 kg m(-2); apnea-hypopnoea index = 41 ± 23 events per hour) and nine control men (45 ± 10 years; body mass index = 27.3 ± 3.3 kg m(-2); apnea-hypopnoea index = 7 ± 4 events per hour). Assessments included diaphragm and Genioglossus expiratory motor thresholds, and transcranial magnetic stimulation-induced motor-evoked potential characteristics obtained while breathing room air or 5% CO2 (random order) and then 7% CO2 both balanced with pure O2. Transcranial magnetic stimulation twitches were applied during early inspiration and end expiration. Diaphragm motor-evoked potential amplitudes increased and expiratory diaphragm motor-evoked potential latencies decreased during CO2-induced increase in ventilatory drive, with no difference in these responses between patients with obstructive sleep apnea and control subjects. Expiratory Genioglossus motor-evoked potential amplitudes were significantly lower in patients with obstructive sleep apnea than in control subjects. Baseline activity of the Genioglossus increased with increasing FiCO2, this effect being significantly higher in patients with obstructive sleep apnea than in control subjects. However, neither Genioglossus motor-evoked potential amplitudes nor latencies were significantly modified with increasing FiCO2 both in patients with obstructive sleep apnea and in control subjects. Corticomotor excitability of Genioglossus and diaphragm are not altered during CO2-induced increase in ventilatory drive in patients with obstructive sleep apnea.
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Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects.
Experimental physiology, 2015Co-Authors: Eric Rousseau, Simon Gakwaya, César Augusto Melo-silva, Frédéric SérièsAbstract:New Findings What is the central question of this study? Can repetitive transcranial magnetic stimulation (rTMS) of the Genioglossus enhance the beneficial effects observed with transcranial magnetic stimulation single twitches on upper airway mechanical properties? What is the main finding and its importance? We found that both inspiratory and expiratory rTMS protocols induce a different activation pattern of upper airway muscles, with evidence for an increase in Genioglossus corticomotor excitability in response to rTMS. This is of major importance because it might open the door for rTMS protocols with the goal of increasing corticomotor excitability and, thus, possibly increasing the tonic Genioglossus activity, which is known to be diminished during sleep in subjects with sleep apnoea. Abstract Stimulation of upper airway (UA) muscles during sleep by isolated transcranial magnetic stimulation (TMS) twitch can improve airflow dynamics without arousal, but the effect of repetitive TMS (rTMS) on UA dynamics is unknown. Phrenic nerve magnetic stimulation (PNMS) can be used to produce painless experimental twitch-induced flow limitation during wakefulness. The aim of this study was to quantify the effects of rTMS applied during wakefulness on UA mechanical properties using PNMS in subjects with obstructive sleep apnoea (OSA). Phrenic nerve magnetic stimulation was applied to 10 subjects, with and without simultaneous rTMS, during inspiration and expiration. Flow-limitation characteristics and UA obstruction level were determined [maximal (VI,max)and minimal inspiratory airflow (VI,min),VI,max−VI,min flow drop (ΔVI),oropharyngeal (POro,peak) and velopharyngeal peak pressures, oropharyngeal k1/k2 ratios with k1 and k2 determined by the polynomial regression model between instantaneous flow and pharyngeal pressure and UA resistance]. Both Genioglossus and diaphragm root mean squares and motor-evoked potential amplitudes (geniolossus, GGAmp) and latencies were computed. A flow-limitation pattern always occurred after PNMS. A decrease in VI,max and an increase in ΔVI occurred following rTMS applied during inspiration, and POro,peak values were more negative with both inspiratory and expiratory rTMS. The GGAmp also increased significantly from the second to the last rTMS expiratory train twitch. All other parameters remained unchanged. These results suggest the following conclusions: (i) rTMS does not improve UA mechanical properties in awake subjects with OSA; (ii) the activation pattern of UA muscles differs following isolated twitch and repetitive cortical stimulation of the Genioglossus; and (iii) rTMS applied during expiration induces corticomotor facilitation.
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Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects.
