Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models associated with tractometry

Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models associated with tractometry | 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 Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models associated with tractometry Renaud Hedouin, Jean-Charles Roy, Thomas Desmidt, Gabriel Robert, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3969943/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Aug, 2024 Read the published version in Scientific Reports → Version 1 posted 9 You are reading this latest preprint version Abstract Late-life depression is a common disorder in the elderly, difficult to treat, where apathy contributes to a poor prognosis. Despite its severity and frequency, the pathophysiology of LLD remains complex and its exploration challenging. While white matter (WM) damages have been assessed using diffusion tensor imaging, this model cannot correctly represent the WM microstructure. We hypothesized that using a more complex multi-compartment model, never used on LLD, would better describe the WM microstructure. In this article, we performed a tract-based approach to investigate novel diffusion-model biomarkers of LLD and apathy, by interpolating the microstructural metrics directly along the fibers. We performed a multivariate statistical analysis along the fiber, combined with a principal component analysis for dimensional data reduction. Then, we tested the utility of our framework by showing classical modifications in LDD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fibers. Our study suggests that new tracts, such as striato-premotor, may be involved in LLD and apathy, which has not been observed in previous studies. We also identified modifications of inflammation metrics in 5 different tracts, already reported in dementia, which may contribute to the cognitive decline observed with apathy. Biological sciences/Neuroscience/Cognitive neuroscience/Motivation Health sciences/Biomarkers/Diagnostic markers Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Aug, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 08 Apr, 2024 Reviews received at journal 29 Mar, 2024 Reviewers agreed at journal 15 Mar, 2024 Reviewers agreed at journal 12 Mar, 2024 Reviewers invited by journal 11 Mar, 2024 Editor assigned by journal 11 Mar, 2024 Editor invited by journal 04 Mar, 2024 Submission checks completed at journal 04 Mar, 2024 First submitted to journal 19 Feb, 2024 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-3969943","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":276738763,"identity":"c16ba20f-0fca-4d6d-be74-80da935230f6","order_by":0,"name":"Renaud Hedouin","email":"","orcid":"","institution":"Inria Rennes - Bretagne Atlantique Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Renaud","middleName":"","lastName":"Hedouin","suffix":""},{"id":276738764,"identity":"8f003722-2831-4b7c-b57a-3ade449d1fab","order_by":1,"name":"Jean-Charles Roy","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Rennes","correspondingAuthor":false,"prefix":"","firstName":"Jean-Charles","middleName":"","lastName":"Roy","suffix":""},{"id":276738765,"identity":"a2288304-f328-447f-af8f-8aa75d6432d3","order_by":2,"name":"Thomas Desmidt","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Tours","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Desmidt","suffix":""},{"id":276738766,"identity":"578e0f6d-538d-455e-885c-6b2f3b6586e1","order_by":3,"name":"Gabriel Robert","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Rennes","correspondingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"","lastName":"Robert","suffix":""},{"id":276738767,"identity":"9fe488c6-3a81-4d87-80f1-0ceb4616865e","order_by":4,"name":"Julie Coloigner","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIie2PsQrCMBCGrxTSJdVVqbSvEOkkgs+S4OAkCi4dHCKBuBTnPk5LwclnEKSjDhUXhyJaUtSlmQXzDcl/yX1cAmAw/CAWt3lah84r1ruPVPA1iqWUphPCJoTaOaAUBVOlRrETtklLmPjIEeK8jI6znZeL8g5k0TojYTxLYBoinMlxcljNZYfJfgxkxDVKjiFlssdk6Eo6l9iSgKEiuil59VYedIawJa4VEL0CShGFyyl9KdzDOiU+8Swm6i823tNh/TBvQNqV4Xaal/do4nedbXHDaxoEsVNcL5FG4fWqrlHvc94qAARf2S7b+wwGg+GfeQIJvFFfESK1kgAAAABJRU5ErkJggg==","orcid":"","institution":"Inria Rennes - Bretagne Atlantique Research Centre","correspondingAuthor":true,"prefix":"","firstName":"Julie","middleName":"","lastName":"Coloigner","suffix":""}],"badges":[],"createdAt":"2024-02-19 12:19:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3969943/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3969943/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-67535-3","type":"published","date":"2024-08-06T15:58:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52183654,"identity":"d2e369ed-9184-4258-8e45-18ee55b92504","added_by":"auto","created_at":"2024-03-07 18:14:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1385772,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentation of the MCM model \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMCM model for one subject in (A) the corpus callosum with only one direction, (B) in a CSF area with isotropic diffusion and \u0026nbsp;in (C) a crossing fiber region near the centrum semiovale.\u003c/p\u003e","description":"","filename":"Fig1Modelaverage.png","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1/6d3ec2c1d7b03ff3e2e909ae.png"},{"id":52183653,"identity":"ea54f17d-b2af-429a-a658-99a1f74dc507","added_by":"auto","created_at":"2024-03-07 18:14:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":677291,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNumber of anisotropic compartments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRepresentation of the average number of anisotropic compartments in the MCM model for the HC group.\u003c/p\u003e","description":"","filename":"Fig2Nbcompartments.png","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1/0097b497211fb670bd175c1b.png"},{"id":52183658,"identity":"2034d574-2069-4cb2-bc74-cf944be3d033","added_by":"auto","created_at":"2024-03-07 18:14:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":354961,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMCM microstructure parameters \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverview of the 5 microstructure measures of the ATR left bundle: FA, FW, MD, AD, RD. Microstructure values are projected \u0026nbsp;onto a central line divided into 100 segments\u003c/p\u003e","description":"","filename":"Fig3ATR.png","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1/5450dc23fedbf4f79e60c5a0.png"},{"id":52185406,"identity":"eb196877-79ed-4e1d-ba7d-83d6bcea9b4b","added_by":"auto","created_at":"2024-03-07 18:22:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":19096,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between the microstructure metrics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAverage on the left and standard deviation on the right over the 29 bundles.