Clinical Response to fMRI-guided Compared to Non-Image Guided rTMS in Depression and PTSD: A Randomized Trial

Background: Image-guided brain stimulation is hypothesized to enhance clinical outcomes but head-to-head comparisons favoring image-guidance are so far lacking. Methods: PTSD/MDD patients were randomized (N=51) to a two-condition sequence in a two period cross-over design. For the first condition, patients were randomized to 10-session rTMS treatment to either a subgenual cingulate (sgACC) functional connectivity cortical target (fMRI-guided) or standard scalp-based target. Additionally, patients were randomized to either watch a nature video or perform a demanding cognitive task with rTMS administration. Patients crossed over to the two conditions not received in period one. rTMS was delivered in an intermittent theta burst (iTBS) pattern with 2400 pulses per session. Among N=49 patients analyzed, 60% identified as female and average age was 34. Results: Compared with the scalp-based target, fMRI-guided rTMS was superior in improving depression symptoms (F(1,43.92)=5.933, p=0.019) as well as PTSD hyperarousal (F(1,40.78)=5.076, p=0.030). The median level of symptom change for fMRI-guided targets exceeded 60% improvement across both scales. Symptom improvements at 6-mo follow-up were durable and both favored fMRI-guidance. For patients reporting symptoms at this timepoint, depression improved by 70% (N13); the PCL improved by 69% with Hyperarousal (N14) and Avoidance (N12) subscales improving by 78% and 79%, respectively, for the fMRI-guided target. Conclusions: We demonstrated preliminary evidence for the clinical superiority of a new fMRI-guided target which should be followed up with larger comparative effectiveness studies that include imaging and clinical outcomes.