Layer-Resolved Connective Fields from Ultrafast fMRI Decode Feedforward and Feedback Information Flow during Spontaneous Activity | 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 Layer-Resolved Connective Fields from Ultrafast fMRI Decode Feedforward and Feedback Information Flow during Spontaneous Activity Noam Shemesh, Joana Carvalho, Francisca Fernandes, Mafalda Valente, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6136435/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 May, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Deciphering the directionality of information flow in cortical circuits is essential for understanding brain dynamics, learning, and neuroplasticity after injury. However, current non-invasive methods cannot distinguish feedforward (FF) from feedback (FB) signals across entire networks, including deep brain regions. Here, we present a novel approach – UltraFast Layer-Resolved Encoding (uFLARE) – that develops ultrahigh spatiotemporal resolution fMRI and a Layer-based Connective Field (lCF) model to disentangle FF from FB signaling. Our findings reveal that lCF size, an indicator of information integration, differentiates FF and FB activity through distinct layer-specific connectivity patterns during spontaneous activity, challenging the notion that FF signals are solely stimulus-driven. FF connectivity follows an inverted U-shape, peaking in layer IV, while FB exhibits a U-shaped pattern, with peaks in layers I and VI. These profiles generalize across sensory pathways (visual, somatosensory, and motor) and reveal injury-induced network reorganization, such as LGN bypassing V1 to provide direct FF input to higher visual areas. Biological sciences/Biological techniques/Imaging/Functional magnetic resonance imaging Biological sciences/Neuroscience/Computational neuroscience/Network models Biological sciences/Biological techniques/Imaging/Magnetic resonance imaging Biological sciences/Neuroscience/Visual system/Pattern vision Full Text Additional Declarations Yes there is potential Competing Interest. NS serves on the scientific advisory board of Bruker Biospon Cite Share Download PDF Status: Published Journal Publication published 04 May, 2026 Read the published version in Nature Communications → 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-6136435","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":443221510,"identity":"ab7ae685-e5e8-4fd5-b7e3-15ad74c82e66","order_by":0,"name":"Noam Shemesh","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0001-6681-5876","institution":"Champalimaud Foundation","correspondingAuthor":true,"prefix":"","firstName":"Noam","middleName":"","lastName":"Shemesh","suffix":""},{"id":443221511,"identity":"e6210542-5de7-48b7-96bd-8bc693ff023b","order_by":1,"name":"Joana Carvalho","email":"","orcid":"","institution":"University of Coimbra","correspondingAuthor":false,"prefix":"","firstName":"Joana","middleName":"","lastName":"Carvalho","suffix":""},{"id":443221512,"identity":"690edfbf-2c91-4e82-bb6b-84e486c01844","order_by":2,"name":"Francisca Fernandes","email":"","orcid":"https://orcid.org/0000-0001-7967-067X","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Francisca","middleName":"","lastName":"Fernandes","suffix":""},{"id":443221513,"identity":"b3e19b91-6519-46cf-92f6-35ad44461372","order_by":3,"name":"Mafalda Valente","email":"","orcid":"https://orcid.org/0000-0002-1824-0462","institution":"Champalimaud Foundation","correspondingAuthor":false,"prefix":"","firstName":"Mafalda","middleName":"","lastName":"Valente","suffix":""},{"id":443221514,"identity":"c771258d-a3eb-44fb-b723-1bbc250b6509","order_by":4,"name":"Koen Haak","email":"","orcid":"https://orcid.org/0000-0001-9309-1906","institution":"Tilburg University","correspondingAuthor":false,"prefix":"","firstName":"Koen","middleName":"","lastName":"Haak","suffix":""}],"badges":[],"createdAt":"2025-03-01 20:35:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6136435/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6136435/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-026-71506-9","type":"published","date":"2026-05-04T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":108476820,"identity":"fc717c31-e43e-4dab-bb45-f799d6f14152","added_by":"auto","created_at":"2026-05-05 07:06:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2038434,"visible":true,"origin":"","legend":"Article File","description":"","filename":"CarvalhoetalFinal2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6136435/v1_covered_50fa9bd5-876f-4ed9-b790-c71b0d65bf3d.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nNS serves on the scientific advisory board of Bruker Biospon","formattedTitle":"Layer-Resolved Connective Fields from Ultrafast fMRI Decode Feedforward and Feedback Information Flow during Spontaneous Activity","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6136435/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6136435/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Deciphering the directionality of information flow in cortical circuits is essential for understanding brain dynamics, learning, and neuroplasticity after injury. However, current non-invasive methods cannot distinguish feedforward (FF) from feedback (FB) signals across entire networks, including deep brain regions. Here, we present a novel approach – UltraFast Layer-Resolved Encoding (uFLARE) – that develops ultrahigh spatiotemporal resolution fMRI and a Layer-based Connective Field (lCF) model to disentangle FF from FB signaling. Our findings reveal that lCF size, an indicator of information integration, differentiates FF and FB activity through distinct layer-specific connectivity patterns during spontaneous activity, challenging the notion that FF signals are solely stimulus-driven. FF connectivity follows an inverted U-shape, peaking in layer IV, while FB exhibits a U-shaped pattern, with peaks in layers I and VI. These profiles generalize across sensory pathways (visual, somatosensory, and motor) and reveal injury-induced network reorganization, such as LGN bypassing V1 to provide direct FF input to higher visual areas.","manuscriptTitle":"Layer-Resolved Connective Fields from Ultrafast fMRI Decode Feedforward and Feedback Information Flow during Spontaneous Activity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 03:48:21","doi":"10.21203/rs.3.rs-6136435/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ce433ae0-3778-40fb-8733-4d45a41c5665","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":47187680,"name":"Biological sciences/Biological techniques/Imaging/Functional magnetic resonance imaging"},{"id":47187681,"name":"Biological sciences/Neuroscience/Computational neuroscience/Network models"},{"id":47187682,"name":"Biological sciences/Biological techniques/Imaging/Magnetic resonance imaging"},{"id":47187683,"name":"Biological sciences/Neuroscience/Visual system/Pattern vision"}],"tags":[],"updatedAt":"2026-05-05T07:06:38+00:00","versionOfRecord":{"articleIdentity":"rs-6136435","link":"https://doi.org/10.1038/s41467-026-71506-9","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2026-05-04 04:00:00","publishedOnDateReadable":"May 4th, 2026"},"versionCreatedAt":"2025-04-16 03:48:21","video":"","vorDoi":"10.1038/s41467-026-71506-9","vorDoiUrl":"https://doi.org/10.1038/s41467-026-71506-9","workflowStages":[]},"version":"v1","identity":"rs-6136435","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6136435","identity":"rs-6136435","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.