Transcranial direct current stimulation in patients with depression: An electric field modeling meta-analysis

Transcranial Direct Current Stimulation (tDCS) has shown potential in modulating cortical activity and treating depression. Despite its promise, variability in electrode montage configurations and electric field strength across studies has resulted in inconsistent outcomes. Traditional meta-analytic methods assessing the effect of tDCS in depression typically do not compare tDCS montage and the anatomical distribution of electric field, which is a major source of inter-experimental variability. We hypothesize that considering these parameters and anatomical variability in a meta-analysis might unravel brain regions associated with tDCS response in patients with depression. We correlate the clinical outcome (Effect size) with electric field intensities across 8 diverse head models, analyzing data from 29 studies involving 1766 patients between 2000 and 2023. Our analysis found a significant effect of tDCS on depression, with a Hedge's g = 0.66 (95 % CI: 0.565 to 0.767). Although studies aimed to target the L-DLPFC, particularly Brodmann area (BA) 46, based on the Frontal Brain Asymmetry theory, our findings show that all the montages do not selectively target the L-DLPFC as intended. Instead, our findings indicated that the electric field impact was dispersing broadly across the frontal lobes and exhibiting significant heterogeneity. We found a correlation between electric field strength and clinical outcomes in BA 10, BA 11, and the anterior part of BA 46 despite tDCS montages heterogeneity and individual variability, suggesting that targeting frontopolar prefrontal and orbitofrontal cortices could be ideal for tDCS in treating depression. Our work underscores brain regions associated with tDCS response and highlights the need for simulation-guided, personalized trials that consider individual anatomical differences.