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bioRxiv · 10.1101/2025.09.29.679395

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

Takemi, M.·Madsen, M. A. J.·Kesselheim, J.·Siebner, H. R.
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Abstract

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.

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Takemi, M., Madsen, M. A. J., Kesselheim, J., Siebner, H. R.. 2025-10-01. Target engagement in human motor cortex induced by constant sinusoidal and amplitude-modulated transcranial AC stimulation. https://doi.org/10.1101/2025.09.29.679395

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