Summary: A new randomized clinical trial suggests that using personalized brain imaging to guide transcranial magnetic stimulation (TMS) may significantly improve outcomes for people with treatment-resistant depression. Investigators demonstrated that targeting brain stimulation based on an individual’s unique functional magnetic resonance imaging (fMRI) scan yields greater antidepressant effects than traditional, scalp-based measurements.
The trial leveraged accelerated TMS (aTMS), a cutting-edge approach that delivers multiple treatment sessions per day, condensing a standard multi-week treatment course into a single week. By analyzing resting-state functional connectivity to track how different brain regions synchronize at rest, researchers were able to pinpoint customized neural circuit targets.
One month post-treatment, patients who received this individualized, connectivity-based targeting showed substantially greater symptom reduction and higher response rates than the group mapped with conventional scalp measurements, paving the way for more precise, scaled psychiatric interventions.
Key Facts
- The Personalization Advantage: Selecting aTMS treatment targets via individual fMRI scans provides a significant clinical advantage over conventional, scalp-measurement methods that ignore personal variations in neural circuitry.
- Condensed Treatment Window: The study utilized accelerated TMS (aTMS), which delivers multiple magnetic pulse sessions per day, condensing a standard multi-week therapy timeline down to just one week.
- Superior Remission & Response: One month after therapy, the connectivity-based imaging group achieved an 80% response rate compared to a 60% response rate in the traditional scalp-targeted group.
- Objective Evaluation: Symptom improvements were rigorously verified using the Montgomery-Åsberg Depression Rating Scale (MADRS), with both the trial participants and clinical evaluators kept strictly blinded to the targeting assignments.
- Prospective Validation: This study moves past mere retrospective hints, delivering concrete, prospective evidence that functional neuroimaging can be scaled directly to improve psychiatric patient care.
Source: Mass General
Mass General Brigham study suggests that functional brain imaging can help guide accelerated transcranial magnetic stimulation for depression.
A new randomized clinical trial from investigators at Mass General Brigham’s Neuroscience Institute and Department of Psychiatry suggests that using personalized brain imaging to guide transcranial magnetic stimulation (TMS) may improve outcomes for people with treatment-resistant depression. Results are published in JAMA Psychiatry.
TMS is a non-invasive form of brain stimulation that uses magnetic pulses to modulate brain activity. TMS has had FDA clearance for treating major depressive disorder in adults since 2008 and is often used for treating depression that has not responded to standard treatments.
However, the conventional way to select the TMS treatment target relies on scalp-based measurements. These methods are practical and widely available, but they do not account for individual differences in brain circuits involved in depression.
In the new study, researchers tested whether TMS has larger antidepressant effects when treatment targets are selected using an individual’s functional magnetic resonance imaging (fMRI) scan rather than conventional scalp-based targeting.
The researchers leveraged accelerated TMS (aTMS), an approach that delivers multiple treatment sessions per day and can condense a course of treatment from several weeks into a single week. Their imaging-based targeting approach used resting-state functional connectivity, a type of functional MRI analysis that measures how different brain regions synchronize with one another at rest.
“Neuroimaging has taught us a tremendous amount about the brain, but it has been difficult to show that imaging can directly improve patient care,” said corresponding author Joseph Taylor, MD, PhD, the Jonathan F. Borus, MD, Endowed Chair in Psychiatry at Mass General Brigham and an Assistant Professor of Psychiatry at Harvard Medical School.
“It is important to address this knowledge gap because imaging adds cost and complexity to TMS treatment. In this study, our goal was to measure how much impact our approach to imaging-based targeting would have above and beyond conventional scalp-based targeting.”
The randomized trial included 40 adults, aged 22 to 80 years old, with major depressive disorder and moderate-to-severe levels of treatment resistance. Before treatment, each participant underwent an fMRI scan. Participants were then randomized to receive aTMS, using either their connectivity-based target or their scalp-based target. Participants and clinical raters were blinded to group assignment.
One month after treatment, participants who received connectivity-based targeting had significantly greater improvement in depressive symptoms than those who received scalp-based targeting. These differences were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), a widely used clinician-rated measure of depression severity. Response rates were also higher in the connectivity-based group, with 80% of participants meeting response criteria compared with 60% in the scalp-based group. Taken together, the results suggest that connectivity-based targeting may have a clinically meaningful impact on outcomes for people receiving aTMS for treatment-resistant depression.
The findings build on previous research by Taylor, including a recent trial published in Molecular Psychiatry that examined circuit-targeted modulation of anxiety symptoms in individuals with major depression.
“Retrospective analyses have hinted that functional imaging could be used to improve outcomes, but prospective evidence has been limited,” Taylor said.
“Our recent clinical trials provide prospective evidence that there may be clinical advantages to using functional imaging to guide aTMS treatment. These findings are important as aTMS becomes more widely available and decisions are made about how to scale this intervention for patients with depression and other psychiatric illnesses.”
The researchers note that the study has several limitations, including a relatively small sample size and single-site design. They plan to conduct a larger trial to further validate the efficacy of connectivity-based aTMS in diverse patient populations and to investigate the long-term effects of this treatment approach.
Authorship: In addition to Taylor, Mass General Brigham authors include Marina R. Kare, Dania Haj-Darwish, Emma Jones, Lauren Sanderson, Sanaz Khosravani, Jessica Leach, Leanna Bomer, Natalie Hall, Nicole Chiulli, Christopher Lin, William Drew, Stephan T. Palm, Anjali Chandra, Summer B. Frandsen, Anastasia Bekou, Tracy Barbour, Sheena R. Baratono, Irene Gonsalvez, Stanley Lyndon, Fredric L.W.V.J. Schaper, David Silbersweig, Shan H. Siddiqi, and Michael D. Fox. Additional authors include Elizabeth Steuber and Wei Wang.
