Repetitive Transcranial Magnetic Stimulation for Executive Functioning in Veterans with TBI and PTSD: Clinical Outcomes and Connectivity Changes in a Pilot Randomized Clinical Trial

Research Objectives

To determine the effect of treatment on stimulation site connectivity, a within-patients general linear model compared pre-treatment versus post-treatment connectivity in active versus sham groups. To determine the relationship between connectivity changes and clinical changes, the linear models were modified to include pre-treatment and post-treatment executive functioning and emotional/mood function.

Design

Cross-sectional.

Setting

VA Palo Alto.

Participants

33 Veterans with mild-moderate traumatic brain injury (TBI) were randomized into active or sham treatment groups. All Veterans received identical baseline and post-treatment testing batteries, as well as structural and resting state functional MRI (rsfMRI) scan.

Interventions

Active rTMS was administered to left dlPFC for 20 sessions. Sham treatment used the same coil, but did not administer stimulation. Resting state functional connectivity was computed for the left anterior middle frontal gyrus (aMFG) stimulation site.

Main Outcome Measures

Primary measure for executive functioning was improvement from baseline to post-rTMS treatment performance on Trail Making Test B. Secondary measures included neuropsychological tests of attention and processing speed, as well as self-report measures of depression, PTSD, and quality of life.

Results

There was no difference between sham and active groups in pre- to post-treatment Trails B change scores (Sham =5.5±7.9 vs. Active=1.5±7.3; p>.1). There was no significant effect of rTMS treatment between active and sham groups in Trails B T-score immediately post-treatment (p>0.1). PTSD symptoms did have a significant effect on Trails B T-score immediately post treatment, suggesting that patients with PTSD improved on executive functioning regardless of treatment group. In comparison with sham, active treatment led to a significant decrease in connectivity between the TMS site and the cingulo-opercular network, F(1,22)=7.1, p=0.014. An exploratory analysis revealed that this connectivity change was correlated with improvement in processing speed, as measured by WAIS-IV coding (β=0.34, p< 0.05).

Conclusions

Our results showed that there were no differences between active and sham groups in the primary outcome measure of executive functioning from pre- to post-rTMS treatment. There was an association between executive functioning and PTSD symptoms regardless of treatment group.

Author(s) Disclosures

None.