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Targeting depression circuitry with H1 coil Transcranial Magnetic Stimulation: a retrospective circuit mapping study

Neuropsychopharmacology volume 50, pages 1674–1682 (2025)Cite this article

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Abstract

The efficacy of transcranial magnetic stimulation (TMS) for depression may depend on targeting specific brain circuits. However, this has not been tested for TMS with the H1 coil, a widely used device believed to target more broadly and deeply than TMS with figure-of-8 coils. This study examined whether targeting a specific brain circuit with H1 coil TMS treatment may impact depressive symptom improvement. We retrospectively analyzed data from 97 patients at McLean Hospital, who received at least 19 TMS sessions and had incidentally completed an anatomical brain MRI. We modeled each patient’s electric (E-)field using SimNIBS and estimated the connectivity of the E-field using a normative connectome (n = 1000), which was correlated with depression improvement as measured by the Quick Inventory of Depressive Symptomatology. H1 E-fields improving depression were preferentially connected to a distinct brain circuit, validated with leave-one-out cross-validation (p = 0.0005). This circuit was significantly similar to a predefined causal depression circuit (spatial r = 0.59, p = 0.04) derived from TMS, deep brain stimulation, and lesion studies. E-fields with greater connectivity similarity to this circuit led to greater symptom improvement (r = 0.41, p < 0.001). Post-hoc analyses revealed that more posterior coil positioning increases H1 E-field overlap with the depression circuit, with high overlap at scalp locations 3–6 cm anterior to the motor hotspot. Thus, H1 coil stimulation sites that improve depression converge on a common causal depression circuit. Prospective studies are needed to validate these findings.

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Fig. 1: Schematic representation of modelling pipeline.
Fig. 2: Clinical outcome is not significantly related to stimulation of brain regions when not considering the underlying brain circuit.
Fig. 3: H1 E-fields that preferentially improve depression are connected to a distinct brain circuit.
Fig. 4: The H1 coil depression circuit is significantly similar to the a priori convergent depression circuit from Siddiqi et al. (2021).
Fig. 5: Simulations of optimal target location maximizing overlap with the convergent depression circuit.

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Data will be shared upon presenting a research proposal to the corresponding author, and signing an institutional data sharing agreement.

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Funding

The current study was supported by an investigator-initiated grant to SHS from BrainsWay Ltd (Jerusalem, Israel), and the NIH (grant nos. K23MH121657 and R21MH126271).

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Authors and Affiliations

  1. Center for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Boston, MA, USA

    Samantha Baldi, Nicole Chiulli, Stephan Palm, Summer Frandsen, Josias Rodriguez-Ponde & Shan H. Siddiqi

  2. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Samantha Baldi, Joshua C. Brown & Shan H. Siddiqi

  3. Department of Life Sciences and the Zlotowski Centre for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Gaby S. Pell & Samuel Zibman

  4. BrainsWay Ltd., Jerusalem, Israel

    Gaby S. Pell & Samuel Zibman

  5. Transcranial Magnetic Stimulation Service, McLean Hospital, Belmont, MA, USA

    Joshua C. Brown

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  1. Samantha Baldi
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  9. Shan H. Siddiqi
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Contributions

SB, GSP, SZ, SHS: conception and design of the work, the analyses, and the interpretation of the results. SB: writing of the manuscript, analysis of the data. NC, SP, SF, JRP: acquisition of the data, analysis of the data. GSP, SZ, SHS, JCB: critical feedback for intellectual content to the manuscript. All authors have approved the manuscript in its final form.

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Correspondence to Samantha Baldi.

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Competing interests

GP and SZ are employed by and have a financial interest in BrainsWay. JCB receives financial support as an editorial stipend from Elsevier. JCB effort is supported by the Brain & Behavior Research Foundation Young Investigator Grant, (#31748), the Cindy & Paul Gamble Fund, the Marlene Zuckerman Fund, the McLean Hospital Center of Excellence in Depression and Anxiety Disorders, and the Department of Defense Advanced Research Projects Agency (HR00112320037). The views, opinions and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. SHS serves as a consultant for Kaizen Brain Center, Acacia Mental Health, and Magnus Medical. SHS owns stock in BrainsWay Inc (publicly traded) and Magnus Medical (not publicly traded). SHS owns independent intellectual property on the use of brain network mapping to target neuromodulation. SHS effort is supported by the NIH (grant nos. K23MH121657 and R21MH126271), the Brain and Behavior Research Foundation Young Investigator Grant, the Baszucki Brain Research Fund and the Department of Veterans Affairs (grant no. I01CX002293). The remaining authors declare no competing interests.

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Baldi, S., Chiulli, N., Palm, S. et al. Targeting depression circuitry with H1 coil Transcranial Magnetic Stimulation: a retrospective circuit mapping study. Neuropsychopharmacol. 50, 1674–1682 (2025). https://doi.org/10.1038/s41386-025-02157-5

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