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

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.

Keywords: corticocortical excitability; corticospinal excitability; tPCS, low frequencies; transcranial magnetic stimulation; transcranial pulsed current stimulation.

FIGURE 1

The study design of the effects of a‐tPCS at low frequencies (0.5, 1, 3, 5 Hz, and sham stimulation) on cortical excitability. a‐tPCS, Anodal transcranial pulsed current stimulation; CSE, Corticospinal excitability; F, Frequency; FDI, First dorsal interosseous; Hz, Hertz; ICF, Intra‐cortical facilitation; IPI, Inter‐pulse interval; LICI, Long‐interval intra‐cortical inhibition; M1, Primary left motor cortex; MEPs, Motor evoked potentials; ms, Milliseconds; PD, Pulse duration; PP, Paired‐pulse; SICI, Short‐interval intra‐cortical inhibition; SP, Single‐pulse; TMS, Transcranial magnetic stimulation.

FIGURE 2

The diagram of the different unidirectional monophasic a‐tPCS including 0.5 Hz frequency of a‐tPCS (A), 1 Hz frequency of a‐tPCS (B), 3 Hz frequency of a‐tPCS (C), 5 Hz frequency of a‐tPCS (D). a‐tPCS, Anodal transcranial pulsed current stimulation; Hz, Hertz; IPI, Inter‐pulse interval; ms, Millisecond; NDCC, Net direct current component; PD, Pulse duration; Sec, Second; SI, Stimulus intensity.

FIGURE 3

Effects of a‐tPCS at low frequencies (0.5, 1, 3, and 5 Hz) and sham stimulation CSE (A). The percentage of changes a‐tPCS at low frequencies (0.5, 1, 3, and 5 Hz) and sham stimulation on CSE (B). *p < 0.05; **p < 0.01; ***p < 0.001. CSE: Corticospinal excitability; a‐tPCS: Anodal transcranial pulse current stimulation.

FIGURE 4

Effects of low frequencies a‐tPCS on CSE and CCE. The effects of a‐tPCS (0.5, 1, 3, and 5 Hz) on ICF, SICI, and LICI compared to sham stimulation. The dotted line at the ratio of 100% represents a baseline or control level of motor evoked potential (MEP) amplitude. This line serves as a reference point, indicating the level of MEP response without any inhibitory or facilitatory conditioning stimulus applied. *p < 0.05; **p < 0.01; ***p < 0.001. CCE, Corticocortical excitability; Con., Conditioned test of averaged 25 MEPs; CSE, Corticospinal excitability; ICF, Intracortical facilitation; LICI, Long interval intracortical inhibition; MEPs, Motor evoked potential; SICI, Short interval intracortical inhibition; Test MEP, Averaged of 25 MEPs 1mv.