Multimodal Assessment of Precentral Anodal TDCS: Individual Rise in Supplementary Motor Activity Scales With Increase in Corticospinal Excitability

Abstract

Background: Transcranial direct current stimulation (TDCS) targeting the primary motor hand area (M1-HAND) may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging (fMRI) can probe after-effects of TDCS on regional neural activity on a whole-brain level.

Objective: Using a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas.

Methods: Seventeen healthy volunteers (10 women) received 20 min of real (0.75 mA) or sham TDCS on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials (MEP) from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation(TMS) of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob (AP-LM MEP latency).

Results: Real TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency.

Conclusion: Functional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability.

Keywords: functional magnetic resonance imaging (fMRI); inter-individual variability; motor evoked potentials; non-invasive brain stimulation; primary motor cortex (M1); supplementary motor area (SMA); transcrancial magnetic stimulation (TMS); transcranial direct current stimulation (tDCS).

FIGURE 1

Experimental procedure. Each session started by a baseline measure consisting of a structural and functional MRI (fMRI) exam and baseline physiological measures of corticospinal excitability. Baseline behavioral measures of motor performance during a visuomotor tracking task were recorded during the fMRI sequence. After baseline measures, 20 min of either active or sham TDCS was applied. Directly after the intervention corticospinal excitability was reassessed, followed by the post-intervention run of the fMRI, Arterial Spin Labeling (ALS) and Resting-state fMRI (rs-fMRI) sequences. The post-intervention was concluded by the second measure of corticospinal excitability. In the second session, the individual latency profile was assessed by measuring the MEP latency following stimulation with different coil orientations.

FIGURE 2

Simulation of the TDCS electric field for the montage, done using SimNIBS 2.1 and the included “Ernie” example dataset.

FIGURE 3

MEP results. (A) Raw amplitudes of MEPs after either anodal or sham TDCS (mean ± SE). At baseline, there was a significant difference in MEP amplitudes between TDCS and sham sessions (p < 0.05, paired t-test). (B) Group results of normalized amplitudes of MEPs after either anodal or sham TDCS (mean ± SE, n = 17). Normalized amplitudes were calculated by dividing the amplitudes of MEPs just after or 1 hour after TDCS by ones at baseline. No interaction could be detected.

FIGURE 4

Relationships between the normalized TMS amplitudes and AP-LM latency. A positive correlation was found just after the anodal session (A), but neither just after the sham session (B), nor 1 h after each stimulation. For the y-axis a value of 1 is equivalent to no change from baseline.

FIGURE 5

BOLD signals during the tracking task. (A) A conjunction analysis between complex and simple visuomotor tasks. The significant regions were the right precentral gyrus, bilateral SMA, contralateral postcentral gyrus, and IPC and SPL (p < 0.05, FWE). (B) A contrast (complex > simple visuomotor tasks). The significant regions were the right middle occipital gyrus, bilateral SPL, right IPC and premotor cortex, and bilateral SMA (p < 0.05, FWE).

FIGURE 6

The t-scores in the contrast visuomotor tracking vs visual baseline correlated with the normalized TMS amplitudes just after anodal TDCS in a region in the bilateral SMA [peak activation [0, -14, 62]; p < 0.05 FWE; small volume correction; 10 mm sphere based on Lee et al. (2003)].