A causal sympathetic arousal circuit and potential neuromodulation target

A causal sympathetic arousal circuit and potential neuromodulation target | 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 Biological Sciences - Article A causal sympathetic arousal circuit and potential neuromodulation target Ryan Webler, Clemens Neudorfer, Eva Dijkstra, Summer Frandsen, and 18 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9247823/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Causal modulation of sympathetic arousal could yield new therapeutic targets for sympathetic hyperactivation. We employed a natural experiment in which different brain regions were incidentally targeted using transcranial magnetic stimulation (TMS) (n=139 sites, n=14 individuals), deep brain stimulation (n=392 sites, n=58 individuals), or low-intensity focused ultrasound (n=46 sites, n=23 individuals). Using the human connectome (n=1000) as a wiring diagram, we identified a convergent brain circuit connecting focal neuromodulation sites that preferentially modified sympathetic arousal across all three modalities. In independent datasets, TMS to the sympathetic circuit reduced anxiety-related sympathetic arousal on a laboratory task (n=28) and clinical questionnaire (n=30). The sympathetic circuit aligned with lesion-derived circuits previously linked to sympathetic hyperactivation (i.e., aggression, anxiety, PTSD), but not other eight other lesion circuits. It was also more similar to a map of norepinephrine transporter distribution versus 20 other neurotransmitters. This sympathetic circuit may be a promising treatment target for sympathetic hyperactivation. Biological sciences/Neuroscience/Neural circuits Biological sciences/Neuroscience/Diseases of the nervous system Full Text Additional Declarations There is NO Competing Interest. Supplementary Files NatureSM.docx Supplementary Materials Cite Share Download PDF Status: Under Review 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-9247823","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":617246594,"identity":"c0a07b9e-34ca-4ab3-b405-4186b5a222df","order_by":0,"name":"Ryan 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