Supraspinal fatigue in human inspiratory muscles with repeated sustained maximal efforts

To investigate the involvement of supraspinal fatigue in the loss of maximal inspiratory pressure (Pi ), we fatigued the inspiratory muscles. Six participants performed 5 sustained maximal isometric inspiratory efforts (15-s contractions, duty cycle ∼75%) which reduced Pi , as measured from esophageal and mouth pressure, to around half of their initial maximums. Transcranial magnetic stimulation (TMS) delivered over the motor cortex near the beginning and end of each maximal effort evoked superimposed twitch-like increments in the ongoing Pi , increasing from ∼1.0% of Pi in the unfatigued contractions to ≥40% of ongoing Pi for esophageal and mouth pressures. The rate of increase in the superimposed twitch as Pi decreased with fatigue was not significantly different between the esophageal and mouth pressure measures. The inverse relationship between superimposed twitch pressure and Pi indicates a progressive decline in the ability of motor cortical output to drive the inspiratory muscles maximally, leading to the development of supraspinal fatigue. TMS also evoked silent periods in the electromyographic recordings of diaphragm, scalenes, and parasternal intercostal. The duration of the silent period increased with fatigue in all three muscles, which suggests greater intracortical inhibition, with the largest change observed in the diaphragm. The peak rate of relaxation in pressure during the silent period slowed as fatigue developed, indicating peripheral contractile changes in the active inspiratory muscles. These changes in the markers of fatigue show that both central and peripheral fatigue contribute to the loss in Pi when inspiratory muscles are fatigued with repeated sustained maximal efforts. When the inspiratory muscles are fatigued with repeated sustained maximal efforts, supraspinal fatigue, a component of central fatigue, contributes to the loss in maximal inspiratory pressure. The presence of supraspinal fatigue was confirmed by the increase in amplitude of twitch-like increments in pressure evoked by motor cortical stimulation during maximal efforts, indicating that motor cortical output was not maximal as extra muscle force could be generated to increase inspiratory pressure.