The application of spaced theta burst protocols induces long-lasting neuroplastic changes in the human motor cortex

There is some limited evidence suggesting that the spaced application of repetitive transcranial magnetic stimulation (rTMS) protocols may extend the duration of induced neuroplastic changes. However, this has yet to be demonstrated in the human primary motor cortex (M1). We evaluated whether the paired application of an inhibitory rTMS protocol [continuous theta burst stimulation (cTBS)] at 10-min intervals prolonged the duration of induced M1 plasticity. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle before and following single and paired cTBS protocols applied with two intensities: 80% of active motor threshold (AMT80) and 70% of resting motor threshold (RMT70). Single cTBS protocols did not significantly influence MEP amplitudes. Whereas paired trains applied at AMT80 had no effect on MEP amplitudes, paired cTBS trains at RMT70 significantly reduced them. MEP amplitudes remained suppressed for at least 2 h following the second train. Control experiments suggested that the contraction used to establish active motor threshold prior to cTBS application may be responsible for blocking the effect of paired cTBS trains at AMT80. The results suggest that the spaced application of cTBS protocols may be an effective approach for establishing long-lasting M1 neuroplasticity only in the absence of prior voluntary motor activation. These findings may have important implications for the therapeutic application of rTMS.