Individualizing TMS treatment targets for PTSD using neuroimaging: Preliminary findings from an ongoing clinical trial

Abstract

Abstract Introduction: Transcranial Magnetic Stimulation (TMS) to the right dorsolateral prefrontal cortex (rDLFPC) is safe and effective for treating posttraumatic stress disorder (PTSD); however, treatment efficacy can likely be improved by individualizing TMS targets using neuroimaging. The right amygdala is a prime candidate given its importance for fear processing and its role in PTSD development, maintenance, and treatment non‐response. However, the amygdala cannot be targeted directly with TMS. Here we use functional connectivity (FC) to define individualized TMS treatment targets and assess target stability. Methods: In this ongoing sham‐controlled double‐blind TMS clinical trial for PTSD (current N=12; NCT04563078), pre‐TMS resting‐state (RS)FC was used to define the area within the rDLPFC most strongly positively connected with the right amygdala for each patient. Using Brainsight neuronavigation, this individualized target was stimulated twice daily with 1Hz (1800 pulses) over 10 weekdays. A second RS scan was collected in the same pre‐TMS scan visit after the amygdala was probed using threatening faces, inhibition, and fear conditioning tasks. Individual variability and target stability were analyzed by comparing the target location using X, Y, Z coordinates for RS scan 1 and 2 using a 3 (coordinates) * 2 (scan 1 vs 2) within‐subject repeated measures ANOVA. Results: Neuroimaging data indicated significant variability in target location between patients (F(1,11)=209.31, p<0.001). The change in target location between RS scan 1 and 2 was not significant (F(1,11)=0.21, p=0.66). Discussion: TMS target locations varied between patients, suggesting the importance of individualized targeting. Second, the target location did not significantly change within patients after probing the fear neurocircuitry using fMRI tasks, suggesting the rDLPFC as defined by this RSFC method is a stable target. Study limitations include the small N and double‐blind nature of this ongoing clinical trial; more data will be available during the meeting. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Posttraumatic Stress Disorder (PTSD), Resting state functional connectivity (RSFC), Neuronavigation, Fear neurocircuitry