Preliminary Guidelines for Safe and Effective Use of Repetitive Transcranial Magnetic Stimulation in Moderate to Severe Traumatic Brain Injury  Dylan M. Nielson, BS, Curtis A. McKnight, MD, Riddhi N. Patel, BS, Andrew J. Kalnin, MD, Walter J. Mysiw, MD  Archives of Physical Medicine and Rehabilitation  Volume 96, Issue 4, Pages S138-S144 (April 2015) DOI: 10.1016/j.apmr.2014.09.010 Copyright © 2015 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 1 Baseline neuroimaging and stimulation target. (A) T1 (top), T2 fluid attenuated inversion recovery (middle), and T2 (bottom) weighted magnetic resonance images from the baseline assessment. These images show extensive cystic encephalomalacia with surrounding gliosis bilaterally in the frontal poles, including the orbitofrontal cortex, and the temporal poles and lateral aspects, with the right greater than the left. Images are shown in radiologic orientation (image right is subject left). (B) Areas correlating with the 13 targets identified as related to responses to right-sided rTMS by Kito et al22 are displayed in orange on a three-dimensional model of the participant's T1-weighted baseline imaging. The stimulation target is shown in red in the right DLPFC. The cortical surface is cutaway slightly in this view to better visualize the stimulation target. The orientation cube in the corner matches the orientation of the model. The green face indicates right; blue face, anterior; and white face, superior. Abbreviations: A, anterior; L, left; R, right; S, superior. Archives of Physical Medicine and Rehabilitation 2015 96, S138-S144DOI: (10.1016/j.apmr.2014.09.010) Copyright © 2015 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 2 Change in depression and depression-related symptoms. (A) Bar charts depicting the average BL score and confidence interval along with the subsequent assessments (PS, F1, F2, F3) for each of the 10 study measures collected. The dashed lines indicate the 95% confidence interval for the BL assessments. The bold dashed line indicates the direction of change corresponding to improvement for that measure. At the PS assessment, 3 measures improved outside of the 95% confidence interval of the BL assessments: HAMD, GAF, and SHPS. These measures continued to improve over the follow-up period. None of the other measures leave the 95% confidence interval of the baseline assessments. (B) The trajectory of the subject's HAMD scores in comparison with data from published studies of rTMS for depression without TBI and pharmacologic treatment of post-TBI depression. In our study, the participant received stimulation over a period of 6 weeks with monthly follow-ups thereafter. His change from the average baseline score is displayed along with the mean change in HAMD scores for the active (n=155) and sham (n=146) stimulation groups reported in a multisite trial of high-frequency (10-Hz) rTMS for depression in participants without TBI, data from O'Reardon et al.4 These subjects received stimulation for 4 weeks with a single follow-up assessment at 6 weeks. For further comparison, we also display the results of a smaller trial of sertraline (n=22) versus placebo (n=19) for treatment of post-TBI depression, data from Ashman et al.27 These subjects received treatment for 10 weeks. To facilitate comparison with these other studies, the study day is referenced to the start of the intervention. Abbreviations: BHS, Beck Hopelessness Scale; BL, baseline; F1, follow-up 1; F2, follow-up 2; F3, follow-up 3; GAD-7, Generalized Anxiety Disorder 7-Item Scale; Mr. E, our study participant; PS, poststimulation; SSES, State Self-Esteem Scale. Archives of Physical Medicine and Rehabilitation 2015 96, S138-S144DOI: (10.1016/j.apmr.2014.09.010) Copyright © 2015 American Congress of Rehabilitation Medicine Terms and Conditions