Effect of HD-tDCS on white matter integrity and associated cognitive function in chronic schizophrenia: A double-blind, sham-controlled randomized trial

Schizophrenia is a disabling major mental disorder, which includes critical deficits in cognitive function, for which no effective intervention currently exists. The aim of our double-blind, randomized, sham-controlled trial was to evaluate the effects of high-definition transcranial direct current stimulation (HD-tDCS) on the cognitive deficits in schizophrenia. This study sample consisted of 56 individuals with chronic schizophrenia, randomly allocated to either the active stimulation or sham group. The treatment consisted of ten consecutive days of HDtDCS, 20 min/day, applied over the left dorsolateral prefrontal lobe. Changes in clinical outcomes, cognitive assessments, and diffusion tensor imaging were evaluated pre- to post-intervention. Matched-healthy controls (HCs) were included to identify white matter changes in patients with schizophrenia before treatment. Compared to HCs, schizophrenia was associated with reduced integrity of the white matter tracts of the corpus callosum and corona radiata. HD-tDCS enhanced integrity in the corpus callosum and anterior and superior corona radiata, which was associated with the change in cognitive performance. HD-tDCS offers a potential approach to improve cognition deficits in schizophrenia through a modulatory effect on white matter tracts. Given the lack of approved treatments for cognitive deficits, these findings are clinically relevant.