Baseline gray matter volume associates with working memory performance after prefrontal transcranial direct current stimulation.

Working memory is crucial for daily life and is often impaired in neuropsychiatric conditions. Attempts to enhance it using transcranial direct current stimulation (tDCS) have shown mixed results, possibly due to large inter-individual variability. This study assessed whether baseline regional brain volume was associated with working memory performance following tDCS. Healthy participants were randomly assigned to three bilateral tDCS protocols (sham, 1.5 mA, and 3 mA) over the dorsolateral prefrontal cortex (dlPFC) (anode-left, cathode-right) for 20 minutes, in a within-subjects design with a 2-week interval, followed by emotional and non-emotional 3-back tasks. Baseline volumetric data were used to extract gray matter volumes of defined regions of interest; the dlPFC, the medial PFC (mPFC), and the posterior cingulate cortex (PCC) bilaterally. Data from thirty-nine participants (69.2 % female, mean age: 24.56 years) across 112 tDCS sessions were analyzed. Findings revealed no significant association between working memory performance post sham-tDCS and gray matter volume. However, larger baseline cortical volumes across all regions were associated with slower reaction times and lower accuracy for the non-emotional task at 1.5 mA, whereas non-significant results were observed at 3 mA. For the emotional task, only a significant association for reaction time after 3 mA and left dlPFC and right PCC were found. Findings highlight not only the association between individual baseline gray matter, but also the impact of methodological choices, such as current intensity and outcome, on the effect of tDCS. Future research should aim to further explore individual variability and methodological factors to deepen our understanding of the mechanisms underlying tDCS.