Target engagement in human motor cortex induced by constant sinusoidal and amplitude-modulated transcranial AC stimulation

Transcranial alternating current stimulation (tACS) is a noninvasive technique for modulating brain oscillations. While sinusoidal tACS (sin-tACS) delivers current at a constant amplitude, amplitude-modulated tACS (AM-tACS) uses a high-frequency carrier modulated by a low-frequency envelope. We systematically compared the acute effects of sin-tACS at theta (5 Hz), alpha (10 Hz), beta (20 Hz), and gamma (140 Hz) frequencies, and AM-tACS (140 Hz carrier frequency modulated at theta, alpha, or beta) on corticospinal excitability. Healthy participants received 2 mA peak-to-peak tACS to the primary motor hand area (M1HAND) via a bipolar montage (M1HAND-Pz). Each tACS block consisted of ten 30-second stimulation periods interleaved with 6-second pauses, followed by 11 minutes without stimulation. Corticospinal excitability was assessed during each block using single-pulse transcranial magnetic stimulation (TMS), delivered at the peak and trough of tACS. MEP amplitudes were generally larger at the trough. Only beta sin-tACS and theta AM-tACS significantly modulated corticospinal excitability. Beta sin-tACS increased MEP amplitudes in early stimulation epochs, while theta AM-tACS facilitated MEPs in later stimulation epochs and this facilitation persisted briefly after stimulation ended. Participants with stronger early responses to beta sin-tACS also tended to show greater delayed effects with theta AM-tACS. These excitability changes during tACS were not predicted by simulated electric field strength. A follow-up EEG experiment revealed that beta sin-tACS increased beta power over left sensorimotor cortex, while theta AM-tACS decreased beta power over midline parietal cortex. These EEG changes were restricted to tACS pauses. The results show that sin-tACS and AM-tACS can both modulate corticospinal excitability, but functional changes differ in temporal dynamics, frequency specificity, and cortical region engagement.