Anodal Transcranial Pulsed Current Stimulation at Alpha-Gamma Frequencies: Effects on Corticospinal and...

Transcranial pulsed current stimulation (tPCS) is a frequency-dependent neuromodulation technique, but its mechanisms at alpha-gamma frequencies remain unexplored. This study investigated the effects of anodal tPCS (a-tPCS) at 10, 25, and 80 Hz and sham stimulation on cortical outcomes and side effects.

In this double-blinded, randomized, counterbalanced crossover trial, 15 healthy participants completed four experimental sessions (2 mA, 20 minutes). Single-pulse transcranial magnetic stimulation (TMS) and paired-pulse TMS were delivered over the primary motor cortex before and after each a-tPCS condition, with a minimum 48-hour washout period to prevent carryover effects.

Findings indicated that a single-session a-tPCS at these frequencies enhanced corticospinal excitability (CSE) compared with sham stimulation (p < 0.05) with minimal side effects during stimulation. CSE increase at 10 Hz (64.6%) and 25 Hz (44.9%) showed concurrent intracortical facilitation (ICF) modulation. However, at 80 Hz, a 27.66% increase in CSE was observed alongside a reduction in short-interval intracortical inhibition, as indicated by an increased conditioned or unconditioned motor evoked potential ratio. These findings should be interpreted with caution, given their proximity to statistical thresholds.

Alpha-beta a-tPCS increased CSE, accompanied by changes in ICF, which may reflect facilitation of excitatory intracortical circuits potentially involving glutamatergic mechanisms. However, gamma-frequency stimulation showed a pattern that may reflect compensatory inhibitory processes potentially related to gamma-aminobutyric acidergic activity. Alpha-gamma a-tPCS may provide a safer neuromodulation approach for further clinical research into its efficacy.