Phase and Frequency-Dependent Effects of Transcranial Alternating Current Stimulation on Motor Cortical Excitability

Transcranial alternating current stimulation (tACS) can entrain ongoing brain oscillations and modulate the motor system in a frequency-dependent manner. Recent animal studies have demonstrated that the phase of a sinusoidal current also has an important role in modulation of neuronal activity. However, the phase effects of tACS on the human motor system are largely unknown. Here, we systematically investigated the effects of tACS phase and frequency on the primary motor cortex (M1) by using motor evoked potentials (MEPs) with transcranial magnetic stimulation (TMS). First, we compared the phase effects (90°, 180°, 270° or 360°) of 10 and 20 Hz tACS on MEPs. The 20 Hz tACS significantly increased M1 excitability compared with the 10 Hz tACS at 90° phase only. Second, we studied the 90° phase effect on MEPs at different tACS frequencies (5, 10, 20 or 40 Hz). The 20 vs. 10 Hz difference was again observed, but the 90° phase in 5 and 40 Hz tACS did not influence M1 excitability. Third, the 90° phase effects of 10 and 20 Hz tACS were compared with sham stimulation. The 90° phase of 20 Hz tACS enhanced MEP amplitudes compared with sham stimulation, but there was no significant effect of 10 Hz tACS. Taken together, we assume that the differential 90° phase effects on 20 Hz and 10 Hz tACS can be attributed to the neural synchronization modulated by tACS. Our results further underline that phase and frequency are the important factors in the effects of tACS on M1 excitability.