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

Abstract

New Findings r 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. r 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.Transcranial magnetic stimulation (TMS) can activate the corticobulbar system and briefly recruit upper airway dilator muscles, improving the inspiratory airflow dynamics of flow-limited respiratory cycles during sleep. The purpose of this investigation was to quantify the effects of TMS-induced twitches applied during sleep on flow-limited respiratory cycles in 14 obstructive sleep apnoea patients. Submental muscle motor threshold (SUB MT ) and motor-evoked potential (SUB MEP ) were examined during wakefulness and sleep. The TMS-induced twitches were applied during stable non-rapid eye movement (NREM) sleep, during non-consecutive flow-limited respiratory cycles at the beginning of inspiration, with intensities varying from sleep SUB MT up to maximal stimulation without arousal. Maximal inspiratory flow, inspiratory volume, shifts of electroencephalogram frequency and pulse rate variability were assessed. Cortical and/or autonomic arousal after TMS was observed in only 13.8% of all twitches applied. The SUB MT increased during NREM sleep (wakefulness, 24.8 ± 9.3%; and NREM sleep, 28.3 ± 9.5%; P = 0.003). Augmenting stimulator output from SUB MT to maximal stimulation before arousal enhanced SUB MEP peak-to-peak amplitude (from 0.09 ± 0.05 to 0.4 ± 0.3 mV; P = 0.005) with a concomitant rise in maximal inspiratory flow (from 376.2 ± 107.9 to 411.9 ± 109.3 ml s −1 ; P = 0.008) and inspiratory volume (from 594.8 ± 189.2 to 663.7 ± 203.1 ml; P = 0.001) in all but one patient. Corticobulbar excitability of submental muscles decreases during NREM sleep. Brief

Direct comparison of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome and restless legs syndrome

“…Accordingly, a recent paper [36] has shown that the activation of the cortical-bulbar pathway was reduced during NREM sleep in apneic patients, as demonstrated by increased MT and prolonged MEP latency recorded from the submentalis muscle. This diminished excitability is hypothesized to result from the combined effects of the thalamo-cortical system hyperpolarization and the modified reactivity to sensory inputs [37,38], leading to a prevailing tonic GABAergic and glycinergic inhibitory inputs to motor neurons [37], and thus probably resulting in a globally decreased excitability of the motor cortex and conductivity of the fastest conducting cortical-spinal projections.…”

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

“…, ; Melo‐Silva et al . a ). Transcranial magnetic stimulation‐induced twitches applied during sleep over the corticomotor somatotopic representation of the tongue on isolated breaths briefly recruit UA dilator muscles and improve the airflow dynamics of flow‐limited respiratory cycles without arousing OSA patients (Dempsey et al .…”

Transcranial magnetic stimulation – a potential unobtrusive, non‐invasive and drug‐free treatment for obstructive sleep apnoea

“…In the study featured in this issue of Experimental Physiology (Melo‐Silva et al 2013), TMS was used to stimulate the somatotopic representation of the tongue in the motor cortex of sleeping patients with obstructive sleep apnoea (OSA) in order to stimulate contraction of upper airway muscles. Obstructive sleep apnoea is a very common condition, in which the contractions of the upper airway muscles, especially the tongue musculature, fail to stabilize or dilate the airway adequately during inspiration in sleep.…”

“…The ‘route one’ approach of stimulating the hypoglossal nerve, the motor nerve to the tongue, has been used with some success, but this method requires surgery (Eastwood et al 2011). The investigation by Melo‐Silva et al (2013) shows that TMS can be used to cause activation of upper airway muscles and improve airflow and inspired volume during episodes of reduced airflow, and this is achieved without waking the patient. There was no effect on activation of chest wall/diaphragm muscles.…”

“…More work is needed in varying stimulus localization, intensity, frequency and timing in relation to the respiratory cycle in order to optimize airflow and tidal volume and to prevent airway collapse. Technological advances may play a significant role, and one future development might be the ability to activate deeper regions using, for example, an H‐coil (Zangen et al 2005) instead of the conventional figure‐of‐eight coil as used by Melo‐Silva et al (2013). In this way, it might be possible to have greater control of upper airway muscle contraction and airway opening, because the motor and premotor neurons within and near the hypoglossal nucleus could be activated directly instead of indirectly through corticobulbar pathways as in the featured paper.…”