Experimental physiology, 2015Co-Authors: Eric Rousseau, Simon Gakwaya, César Augusto Melo-silva, Frédéric SérièsAbstract:What is the central question of this study? Can repetitive transcranial magnetic stimulation (rTMS) of the Genioglossus enhance the beneficial effects observed with transcranial magnetic stimulation single twitches on upper airway mechanical properties? What is the main finding and its importance? We found that both inspiratory and expiratory rTMS protocols induce a different activation pattern of upper airway muscles, with evidence for an increase in Genioglossus corticomotor excitability in response to rTMS. This is of major importance because it might open the door for rTMS protocols with the goal of increasing corticomotor excitability and, thus, possibly increasing the tonic Genioglossus activity, which is known to be diminished during sleep in subjects with sleep apnoea. Stimulation of upper airway (UA) muscles during sleep by isolated transcranial magnetic stimulation (TMS) twitch can improve airflow dynamics without arousal, but the effect of repetitive TMS (rTMS) on UA dynamics is unknown. Phrenic nerve magnetic stimulation (PNMS) can be used to produce painless experimental twitch-induced flow limitation during wakefulness. The aim of this study was to quantify the effects of rTMS applied during wakefulness on UA mechanical properties using PNMS in subjects with obstructive sleep apnoea (OSA). Phrenic nerve magnetic stimulation was applied to 10 subjects, with and without simultaneous rTMS, during inspiration and expiration. Flow-limitation characteristics and UA obstruction level were determined [maximal (V̇I,max)and minimal inspiratory airflow (V̇I,min),V̇I,max-V̇I,min flow drop (ΔV̇I),oropharyngeal (POro,peak ) and velopharyngeal peak pressures, oropharyngeal k1 /k2 ratios with k1 and k2 determined by the polynomial regression model between instantaneous flow and pharyngeal pressure and UA resistance]. Both Genioglossus and diaphragm root mean squares and motor-evoked potential amplitudes (geniolossus, GGAmp ) and latencies were computed. A flow-limitation pattern always occurred after PNMS. A decrease in V̇I,max and an increase in ΔV̇I occurred following rTMS applied during inspiration, and POro,peak values were more negative with both inspiratory and expiratory rTMS. The GGAmp also increased significantly from the second to the last rTMS expiratory train twitch. All other parameters remained unchanged. These results suggest the following conclusions: (i) rTMS does not improve UA mechanical properties in awake subjects with OSA; (ii) the activation pattern of UA muscles differs following isolated twitch and repetitive cortical stimulation of the Genioglossus; and (iii) rTMS applied during expiration induces corticomotor facilitation. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.
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Corticomotor control of the Genioglossus in awake OSAS patients: a transcranial magnetic stimulation study
Respiratory research, 2009Co-Authors: Frédéric Sériès, Wei Wang, Thomas SimilowskiAbstract:Upper airway collapse does not occur during wake in obstructive sleep apnea patients. This points to wake-related compensatory mechanisms, and possibly to a modified corticomotor control of upper airway dilator muscles. The objectives of the study were to characterize the responsiveness of the Genioglossus to transcranial magnetic stimulation during respiratory and non-respiratory facilitatory maneuvers in obstructive sleep apnea patients, and to compare it to the responsiveness of the diaphragm, with reference to normal controls. Motor evoked potentials of the Genioglossus and of the diaphragm, with the corresponding motor thresholds, were recorded in response to transcranial magnetic stimulation applied during expiration, inspiration and during maximal tongue protraction in 13 sleep apnea patients and 8 normal controls. In the sleep apnea patients: 1) combined Genioglossus and diaphragm responses occurred more frequently than in controls (P < 0.0001); 2) the amplitude of the Genioglossus response increased during inspiratory maneuvers (not observed in controls); 3) the latency of the Genioglossus response decreased during tongue protraction (not observed in controls). A significant negative correlation was found between the latency of the Genioglossus response and the apnea-hypopnea index; 4) the difference in diaphragm and Genioglossus cortico-motor responses during tongue protraction and inspiratory loading differed between sleep apnea and controls. Sleep apnea patients and control subjects differ in the response pattern of the Genioglossus and of the diaphragm to facilitatory maneuvers, some of the differences being related to the frequency of sleep-related events.
