What are the optimal transcranial direct current stimulation parameters and design elements to modulate corticospinal excitability? A systematic review and longitudinal meta-analysis.

BACKGROUND: Corticospinal excitability, measured by motor-evoked potentials (MEPs), is often impaired in neurological and musculoskeletal conditions. Transcranial direct current stimulation (tDCS) can modulate cortical excitability and improve clinical outcomes, yet inconsistencies in parameter settings complicate identification of optimal protocols. OBJECTIVE: Our primary objective was to examine the effects of: (i) stimulation polarity, (ii) duration, (iii) intensity, (iv) frequency, (v) electrode montage, and (vi) electrode design (size/shape) on MEP size. METHODS: Nine databases were searched from inception to 24th November 2023. We identified 84 individual cohorts (1,709 participants) and assessed time-dependent effects of each parameter on M1 MEP-to-baseline ratio in healthy and clinical populations using multi-level longitudinal meta-analysis. RESULTS: Anodal tDCS increased MEP size, with effects lasting up to 120 min post-stimulation. Consistent effects were observed with anodal tDCS durations ≥ 20 min and intensities ≥ 1.5 mA. Despite cohorts being matched, cathodal tDCS reduced MEP size for approximately 15 min post-stimulation, with significant effects at durations ≥ 9 min, intensity effects were inconclusive. Electrode montage and electrode size/shape influenced MEP, with greatest effect for electrodes over both the primary motor cortex and the dorsolateral pre-frontal cortex or over the cerebellar region, using 4 cm2 ring and 35 cm2 rectangular electrodes. CONCLUSION: tDCS effects on corticospinal excitability are parameter dependent. Anodal tDCS tends to facilitate excitability, whereas cathodal tDCS tends to inhibit excitability (depending on stimulation parameters). Specific durations, intensities, electrode placements and designs will ensure effectiveness and optimise safety. Findings support a parameter-specific approach to guide tailored neuromodulation interventions to enhance motor cortex rehabilitation outcomes.