Fractional anisotropy changes after several weeks of daily left high-frequency repetitive transcranial magnetic stimulation of the prefrontal cortex to treat major depression

Objectives: As part of a sham controlled treatment trial using daily left repetitive transcranial magnetic stimulation (rTMS), brain changes associated with 4 to 6 weeks of treatment were examined using diffusion tensor imaging to noninvasively evaluate prefrontal white matter (WM) microstructure. A decrease in fractional anisotropy values of the left prefrontal WM could indicate damage to the region. Methods: Diffusion tensor imaging was performed before and after 4 to 6 weeks of daily rTMS treatments. Mean fractional anisotropy levels associated with active rTMS and sham rTMS for the right and left prefrontal WM were assessed. Results: Adequate images were acquired for 8 participants (active n = 4, sham n = 4) before and after rTMS. A mean increase was found for the left prefrontal WM. The mixed model revealed a trend toward a significant treatment group × region interaction effect (P = 0.11). Furthermore, simple region effects (left prefrontal WM vs right prefrontal WM) were at a trend toward significance for difference after treatment within the active rTMS group (P = 0.07), but not within the sham rTMS group (P = 0.88). Conclusions: Repetitive transcranial magnetic stimulation resulted in no evidence of damage to WM on the side of stimulation. Diffusion tensor imaging may offer a unique modality to increase our understanding of mechanisms of action for rTMS.