Abstract
Neuromodulatory effects of transcranial direct current stimulation (tDCS) on the primary motor cortex (M1) have been reported in terms of changes in corticospinal excitability using motor evoked potentials (MEPs), as well as behavioral effects during motor skill learning. While both effects are thought to be mediated by synaptic plasticity, empirical evidence of a common neural substrate is lacking. Complicating matters, the effects are relatively small, leading to mixed results, or even reversing effects when applying currents up to 2mA. In this ongoing preregistered study we aim to determine the dose-response of tDCS on cortical excitability and motor skill learning at higher current intensities in humans. In a double-blind, sham-controlled, counterbalanced design, 120 healthy subjects are assigned to one of three groups (N=40 each), receiving either 4mA, 6mA, or 0mA tDCS. tDCS is applied concurrently targeting M1, while the subject performs a 12-minute long explicit sequence learning task using their left hand. Using transcranial magnetic stimulation (TMS), motor evoked potentials (MEPs) are measured on the left first dorsal interosseus (FDI) immediately before and after the task. TMS-evoked potentials (TEPs) are recorded simultaneously with MEPs using electroencephalography (EEG) as a measure of cortico-cortical excitability. The trial is powered to test for a monotonic or non-monotonic dose-response relationship between tDCS intensity and motor skill performance as well as change in MEP amplitude. Correlation between physiological and behavioral effects would provide support for the notion that these stimulation effects share a common neural substrate. More importantly, this trial aims to establish whether tDCS can have robust effects on motor skill learning. Multiple studies have demonstrated that transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can influence corticospinal excitability and motor skill acquisition. However, the evidence for these effects is inconsistent, and a common neural substrate for these effects has not been directly demonstrated. To address this, we hypothesized that higher tDCS intensities would produce more robust effects, and uncover their relationship. In this preregistered study, 120 participants engaged in a motor skill learning task while receiving tDCS with posterior-to-anterior currents through M1. We employed a double-blind, between-subjects design, with groups of 4mA, 6mA, or sham stimulation, while ensuring balanced groups in terms of typing speed. Cortical excitability was assessed via motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) before and after motor skill learning with concurrent tDCS. tDCS at these higher intensities was well-tolerated, and motor learning correlated with pretraining typing speed. Planned analyses found no dose-response effect of tDCS on motor skill performance or MEP amplitude. This suggests that, under our experimental conditions, tDCS did not significantly modulate motor skill learning or corticospinal excitability. Furthermore, there was no correlation between motor performance and MEP, and thus no evidence for a common neural substrate. Exploratory analyses found an increase in MEP and TEP amplitudes following the sequence learning task. Motor skill gains positively correlated with TEP changes over the stimulated M1, which were more negative with increasing tDCS intensity. The effects of tDCS on motor skill learning and MEPs, if they exist, may require particular experimental conditions that have not been tested here. Pre-registration: https://osf.io/jyuev (in-principle acceptance: 2024/06/05) transcranial electric stimulation, neuromodulation, motor task, TMS, EEG, plasticity
Authors
Gavin Hsu, Zhenous Hadi Jafari, Abdelrahman Ahmed, Dylan J Edwards, Leonardo G Cohen, Lucas C Parra
https://doi.org/10.1162/imag_a_00431