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Interaction between Genioglossus and diaphragm responses to transcranial magnetic stimulation in awake humans
Experimental physiology, 2007Co-Authors: Wei Wang, Thomas Similowski, Frédéric SérièsAbstract:The modulation of activity of the upper airway dilator and respiratory muscles plays a key role in the regulation of ventilation, but little is known about the link between their neuromuscular activation processes in vivo. This study investigated Genioglossus and diaphragm responses to transcranial magnetic stimulation applied in different facilitatory conditions. The amplitude and latency of motor-evoked potential responses and the stimulation intensity threshold leading to a motor response (motor threshold) were recorded with stimulation applied at the vertex and anterolateral area in 13 awake normal subjects. Stimuli were applied during inspiration with and without resistance, during expiration with and without maximal tongue protrusion and during deep inspiration. In each stimulation location and condition, no diaphragmatic response was obtained without previous Genioglossus activity (diaphragmatic and Genioglossus responses latencies during expiration: 18.1 ± 2.9 and 6.3 ± 2.6 ms, respectively, mean ±s.d., P < 0.01). Genioglossus motor-evoked potential amplitude, latency and motor threshold were significantly modified with tongue protrusion with a maximal effect observed for stimulation in the anterolateral area. Deep inspiration was associated with a significant facilitatory effect on both Genioglossus and diaphragm motor responses. The facilitatory effects of respiratory and non-respiratory manoeuvres were also observed during focal stimulation where isolated Genioglossus responses were observed. Genioglossus and diaphragm differed in their motor threshold both at baseline and following facilitatory manoeuvres. Conclusions: (1) transcranial magnetic stimulation-induced Genioglossus response systematically precedes that of diaphragm; (2) this sequence of activation is not modified by respiratory and non-respiratory manoeuvres; and (3) the Genioglossus and diaphragm are differently influenced by these manoeuvres in terms of latency of the motor response and of motor threshold.
Richard L. Horner - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of serotonergic medullary raphe obscurus neurons suppresses Genioglossus and diaphragm activities in anesthetized but not conscious rats
2016Co-Authors: Eep Sood, Xia Liu, Hattie Liu, Richard L. Horner, Eric Raddatz, Richard LAbstract:suppresses Genioglossus and diaphragm activities in anesthetized but no
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Control of Genioglossus muscle by sleep state-dependent neuromodulators.
Advances in experimental medicine and biology, 2008Co-Authors: Richard L. HornerAbstract:Pharyngeal muscle tone decreases in sleep and this predisposes some individuals to obstructive sleep apnea. This review summarizes the control of the Genioglossus muscle by sleep-state dependent neuromodulators at the hypoglossal motor nucleus, the source of motor output to the Genioglossus muscle of the tongue. Knowledge of such mechanisms is relevant to identifying and developing new strategies to augment pharyngeal muscle activity in sleep, potentially as treatments for obstructive sleep apnea.
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Pentobarbital sedation increases Genioglossus respiratory activity in sleeping rats.
Sleep, 2007Co-Authors: Magdy Younes, Eileen Park, Richard L. HornerAbstract:OBJECTIVE To determine whether certain sedatives may, by increasing arousal threshold, allow pharyngeal dilator muscle activity to increase more in response to chemical stimuli before arousal occurs. DESIGN, PARTICIPANTS AND INTERVENTIONS: Thirteen chronically instrumented rats were studied during sleep following injections of placebo or sedating doses of pentobarbital (10 mg/kg). Intermittently, inspired CO2 was increased gradually until arousal occurred. MEASUREMENTS AND RESULTS Maximum Genioglossus activity reached before arousal was higher with pentobarbital than placebo (34.5 +/- 24.3 vs 3.7 +/- 2.9mV; P < 0.001) for 2 reasons. First, Genioglossus activity was greater during undisturbed sleep before CO2 was applied (23.3 +/- 15.3 vs 2.5 +/- 1.5 mV, P < 0.001). When sleep periods were long, a ramp-like increase in Genioglossus activity (GG-Ramp) began and progressed until arousal. GG-Ramps developed with both placebo and pentobarbital but reached higher levels with pentobarbital due to longer sleep periods and faster increase in Genioglossus activity during the ramp. GG-Ramps began when diaphragm activity was lowest and progressed despite unchanged diaphragm activity. Second, as hypothesized, the increase in Genioglossus activity with CO2 before arousal was greater than with placebo (11.2 +/- 2.5 vs 1.2 +/- 2.5mV; P < 0.05) due to increased arousal threshold. In 27 of 126 CO2 challenges delivered while GG-Ramps were in progress, Genioglossus activity paradoxically decreased despite increased diaphragmatic activity. These negative responses occurred randomly in 7 of 13 rats. CONCLUSIONS In rats: 1) Sedatives may allow Genioglossus activity to reach higher levels during sleep. 2) A time-dependent increase in Genioglossus activity occurs during undisturbed sleep that is unrelated to chemical drive. 3) Transient hypercapnia may elicit inhibition of Genioglossus activity under currently unidentified circumstances.
