Exploring inter-subject variability in the emotional domain to characterize typical and atypical neural responses in longitudinal settings: insights from Eye Movement Desensitization and Reprocessing rehabilitative treatment

Exploring inter-subject variability in the emotional domain to characterize typical and atypical neural responses in longitudinal settings: insights from Eye Movement Desensitization and Reprocessing rehabilitative treatment | 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 Method Article Exploring inter-subject variability in the emotional domain to characterize typical and atypical neural responses in longitudinal settings: insights from Eye Movement Desensitization and Reprocessing rehabilitative treatment Alice Pirastru, Valeria Blasi, Diego Michael Cacciatore, Marco Rovaris, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8375274/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 The emotional domain is often impaired in several neurological condition and consequently targeted by rehabilitation interventions. When investigating the neural underpinnings of this domain by functional magnetic resonance imaging (fMRI) a high inter-subject variability (ISV) in neural activity is measured. Rather than reflecting mere noise, such variability may play a critical role in revealing neuroplasticity mechanisms associated with therapeutic interventions, particularly in clinical populations. Objective The aim of this study was to compare a conventional fMRI data analysis approach based on the General Linear Model (GLM), which relies on group-averaged effects, with an innovative method based on threshold-weighted overlap maps (OMth-w) that explicitly exploits ISV to detect neuroplasticity-related changes in fMRI signals before and after a rehabilitation intervention. Methods Thirty healthy controls (HC) and thirteen people with multiple sclerosis (pwMS) undergoing Eye Movement Desensitization and Reprocessing (EMDR) treatment for depression were enrolled. Participants performed an emotional visual stimulation task during fMRI, comprising two conditions with positive and negative emotions. fMRI data were acquired at two time points (pre- and post-EMDR for pwMS). Data analysis compared two approaches: (1) conventional second-level general linear model (GLM) analyses using paired t-tests; (2) normalized individual threshold-weighted overlap maps (OMth-w) to quantify ISV. Results Standard GLM analyses did not reveal significant longitudinal changes in either group. In contrast, the OMth-w approach showed increased neural variability over time in HC and reduced variability in pwMS following EMDR treatment, concomitant with a significant reduction in depressive symptoms (p < 0.001). Conclusions These results underscore the relevance of variability-based analytical approaches for identifying neuroplasticity-related changes that may remain undetected using traditional mean-based inference methods. Depression EMDR Emotion Stimulation Task-fMRI inter-subject variability Multiple Sclerosis Rehabilitation Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx 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-8375274","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Method Article","associatedPublications":[],"authors":[{"id":571817114,"identity":"0ba74c52-2584-4514-bd3c-34c21e9ef07f","order_by":0,"name":"Alice Pirastru","email":"","orcid":"","institution":"IRCCS Fondazione Don Carlo Gnocchi ONLUS","correspondingAuthor":false,"prefix":"","firstName":"Alice","middleName":"","lastName":"Pirastru","suffix":""},{"id":571817115,"identity":"18b07bd7-e161-4eff-8460-0464b4c10588","order_by":1,"name":"Valeria 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Desensitization and Reprocessing rehabilitative treatment","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":"Depression, EMDR, Emotion Stimulation Task-fMRI, inter-subject variability, Multiple Sclerosis, Rehabilitation","lastPublishedDoi":"10.21203/rs.3.rs-8375274/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8375274/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe emotional domain is often impaired in several neurological condition and consequently targeted by rehabilitation interventions. When investigating the neural underpinnings of this domain by functional magnetic resonance imaging (fMRI) a high inter-subject variability (ISV) in neural activity is measured. Rather than reflecting mere noise, such variability may play a critical role in revealing neuroplasticity mechanisms associated with therapeutic interventions, particularly in clinical populations.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe aim of this study was to compare a conventional fMRI data analysis approach based on the General Linear Model (GLM), which relies on group-averaged effects, with an innovative method based on threshold-weighted overlap maps (OMth-w) that explicitly exploits ISV to detect neuroplasticity-related changes in fMRI signals before and after a rehabilitation intervention.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty healthy controls (HC) and thirteen people with multiple sclerosis (pwMS) undergoing Eye Movement Desensitization and Reprocessing (EMDR) treatment for depression were enrolled. Participants performed an emotional visual stimulation task during fMRI, comprising two conditions with positive and negative emotions. fMRI data were acquired at two time points (pre- and post-EMDR for pwMS). Data analysis compared two approaches: (1) conventional second-level general linear model (GLM) analyses using paired t-tests; (2) normalized individual threshold-weighted overlap maps (OMth-w) to quantify ISV.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eStandard GLM analyses did not reveal significant longitudinal changes in either group. In contrast, the OMth-w approach showed increased neural variability over time in HC and reduced variability in pwMS following EMDR treatment, concomitant with a significant reduction in depressive symptoms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThese results underscore the relevance of variability-based analytical approaches for identifying neuroplasticity-related changes that may remain undetected using traditional mean-based inference methods.\u003c/p\u003e","manuscriptTitle":"Exploring inter-subject variability in the emotional domain to characterize typical and atypical neural responses in longitudinal settings: insights from Eye Movement Desensitization and Reprocessing rehabilitative treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-09 11:49:58","doi":"10.21203/rs.3.rs-8375274/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":"f275e9a9-c4e6-42f8-b4e4-3bac6de4648b","owner":[],"postedDate":"January 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-03T12:55:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-09 11:49:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8375274","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8375274","identity":"rs-8375274","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}