Multimodal biomarker based on eye movement complexity and pupil diameter in attention-deficit/hyperactivity disorder

Multimodal biomarker based on eye movement complexity and pupil diameter in attention-deficit/hyperactivity disorder | 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 Multimodal biomarker based on eye movement complexity and pupil diameter in attention-deficit/hyperactivity disorder Ayumu Ueno, Sou Nobukawa, Aya Shirama This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5778715/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders without established biomarkers. Pupil diameter, regulated by the locus coeruleus-norepinephrine (LC-NE) system, and eye movements controlled by diverse brain regions exhibit specific patterns in patients with ADHD due to abnormal activity in these brain regions. Previous studies reported that patients with ADHD have larger pupil diameters and reduced temporal complexity. However, although eye movement complexity has been associated with major movement disorders in previous studies, its relevance in conditions without primary movement disorders, such as ADHD, remains unclear. In this context, we hypothesised that eye movement complexity would provide a more comprehensive understanding of eye movements in ADHD. This study aimed to analyse eye movement complexity in patients with ADHD using multiscale entropy analysis and examine its diagnostic utility alongside pupil size. The results showed that patients with ADHD had less complex eye movements and larger pupil diameters, consistent with prior findings. Moreover, combining these features enhanced the accuracy of ADHD diagnosis. These findings support the potential of a multimodal approach for diagnosing adult ADHD, potentially improving clinical diagnostic accuracy. Biological sciences/Neuroscience/Diseases of the nervous system Health sciences/Biomarkers/Diagnostic markers Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted 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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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-5778715","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":408341114,"identity":"0c30126a-696f-42f7-9e55-85b8ce362afc","order_by":0,"name":"Ayumu Ueno","email":"","orcid":"","institution":"Chiba Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Ayumu","middleName":"","lastName":"Ueno","suffix":""},{"id":408341116,"identity":"6309ab0e-5fb5-4107-b1e3-1cc404a7fd51","order_by":1,"name":"Sou Nobukawa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYFACHgbGBiDFD2InALEBMw9EAiyMT4skiEhIIEWLwQGoNQYMPPidZc7ee0xyRs1heePjxx8wPPzBIG/OznvwA0ONHQPzbOzWWPacS5PccOyw4bYzOQYghxnubOZLlmA4lszAOOcAVi0GN3LMJB+w3WbcdoMH5Jf/CQaHeQwkGNgOMDDOSMCj5d9t+80z2B+AbAFpMf7B8I+Alo1ttxM3SDAYwLSYSTC24dFy5lyy5cy+/8kzgH45kJDGYLjhMF+aRWJfMg9OvxzvPXiz51uabX/78YcPf9gwyBucP3v4xodvdnKGOEIMBSBMBTqJx3AGYR1oQF6CZC2jYBSMglEwPAEAtxRgQhr5MmMAAAAASUVORK5CYII=","orcid":"","institution":"Chiba Institute of Technology","correspondingAuthor":true,"prefix":"","firstName":"Sou","middleName":"","lastName":"Nobukawa","suffix":""},{"id":408341117,"identity":"faa6167b-6096-4d25-a896-0f3d691b7e3e","order_by":2,"name":"Aya Shirama","email":"","orcid":"","institution":"National Center of Neurology and Psychiatry","correspondingAuthor":false,"prefix":"","firstName":"Aya","middleName":"","lastName":"Shirama","suffix":""}],"badges":[],"createdAt":"2025-01-07 07:08:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5778715/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5778715/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75140150,"identity":"365cbc12-8158-499f-86a7-7de774588e35","added_by":"auto","created_at":"2025-01-31 04:33:12","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":701196,"visible":true,"origin":"","legend":"","description":"","filename":"mainadhdscireprevision.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5778715/v1_covered_543e6b0c-3f80-4139-9a67-130a0cabdf49.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Multimodal biomarker based on eye movement complexity and pupil diameter in attention-deficit/hyperactivity disorder","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5778715/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5778715/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders without established biomarkers. 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