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 (PImax) we fatigued the inspiratory muscles. Six participants performed 5 sustained maximal isometric inspiratory efforts (15-s contractions, duty cycle ~75%) which reduced PImax, 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 PImax, increasing from ~1.0% of PImax in the unfatigued contractions to ≥40% of ongoing PImax for esophageal and mouth pressures. The rate of increase in the superimposed twitch as PImax decreased with fatigue was not significantly different between the esophageal and mouth pressure measures. The inverse relationship between superimposed twitch pressure and PImax 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 intercostals. The duration of the silent period increased with fatigue in all three muscles, which suggests greater intracortical inhibition, with the largest change observed in 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 PImax when inspiratory muscles are fatigued with repeated sustained maximal efforts.