Functional brain imaging can help guide accelerated TMS for depression

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. 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."

Joseph Taylor, MD, PhD, corresponding author, the Jonathan F. Borus, MD, Endowed Chair in Psychiatry, Mass General Brigham and Assistant Professor of Psychiatry, Harvard Medical School

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.