Preliminary evidence for high-definition transcranial direct current stimulation effects on white matter microstructure and executive function in mild cognitive impairment

Background Mild cognitive impairment (MCI) represents a critical window for intervention before Alzheimer’s disease progression. This study investigated whether high-definition transcranial direct current stimulation (HD-tDCS) targeting the left dorsolateral prefrontal cortex (L-DLPFC) could modulate white matter microstructure and thereby influence cognitive function. Methods Twenty-four patients with MCI received 10 sessions of active HD-tDCS over the L-DLPFC. White matter integrity was assessed using diffusion tensor imaging (DTI) to quantify fractional anisotropy in corticospinal tracts (CSTs) and anterior thalamic radiations (ATR). Cognitive function was evaluated with the trail making test B (TMT-B), mini-mental state examination (MMSE), and Montreal cognitive assessment (MoCA) at baseline and postintervention. Forty healthy controls provided baseline DTI data. Results At baseline, patients with MCI showed significantly reduced fractional anisotropy in the bilateral CST and ATR compared with healthy controls. Following HD-tDCS, increases in fractional anisotropy were observed in these tracts. While MMSE and MoCA scores showed no significant change, TMT-B performance appeared to improve. Notably, increased fractional anisotropy in the left ATR showed an association with improved TMT-B performance ( r = 0.467, P < 0.05). Conclusion The findings suggest that HD-tDCS targeting the L-DLPFC may promote microstructural remodeling in white matter tracts, evidenced by elevated fractional anisotropy within the corticospinal and anterior thalamic pathways. While global cognitive measures remained stable, a trend toward improved executive function (TMT-B) was observed, potentially associated with left ATR fractional anisotropy enhancement. This positions HD-tDCS as a candidate neuromodulatory intervention for MCI, warranting further investigation to confirm functional outcomes.