Using brain imaging to improve spatial targeting of transcranial magnetic stimulation for depression
Open accessAbstract
Transcranial magnetic stimulation (TMS) is an effective treatment for depression but is limited in that the optimal therapeutic target remains unknown. Early TMS trials lacked a focal target and thus positioned the TMS coil over the prefrontal cortex using scalp measurements. Over time, it became clear that this method leads to variation in the stimulation site and that this could contribute to heterogeneity in antidepressant response. Newer methods allow for precise positioning of the TMS coil over a specific brain location, but leveraging these precise methods requires a more precise therapeutic target. We review how neuroimaging is being used to identify a more focal therapeutic target for depression. We highlight recent studies showing that more effective TMS targets in the frontal cortex are functionally connected to deep limbic regions such as the subgenual cingulate cortex. We review how connectivity might be used to identify an optimal TMS target for use in all patients and potentially even a personalized target for each individual patient. We address the clinical implications of this emerging field and highlight critical questions for future research.
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Most clinical rTMS treatments for MDD occur daily and are applied using scalp-based targeting of DLPFC; these standard treatments are only modestly effective, even in the general MDD population.
“Most clinical rTMS treatments for MDD occur daily (one rTMS session per day) and are applied using scalp-based targeting of DLPFC. These standard treatments are only modestly effective, even in the general MDD population (17, 24–31).”
From Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): rationale, design and methods (2025) · cites this paper as [31]
The ‘Targeting TMS Using Scalp Measurements’ section says scalp-based DLPFC targeting was the most common method in randomized trials. The Conclusions table describes a once-daily regimen, and the opening section reports typical response rates of 29–46% and remission rates of 18–31%. However, the paper discusses these outcomes in the context of treatment-resistant depression; it does not establish the same modest effectiveness for the general MDD population. (LLM, conf=0.84)
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- Authors
- Cash, R. F. H., Weigand, A., Zalesky, A., Siddiqi, S. H., Downar, J., Fitzgerald, P. B., & Fox, M. D.
- Affiliations
- The University of Melbourne (AU)
- Beth Israel Deaconess Medical Center (US)
- University of Toronto (CA)
- Epworth Hospital (AU)
- Brigham and Women's Hospital (US)
- Corresponding author
- Cash, Robin F.H.
- Fox, Michael D.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 90
- Issue
- 10
- Pages
- 689-700
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W3033781588
- Cited by
- 366
- References
- 20
- Citations by year
- 2026: 63 · 2025: 83 · 2024: 71 · 2023: 70 · 2022: 47 · 2021: 27 · 2020: 5
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Funders
- BrainsWay
- Klarman Family Foundation
- Canadian Institutes of Health Research
- Nancy Lurie Marks Family Foundation
- Ontario Brain Institute
- Sidney R. Baer, Jr. Foundation
- National Institute of Mental Health
- Brain and Behavior Research Foundation
- National Institutes of Health
- Arrell Family Foundation
- G. Harold and Leila Y. Mathers Charitable Foundation
- H. Lundbeck A/S
- Fondation Brain Canada
- Australian Research Council (DE200101708)
- Weston Family Foundation
- Toronto General and Western Hospital Foundation
- National Health and Medical Research Council (1136649, 1078567)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- transcranial magnetic stimulation, depression, neuroimaging, functional connectivity, subgenual anterior cingulate cortex, prefrontal cortex, personalized treatment
- MeSH terms
- Brain, Depression, Major Depressive Disorder, Depressive Disorder, Major, Humans, Transcranial Magnetic Stimulation, Neuroimaging
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