In the latest neurocare Academy interview, Dr. Trevor Brown speaks with Dr. Shan Siddiqi, Assistant Professor of Psychiatry at Harvard Medical School, about a recent randomized clinical trial exploring a new approach to TMS treatment selection. The study examined whether stimulating different brain circuits could lead to different outcomes in patients experiencing both depression and anxiety.
While TMS has become an established treatment option for depression, clinicians frequently encounter patients whose symptoms extend beyond depression alone. Anxiety disorders, obsessive-compulsive symptoms, and chronic worry often coexist with depression, raising important questions about whether the same stimulation target is optimal for every patient.
Different Symptoms, Different Circuits
Dr. Siddiqi and his colleagues have spent several years investigating how distinct symptom clusters map onto different brain networks.
Previous work identified two functional circuits associated with different symptom dimensions. One circuit, linked to the dorsomedial prefrontal cortex (DMPFC), appeared to be associated more strongly with anxiety-related symptoms. Another, associated with the dorsolateral prefrontal cortex (DLPFC), aligned more closely with depressive symptoms.
To test whether these differences could translate into meaningful clinical outcomes, the team conducted a randomized head-to-head trial comparing stimulation of these targets in patients experiencing both depression and anxiety.
The findings were noteworthy. Patients receiving stimulation of the anxiety-related target experienced substantially greater improvements in anxiety symptoms while achieving comparable improvements in depressive symptoms.
For Dr. Siddiqi, the most significant finding was not that the traditional depression target worked - which is already well established - but that a different target appeared capable of addressing anxiety symptoms more effectively in this specific patient population.
A Step Toward Precision Psychiatry
One of the central themes of the discussion was precision psychiatry.
Rather than viewing depression as a single condition requiring a single intervention, the study supports a growing body of evidence suggesting that treatment strategies may need to be adapted to individual symptom profiles.
Importantly, Dr. Siddiqi emphasised that, even though patients in both groups improved their depression equally, the findings should not be interpreted as evidence that all patients with depression (with or without anxiety) should receive dorsomedial stimulation. The trial specifically enrolled patients with significant anxiety alongside depression, and further work is needed to better define which patients are most likely to benefit from each target.
Research is already underway to identify biomarkers and behavioural profiles that could support more personalised target selection in the future.
From Research to Clinical Practice
One of the most encouraging aspects of the study is its potential clinical practicality.
As highlighted during the interview, the methods used in the trial can largely be translated into everyday clinical settings. The target investigated in the study can often be identified using straightforward scalp-based measurements and stimulated using standard figure-eight coils commonly available in TMS clinics.
This is an important consideration for any new protocol. Scientific advances are most impactful when they can be implemented safely and consistently in real-world clinical environments.
Building on a Growing Evidence Base
The study itself involved a relatively modest number of participants, but the discussion highlighted that it forms part of a much larger body of work.
According to Dr. Siddiqi, the target selection strategy has been informed by multiple previous datasets involving hundreds of patients across TMS, deep brain stimulation, lesion-network mapping and neuroimaging research. Additional studies have produced findings that support the clinical relevance of the dorsomedial target, particularly in patients with prominent anxiety symptoms.
This growing accumulation of evidence has led some centres, including Dr. Siddiqi's own clinical programme, to begin implementing the approach in carefully selected patients while further research continues.
Looking Ahead
The conversation concluded with a look toward the future of individualized brain stimulation.
As researchers continue investigating imaging biomarkers, symptom-based phenotypes and circuit-specific interventions, TMS may increasingly move beyond diagnostic labels toward more personalized treatment strategies.
While further replication and validation remain essential, this work offers a compelling example of how advances in neuroscience can help refine and improve care for patients living with complex mental health conditions.
Related publication
Readers interested in the full study can access the publication discussed in this interview:
Taylor J, Siddiqi SH et al. "Circuit-targeted modulation of anxiety symptoms in individuals with major depression: A randomized head-to-head TMS trial" - Read the paper in Molecular Psychiatry.
Watch the Full Interview
This article highlights some of the key insights from our conversation with Dr. Shan Siddiqi. To hear the full discussion - including the study design, practical implications for clinical implementation, and future directions for precision psychiatry - watch the complete neurocare Academy interview below.
Watch the full YouTube Video
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