Global white matter microstructure changes induced by repetitive transcranial magnetic stimulation in cocaine use disorder: a longitudinal correlational tractography study

Cocaine use disorder (CUD) is a significant public health problem with few treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) targeting the left dorsolateral prefrontal cortex has shown promise as a therapeutic tool for neural alterations in CUD. However, its effects on white matter (WM) microstructure and their role in treatment efficacy remain uncertain. This study aimed to assess the global impact of rTMS on WM microstructure in CUD patients. In this study, we made a longitudinal correlational tractography analysis that was conducted using Quantitative Anisotropy (QA) on diffusion MRI data from CUD patients who received either active rTMS (n = 22) or sham rTMS (n = 18) treatment. Imaging data were collected before (T0) and after two weeks of treatment (T1). Correlations were derived using nonparametric Spearman partial correlation, accounting for gender, age, and age at substance initiation through multiple regression. Tracks were selected using a p-FDR threshold of 0.05. A significant QA increase was found in 9718 tracts across the whole brain in the active rTMS group compared to the sham group, with no observed reduction in QA. The affected WM tracts included cerebellar, commissural, associative, and projective fibers, mainly in the left hemisphere. The study suggests that rTMS induces widespread changes in WM microstructure, potentially improving communication between brain regions and cognitive control in CUD patients. However, the small sample size limits the findings' generalizability, highlighting the need for larger, longitudinal studies.