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Inhibition of serotonergic medullary raphe obscurus neurons suppresses Genioglossus and diaphragm activities in anesthetized but not conscious rats
Journal of applied physiology (Bethesda Md. : 1985), 2006Co-Authors: Sandeep Sood, Xia Liu, Hattie Liu, Eric Raddatz, Richard L. HornerAbstract:Although exogenous serotonin at the hypoglossal motor nucleus (HMN) activates the Genioglossus muscle, endogenous serotonin plays a minimal role in modulating Genioglossus activity in awake and sle...
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respiratory activation of the Genioglossus muscle involves both non nmda and nmda glutamate receptors at the hypoglossal motor nucleus in vivo
Neuroscience, 2006Co-Authors: H W Steenland, Xia Liu, Sandeep Sood, Hattie Liu, Richard L. HornerAbstract:Brainstem respiratory neurons innervate the hypoglossal motor nucleus which in turn transmits this respiratory drive signal to the Genioglossus muscle of the tongue. The mechanism of this transmission is important to help maintain an open airspace for effective breathing, and is thought to rely almost exclusively on non-N-methyl-d-aspartate (non-NMDA) glutamate receptor activation during respiration. However those studies were performed in slices of medulla from neonatal animals in vitro which may have led to an underestimation of the contribution of NMDA glutamate receptors that may normally operate in intact preparations. The current study tests the hypothesis that both NMDA and non-NMDA receptors contribute to respiratory drive transmission at the hypoglossal motor nucleus in vivo. Experiments were performed in urethane-anesthetized and tracheotomized adult Wistar rats in which vagus nerves were either intact or sectioned. In the presence of augmented Genioglossus activity produced by vagotomy, microdialysis perfusion of either an NMDA receptor antagonist (D-2-amino-5-phosphonovaleric acid, 0.001-10 mM) or a non-NMDA receptor antagonist (6-cyano-7-nitroquinoxaline-2, 3-dione disodium salt, 0.001-1 mM) to the hypoglossal motor nucleus reduced respiratory-related Genioglossus activity in a dose-dependent manner (P < 0.001) indicating that both NMDA and non-NMDA glutamate receptors are necessary for transmission of the respiratory drive signal to Genioglossus muscle in vivo. Similar effects were observed in the vagus nerve intact rats. Further experiments demonstrated that each delivered antagonist had effects that were specific to its respective receptor. Regression analysis also revealed that the activity of both NMDA and non-NMDA receptors at the hypoglossal motor nucleus is related to levels of the prevailing respiratory drive. These results show that both NMDA and non-NMDA glutamate receptors at the hypoglossal motor nucleus are involved in transmission of the respiratory drive signal to Genioglossus muscle in vivo.
Danny J Eckert - One of the best experts on this subject based on the ideXlab platform.
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changes in pharyngeal collapsibility and Genioglossus reflex responses to negative pressure during the respiratory cycle in obstructive sleep apnoea
The Journal of Physiology, 2020Co-Authors: Amal M Osman, Simon C. Gandevia, Jane E. Butler, Jayne C. Carberry, Danny J EckertAbstract:KEY POINTS 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. ABSTRACT 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 (∼250 ms) pressure pulses (∼-11 cmH2 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 100 ms 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 ± 23 vs. 127 ± 41% of early-inspiration, P < 0.001). Similarly, Genioglossus reflex excitation was delayed (39 ± 11 vs. 23 ± 7 ms, P < 0.001) and reflex excitation amplitude attenuated during mid-expiration versus early inspiration (209 ± 36 vs. 286 ± 80%, P = 0.009). These findings may provide insight into the physiological mechanisms of pharyngeal collapse in OSA.
