Spontaneous brain fluctuation abnormalities in retired football players

Spontaneous brain fluctuation abnormalities in retired football players | 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 Research Article Spontaneous brain fluctuation abnormalities in retired football players Ethan Danielli, Bhanu Sharma, Cameron Nowikow, Michael D Noseworthy This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4253396/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 BACKGROUND New measures of the spontaneity of signal amplitudes of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) present in resting state functional MRI (rsfMRI) may provide useful objective information when applied to concussion. These metrics provide a spatial map of where signal spontaneity departs from normal values to indicate areas of impairment or over-compensation. Former professional American-style football players would show diffusely decreased ALFF and fALFF. METHODS: This was a prospective cohort study of 18 retired Canadian Football League (rCFL) players (male, aged 58.78 ± 6.10) recruited and 62 healthy age and sex-matched controls (male, aged 58.81 ± 5.69) downloaded from OASIS-3. High resolution 3D T1-weighted and rsfMRI data was collected on a 3T GE MRI. CONN was used to preprocess the rsfMRI data and compute ALFF/fALFF metrics, while voxel-wise and brain region-of-interest (ROI) Z-scoring analyses were computed in MATLAB. The rCFL participants also completed self-reporting clinical behavioural tests. Significant ALFF and fALFF differences were calculated as clusters (Threshold Free Cluster Enhancement, FWE-corrected p < 0.05) and ROI Z-scoring (Abnormal ROI, +3≤Z-score≤-3). Correlations and multiple linear regression analyses between participant demographics, clinical test data, and total number of abnormal brain ROIs were also computed. RESULTS: Two large clusters of decreased signal spontaneity and one large cluster of increased signal spontaneity were found in retired athletes compared to controls. The Z-scoring analysis found consistently abnormal ROIs from ALFF and fALFF data from the right amygdala, right thalamus, bilateral occipital pole, and bilateral cerebellum crus II. The total number of positive fALFF Z-score outliers correlated with a longer career length. CONCLUSIONS: Our analyses showed that cerebellar and central sub-cortical brain regions were most frequently and seriously abnormal. Spontaneous brain activity, a measure of brain health, was compromised in retired athletes years after competitive sport. resting state functional magnetic resonance imaging (rsfMRI) concussions retired professional athletes amplitude of low-frequency fluctuations (ALFF) fractional ALFF (fALFF) Full Text Additional Declarations Competing interest reported. Dr. Noseworthy is the CEO and co-founder of TBIFinder Inc. and Dr. Danielli is a research intern at TBIFinder Inc., which is not relevant to this current work and did not influence the findings of this paper. All other authors declare that they have no conflict of interest. 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. 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-4253396","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":290507592,"identity":"3038fa4e-4d11-4c78-96fa-ed15011d716d","order_by":0,"name":"Ethan Danielli","email":"","orcid":"","institution":"McMaster University","correspondingAuthor":false,"prefix":"","firstName":"Ethan","middleName":"","lastName":"Danielli","suffix":""},{"id":290507593,"identity":"55d0219e-3142-41ab-9633-abe78c50472c","order_by":1,"name":"Bhanu Sharma","email":"","orcid":"","institution":"McMaster University","correspondingAuthor":false,"prefix":"","firstName":"Bhanu","middleName":"","lastName":"Sharma","suffix":""},{"id":290507594,"identity":"47954b62-1bf3-4412-874a-2dced524968c","order_by":2,"name":"Cameron Nowikow","email":"","orcid":"","institution":"McMaster University","correspondingAuthor":false,"prefix":"","firstName":"Cameron","middleName":"","lastName":"Nowikow","suffix":""},{"id":290507595,"identity":"f1676617-064d-444f-9425-08cd30a3131e","order_by":3,"name":"Michael D Noseworthy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBADOdK1GEOoBBK0JDYQrcWcvf3hY56Ke+lr208nfvz5wyafgf3wA7xaLHvOGBvznCnO3XYmd7M0T0KaZQNPmgFeLQY3ctikc9sScrfd4N0gzZBw2IBBgoGQlvTnv4Fa0s1u8G7++SPhP1AL+wcCWhLMmIFaEoBatknwJBwAauEhYMuZM8bSf84kGAL9ss2aJy3ZgI0npwC/luPtDz/OqEiQNzt+dvPNHzZ2Bvzsxzfg1YIJ2EhUPwpGwSgYBaMACwAAqqxEzFwQIakAAAAASUVORK5CYII=","orcid":"","institution":"McMaster