# Investigating the Effects of Anodal Transcranial Pulsed Current Stimulation at Low Frequencies (0.5 to 5 Hz) on Corticospinal and Corticocortical Excitability

## TL;DR

This study explores how low-frequency anodal transcranial pulsed current stimulation affects brain excitability and finds frequency-dependent effects with potential for non-invasive treatment.

## Contribution

The study is the first to investigate the effects of anodal tPCS at low frequencies (0.5–5 Hz) on cortical excitability and adverse effects.

## Key findings

- Anodal tPCS at 1, 3, and 5 Hz increased corticospinal excitability compared to sham stimulation.
- Higher frequencies (1 and 5 Hz) were associated with increased intracortical facilitation and fewer adverse effects.
- 0.5 Hz stimulation decreased corticospinal excitability and increased short intracortical inhibition.

## Abstract

The mechanism underlying transcranial pulsed current stimulation (tPCS) as a non‐invasive neuromodulation technique has garnered considerable attention in recent years. However, the effects of anodal tPCS (a‐tPCS) at low frequencies remain unexplored. This study aimed to investigate the a‐tPCS effects at 0.5, 1, 3, and 5 Hz on cortical outcomes and its adverse side effects. This double‐blinded, randomized, counterbalanced crossover trial included 18 healthy young participants who completed five experimental sessions with 2 mA of a‐tPCS for 20 min in a randomized order of frequencies (0.5, 1, 3, and 5 Hz). Single‐pulse and paired‐pulse transcranial magnetic stimulation (TMS) on the left primary motor cortex (M1) was delivered before and immediately after the stimulation at rest. Sessions were spaced at least 48 h apart to minimize carry‐over effects. The results indicated that a single session of a‐tPCS at frequencies of 1, 3, and 5 Hz significantly (p < 0.05) enhanced corticospinal excitability (CSE), while 0.5 Hz decreased CSE compared to sham stimulation. The CSE changes at 1 and 5 Hz were associated with increased intracortical facilitation (ICF), with reduced adverse effects observed at higher frequencies. In contrast, the cortical effects of 0.5 Hz were linked to increased short intracortical inhibition (SICI) with minimal side effects. However, all frequencies except 0.5 Hz were associated with phosphenes or flashing lights during stimulation. Given the similar effects of a‐tPCS with other pulsatile current stimulation, it is plausible that tPCS could serve as a complementary or superior alternative to TMS, particularly for at‐risk and diverse patient populations. However, this claim needs further comparative studies before suggesting clinical superiority for epilepsy and neuro‐rehabilitation. Furthermore, like other neuromodulation techniques, tPCS shows potential as an affordable, home‐based treatment option. Further research is needed to establish the efficacy of tPCS relative to TMS methodologies through rigorous experimental testing.

Transcranial pulsed current stimulation (tPCS) is a non‐invasive method for modulating cortical excitability via entrainment and polarization. Our findings show that anodal tPCS below 1 Hz reduces CE through GABAergic activity, while above 1 Hz enhances it via glutamatergic mechanisms. These effects align with transcranial magnetic stimulation (TMS) but with fewer adverse effects at delta/theta frequencies. Given its safety and affordability, tPCS holds promise as a neuromodulatory intervention for conditions with altered CE.