Influence of gamma transcranial alternating current stimulation frequency and intensity on motor cortex excitability in young and older adults

Date

2025

Authors

Cirillo, J.
Hand, B.J.
Liao, W.-Y.
Opie, G.M.
Sasaki, R.
Semmler, J.

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Journal of Neurophysiology, 2025; 134(2):619-627

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John Cirillo, Brodie J. Hand, Wei-Yeh Liao, George M. Opie, Ryoki Sasaki, and John G. Semmler

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Abstract

Gamma transcranial alternating current stimulation (tACS) over primary motor cortex (M1) has been shown to reduce gamma-aminobutyric acid (GABA)-mediated inhibition during stimulation. However, the effectiveness of gamma tACS may be influenced by various factors, such as stimulation frequency, current intensity, and age. The aim of this study was to examine whether corticomotor excitability and GABA-mediated inhibition is influenced by gamma tACS when applied at different frequencies and intensities over M1 of young and older adults. Electromyographic recordings were obtained from the right hand first dorsal interosseous muscle of 18 young and 17 older adults. Motor-evoked potential (MEP) amplitudes elicited by single- and pairedpulse transcranial magnetic stimulation were used to examine corticomotor excitability and short-interval intracortical inhibition (SICI) during gamma and sham tACS. Gamma tACS was applied at three frequencies (60 Hz, 75 Hz, and 90 Hz) and three current intensities (1.0 mA, 1.5 mA, and 2.0 mA). Corticomotor excitability during tACS was not altered by the different gamma frequencies and intensities in young and older adults. Modulation of SICI during gamma tACS was both frequency- and intensity- dependent, with more inhibition than sham for 75 Hz and at 1.5–2.0 mA, but neither was influenced by age. These findings contrast with previous studies, showing that reduced SICI during gamma tACS is not a consistent outcome. Further investigation that includes a greater range of frequencies and intensities is needed to identify the optimal dose for modulating human M1 excitability and intracortical inhibition with gamma tACS

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© 2025 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society

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