High-frequency rTMS treatment increases white matter FA in the left middle frontal gyrus in young patients with treatment-resistant depression

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for treatment-resistant depression (TRD), but its therapeutic mechanisms are unclear. White matter abnormalities are thought to cause network dysfunction underlying TRD. Diffusion tensor imaging (DTI) is an ideal tool for examining neural connections and the integrity of white matter. Few studies have used DTI to investigate the impact of rTMS on alterations of whiter matter in TRD. 30 young treatment-resistant unipolar depression patients (19 males and 11 females) were enrolled in a double-blind, randomized high-frequency (15 Hz) rTMS treatment study. Seventeen patients were treated with real stimulation, and 13 were treated with sham stimulation. White-matter fractional anisotropy (FA) was evaluated using voxel-based analysis (VBA) of FA maps derived from DTI before and after treatment. Twenty-five age- and gender-matched subjects were examined as a control group. In an exploratory VBA method, clusters of fifty voxels or greater that survived a family-wise error (FWE)-corrected threshold of p<0.05 were considered significant. The results revealed significantly reduced FA in the left middle frontal gyrus, with peak coordinates [-18 46 -14] in TRD patients. This reduced FA was significantly improved after active rTMS treatment, but not sham stimulation. FA increases were correlated with decreased depressive symptoms. This study requires replication and further clarification in a larger patient population, and optimization of stimulation locations and methods. These results suggest that the efficacy of rTMS on TRD is related to increased white-matter FA in the left middle frontal gyrus.