Multi-task fMRI outperforms resting-state fMRI for revealing task-invariant organization of the human brain | 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 Multi-task fMRI outperforms resting-state fMRI for revealing task-invariant organization of the human brain Caroline Nettekoven, Ali Shahbazi, Bassel Arafat, Matea Skenderija, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9326213/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 Resting-state functional Magnetic Resonance Imaging (fMRI) is widely used to infer the intrinsic functional organization of the brain, yet it remains unclear how well this approach can predict the structure of brain activity observed across a diverse set of mental states. Here we compare resting-state to task-based fMRI using diverse task batteries within the same individuals. We find that multi-task fMRI data consistently outperform resting-state estimates in predicting functional organization during novel tasks. This advantage persists across preprocessing strategies, brain regions, and independent datasets. While task activation estimates do show task-dependency when using only few tasks, increasing task diversity reduced task-specific bias, with convergence achieved using modest task sets. These improvements translate into superior individual parcellations and connectivity models. Together, our results dissociate reliability from validity in neuroimaging and challenge the prevailing assumption that rest provides a privileged window into intrinsic brain organization. Instead, functional architecture appears most faithfully revealed when the brain is actively driven through diverse task states. Biological sciences/Neuroscience/Cognitive neuroscience Biological sciences/Neuroscience/Computational neuroscience Biological sciences/Neuroscience/Neural circuits Health sciences/Medical research/Biomarkers task-based fMRI resting-state fMRI functional connectivity brain parcellation multi-task fMRI individual differences functional precision mapping Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TaskRestpapersupplementary.pdf 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. 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