Simon Gakwaya

Acute upper airway muscle and inspiratory flow responses to transcranial magnetic stimulation during sleep in apnoeic patients

•  What is the central question of this study? Peripheral hypoglossal nerve stimulation is a novel therapeutic approach aimed at recruiting lingual muscles electrically and thus relieving pharyngeal airflow obstruction during sleep but the effects of corticomotor stimulation of upper airway muscles during sleep are unknown. •  What is the main finding and its importance? Using transcranial magnetic stimulation, we show that corticobulbar excitability of the submental muscles is decreased during sleep in apnoeic patients. Furthermore, we demonstrate that transcranial magnetic stimulation briefly recruits submental muscles and increases maximal inspiratory flow as well as the inspiratory volume of flow‐limited respiratory cycles without arousing patients from sleep. We suggest that this central neurostimulation approach is capable of improving upper airway mechanics in sleep apnoea patients.

Influence of CO2 on upper airway muscles and chest wall/diaphragm corticomotor responses assessed by transcranial magnetic stimulation in awake healthy subjects

RATIONALE Functional interaction between upper airway (UA) dilator muscles and the diaphragm is crucial in the maintenance of UA patency. This interaction could be altered by increasing respiratory drive. The aim of our study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor responses to transcranial magnetic stimulation (TMS). METHODS 10 self-reported healthy men (32 ± 9 yr; body mass index = 24 ± 3 kg/m(-2)) breathed, in random order, room air or 5% and then 7% Fi(CO(2)), both balanced with pure O(2). Assessments included ventilatory variables, isoflow UA resistance (at 300 ml/s), measurement of lower chest wall/diaphragm (LCW/diaphragm), and genioglossus motor threshold (MT) and motor-evoked potential (MEP) characteristics. TMS twitches were applied during early inspiration and end expiration at stimulation intensity 30% above LCW/diaphragm and genioglossus MT. RESULTS Compared with room air, CO(2) inhalation significantly augmented minute ventilation, maximal inspiratory flow, tidal volume, and tidal volume/respiratory time ratio. UA resistance was unchanged with CO(2) inhalation. During 7% CO(2) breathing, LCW/diaphragm MT decreased by 9.6 ± 10.1% whereas genioglossus MT increased by 7.2 ± 9%. CO(2)-induced ventilatory stimulation led to elevation of LCW/diaphragm MEP amplitudes during inspiration but not during expiration. LCW/diaphragm MEP latencies remained unaltered both during inspiration and expiration. Genioglossus MEP latencies and amplitudes were unchanged with CO(2). CONCLUSION In awake, healthy subjects, CO(2)-induced hyperventilation is associated with heightened LCW/diaphragm corticomotor activation without modulating genioglossus MEP responses. This imbalance may promote UA instability during increased respiratory drive.

Consecutive transcranial magnetic stimulation twitches reduce flow limitation during sleep in apnoeic patients

•  What is the central question of this study? A transcranial magnetic stimulation (TMS)‐induced twitch applied on isolated single breaths over the motor cortex somatotopic representation of the tongue briefly recruits submental muscles and improves airflow dynamics of flow‐limited respiratory cycles without arousing sleep apnoea patients. However, the mechanical impact of the TMS‐induced twitch applied during consecutive breathing cycles on airflow dynamics remains unknown. •  What is the main finding and what is its importance? Our results show that application of TMS with the stimulator output set at the sleep submental motor threshold intensity on consecutive respiratory cycles increases inspiratory flow and reduces the turbulent airflow component. These results indicate an improvement of airflow pattern after two single consecutive TMS‐induced twitches without arousing sleep apnoea patients.