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Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults.
Annals of the American Thoracic Society, 2017Co-Authors: Luigi Taranto-montemurro, Danny J Eckert, David P. White, Bradley A Edwards, Scott A Sands, Melania Marques, Ali Azarbarzin, Camila Maria De Melo, Ludovico Messineo, Andrew WellmanAbstract:Rationale: The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non-rapid eye movement (NREM) sleep and REM sleep. In animal models, the administration of 4-aminopyridine (4-AP), a voltage-gated K+ channel blocker, increased Genioglossus activity during wakefulness and across all sleep stages.Objectives: We tested the hypothesis that administration of a single dose of 4-AP 10 mg extended release would increase Genioglossus activity (electromyography of the Genioglossus muscle [EMGGG]) during wakefulness and sleep, and thereby decrease pharyngeal collapsibility.Methods: We performed a randomized controlled crossover proof-of-concept trial in 10 healthy participants. Participants received active treatment or placebo in randomized order 3 hours before bedtime in the ph...
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desipramine increases Genioglossus activity and reduces upper airway collapsibility during non rem sleep in healthy subjects
American Journal of Respiratory and Critical Care Medicine, 2016Co-Authors: Luigi Tarantomontemurro, Danny J Eckert, David P. White, Bradley A Edwards, Scott A Sands, Melania Marques, Andrew WellmanAbstract:Rationale: Obstructive sleep apnea is a state-dependent disease. One of the key factors that triggers upper airway collapse is decreased pharyngeal dilator muscle activity during sleep. To date, there have not been effective methods to reverse pharyngeal hypotonia pharmacologically in sleeping humans.Objectives: We tested the hypothesis that administration of desipramine 200 mg prevents the state-related reduction in Genioglossus activity that occurs during sleep and thereby decreases pharyngeal collapsibility.Methods: We conducted a placebo-controlled, double-blind, crossover trial with 10 healthy participants. Participants received active treatment or placebo in randomized order 2 hours before sleep in the physiology laboratory.Measurements and Main Results: Genioglossus activity during wakefulness and sleep, Genioglossus muscle responsiveness to negative epiglottic pressure, and upper airway collapsibility during passive and active conditions were compared between on- and off-drug states. Desipramine a...
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effects of pentobarbital on upper airway patency during sleep
European Respiratory Journal, 2010Co-Authors: Matthias Eikermann, Danny J Eckert, Nancy L Chamberlin, Amy S Jordan, Carl E Rosow, Scott Smith, Sam Zaremba, Atul MalhotraAbstract:We hypothesised that pentobarbital would improve upper airway mechanics based on an increase in latency to arousal and amplitude of the phasic Genioglossus electromyogram (EMG), and a decrease in the active upper airway critical closing pressure ( P crit ). 12 healthy subjects received pentobarbital (100 mg) or placebo in a double-blind, crossover protocol. During wakefulness, we measured the Genioglossus reflex response to negative pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep. With basal breathing during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal CO 2 concentration and upper airway resistance were greater; and P crit was unaffected (pentobarbital mean±sd -11.7±4.5 versus placebo -10.25±3.6 cmH 2 O; p = 0.11). Pentobarbital increased the time to arousal (297±63s versus 232±67 s; p versus 3.1±3%; p 2 levels. The increase in Genioglossus EMG after CO 2 administration was greater after pentobarbital versus placebo. Pentobarbital did not affect the Genioglossus negative-pressure reflex. Pentobarbital increases the time to arousal and stimulates Genioglossus muscle activity, but it also increases upper airway resistance during sleep.
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Genioglossus reflex inhibition to upper-airway negative-pressure stimuli during wakefulness and sleep in healthy males
The Journal of Physiology, 2007Co-Authors: Danny J Eckert, R. Doug Mcevoy, K George, Kieron J. Thomson, Peter CatchesideAbstract: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 (∼−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 ∼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.
