Whole-Brain c-Fos Connectomics Reveals Biphasic Integration-Distribution Architecture in Valence-Specific Emotional Processing

Whole-Brain c-Fos Connectomics Reveals Biphasic Integration-Distribution Architecture in Valence-Specific Emotional Processing | 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 Whole-Brain c-Fos Connectomics Reveals Biphasic Integration-Distribution Architecture in Valence-Specific Emotional Processing Xiang-Shan Yuan, Hanglei Lin, Ming-yi Huang, Ning-yuan Fu, Jin-sen Xi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7794939/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Emotions emerge from coordinated neural dynamics across distributed brain circuits, but the architectural principles underlying valence-specific emotional processing remain poorly understood. Here, we leverage whole-brain c-Fos connectomics in combination with anatomical projection data to delineate the organizational logic of valence-dependent neural networks in mice responding to ethologically relevant pheromone cues. This approach revealed widespread yet distinct activation patterns, with 13 core nuclei consistently recruited across both valences, spanning olfactory bulb, limbic system, thalamus, and brainstem regions. Critically, network-based analysis uncovered fundamentally different organizational strategies: positive emotional states assembled into compact, highly integrated functional communities, while negative states engaged distributed, multi-modular architectures. Integrating these functional insights with anatomical connectivity data from the Allen Brain Atlas, we uncover a biphasic “integration-distribution” network architecture: positive emotional processing relies on centralized, streamlined hubs anchored in the central amygdala and posterior hypothalamic axis, whereas negative emotional processing employs redundant, parallelized pathways for robust and flexible responses. By bridging cellular-level activation patterns, mesoscale circuit organization, and behavioral relevance, our findings provide a novel conceptual framework for emotion neuroscience and lay the groundwork for understanding the network-level dysfunctions characteristic of psychiatric disorders. Biological sciences/Neuroscience Biological sciences/Molecular biology Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Supplementary Files SupplementaryData1.xlsx Supplementary Data1 SupplementaryInformation.docx Supplementary Information Cite Share Download PDF Status: Posted 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-7794939","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":539977418,"identity":"7aa9d7ca-0b39-42f4-a506-b2af7ca946f7","order_by":0,"name":"Xiang-Shan 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Processing","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research 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