Symptom-specific brain circuit stimulation: A head-to-head randomized trial

Symptom-specific brain circuit stimulation: A head-to-head randomized trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Symptom-specific brain circuit stimulation: A head-to-head randomized trial Joseph Taylor, Jing Li, Christopher Lin, Emma Jones, Summer Frandsen, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4791291/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Mar, 2026 Read the published version in Molecular Psychiatry → Version 1 posted You are reading this latest preprint version Abstract Transcranial magnetic stimulation (TMS) is effective for major depressive disorder (MDD) despite imprecise scalp-based targeting. Retrospective analyses suggest that targeting one brain circuit improves “dysphoric” symptoms, while targeting a different brain circuit improves “anxiosomatic” symptoms. Here, we tested this hypothesis prospectively. Individuals with moderate-to-severe MDD and moderate-to-severe anxiety (n=40) were randomized to receive TMS with dysphoric circuit targeting (dorsolateral prefrontal cortex) or anxiosomatic circuit targeting (dorsomedial prefrontal cortex). As hypothesized, dysphoric circuit targeting (n=16) improved BDI more than BAI (ratio 1.08, IQR 0.69-2.02), while anxiosomatic circuit targeting (n=20) improved BAI more than BDI (ratio 0.70, IQR 0.01-1.01) (Wilcoxon rank-sum test p=0.0195). This result was driven by larger improvements in anxiety with -anxiosomatic circuit targeting (p=0.0301). Thus, TMS targeting different brain circuits differentially modulates comorbid anxiety and depression symptoms. Symptom- and circuit-specific trial designs may improve power and better control for placebo and non-specific effects. Health sciences/Medical research/Translational research Biological sciences/Neuroscience Full Text Additional Declarations Yes there is potential Competing Interest. SS: Owner of intellectual property involving the use of brain connectivity to target TMS, scientific consultant for Magnus Medical, investigator-initiated research funding from Neuronetics and Brainsway, speaking fees from Brainsway and Otsuka (for PsychU.org), shareholder in Brainsway (publicly traded) and Magnus Medical (not publicly traded). None of these entities were involved in the present manuscript. MDF: Scientific consultant for Magnus Medical, owns independent intellectual property involving the use of functional connectivity to target TMS. This intellectual property was not used in the present manuscript. All other others deny conflicts of interest. It was approved by the Mass General Brigham Institutional Review Board (2020P002296) and posted on ClincialTrials.gov (NCT04604210). Supplementary Files IRBprotocol101320002.docx Cite Share Download PDF Status: Published Journal Publication published 30 Mar, 2026 Read the published version in Molecular Psychiatry → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4791291","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":356487035,"identity":"2a1b0314-13d7-4725-bfc5-ae07b7669071","order_by":0,"name":"Joseph 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