\u003c/p\u003e","description":"","filename":"Fig4Matricesbundles.png","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1/72604d82439985d75581fa92.png"},{"id":52183656,"identity":"83df59d5-7424-494b-b6eb-81f640e7ceaa","added_by":"auto","created_at":"2024-03-07 18:14:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":557496,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison between the HC group and the LLD group.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTop row: For each group, the lines represent the average and standard deviation of the PC1 and/or PC2 and the gray bar shows the −log10 (p-values). A part of the fiber is considered significant, highlighted with red dots when the p-value is lower than the alpha value (5%) along a minimum cluster size which is estimated individually with the permutation test for each fiber. The PC is represented by the blue (PC1) and green (PC2) lines for the HC group and by the orange (PC1) and red (PC2) lines for the LLD group. Bottom row: Illustration of the 6 bundles corresponding to a HC subject. The red parts correspond to the significant areas of the bundles.\u003c/p\u003e","description":"","filename":"Fig5LLDvsHC.png","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1/5b5d74a559d8da0e6085892f.png"},{"id":52185407,"identity":"7ca6e9b1-9404-406f-a549-011b67a42946","added_by":"auto","created_at":"2024-03-07 18:22:16","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":482442,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eApathy relationship captures by the PC1 and PC2 over 5 bundles. \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTop line: The lines represent the average and standard deviation of PC1 (blue) and PC2 (orange) and the gray bar shows the \u0026nbsp;−log10 (p-values)). The significant fiber areas estimated in the correlation analysis using PCs are highlighted with red dots. \u0026nbsp;Bottom row: Illustration of the 5 bundles corresponding to a HC subject. The red parts correspond to the significant areas of the \u0026nbsp;bundles.\u003c/p\u003e","description":"","filename":"Fig6Apathy.png","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1/b4bb22c8d48482062296ad3c.png"},{"id":62299195,"identity":"7db2bc5b-82dc-45fb-84ae-8f1676529269","added_by":"auto","created_at":"2024-08-12 16:18:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":885090,"visible":true,"origin":"","legend":"","description":"","filename":"RHManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3969943/v1_covered_fca96816-50c4-4c1f-8add-650bc25aa973.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models associated with tractometry","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3969943/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3969943/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Late-life depression is a common disorder in the elderly, difficult to treat, where apathy contributes to a poor prognosis. Despite its severity and frequency, the pathophysiology of LLD remains complex and its exploration challenging. While white matter (WM) damages have been assessed using diffusion tensor imaging, this model cannot correctly represent the WM microstructure. We hypothesized that using a more complex multi-compartment model, never used on LLD, would better describe the WM microstructure. In this article, we performed a tract-based approach to investigate novel diffusion-model biomarkers of LLD and apathy, by interpolating the microstructural metrics directly along the fibers. We performed a multivariate statistical analysis along the fiber, combined with a principal component analysis for dimensional data reduction. Then, we tested the utility of our framework by showing classical modifications in LDD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fibers. Our study suggests that new tracts, such as striato-premotor, may be involved in LLD and apathy, which has not been observed in previous studies. We also identified modifications of inflammation metrics in 5 different tracts, already reported in dementia, which may contribute to the cognitive decline observed with apathy.","manuscriptTitle":"Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models associated with tractometry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-07 18:14:11","doi":"10.21203/rs.3.rs-3969943/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-08T04:47:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-29T19:49:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e3f11f53-1cdf-4b25-afa0-fdcde970c852","date":"2024-03-15T18:22:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7b472c40-1386-4669-ba29-99b1ea6e925a_SNPRID","date":"2024-03-12T14:55:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-11T17:19:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-11T17:16:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-04T14:08:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-04T14:04:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-02-19T12:06:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"24cbbddf-5797-4dc5-8348-12f5d482123f","owner":[],"postedDate":"March 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":29167578,"name":"Biological sciences/Neuroscience/Cognitive neuroscience/Motivation"},{"id":29167579,"name":"Health sciences/Biomarkers/Diagnostic markers"}],"tags":[],"updatedAt":"2024-08-12T16:14:29+00:00","versionOfRecord":{"articleIdentity":"rs-3969943","link":"https://doi.org/10.1038/s41598-024-67535-3","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-08-06 15:58:08","publishedOnDateReadable":"August 6th, 2024"},"versionCreatedAt":"2024-03-07 18:14:11","video":"","vorDoi":"10.1038/s41598-024-67535-3","vorDoiUrl":"https://doi.org/10.1038/s41598-024-67535-3","workflowStages":[]},"version":"v1","identity":"rs-3969943","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3969943","identity":"rs-3969943","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}