Integrated Anatomical and Functional Connectivity Mapping in Episodic Migraine: A Spectral Graph Theory Approach | 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 Integrated Anatomical and Functional Connectivity Mapping in Episodic Migraine: A Spectral Graph Theory Approach Gonçalo Grácio, Ana Matoso, Inês Esteves, Ana R. Fouto, Amparo Ruiz-Tagle, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7643639/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Migraine disproportionately affects women, yet how menstrual physiology reshapes large-scale brain communication remains unclear. We combined diffusion-weighted imaging (DWI) and resting-state fMRI in female participants (14 patients with episodic migraine without aura; 15 matched healthy controls) to test how direct and indirect anatomical communication paths in the brain can predict brain fucntion. We used a spectral mapping framework that isolates the contribution of communication paths of a specific length and evaluated, how well brain structure predicts brain function within individuals. Analyses of individual path lengths revealed a non-monotonic dissociation: no difference at one-step (direct) paths, but higher mapping accuracy in patients at intermediate polysynaptic scales (four to six steps). At longer scales, contributions attenuated in both groups. Spatial correspondence analyses localized patient-specific effects to default mode network subsystems across multiple atlas. These findings indicate that migraine-related dysfunction reflects altered mesoscale integration along indirect anatomical routes rather than global disconnection, and they provide a general approach to dissect structure-function coupling by communication scale in disease. Health sciences/Neurology Biological sciences/Neuroscience Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformationIntegratedAnatomical.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 24 Feb, 2026 Reviews received at journal 21 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers agreed at journal 29 Nov, 2025 Reviewers agreed at journal 19 Oct, 2025 Reviews received at journal 16 Oct, 2025 Reviewers agreed at journal 28 Sep, 2025 Reviewers invited by journal 26 Sep, 2025 Editor assigned by journal 26 Sep, 2025 Editor invited by journal 26 Sep, 2025 Submission checks completed at journal 25 Sep, 2025 First submitted to journal 25 Sep, 2025 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-7643639","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":525430682,"identity":"0829a628-faf0-470a-b7bf-e6b006d50f5e","order_by":0,"name":"Gonçalo Grácio","email":"data:image/png;base64,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","orcid":"","institution":"University of Lisbon","correspondingAuthor":true,"prefix":"","firstName":"Gonçalo","middleName":"","lastName":"Grácio","suffix":""},{"id":525430683,"identity":"70dcc5ad-feb0-43bb-85c2-5613723f5c3f","order_by":1,"name":"Ana Matoso","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Matoso","suffix":""},{"id":525430686,"identity":"50988b62-e215-425d-a638-fa20dc86b0f0","order_by":2,"name":"Inês Esteves","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Inês","middleName":"","lastName":"Esteves","suffix":""},{"id":525430687,"identity":"4d84cec0-3549-41af-8d6b-92714de2edea","order_by":3,"name":"Ana R. Fouto","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"R.","lastName":"Fouto","suffix":""},{"id":525430688,"identity":"b3f84f27-c1de-4a34-869f-71c4a316415e","order_by":4,"name":"Amparo Ruiz-Tagle","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Amparo","middleName":"","lastName":"Ruiz-Tagle","suffix":""},{"id":525430691,"identity":"e7d9f448-a1bc-4179-a393-4f69f9e193bb","order_by":5,"name":"Gina Caetano","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Gina","middleName":"","lastName":"Caetano","suffix":""},{"id":525430693,"identity":"97c94a66-947f-4365-909d-21ba9a516d47","order_by":6,"name":"Raquel Gil-Gouveia","email":"","orcid":"","institution":"Hospital da Luz","correspondingAuthor":false,"prefix":"","firstName":"Raquel","middleName":"","lastName":"Gil-Gouveia","suffix":""},{"id":525430694,"identity":"cc55ecdf-9b33-46ca-b6fc-8cb85fdcd4f9","order_by":7,"name":"Patrícia Figueiredo","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Patrícia","middleName":"","lastName":"Figueiredo","suffix":""},{"id":525430697,"identity":"c2f5f8a6-6b20-4714-8853-292b2773ef8d","order_by":8,"name":"Rita G. Nunes","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Rita","middleName":"G.","lastName":"Nunes","suffix":""},{"id":525430702,"identity":"b8d20e6d-ec98-43f6-a3ca-06bb89927ef8","order_by":9,"name":"Sérgio Pequito","email":"","orcid":"","institution":"University of Lisbon","correspondingAuthor":false,"prefix":"","firstName":"Sérgio","middleName":"","lastName":"Pequito","suffix":""}],"badges":[],"createdAt":"2025-09-17 21:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7643639/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7643639/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93140564,"identity":"e4a5c859-8146-46d0-9f33-89964809662d","added_by":"auto","created_at":"2025-10-09 