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White matter integrity and functional predictors of response to repetitive transcranial magnetic stimulation for posttraumatic stress disorder and major depression.

Authors
  • Barredo, Jennifer1, 2
  • Bellone, John A1, 2
  • Edwards, Melissa1
  • Carpenter, Linda L1, 3
  • Correia, Stephen1, 2, 3
  • Philip, Noah S1, 2, 3
  • 1 Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island.
  • 2 Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island.
  • 3 Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island.
Type
Published Article
Journal
Depression and anxiety
Publication Date
Nov 01, 2019
Volume
36
Issue
11
Pages
1047–1057
Identifiers
DOI: 10.1002/da.22952
PMID: 31475432
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Recent evidence suggests that therapeutic repetitive transcranial magnetic stimulation (TMS) is an effective treatment for pharmacoresistant posttraumatic stress disorder (PTSD) and comorbid major depressive disorder (MDD). We recently demonstrated that response to 5 Hz TMS administered to the dorsolateral prefrontal cortex was predicted by functional connectivity of the medial prefrontal (MPFC) and subgenual anterior cingulate cortex (sgACC). This functionally-defined circuit is a novel target for treatment optimization research, however, our limited knowledge of the structural pathways that underlie this functional predisposition is a barrier to target engagement research. To investigate underlying structural elements of our previous functional connectivity findings, we submitted pre-TMS diffusion-weighted imaging data from 20 patients with PTSD and MDD to anatomically constrained tract-based probabilistic tractography (FreeSurfer's TRActs Constrained by UnderLying Anatomy). Averaged pathway fractional anisotropy (FA) was extracted from four frontal white matter tracts: the forceps minor, cingulum, anterior thalamic radiations (ATRs), and uncinate fasciculi. Tract FA statistics were treated as explanatory variables in backward regressions testing the relationship between tract integrity and functional connectivity coefficients from MPFC and sgACC predictors of symptom improvement after TMS. FA in the ATRs was consistently associated with symptom improvement in PTSD and MDD (Bonferroni-corrected p < .05). We found that structural characteristics of the ATR account for significant variance in individual-level functional predictors of post-TMS improvement. TMS optimization studies should target this circuit either in stand-alone or successive TMS stimulation protocols. © Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

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