186 Targeting rumination in depression with transcranial magnetic stimulation

Objectives/Goals: Major depression is a common, debilitating illness. Rumination is common in depression and associated with worse outcomes. Hyperconnectivity within the Default Mode Network, particularly from ventromedial frontal cortex, underlies rumination. This study uses TMS to target this network and symptom. Methods/Study Population: This is a single-site open-label pilot K12 study that aims to recruit n = 20 adult patients with major depressive disorder. The study intervention is 20 once-daily sessions consisting of 1800 pulses of image-guided continuous theta burst stimulation (cTBS) to the ventromedial prefrontal cortex within the default mode network. Participants will undergo three MRI scans: prior to first TMS, early in the treatment course, and post-TMS. The first MRI includes a high-resolution structural scan used for TMS targeting. All scans include resting state and task-based fMRI. Outcomes include rumination (Ruminative Response Scale) and depression (Hamilton Depression Rating Scale) scores, as well as connectivity in functional MRI. Results/Anticipated Results: At the time of this writing, four participants have completed the study; two additional participants dropped out (one due to family circumstances and one due to MRI claustrophobia). The intervention and other study procedures have been well tolerated, and no serious adverse events have occurred. All participants showed decreased depression and rumination scores at the end of the intervention compared to pretreatment baseline; repeated measures general linear models indicate statistically significant effects for both overall depression and rumination. We anticipate updated symptom-based and preliminary fMRI results at the conference. Discussion/Significance of Impact: This image-guided novel TMS protocol appears to be well tolerated in our target population and feasible at our institution. Preliminary results for depression and rumination symptoms, although open label with a very small sample, are promising. We aim to complete the study by July 2026.