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Fractional Anisotropy Changes After Several Weeks of Daily Left High-Frequency Repetitive Transcranial Magnetic Stimulation of the Prefrontal Cortex to Treat Major Depression

Kozel, F. Andrew MD, MSCR*†‡; Johnson, Kevin A. PhD†‡; Nahas, Ziad MD, MSCR†‡; Nakonezny, Paul A. PhD§; Morgan, Paul S. PhD∥¶; Anderson, Berry S. PhD, RN†‡; Kose, Samet MD†‡; Li, Xingbao MD†‡; Lim, Kelvin O. MD#; Trivedi, Madhukar H. MD*; George, Mark S. MD†‡

doi: 10.1097/YCT.0b013e3181e6317d
Original Study

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.

From the *Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX; †Center for Advanced Imaging Research and ‡Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina (MUSC), Charleston, SC; §Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX; ∥Academic Radiology, University of Nottingham, Nottingham, UK; ¶Physics and Astronomy, University of South Carolina, Columbia, SC; and #Department of Psychiatry, University of Minnesota, Minneapolis, MN.

Received for publication March 3, 2009; accepted April 8, 2010.

Reprints: F. Andrew Kozel, MD, MSCR, UT Southwestern Medical Center Department of Psychiatry, 5323 Harry Hines Blvd, Dallas, TX 75390-9119 (e-mail:

Dr Kozel received supported from a K23 from the National Institute of Mental Health (5K23MH070897-01) and a VA Special Fellowship in Psychiatric Research/Neurosciences at Ralph H. Johnson VA, Charleston, SC. Neuronetics provided the funding for the rTMS treatment trial at the MUSC and agreed to let us image subjects involved in their trial. Neuronetics did not have any part in image data acquisition, data analysis, or manuscript preparation. A copy of the manuscript was provided for their review and comment before submission. Scanning was performed as a grant-in-kind from the Center for Advanced Imaging Research at MUSC.

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the US Department of Veteran Affairs, the National Institute of Mental Health, the National Institutes of Health, or the US Government.

© 2011 Lippincott Williams & Wilkins, Inc.