Functional network collapse in neurodegenerative disease

Functional network collapse in neurodegenerative disease | 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 Functional network collapse in neurodegenerative disease Jesse Brown, Alex Lee, Kristen Fernhoff, Taylor Pistone, Lorenzo Pasquini, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6397290/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Nov, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Cognitive and behavioral deficits in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) result from brain atrophy and altered functional connectivity. However, it is unclear how atrophy relates to functional connectivity disruptions across dementia subtypes and stages. We addressed this question using structural and functional MRI from 221 patients with AD (n=82), behavioral variant FTD (n=41), corticobasal syndrome (n=27), nonfluent (n=34) and semantic (n=37) variant primary progressive aphasia, and 100 cognitively normal individuals. Using partial least squares regression, we identified three principal structure-function components. The first component showed cingulo-insular atrophy correlating with primary cortical hypo-connectivity and subcortical/association cortical hyper-connectivity. Components two and three linked focal syndrome-specific atrophy to peri-lesional hypo-connectivity and distal hyper- connectivity. Structural and functional component scores predicted global and domain- specific cognitive deficits. Anatomically, functional connectivity changes reflected alterations in specific brain activity gradients. Eigenmode analysis identified temporal phase and amplitude collapse as an explanation for atrophy-driven functional connectivity changes. Biological sciences/Neuroscience/Diseases of the nervous system/Neurodegeneration Biological sciences/Neuroscience/Computational neuroscience/Dynamical systems Full Text Additional Declarations Yes there is potential Competing Interest. J.A.B. is the founder of Radiata, Inc., which is developing biomarkers based on this research, and is a named inventor on a patent application related to the methods described in this manuscript. The remaining authors declare no competing interests. Cite Share Download PDF Status: Published Journal Publication published 21 Nov, 2025 Read the published version in Nature Communications → 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. 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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-6397290","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":444821334,"identity":"0c540a73-6a9e-4034-8618-8d6eafaf1ce5","order_by":0,"name":"Jesse 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