Simon C. Gandevia - One of the best experts on this subject based on the ideXlab platform.
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changes in pharyngeal collapsibility and Genioglossus reflex responses to negative pressure during the respiratory cycle in obstructive sleep apnoea
The Journal of Physiology, 2020Co-Authors: Amal M Osman, Simon C. Gandevia, Jane E. Butler, Jayne C. Carberry, Danny J EckertAbstract:KEY POINTS 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. ABSTRACT 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 (∼250 ms) pressure pulses (∼-11 cmH2 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 100 ms 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 ± 23 vs. 127 ± 41% of early-inspiration, P < 0.001). Similarly, Genioglossus reflex excitation was delayed (39 ± 11 vs. 23 ± 7 ms, P < 0.001) and reflex excitation amplitude attenuated during mid-expiration versus early inspiration (209 ± 36 vs. 286 ± 80%, P = 0.009). These findings may provide insight into the physiological mechanisms of pharyngeal collapse in OSA.
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Influence of respiratory mechanics and drive on Genioglossus movement under ultrasound imaging.
PloS one, 2018Co-Authors: Benjamin C. H. Kwan, Rachel A. Mcbain, Billy L. Luu, Jane E. Butler, Lynne E. Bilston, Simon C. GandeviaAbstract:Genioglossus is the largest upper airway dilator and its dilatory movement can be measured non-invasively with magnetic resonance imaging and ultrasound. The present study used a novel ultrasound method to assess Genioglossus movement in conditions in which ventilatory drive or respiratory mechanics were changed. Methods Twenty healthy subjects (10 males, age 28±5 years [mean ± SD]) lay supine, awake, with the head in a neutral position. Ventilation was monitored with inductance bands. Real-time B-mode ultrasound movies were analysed. We measured Genioglossus motion (i) during spontaneous breathing, voluntary targeted breathing (normal tidal volume Vt), and voluntary hyperpnoea (at 1.5Vt and 2 Vt); (ii) during inspiratory flow resistive loading; (iii) with changes in end-expiratory lung volume (EELV). Results Average peak inspiratory displacement of the infero-posterior region of Genioglossus was 0.89±0.56 mm; 1.02±0.88 mm; 1.27±0.70 mm respectively for voluntary Vt, and during voluntary hyperpnoea at 1.5Vt and 2Vt. A change in Genioglossus motion was observed with increased Vt. During increasing inspiratory resistive loading, the Genioglossus displaced less anteriorly (p = 0.005) but more inferiorly (p = 0.027). When lung volume was altered, no significant changes in Genioglossus movement were observed (p = 0.115). Conclusion In healthy subjects, we observed non-uniform heterogeneous inspiratory motion within the inferoposterior part of Genioglossus during spontaneous quiet breathing with mean peak displacement between 0.5–2 mm, with more displacement in the posterior region than the anterior. This regional heterogeneity disappeared during voluntary targeted breathing. This may be due to different neural drive to Genioglossus during voluntary breathing. During inspiratory resistive loading, the observed Genioglossus motion may serve to maintain upper airway patency by balancing intraluminal negative pressure with positive pressure generated by upper airway dilatory muscles. In contrast, changes in EELV were not accompanied by major changes in Genioglossus motion.
