Reinforcement learning for repetitive transcranial magnetic stimulation protocol selection in treatment-resistant depression

Reinforcement learning for repetitive transcranial magnetic stimulation protocol selection in treatment-resistant depression. Download PDF Abstract Repetitive transcranial magnetic stimulation (rTMS), including intermittent theta-burst stimulation (iTBS), is an established treatment for treatment-resistant depression, but clinicians lack evidence-based guidance for session-level choices among stimulation type, intensity, and laterality. In this study, we investigated whether a reinforcement learning (RL) algorithm trained on routine clinical data could recommend session-level rTMS protocols associated with greater symptom improvement using electronic health record data from 1609 adults treated with rTMS between January 2023 and June 2025 across 19 clinic groups.

Among 370 patients from held-out clinics, treatment decisions matching algorithm recommendations were associated with 0.788 points greater next-session Patient Health Questionnaire-9 improvement than treatments that differed (95% CI: 0.634–0.940). Following every recommendation was projected to produce 3.22 points of additional improvement (95% CI: 2.72–3.75). These findings suggest RL can find treatment patterns associated with greater next-session improvement and potentially meaningful improvement accumulated across a treatment episode.

Explore related subjects Discover the latest articles and news in related subjects. Diseases Health care Medical research Neurology Neuroscience Psychology Funding This work was supported by the National Institute on Drug Abuse under award 1K01DA061975 and the National Institute of Mental Health under award 1UG3MH141096-01. The funders had no role in study design, analysis, or the decision to submit.

Researchers have uncovered three brain pathways linked to lasting improvements in people receiving deep brain stimulation for severe, treatment-resistant depression. They also discovered that patients who failed to improve after two years shared a striking pattern: insufficient stimulation of a crucial brain connection.

The findings suggest that millimeters in electrode placement could make a major difference in treatment outcomes. Scientists uncover 3 key brain pathways linked to lasting depression relief.

The discovery could help researchers make this experimental therapy more precise and effective. Published October 1 in the American Journal of Psychiatry, the research examined the largest group of patients assembled across multiple independent cohorts to date who had received subcallosal cingulate deep brain stimulation (SCC DBS) for treatment-resistant depression.

The researchers found that lasting improvements were consistently associated with electrical stimulation reaching three specific white matter pathways: the cingulum bundle, forceps minor, and medial uncinate fasciculus/ventral amygdalofugal pathways. These findings strengthen the case for using detailed maps of the brain’s connections to determine exactly where electrodes should be implanted, rather than choosing their positions based primarily on anatomical landmarks.

Known as connectome-based targeting, this strategy has already helped shape the ongoing Abbott TRANSCEND clinical trial, a randomized, controlled study that uses individualized brain connectivity maps to guide SCC DBS treatment.

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