Theta-burst stimulation (TBS) over the primary motor cortex modulates activity of the underlying neural tissue, but little is known about its consequence on neuromuscular fatigue (NMF) and its neural correlates. This study aimed to compare the effects of facilitatory versus inhibitory TBS on the NMF and excitability/inhibition of the corticospinal pathway in an unfatigued/fatigued muscle. The effects of three TBS protocols (facilitatory/intermittent: iTBS; inhibitory/continuous: cTBS, and sham: sTBS) were tested on exercise performance, neuromuscular function, corticospinal excitability and inhibition in twenty young healthy participants. Transcranial magnetic and peripheral electrical stimulations were used at baseline, following TBS (unfatigued state), and after a fatiguing sustained contraction (fatigued state) at 35% of the maximal voluntary isometric contraction (MVIC) of the elbow flexors. Time-to-task failure was shorter for cTBS (142±51 s) and longer for iTBS (214±68 s) compared with sTBS (173±65 s) (P < .05). In an unfatigued state, cTBS reduced MVIC and voluntary activation (VA), increased motor-evoked potential (MEP), and silent period (SP) (P < 0.05), while iTBS did not cause any change. In a fatigued state, MVIC and VA decreased in all TBS sessions (P < 0.05). However, the reduction in VA was larger after cTBS (Δ-18±18%) compared with iTBS (Δ-3±5%), and sTBS (Δ-9±9%) (P < 0.001). Furthermore, the increase in MEP and SP were greater for cTBS (P < .05), compared to iTBS and sTBS (P < .05). Facilitatory TBS augments exercise performance that is independent of central parameters and corticospinal mechanisms whilst inhibitory TBS attenuates exercise performance through an exacerbation in the development of central fatigue and possibly intracortical inhibition.
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