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Influence of respiratory mechanics and drive on Genioglossus movement under ultrasound imaging
'Public Library of Science (PLoS)', 2018Co-Authors: Kwan Bch, Lynne E. Bilston, Ra Mcbain, Bl Luu, Je Butler, Simon C. GandeviaAbstract:© 2018 Kwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Genioglossus is the largest upper airway dilator and its dilatory movement can be measured non-invasively with magnetic resonance imaging and ultrasound. The present study used a novel ultrasound method to assess Genioglossus movement in conditions in which ventilatory drive or respiratory mechanics were changed. Methods Twenty healthy subjects (10 males, age 28±5 years [mean ± SD]) lay supine, awake, with the head in a neutral position. Ventilation was monitored with inductance bands. Real-time B-mode ultrasound movies were analysed. We measured Genioglossus motion (i) during spontaneous breathing, voluntary targeted breathing (normal tidal volume Vt), and voluntary hyperpnoea (at 1.5Vt and 2 Vt); (ii) during inspiratory flow resistive loading; (iii) with changes in end-expiratory lung volume (EELV). Results Average peak inspiratory displacement of the infero-posterior region of Genioglossus was 0.89±0.56 mm; 1.02±0.88 mm; 1.27±0.70 mm respectively for voluntary Vt, and during voluntary hyperpnoea at 1.5Vt and 2Vt. A change in Genioglossus motion was observed with increased Vt. During increasing inspiratory resistive loading, the Genioglossus displaced less anteriorly (p = 0.005) but more inferiorly (p = 0.027). When lung volume was altered, no significant changes in Genioglossus movement were observed (p = 0.115). Conclusion In healthy subjects, we observed non-uniform heterogeneous inspiratory motion within the inferoposterior part of Genioglossus during spontaneous quiet breathing with mean peak displacement between 0.5–2 mm, with more displacement in the posterior region than the anterior. This regional heterogeneity disappeared during voluntary targeted breathing. This may be due to different neural drive to Genioglossus during voluntary breathing. During inspiratory resistive loading, the observed Genioglossus motion may serve to maintain upper airway patency by balancing intraluminal negative pressure with positive pressure generated by upper airway dilatory muscles. In contrast, changes in EELV were not accompanied by major changes in Genioglossus motion
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Schematic representation of ultrasound image, grid position and numbering system.
2018Co-Authors: Benjamin C. H. Kwan, Rachel A. Mcbain, Billy L. Luu, Jane E. Butler, Lynne E. Bilston, Simon C. GandeviaAbstract:(a) Ultrasound image of the placement of grid with red line outlining the Genioglossus and 15 black dots denoting the tracking points. GG–Genioglossus, M–mucosa, S–tongue surface, GH–geniohyoid, MH–myohyoid (b) 15 grid points and columns represented. Points 1–5 are defined as the “anterior” column, 6–10 as the “middle” column and 11–15 as the “posterior” column. Points 11, 12 are defined as the “infero-posterior” points.
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Average displacement of Genioglossus (lung volume alteration).
2018Co-Authors: Benjamin C. H. Kwan, Rachel A. Mcbain, Billy L. Luu, Jane E. Butler, Lynne E. Bilston, Simon C. GandeviaAbstract:Average displacement of Genioglossus (lung volume alteration).
Wei Wang - One of the best experts on this subject based on the ideXlab platform.
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Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity.
Canadian respiratory journal, 2018Co-Authors: Ying Zou, Wei Wang, Xinshi Nie, Jian KangAbstract:Obstructive sleep apnea (OSA) is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH) during sleep. It has been reported that CIH can increase the EMG activity of Genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF) of Genioglossus corticomotor activity. 16 rats were divided into the air group ( ) and the CIH group ( ). The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS) was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of Genioglossus corticomotor activity in rats.
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The influence of 5-HT 1A receptors in the dorsal raphé nucleus on Genioglossus activity
Respiratory physiology & neurobiology, 2017Co-Authors: Ying Zou, Wei Wang, Hongyu Jin, Xinshi Nie, Ying Liu, Jian KangAbstract:Abstract Genioglossus activity maintains the patency of the upper airway. 5-HT neurons in the raphe nucleus regulate Genioglossus activity. In order to study the influence of 5-HT1A receptors in dorsal raphe nucleus (DRN) on Genioglossus EMG during normoxia, adult male Wistar rats were randomly divided into four groups: the artificial cerebrospinal fluid group (ACSF group), the low-concentration of 5-HT1A receptors agonist 8-OH-DPAT group (0.1 mM group), the mid-concentration 8-OH-DPAT group (0.4 mM group) and the high-concentration 8-OH-DPAT group (1.0 mM group). Rats received 0.1 μl ACSF/8-OH-DPAT microinjections into the DRN. EMG activity of the Genioglossus was recorded at 5 min, 15 min and 30 min after microinjection. In three 8-OH-DPAT groups, Genioglossus EMG activity significantly decreased at 5 min after microinjection and persisted for 30 min. The significantly decreased EMG activity was more pronounced in the mid- and high-concentration groups than in the low-concentration group, indicating that 5-HT1A receptors in the DRN could rapidly and continuously inhibit Genioglossus EMG activity during normoxia.
