Motor network connectivity predicts neuroplastic response following theta burst stimulation in healthy adults

A patterned repetitive transcranial magnetic stimulation protocol, known as continuous theta burst stimulation (cTBS), can suppress corticospinal excitability via mechanisms that appear similar to long-term depression synaptic plasticity. Despite much potential, this technique is currently limited by substantial response variability. The purpose of this study was to investigate whether baseline resting state functional connectivity is a determinant of response to cTBS. Eighteen healthy young adults participated in up to three experimental sessions. Single-pulse transcranial magnetic stimulation was used to quantify change in corticospinal excitability following cTBS. Three minutes of resting electroencephalographic activity was recorded, and functional connectivity was estimated using the debiased weighted phase lag index across different frequency bands. Partial least squares regression identified models of connectivity between a seed region (C3) and the whole scalp that maximally accounted for variance in cTBS responses. There was no group-level effect of a single cTBS train or spaced cTBS trains on corticospinal excitability (p = 0.092). A low beta frequency band model of connectivity accounted for the largest proportion of variance in spaced cTBS response (R² = 0.50). Based on the low beta frequency model, a-priori regions of interest were identified and predicted 39% of variance in response to spaced cTBS at a subsequent session. Importantly, weaker connectivity between the seed electrode (C3) and a cluster approximating a frontocentral region was associated with greater spaced cTBS response (p = 0.02). It appears M1-frontocentral networks may have an important role in determining the effects of cTBS on corticospinal excitability.