A specific phase of transcranial alternating current stimulation at the β frequency boosts repetitive paired-pulse TMS-induced plasticity

Abstract

Transcranial alternating current stimulation (tACS) at 20 Hz (β) has been shown to modulate motor evoked potentials (MEPs) when paired with transcranial magnetic stimulation (TMS) in a phase-dependent manner. Repetitive paired-pulse TMS (rPPS) with I-wave periodicity (1.5 ms) induced short-lived facilitation of MEPs. We hypothesized that tACS would modulate the facilitatory effects of rPPS in a frequency- and phase-dependent manner. To test our hypothesis, we investigated the effects of combined tACS and rPPS. We applied rPPS in combination with peak or trough phase tACS at 10 Hz (α) or β, or sham tACS (rPPS alone). The facilitatory effects of rPPS in the sham condition were temporary and variable among participants. In the β tACS peak condition, significant increases in single-pulse MEPs persisted for over 30 min after the stimulation, and this effect was stable across participants. In contrast, β tACS in the trough condition did not modulate MEPs. Further, α tACS parameters did not affect single-pulse MEPs after the intervention. These results suggest that a rPPS-induced increase in trans-synaptic efficacy could be strengthened depending on the β tACS phase, and that this technique could produce long-lasting plasticity with respect to cortical excitability.

After-Effects of Intermittent Theta-Burst Stimulation Are Differentially and Phase-Dependently Suppressed by α- and β-Frequency Transcranial Alternating Current Stimulation

“…Thus, we assumed that β-tACS synchronized with iTBS might reveal facilitatory effects beyond what is seen after M1 iTBS. Indeed, we recently found that the facilitatory after-effects of rPPS over M1 were more pronounced with β-ACS when the TMS pulses were synchronized to the peak phase but not the trough phase ( Nakazono et al, 2021 ). Conversely, α-tACS did not significantly modulate the effects of rPPS.…”

“…tACS was delivered using a battery-driven current stimulator (DC Stimulator-Plus, NeuroConn GmbH, Ilmenau, Germany) with an intensity of 1 mA. The electrode size, position, and current intensity were chosen based on previous studies ( Feurra et al, 2011 ; Helfrich et al, 2014 ; Guerra et al, 2016 ; Nakazono et al, 2016 , 2021 ). The tACS duration was 260 s, and the stimulation began 60 s before iTBS onset and lasted until iTBS offset.…”

“…Transcranial alternating current stimulation was administered as in our previous studies (Nakazono et al, 2016(Nakazono et al, , 2021. Two 5 × 7 cm self-adhesive electrodes (PALS electrodes, Axelgaard Manufacturing Co., Ltd., Fallbrook, CA, United States) were attached with electrically conductive gel (Gelaid, Nihonkohden, Tokyo, Japan) over the left M1 hot spot and Pz according to the international 10-20 system (Figure 1A).…”

“…However, the tACS phase was not aligned with the TMS pulses in that study. In our recent study ( Nakazono et al, 2021 ), synchronized tACS with repetitive paired-pulse stimulation (rPPS) enhanced M1 excitability more than rPPS alone at the peak phase of 20-Hz tACS, but not at the trough phase. Conversely, 10-Hz tACS did not facilitate rPPS after-effects at either the peak or trough phases.…”

Phase-dependent modulation of the vestibular–cerebellar network via combined alternating current stimulation influences human locomotion and posture

“…Transcranial alternating current stimulation can entrain brain oscillations and modulate brain functions in a frequency-dependent manner (Herrmann et al, 2013;Nakazono et al, 2020;Vogeti et al, 2022). Phase-dependent effects of tACS have also been found in motor (Goldsworthy et al, 2016;Guerra et al, 2016;Nakazono et al, 2016Nakazono et al, , 2021Schilberg et al, 2018;Ogata et al, 2021), auditory (Neuling et al, 2012;Riecke et al, 2015), and visual function (Helfrich et al, 2014). In the locomotor system, tACS at the gait frequency over the cerebellum synchronized the natural walking rhythm (Koganemaru et al, 2020).…”