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Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats
Frontiers in neurology, 2017Co-Authors: Xinshi Nie, Wei Wang, Hongyu Jin, Ling Zhou, Aidi Wang, Jian Pang, Qin Zheng, Jian KangAbstract:Neuromuscular compensation of the Genioglossus muscle can be induced by chronic intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the Genioglossus. However, it remains unknown whether norepinephrine (NE) takes part in the central regulation of the Genioglossus during CIH. Adult male Wister rats (n = 32) were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the Genioglossus at different stages of CIH. The rats were divided into four groups; normal control or normoxic (NO) group, CIH group, CIH + normal saline (NS) group, and CIH + prazosin (PZ, α1-adrenergic antagonist) group. Prasozin (0.2 mM, 60 nl) and NS (0.9%, 60 nl) were microinjected into the hypoglossal nucleus. The responses of the Genioglossus corticomotor area to transcranial magnetic stimulation (TMS) were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 ms vs. 4.58 ± 0.42 ms, 3.93 ± 0.17 ms vs. 4.49 ± 0.55 ms, 3.79 ± 0.38 ms vs. 4.39 ± 0.30 ms, P < 0.05), and higher TMS amplitudes on day 1 (2.74 ± 0.87 mV vs. 1.60 ± 0.52 mV, P < 0.05) of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes) only on the 14th day of CIH (3.99 ± 0.28 ms vs. 4.61±0.48 ms, 2.51 ± 0.67 mV vs. 1.18 ± 0.62 mV, P < 0.05). These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of Genioglossus through α1-adrenoceptor on the 14th day of CIH.
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Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats
Frontiers Media S.A., 2017Co-Authors: Wei Wang, Hongyu Jin, Xinshi Nie, Ling Zhou, Aidi Wang, Zheng Qin, Jian Pang, Jian KangAbstract:Neuromuscular compensation of the Genioglossus muscle can be induced by chronic intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the Genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the Genioglossus during CIH. Adult male Wistar rats (n = 32) were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the Genioglossus at different stages of CIH. The rats were divided into four groups: normal control or normoxic (NO) group, CIH group, CIH + normal saline (NS) group, and CIH + prazosin (PZ, α1-adrenergic antagonist) group. PZ (0.2 mM, 60 nl) and NS (0.9%, 60 nl) were microinjected into the hypoglossal nucleus. The responses of the Genioglossus corticomotor area to transcranial magnetic stimulation (TMS) were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 vs. 4.58 ± 0.42, 3.93 ± 0.17 vs. 4.49 ± 0.55, 3.79 ± 0.38 vs. 4.39 ± 0.30 ms, P < 0.05), and higher TMS amplitudes on day 1 (2.74 ± 0.87 vs. 1.60 ± 0.52 mV, P < 0.05) of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes) only on the 14th day of CIH (3.99 ± 0.28 vs. 4.61 ± 0.48 ms, 2.51 ± 0.67 vs. 1.18 ± 0.62 mV, P < 0.05). These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of Genioglossus through α1-adrenoceptor on the 14th day of CIH
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Raphe serotonergic neurons modulate Genioglossus corticomotor activity in intermittent hypoxic rats
Respiratory research, 2014Co-Authors: Wei Wang, Long-feng Sun, Delei Kong, Jian KangAbstract:Background Genioglossus activity is greater during wakefulness but decreases to a weaker state during sleep in obstructive sleep apnea syndrome (OSAS) patients, compared to healthy subjects. Previous studies suggested that the corticomotor control of the Genioglossus was modified in OSAS patients. Intermittent hypoxia (IH), the typical pathophysiological change in OSAS, can induce Genioglossus facilitation. The serotonergic neurons of the raphe dorsal (DRN) and magnus nuclei (RMg) are responsive to hypoxia and play important roles in the control of the Genioglossus. However, it remains unknown whether DRN and RMg serotonergic neurons are responsible for the facilitated corticomotor activity of the Genioglossus during IH. This study explored the influence of IH on the corticomotor activity of the Genioglossus by transcranial magnetic stimulation (TMS), and the role of DRN and RMg serotonergic neurons in this effect.
