Brain metabolic-functional (de)coupling: from health to glioma dysfunction

Brain metabolic-functional (de)coupling: from health to glioma dysfunction | 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 Brain metabolic-functional (de)coupling: from health to glioma dysfunction Giulia Vallini, Giorgia Baron, Erica Silvestri, Tommaso Volpi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5291237/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Dec, 2025 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract The intricate interplay between metabolism and neuronal function plays a pivotal role in facilitating the human brain's adaptive engagement in cognitively demanding processes 1 . Although many studies have examined the large-scale coupling between glucose metabolism, using [ 18 F]fluorodeoxyglucose PET, and resting-state fMRI activity, they often overlook the BOLD signal's sensitivity to hemodynamic confounders and the brain's dynamic nature 2–6 . To address these limitations, we propose using effective connectivity, decomposing it into a symmetric partial covariance, capturing the “true” statistical dependencies between two regions after controlling for all other regions, and an antisymmetric differential covariance, revealing the directional flow of brain dynamics. Here we investigate the neuro-metabolic associations governing brain function, demonstrating that partial covariance is related to metabolic connectivity 2 , i.e., the relationship between metabolic signals of different brain areas, while node directionality relates to standardized uptake value ratio, a proxy for local glucose consumption. Moreover, we show how the nature of the effective-metabolic (de)coupling is tied to the anatomical location of brain tumors, reinforcing the notion that glioma progression induces multimodal dysfunctions. This study pioneers the characterization of the mechanisms underlying brain metabolism and the associated functional behaviour during resting-state, in both physiological and pathophysiological conditions. Biological sciences/Neuroscience/Computational neuroscience/Network models Health sciences/Neurology/Neurological disorders/CNS cancer Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementary.docx Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 04 Dec, 2025 Read the published version in Communications Biology → 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-5291237","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":367800470,"identity":"412ab521-b9f6-464c-b539-768aa96f3d98","order_by":0,"name":"Giulia Vallini","email":"","orcid":"https://orcid.org/0000-0002-9634-8401","institution":"Department of Information Engineering, University of Padova, Padova, Italy","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Vallini","suffix":""},{"id":367800471,"identity":"2a619987-30a6-4cd4-8016-9e6b16a37e00","order_by":1,"name":"Giorgia Baron","email":"","orcid":"https://orcid.org/0000-0002-0866-4982","institution":"Department of Information Engineering, University of Padova, Padova, Italy Neuropsychology Department, IRCCS San Camillo Hospital, Venice, Italy","correspondingAuthor":false,"prefix":"","firstName":"Giorgia","middleName":"","lastName":"Baron","suffix":""},{"id":367800472,"identity":"591dee7f-5efd-4220-af38-7c1a1b935594","order_by":2,"name":"Erica Silvestri","email":"","orcid":"https://orcid.org/0000-0002-1853-0777","institution":"Department of Information Engineering, University of Padova, Padova, Italy","correspondingAuthor":false,"prefix":"","firstName":"Erica","middleName":"","lastName":"Silvestri","suffix":""},{"id":367800473,"identity":"b3e6c584-2cf0-449d-8190-536d7dbb5e5d","order_by":3,"name":"Tommaso Volpi","email":"","orcid":"https://orcid.org/0000-0002-5451-6710","institution":"Padova Neuroscience Center, University of Padova, Padova, Italy; 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