Effect of rTMS on fractional anisotropy, radial diffusivity, and axonal volume in select fiber tract
Poster No:
1794
Submission Type:
Abstract Submission
Authors:
John Coetzee1, Xiaojian Kang2, Tim Herron3, Maheen Adamson4
Institutions:
1Stanford, Palo Alto, CA, 2VA Palo Alto Health Care System, Palo Alto, CA, 3VA Northern California Health Care System, Martinez, CA, 4Women’s Operational Military Exposure Network Center of Excellence, Palo Alto, CA
First Author:
Co-Author(s):
Maheen Adamson, PhD
Women’s Operational Military Exposure Network Center of Excellence
Palo Alto, CA
Women’s Operational Military Exposure Network Center of Excellence
Palo Alto, CA
Introduction:
Many returning OEF/OIF Veterans with concussion histories report cognitive problems that last for months or years (Holtkamp et al., 2016). Comorbid conditions such as PTSD may prolong symptoms of TBI (Cifu et al., 2013). We conducted a pilot study where Veterans with TBI were treated with rTMS (Active vs. Sham) to improve executive function. DTI data was analyzed using the Automated Fiber Quantification (AFQ) method in which software identifies 20 major fiber tracts and subdivides the central portion of each into 100 segments (Yeatman et al., 2012). This allows for a more granular characterization of white matter changes compared to standard DTI. TBI patients frequently experience white matter degeneration, and this may underlie many sequalae (Main et al., 2017). One route by which rTMS may help TBI symptoms is by promoting the release of BDNF (Brunoni et al., 2008). In this longitudinal study (three timepoints) we tested whether rTMS could improve white matter integrity. There were a number of fiber tracts of interest, because of either spatial proximity to left DLPFC, or association with symptoms.
Methods:
33 Veterans with TBI (mild (n = 27) and moderate (n = 6) enrolled in either the treatment (n = 17) or the sham (n = 16) arm in an RCT conducted at the VAPA. Treatment was administered over left DLPFC with intensity 120% of MT in 80 five-second trains at 10 Hz frequency with 10-second inter-train interval (20 sessions total). All participants underwent MRIs (pre and post and 6 month followup) using standard 8 channel head coil at GE 3T MRI at VAPA: a high-resolution structural MRI, DTI and resting state fMRI. DTIs were processed by the AFQ pipeline (Yeatman et al. 2012). Data was preprocessed. Then z scores of magnitude >3 were eliminated. LMM analysis of the z-scores was done using the R (v 3.6.3) package "lme4" (v 1.1-21-2). Dependent variables in model included Session(time), Treatment Group, Session X Treatment, PCL score and Age at enrollment, and fiber location. The first 5 (orthogonal) Legendre polynomials of sample location were used to model up to fifth order spatial variation (i.e. linear, quadratic, etc.) in the diffusion quantity z-scores. Control fibers (IFOF, forceps major, arcuate, corticospinal tract) were analyzed in order to look for data variability and large spurious effects. All 5 spatial location polynomial terms were often significant in the FA and RD z-score LMMs and thus were kept in the following analyses. For fibers of interest, we looked for the following pattern: significant increases at times 2 (post) and 3 (6 mo) in FA zscores for the rTMS group, and conversely significant drops at times 2 and 3 in RD z-scores for the rTMS group (i.e. the Session X Group interaction term in both cases).
Results:
At the immediate post timepoint, differences in FA and RD in excess of the standard error were present for the cingulate hippocampus (CH) and for the uncinate (UN). For the CH FA was higher for sham, and RD was higher for active, but these disappeared by the 6 month timepoint. For the UN, RD was higher for sham, but this difference disappeared by the 6 month timepoint. At the 6 month timepoint, differences existed for the arcuate (RD higher for sham), the cingulum cingulate (FA higher for active, RD higher for sham), and the inferior longitudinal fasciculus (ILF) (FA higher for active, RD higher for sham).
Conclusions:
Our results suggest that rTMS treatment of TBI patients may enhance white matter integrity in specific fiber tracts. Larger FA and lower RD values are associated with better structural integrity in white matter. This was especially pronounced at the ILF, which is important, given that this tract is frequently damaged in TBI and is implicated in a variety of TBI associated cognitive deficits. One potential pathway for this improvement is increased release of BDNF resulting from rTMS therapy. This supports increased efforts at developing rTMS as a promising new treatment for TBI.
Brain Stimulation:
TMS
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 1
Keywords:
Degenerative Disease
Transcranial Magnetic Stimulation (TMS)
Trauma
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Provide references using APA citation style.
Cifu, D. X., Taylor, B. C., Carne, W. F., Bidelspach, D., Sayer, N. A., Scholten, J., & Campbell, E. H. (2013). Traumatic brain injury, posttraumatic stress disorder, and pain diagnoses in OIF/OEF/OND Veterans. Journal of Rehabilitation Research and Development, 50(9), 1169–1176. https://doi.org/10.1682/JRRD.2013.01.0006
Holtkamp, M. D., Grimes, J., & Ling, G. (2016). Concussion in the Military: An Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache. Current Pain and Headache Reports, 20(6), 37. https://doi.org/10.1007/s11916-016-0572-x
Main, K. L., Soman, S., Pestilli, F., Furst, A., Noda, A., Hernandez, B., Kong, J., Cheng, J., Fairchild, J. K., Taylor, J., Yesavage, J., Wesson Ashford, J., Kraemer, H., & Adamson, M. M. (2017). DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans. NeuroImage. Clinical, 16, 1–16. https://doi.org/10.1016/j.nicl.2017.06.031