University","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"D","lastName":"Noseworthy","suffix":""}],"badges":[],"createdAt":"2024-04-11 15:44:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4253396/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4253396/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81244959,"identity":"be098fae-6ce0-4b3b-ae04-30e5aa30c8f2","added_by":"auto","created_at":"2025-04-24 01:31:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1182302,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptJan2024v5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4253396/v1_covered_dc73f729-ebe2-4d63-a185-2362708f81d7.pdf"}],"financialInterests":"Competing interest reported. Dr. Noseworthy is the CEO and co-founder of TBIFinder Inc. and Dr. Danielli is a research intern at TBIFinder Inc., which is not relevant to this current work and did not influence the findings of this paper. All other authors declare that they have no conflict of interest.","formattedTitle":"Spontaneous brain fluctuation abnormalities in retired football players","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"resting state functional magnetic resonance imaging (rsfMRI), concussions, retired professional athletes, amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF)","lastPublishedDoi":"10.21203/rs.3.rs-4253396/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4253396/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBACKGROUND\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNew measures of the spontaneity of signal amplitudes of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) present in resting state functional MRI (rsfMRI) may provide useful objective information when applied to concussion. These metrics provide a spatial map of where signal spontaneity departs from normal values to indicate areas of impairment or over-compensation. Former professional American-style football players would show diffusely decreased ALFF and fALFF.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMETHODS: This was a prospective cohort study of 18 retired Canadian Football League (rCFL) players (male, aged 58.78 ± 6.10) recruited and 62 healthy age and sex-matched controls (male, aged 58.81 ± 5.69) downloaded from OASIS-3. High resolution 3D T1-weighted and rsfMRI data was collected on a 3T GE MRI. CONN was used to preprocess the rsfMRI data and compute ALFF/fALFF metrics, while voxel-wise and brain region-of-interest (ROI) Z-scoring analyses were computed in MATLAB. The rCFL participants also completed self-reporting clinical behavioural tests. Significant ALFF and fALFF differences were calculated as clusters (Threshold Free Cluster Enhancement, FWE-corrected p \u0026lt; 0.05) and ROI Z-scoring (Abnormal ROI, +3≤Z-score≤-3). Correlations and multiple linear regression analyses between participant demographics, clinical test data, and total number of abnormal brain ROIs were also computed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRESULTS: Two large clusters of decreased signal spontaneity and one large cluster of increased signal spontaneity were found in retired athletes compared to controls. The Z-scoring analysis found consistently abnormal ROIs from ALFF and fALFF data from the right amygdala, right thalamus, bilateral occipital pole, and bilateral cerebellum crus II. The total number of positive fALFF Z-score outliers correlated with a longer career length.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCONCLUSIONS: Our analyses showed that cerebellar and central sub-cortical brain regions were most frequently and seriously abnormal. Spontaneous brain activity, a measure of brain health, was compromised in retired athletes years after competitive sport.\u003c/p\u003e","manuscriptTitle":"Spontaneous brain fluctuation abnormalities in retired football players","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-16 19:10:17","doi":"10.21203/rs.3.rs-4253396/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"832a440f-3a02-4822-bfff-ad9c8a132431","owner":[],"postedDate":"April 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-24T01:23:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-16 19:10:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4253396","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4253396","identity":"rs-4253396","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}