Gamma Transcranial Alternating Current Stimulation Has Frequency-Dependent Effects on Human Motor Cortex Plasticity Induced by Theta-Burst Stimulation

Long-term potentiation (LTP)-like plasticity in primary motor cortex (M1) induced by intermittent theta burst stimulation (iTBS) can be enhanced by transcranial alternating current stimulation (tACS) at a gamma frequency of 70 Hz. Recent evidence suggests that there is some frequency specificity in the effects of tACS on motor function within the midgamma band (60-90 Hz). The purpose of this study was to examine the effect of different tACS frequencies within the gamma band on the neuroplastic response to iTBS. Seventeen healthy young adults performed four experimental sessions, where iTBS was combined with different tACS conditions (60, 75 and 90 Hz, sham) over M1 using a tACS-iTBS costimulation approach. Motor evoked potential (MEP) amplitude and short-interval intracortical inhibition (SICI) were assessed from a hand muscle before and after the intervention using transcranial magnetic stimulation with posterior-anterior (PA) and anterior-posterior (AP) coil orientations. Gamma tACS-iTBS costimulation increased PA and AP MEPs when gamma tACS was applied at 90 Hz, but not at 75 or 60 Hz, compared with sham tACS. PA and AP SICI was reduced by tACS-iTBS costimulation, but this was not influenced by gamma tACS frequency. Gamma tACS can increase LTP-like plasticity when combined with iTBS over M1, with the largest effect observed when tACS was applied at higher gamma frequencies. The functional relevance of targeting higher gamma frequencies within different brain areas and study populations remains to be determined.