The ups and downs of brain stress: Extending the triple network hypothesis

The ups and downs of brain stress: Extending the triple network hypothesis | 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 The ups and downs of brain stress: Extending the triple network hypothesis Gina-Isabelle Henze This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5675195/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 Background : This pre-registered functional magnetic resonance imaging study aimed to test and possibly extend the triple network hypothesis of psychosocial stress processing, positing that responses in the salience (SN) and default mode network (DMN) dominate at the expense of the central executive network (CEN). Methods : We reviewed psychosocial stress studies and conducted a mega-analysis of N=459 ScanSTRESS-datasets (222 women) with harmonized preprocessing (ENIGMA HALFpipe). Results : Our findings disconfirmed the original hypothesis, revealing activations and deactivations across all three networks, related in a complex way to hormonal, cardiac, subjective, and performance parameters. Additionally, we replicated an exposure-time effect of decreasing activation, identified a novel age effect of increasing DMN-activation, sex-specific patterns, and confirmed the involvement of all networks by task-based connectivity. Conclusions : These results suggest a new, extended triple network hypothesis of psychosocial stress processing, describing that SN- and DMN-structures orchestrate hormonal, cardiac, and subjective stress responses, while CEN- and DMN-structures process the stress-eliciting tasks. Social science/Psychology/Human behaviour Biological sciences/Neuroscience/Cognitive neuroscience salience network central executive network default mode network psychosocial stress ScanSTRESS Full Text Additional Declarations There is NO Competing Interest. Supplementary Files HenzeetalSupplementalMaterial1912.pdf Supplemental Material 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-5675195","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":398504546,"identity":"ec7001ab-7ea3-4ded-85ca-b09a6b18a16f","order_by":0,"name":"Gina-Isabelle Henze","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-3397-1351","institution":"Charité Universitätsmedizin","correspondingAuthor":true,"prefix":"","firstName":"Gina-Isabelle","middleName":"","lastName":"Henze","suffix":""}],"badges":[],"createdAt":"2024-12-19 09:00:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5675195/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5675195/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73440250,"identity":"3f69d900-f9dd-4fdb-bd6a-e853fb25c8f7","added_by":"auto","created_at":"2025-01-10 03:24:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1385119,"visible":true,"origin":"","legend":"Article File","description":"","filename":"HenzeetalMegaAnalysis1912.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5675195/v1_covered_2ab49f40-cf24-4517-95cc-83ae5a5cf1c2.pdf"},{"id":73439464,"identity":"9d9a3b6e-c96a-45b6-8e08-c22285fcf65a","added_by":"auto","created_at":"2025-01-10 03:16:56","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1064234,"visible":true,"origin":"","legend":"Supplemental Material","description":"","filename":"HenzeetalSupplementalMaterial1912.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5675195/v1/fb39b684c41d81acb98f3c97.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"The ups and downs of brain stress: Extending the triple network hypothesis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"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":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"salience network, central executive network, default mode network, psychosocial stress, ScanSTRESS","lastPublishedDoi":"10.21203/rs.3.rs-5675195/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5675195/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: This pre-registered functional magnetic resonance imaging study aimed to test and possibly extend the triple network hypothesis of psychosocial stress processing, positing that responses in the salience (SN) and default mode network (DMN) dominate at the expense of the central executive network (CEN).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We reviewed psychosocial stress studies and conducted a mega-analysis of N=459 ScanSTRESS-datasets (222 women) with harmonized preprocessing (ENIGMA HALFpipe).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Our findings disconfirmed the original hypothesis, revealing activations and deactivations across all three networks, related in a complex way to hormonal, cardiac, subjective, and performance parameters. 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