BOSTON — A randomized clinical trial conducted by investigators at Mass General Brigham's Neuroscience Institute and Department of Psychiatry suggests that personalized brain imaging to guide transcranial magnetic stimulation (TMS) may improve outcomes for individuals with treatment-resistant depression. The results of this study were published in JAMA Psychiatry on June 24, 2026.

The trial included 40 adults, ranging from 22 to 80 years old, who had major depressive disorder with moderate-to-severe levels of treatment resistance. Participants were randomly assigned to receive accelerated TMS (aTMS) guided by either their connectivity-based brain imaging target or a conventional scalp-based target. Participants and clinical raters remained unaware of the group assignments throughout the study.

One month following treatment, participants who received connectivity-based targeting experienced greater improvement in depressive symptoms compared to those who received scalp-based targeting. These differences in depressive symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). Response rates for the connectivity-based group were 80%, while the scalp-based group had a 60% response rate.

Joseph Taylor, MD, PhD, an investigator on the study, said that the goal of the study was to measure the impact of imaging-based targeting compared to conventional methods. Taylor, who is also the corresponding author of the study, is an Assistant Professor of Psychiatry at Harvard Medical School and holds the Jonathan F. Borus, MD, Endowed Chair in Psychiatry at Mass General Brigham. TMS has received FDA clearance for treating major depressive disorder in adults since 2008.

Conventional TMS treatment target selection typically uses scalp-based measurements. Accelerated TMS delivers multiple treatment sessions per day, condensing a course of treatment from several weeks into a single week. The imaging-based targeting approach utilized resting-state functional connectivity, a type of functional MRI analysis that assesses how different brain regions synchronize while at rest. Taylor stated that previous retrospective analyses had indicated that functional imaging could improve outcomes, but prospective evidence was limited.

The study acknowledged limitations, including a relatively small sample size and a single-site design. Researchers plan to conduct a larger trial to further validate the effectiveness of connectivity-based accelerated TMS across diverse patient populations. They also intend to investigate the long-term effects of this connectivity-based approach.