13:00:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":20802604,"visible":true,"origin":"","legend":"","description":"","filename":"IntegratedAnatomicalandFunctionalConnectivityMapping4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7643639/v1/d67ccfb2745ac0f6ea731e12.pdf"},{"id":93141234,"identity":"67f92877-6b48-44d1-97cd-066b02307bb5","added_by":"auto","created_at":"2025-10-09 13:08:03","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":11008,"visible":true,"origin":"","legend":"","description":"","filename":"9e8e1d5620214667a123181d24971dba.json","url":"https://assets-eu.researchsquare.com/files/rs-7643639/v1/625bacb188a01775121dbc4c.json"},{"id":93140563,"identity":"bc7355e0-06f8-4c68-a67e-33441dcf2a2f","added_by":"auto","created_at":"2025-10-09 13:00:03","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6422017,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformationIntegratedAnatomical.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7643639/v1/17b5fe1a9c3820876589a793.pdf"},{"id":93142826,"identity":"00ab2481-b7ad-4b1e-bd17-add06996c54d","added_by":"auto","created_at":"2025-10-09 13:16:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2362449,"visible":true,"origin":"","legend":"","description":"","filename":"IntegratedAnatomicalandFunctionalConnectivityMapping4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7643639/v1_covered_106d93a4-5549-4781-8025-80a90e03dc54.pdf"},{"id":93140561,"identity":"2bf97d9e-efd9-4a86-8862-c10695e2c793","added_by":"auto","created_at":"2025-10-09 13:00:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":6422017,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformationIntegratedAnatomical.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7643639/v1/56411aa48054c4972fb8a091.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Integrated Anatomical and Functional Connectivity Mapping in Episodic Migraine: A Spectral Graph Theory Approach","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-7643639/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7643639/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Migraine disproportionately affects women, yet how menstrual physiology reshapes large-scale brain communication remains unclear. We combined diffusion-weighted imaging (DWI) and resting-state fMRI in female participants (14 patients with episodic migraine without aura; 15 matched healthy controls) to test how direct and indirect anatomical communication paths in the brain can predict brain fucntion. We used a spectral mapping framework that isolates the contribution of communication paths of a specific length and evaluated, how well brain structure predicts brain function within individuals. Analyses of individual path lengths revealed a non-monotonic dissociation: no difference at one-step (direct) paths, but higher mapping accuracy in patients at intermediate polysynaptic scales (four to six steps). At longer scales, contributions attenuated in both groups. Spatial correspondence analyses localized patient-specific effects to default mode network subsystems across multiple atlas. These findings indicate that migraine-related dysfunction reflects altered mesoscale integration along indirect anatomical routes rather than global disconnection, and they provide a general approach to dissect structure-function coupling by communication scale in disease.","manuscriptTitle":"Integrated Anatomical and Functional Connectivity Mapping in Episodic Migraine: A Spectral Graph Theory Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-09 12:59:58","doi":"10.21203/rs.3.rs-7643639/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-24T09:37:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-21T13:15:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40217791255112190415805977163636872516","date":"2026-02-11T12:15:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"49303807113267492774352799700344390366","date":"2025-11-29T14:09:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"123995549700440942355436003607496050207","date":"2025-10-19T12:40:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-16T22:33:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144629696800016049693522774595465008156","date":"2025-09-28T05:14:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-26T13:49:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-26T13:15:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-26T12:57:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-25T09:03:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-09-25T09:01:41+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":"16dcd0b3-51fd-40ce-be35-44a79966dc45","owner":[],"postedDate":"October 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":55840204,"name":"Health sciences/Neurology"},{"id":55840205,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-05-13T17:54:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-09 12:59:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7643639","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7643639","identity":"rs-7643639","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.