Assessment of upper airway dynamic properties using sternal phrenic nerve magnetic stimulation in awake subjects

To assess upper airway (UA) dynamic properties, magnetic stimulation of the phrenic nerves (MSPN) is usually performed at cervical level or anterior-laterally at the neck base. We hypothesized that UA dynamic properties could be effectively assessed by MSPN performed at the sternal level. Instantaneous flow, pharyngeal and mask pressures were recorded in 12 healthy awake subjects. End-expiratory MSPN were applied in random order with a non-focal coil placed behind the 7th cervical vertebrae (C7-MS) and at the sternal level (a-MS). The percentage of flow-limited twitches was greater with a-MS (a-MS: 33% and C7-MS: 2%; P<0.0001). For the non flow-limited twitches, maximal inspiratory flow was 36% greater (P<0.001) and isoflow UA resistance was lower with a-MS (0.6±0.1 and 0.9±0.1 cmH2Ol(-1)s; P=0.02). Maximal inspiratory flow of flow-limited twitches was 78% greater (P=0.05) and isoflow UA resistance tended to be lesser with a-MS (0.9±0.3 and 1.8±0.7 cmH2Ol(-1)s; P=0.09). a-MS could be a practical approach for assessing UA dynamic properties in awake subjects.

Diaphragm and genioglossus corticomotor excitability in patients with obstructive sleep apnea and control subjects.

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.

Assessment of upper airway dynamics by anterior magnetic phrenic stimulation in conscious sleep apnea patients

Phrenic nerve magnetic stimulation (PNMS) performed anterolaterally at the base of the neck (BAMPS) and cervical magnetic stimulation are common techniques for assessing upper airway (UA) mechanical properties in conscious humans. We considered that if NMS performed at the sternal level (a-MS) could induce a similar percentage of flow-limited twitches as BAMPS in conscious subjects, gauging UA dynamic properties by PNMS would be simplified. Instantaneous flow, pharyngeal and esophageal pressures, as well as thoraco-abdominal motion were recorded in 10 conscious sleep apnea patients. BAMPS and a-MS were applied at end expiration. The percentage of flow-limited twitches, maximal tolerated intensity, and minimal stimulator output associated with flow-limited twitches were similar between BAMPS and a-MS. Examining the effects of stimulation site, stimulation intensity and site*intensity interaction on the characteristics of flow-limited twitches, the former was responsible for more negative peak esophageal pressure (BAMPS: -11.5 ± 0.9 cmH(2)O; a-MS: -6.5 ± 1.1 cmH(2)O; P = 0.002) and UA closing pressure (BAMPS: -7.7 ± 0.5 cmH(2)O; a-MS: -5.8 ± 0.6 cmH(2)O; P = 0.02) as well as for lower mean linear upper airway resistance (UAR) (BAMPS 3.5 ± 0.4 cmH(2)O·l(-1)·s(-1); a-MS 2.2 ± 0.4 cmH(2)O·l(-1)·s(-1); P = 0.02). a-MS systematically evoked outward/inward thoracic displacement, although this movement pattern was observed in only 50% of patients when they were subjected to BAMPS. Linear UAR of BAMPS-induced flow-limited twitches was lower in the presence of initial outward thoracic movement (2 ± 0.05 cmH(2)O·l(-1)·s(-1)) than with inward motion (4.3 ± 1.5 cmH(2)O·l(-1)·s(-1); P = 0.03). We conclude that a-MS represents a practical and functional technique to evaluate UA mechanical properties in conscious sleep apnea patients.

Effects of repetitive transcranial magnetic stimulation of upper airway muscles during sleep in obstructive sleep apnea patients.

