Aberrant Recovery of Timescale-Aligned Amplitude Balance Links to Symptoms and Cognition in Schizophrenia

Aberrant Recovery of Timescale-Aligned Amplitude Balance Links to Symptoms and Cognition in Schizophrenia | 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 Aberrant Recovery of Timescale-Aligned Amplitude Balance Links to Symptoms and Cognition in Schizophrenia Sir-Lord Wiafe, Spencer Kinsey, Najme Soleimani, Raymond Nsafoa, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8282691/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 Schizophrenia has long been linked to impaired coordination of brain activity, yet most frameworks overlook two key dimensions: the amplitude of brain signals and the differing timescales on which regions operate. These factors are critical in disorders where neural activity is exaggerated and slowed. In healthy adults, networks compensate for mismatched processing speeds to maintain proportionate activity, but this process is poorly understood in schizophrenia. We developed a timescale-aligned, time-resolved framework that separates temporal distortions from genuine amplitude differences, enabling measurement of amplitude balance between networks across timescales. This approach was applied to large-scale fMRI datasets, including the Human Connectome Project and a multi-site schizophrenia cohort. Patients with schizophrenia showed greater amplitude imbalance, especially during fast fluctuations, along with more frequent re-entry into unbalanced states and slower recovery to stable coordination. We further identified a flexible intermediate state that patients occupied more often, and that predicted better working-memory performance. Across cohorts, amplitude imbalance was associated with greater symptom severity and poorer reasoning ability. These findings provide a new mechanistic view of dyscoordination in schizophrenia grounded in timescale-normalized amplitude dynamics, highlight aberrant recovery of amplitude balance as a core feature of the illness, and suggest that timescale-aligned amplitude imbalance may serve as a promising target for biomarker development. Biological sciences/Neuroscience/Computational neuroscience Health sciences/Biomarkers/Diagnostic markers Schizophrenia fMRI timescale alignment BOLD amplitude dynamic time warping Full Text Additional Declarations There is NO Competing Interest. 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. 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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-8282691","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":562902342,"identity":"1089f6e6-52cb-4bdb-8683-b3438b7f0b90","order_by":0,"name":"Sir-Lord Wiafe","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYBACPgbGBoYKBgk5CJeNCC1sIC1nGCyMSdECBGcYKhIbiNcikdz44UCFRPp8/zMGDB/KDhOjJbFZ4sAZidyNN3IMGGecI0aLdGKD9Mc2oJYZPAbMvG3EaWn+cfCfRLph/xkD5r9EammTONggkSDPkGPAzEiUFvmHbRYHjkkYbpBIKzjYcy6dsBZ+nuOPbxyoqZOX7z+88cGPMmvCWuDA4AADwwES1AOBfANp6kfBKBgFo2AEAQBROTqqw2QhiwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0002-8583-7987","institution":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University","correspondingAuthor":true,"prefix":"","firstName":"Sir-Lord","middleName":"","lastName":"Wiafe","suffix":""},{"id":562902343,"identity":"c7db1abf-7e74-46de-89f0-762b8e04f25e","order_by":1,"name":"Spencer Kinsey","email":"","orcid":"https://orcid.org/0009-0002-4743-380X","institution":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS); 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