Disclosures: Taylor reported grants from the Brain and Behavior Research Foundation during the conduct of the study. Taylor, Fox, and Siddiqi are coinventors on a provisional patent application related to methods described in this study. Siddiqi and Fox report consultancy fees from companies. Additional author disclosures can be found in the paper.
Funding: Study funded by the Brain and Behavior Research Foundation (31081). Taylor received funding from Harvard Medical School (Dupont Warren Fellowship Award, Livingston Award), Sidney R. Baer, Jr. Foundation, Baszucki Brain Research Fund, Mass General Brigham Women’s Brain Initiative, Mass General Brigham Accelerator Award, and the NIH (K23MH129829, R01MH113929).
Key Questions Answered:
A: Traditional TMS is an FDA-cleared, non-invasive method that uses magnetic pulses to stimulate brain regions tied to depression, typically spaced out over several weeks. Accelerated TMS (aTMS) condenses this timeline into a single week by administering multiple sessions per day. Because this high-density format delivers therapy rapidly, using functional neuroimaging (fMRI) ensures the intense stimulation is tuned precisely to the patient’s unique, resting-state brain network connectivity rather than an estimated physical scalp location.
A: The researchers tracked clinical improvement one month post-treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), a gold-standard clinician-rated metric for depression severity. Patients mapped with individualized fMRI connectivity targets showed significantly greater reduction in depressive symptoms. Furthermore, the overall response rate reached 80% in the connectivity-mapped group, compared to just 60% in the group that received standard scalp-based targeting.
A: The primary limitations of this randomized trial are its relatively small sample size (40 adult participants) and its single-site design. To build on these promising findings, the researchers plan to launch a larger, multi-site clinical trial. This next phase will further validate the efficacy of connectivity-based aTMS across highly diverse patient populations and investigate the long-term sustainability of the treatment’s antidepressant effects over time.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this TMS and depression research news
Author: Cassandra Falone
Source: Mass General
Contact: Cassandra Falone – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Connectivity- versus scalp-based targeting of accelerated TMS for depression: A randomized trial” by Joseph J. Taylor, Marina R. Kare, Dania Haj-Darwish, Emma Jones, Lauren Sanderson, Sanaz Khosravani, Jessica Leach, Leanna Bomer, Natalie Hall, Nicole Chiulli, Elizabeth Steuber, Christopher Lin, William Drew, Stephan T. Palm, Anjali Chandra, Summer B. Frandsen, Anastasia Bekou, Tracy Barbour, Sheena R. Baratono, Irene Gonsalvez, Stanley Lyndon, Frederic L. W. V. J. Schaper, Wei Wang, David Silbersweig, Shan H. Siddiqi, Michael D. Fox. JAMA Psychiatry
DOI:10.1001/jamapsychiatry.2026.1100
Abstract
Connectivity- versus scalp-based targeting of accelerated TMS for depression: A randomized trial
Importance
Neuroimaging is prevalent in psychiatric research, but there is limited evidence that it improves clinical outcomes. Functional connectivity neuroimaging was recently used to target individualized brain circuits with accelerated transcranial magnetic stimulation (aTMS), with rapid antidepressant effects and US Food and Drug Administration clearance, but the importance of connectivity-based targeting remains unclear.
Objective
To estimate the effect size of connectivity- vs scalp-based targeting of aTMS for treatment-resistant depression.
Design, Setting, and Participants
This randomized clinical trial comparing connectivity- to scalp-based aTMS treatment was conducted between July 2023 and March 2025 with the primary outcome assessed at 1 month posttreatment and follow-up every 3 months for 1 year. Participants, TMS technicians, and study physicians were blinded.
The study took place at the Center for Brain Circuit Therapeutics at Mass General Brigham and Harvard Medical School in Boston, Massachusetts. Forty adults aged 22 to 80 years with a primary diagnosis of major depressive disorder with moderate to severe depression per Montgomery-Åsberg Depression Rating Scale (MADRS) score and moderate to severe treatment resistance per Maudsley Staging Method were included.
Key exclusion criteria included contraindications to TMS or magnetic resonance imaging, primary psychiatric diagnoses other than major depressive disorder or anxiety disorders, recent rapid-acting antidepressant treatments, and significant neurological or substance use disorders.
Interventions
All participants underwent a 41-minute multiecho resting-state functional connectivity scan prior to aTMS, and half of them received treatment guided by these data. The connectivity-based target was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions linked to depression, including negative connectivity to the subgenual cingulate cortex. The scalp-based target was identified with the Beam F3 method.
Main Outcomes and Measures
MADRS score 1 month after treatment, adjusted for baseline.
Results
In total, 40 participants (22 female [55%]; mean [SD] age, 45.7 [15.2] years) were randomized and treated. The median (IQR) MADRS score reduction was 24 (19-28) vs 18 (10-23) points with connectivity- vs scalp-based targeting, respectively (P = .02). Connectivity-based targeting had an effect size of 0.8 (Cohen d analog) and 95% CI of 0.26-1.54, with a number needed to scan of 5 individuals. Individualized targets were reproducible within an individual (4.47 mm split-half distance) and different between individuals (12.97 mm) (P < .001).
Conclusions and Relevance
In this randomized clinical trial, individualized, connectivity-based targeting of the convergent depression circuit enhanced the antidepressant effects of high-dose aTMS. These results could facilitate cost-effectiveness analyses and help to power a confirmatory efficacy trial.
Trial Registration
ClinicalTrials.gov Identifier: NCT05680727
