Neuromodulation : journal of the International Neuromodulation Society · 2026
Influence of Concurrent Theta-Gamma Transcranial Alternating Current Stimulation and Repetitive Transcranial Magnetic Stimulation on Primary Motor Cortex Plasticity.
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Meadows Amy C, Liao Wei-Yeh, Cirillo John, Opie George M, Semmler John G
Аннотация
OBJECTIVES: Transcranial alternating current stimulation (tACS) with a combined theta-gamma (TG) waveform can boost human motor performance, but its effects on primary motor cortex (M1) plasticity remain unclear. This study investigated the effects of concurrent TG tACS and repetitive paired-pulse transcranial magnetic stimulation (rppTMS) on M1 excitability and plasticity.
MATERIALS AND METHODS: A total of 22 healthy young adults completed four experimental sessions involving concurrent application of tACS and rppTMS over M1. Fifteen minutes of rppTMS (1.5 ms interstimulus interval, [ISI]) was applied during tACS with either a 75-Hz gamma burst nested in the peak (TGP) or trough (TGT) of a 6-Hz theta carrier wave, theta in isolation (TP), or sham (ten second ramp at start/end). Single- and paired-pulse TMS was performed before and after the rppTMS intervention to assess motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (2 ms ISI), and short-interval intracortical facilitation (1.5 ms ISI).
RESULTS: Paired-pulse MEP amplitude during rppTMS (online effects) increased with active (TGP, TGT, TP; all p < 0.045) but not sham (all p > 0.222) tACS. In contrast, examination of offline responses showed that single-pulse MEP amplitude and short-interval intracortical facilitation increased, whereas short-interval intracortical inhibition decreased, after the intervention (all p < 0.008), but this change was not different across tACS conditions (all p > 0.050).
CONCLUSIONS: Our study shows that tACS resulted in an increase in M1 excitability during rppTMS, but this was not different between peak- and trough-coupled TG tACS, or theta tACS. Furthermore, TG tACS did not influence offline neuroplastic effects with rppTMS. As these studies were performed at rest, it is possible that tACS may be more effective during a motor task that activates a broader motor network.
MATERIALS AND METHODS: A total of 22 healthy young adults completed four experimental sessions involving concurrent application of tACS and rppTMS over M1. Fifteen minutes of rppTMS (1.5 ms interstimulus interval, [ISI]) was applied during tACS with either a 75-Hz gamma burst nested in the peak (TGP) or trough (TGT) of a 6-Hz theta carrier wave, theta in isolation (TP), or sham (ten second ramp at start/end). Single- and paired-pulse TMS was performed before and after the rppTMS intervention to assess motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (2 ms ISI), and short-interval intracortical facilitation (1.5 ms ISI).
RESULTS: Paired-pulse MEP amplitude during rppTMS (online effects) increased with active (TGP, TGT, TP; all p < 0.045) but not sham (all p > 0.222) tACS. In contrast, examination of offline responses showed that single-pulse MEP amplitude and short-interval intracortical facilitation increased, whereas short-interval intracortical inhibition decreased, after the intervention (all p < 0.008), but this change was not different across tACS conditions (all p > 0.050).
CONCLUSIONS: Our study shows that tACS resulted in an increase in M1 excitability during rppTMS, but this was not different between peak- and trough-coupled TG tACS, or theta tACS. Furthermore, TG tACS did not influence offline neuroplastic effects with rppTMS. As these studies were performed at rest, it is possible that tACS may be more effective during a motor task that activates a broader motor network.