We tested the hypothesis that stimulating the genioglossus by repetitive transcranial magnetic stimulation (rTMS) during the ascendant portion of the inspiratory flow of airflow-limited breaths would sustain the recruitment of upper airway dilator muscles over time and improve airway dynamics without arousing obstructive sleep apnea (OSA) patients. In a cross-sectional design, nine OSA patients underwent a rTMS trial during stable non-rapid eye movement (NREM) sleep. Submental muscle motor threshold (SUB) and motor-evoked potential were evaluated during wakefulness and sleep. During NREM sleep, maximal inspiratory flow, inspiratory volume, inspiratory time, shifts of electroencephalogram frequency, and pulse rate variability were assessed under three different stimulation paradigms completed at 1.2 sleep SUB stimulation output: 1) 5Hz-08 (stimulation frequency: 5 Hz; duration of train stimulation: 0.8 s); 2) 25Hz-02 (stimulation frequency: 25 Hz; duration of train stimulation: 0.2 s); and 3) 25Hz-04 (stimulation frequency: 25 Hz; duration of train stimulation: 0.4 s). SUB increased during NREM sleep (wakefulness: 23.8 ± 6.1%; NREM: 26.8 ± 5.2%; = 0.001). Two distinct airflow patterns were observed in response to rTMS: with and without initial airflow drops, without other airflow variables change regardless the stimulation paradigm applied. Finally, rTMS-induced cortical and/or autonomic arousal were observed in 36, 26, and 35% of all delivered rTMS trains during 5Hz-08, 25Hz-02, and 25Hz-04 stimulation paradigms, respectively. In conclusion, rTMS does not provide any airflow improvement of flow-limited breaths as seen with nonrepetitive TMS of upper airway dilator muscles. However, rTMS trains were free of arousals in the majority of cases.

Influence of negative airway pressure on upper airway dynamic and impact on night-time apnea worsening

BACKGROUND Negative airway pressure loading such as seen during obstructive apnea/hypopnea may influence upper airway (UA) mechanical properties. We measured the effects of such loading on UA mechanical properties during wakefulness and assessed the potential link with night-time apnea worsening. METHODS Twitch stimulations of the phrenic nerve were applied before and after a step-by-step increase in UA suction flow in 10 sleep apnea and 10 control males. RESULTS Inspiratory closing pressure was lower in control than in apneic subjects. No consistent changes were observed in UA mechanical properties before and after the trial. In apneic patients, changes in the apnea index from the beginning to the end of the night correlated with changes in inspiratory closing pressure following suction flow. CONCLUSION (1) Apnea phenotype does not influence the impact of negative airway pressure on UA dynamic properties during wakefulness and (2) worsening of sleep apnea frequency during the night may relate to the exposure to recurrent UA negative pressure.

Assessment of tongue mechanical properties using different contraction tasks

Inadequate upper airway (UA) dilator muscle function may play an important role in the pathophysiology of obstructive sleep apnea (OSA). To date, tongue mechanical properties have been assessed mainly using protrusion protocol with conflicting results. Performance during elevation tasks among patients with OSA remains unknown. This study aimed at assessing tongue muscle strength, strength stability, endurance time, fatigue indices, and total muscle work, using elevation and protrusion tasks with repetitive isometric fatiguing contractions in 12 normal plus mild, 17 moderate, and 11 severe patients with OSA, and to assess the influence of body mass index (BMI) and age. Endurance time was longer in protrusion than elevation task (P = 0.01). In both tasks, endurance time was negatively correlated with baseline value of strength coefficient of variation (P < 0.01). Compared with other groups, patients with moderate OSA had the lowest total muscle work for protrusion (P = 0.01) and shortest endurance time (P = 0.04), regardless of the type of task. Additionally, in patients with moderate-severe OSA, the total muscle work for both tasks was lower in nonobese compared with obese (P < 0.05). Total muscle work for protrusion was positively correlated with apnea hypopnea index (AHI) in obese subjects (P < 0.01). Endurance time was shorter (P < 0.01) and recovery time longer (P = 0.02) in the old compared with young subjects. In conclusion, the tongue is more prone to fatigue during the elevation task and in patients with moderate OSA. Obesity appeared to prevent alteration of tongue mechanical properties in patients with OSA. Baseline strength stability and endurance were related, illustrating the role of central neuromuscular output in tongue resistance to fatigue.NEW & NOTEWORTHY To our knowledge, this is the first study to assess and compare tongue function using both elevation and protrusion tasks with repetitive isometric fatiguing contractions in subjects with different OSA status. Tongue mechanical performance seemed to differ between protrusion and elevation tasks and depend on the severity of OSA.

Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects

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.