Abstract
In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea.
Highlights
Materials and MethodsIn awake humans at rest, lung ventilation depends on the homeostatically regulated cyclical activity of brainstem pattern generators
Because the effects of repetitive magnetic stimulation (rTMS) on motor behaviors are complex and influenced by many factors, we investigated the effects of both an excitatory protocol (5 Hz stimulation) and an inhibitory protocol on breathing pattern and respiratory discomfort during inspiratory threshold loading in healthy subjects
first dorsal interosseous (FDI) Electromyographic recordings (EMG) did not suggest spread of the rTMS stimulus to the primary motor cortex that would have been indicative of a seizure risk
Summary
In awake humans at rest, lung ventilation depends on the homeostatically regulated cyclical activity of brainstem pattern generators. The SMA and other cortical areas that contribute to premotor potentials are activated in response to inspiratory mechanical constraints (generally referred to as “inspiratory loads,” a generic term that designate any experimental device imposing an increased effort on the respiratory system, e.g., resistances, elastances, and threshold valves) in normal humans (Raux et al, 2007a,b, 2013). Each session consisted of (1) a 15-min epoch of inspiratory threshold loading (ITL); (2) 15 min of unloaded free breathing to let the subject recover; (3) rTMS conditioning of the supplementary motor area (SMA) with excitatory, inhibitory or sham stimulation; (4) a second 15-min session of ITL. All calculations were performed using Sigmaplot (Systat Software, San Jose, CA), except for the multiplicity correction that was performed with a custom Microsoft Excel R spread sheet (courtesy Manuel Weinkauf, http://www.marum.de/en/Manuel_Weinkauf.html)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call