Is it the frequency, cumulative dose, or both? A prospective study of the excitability enhancing effects of tACS at individual alpha or beta frequency

Previous work suggests that transcranial alternating current stimulation (tACS) of the pericentral motor hand area (M1-HAND) may increase corticomotor excitability. Here we studied whether this neuromodulatory effect of tACS depends on the frequency as well as the “cumulative dose” in the targeted M1-HAND. On two separate days, twenty healthy participants received two 16-minute blocks of focal tACS targeting left M1-HAND at individual pericentral alpha or beta frequency. Stimulation intensity was either set to 0.4 or 1.0 mA peak-to-peak amplitude. TMS was applied to trace changes in corticomotor excitability. 480 motor evoked potentials (MEPs) were recorded from a contralateral hand muscle before, during, and after tACS. In the targeted M1-HAND, tACS-induced current density varied substantially among subjects in M1-HAND. The current density of 0.4 mA tACS is sometimes stronger than that of 1.0 mA. We divided the twenty participants into two groups based on the tACS-induced current density: For beta-tACS, an increase in MEP amplitude only emerged in the group in which beta-tACS resulted in lower current density, whereas alpha-tACS resulted in an MEP increase in both groups. We also found a relationship between online changes in MEP and the cumulatively applied current in the M1-HAND (i.e., defined as the product between current density and tACS running time), which again differed between alpha- and beta-tACS. A significant enhancement of mean MEP amplitude was observed within the range of 2.9−6.8 As/m² for alpha-tACS and 1.9−4.5 As/m² for beta-tACS. Cumulative doses exceeding these ranges were associated with a reduced ability of tACS to boost corticomotor excitability, possibly reflecting homeostatic plasticity. tACS at alpha- and beta-band frequency can enhance corticomotor excitability. The optimal cumulative dose for inducing this effect may differ between the frequencies. More research into the dose-response relationship is warranted to fully leverage the neuromodulatory potential of tACS in humans.