Cortical Circuits for Cross-Modal Generalization

Cortical Circuits for Cross-Modal Generalization | 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 Cortical Circuits for Cross-Modal Generalization Sami El-Boustani, Maëlle Guyoton, Giulio Matteucci, Charlie Foucher, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4518375/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 May, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Adapting goal-directed behaviors to changing sensory conditions is a fundamental aspect of intelligence. The brain uses abstract representations of the environment to generalize learned associations across sensory modalities. The circuit organization that mediates such cross-modal generalizations remains, however, unknown. Here, we demonstrate that mice can bidirectionally generalize sensorimotor task rules between touch and vision by using abstract representations of peri-personal space within the cortex. Using large-scale mapping in the dorsal cortex at single-cell resolution, we discovered multimodal neurons with congruent spatial representations within multiple associative areas of the dorsal and ventral stream. Optogenetic sensory substitution and systematic silencing of these associative areas revealed that a single area in the dorsal stream is necessary and sufficient for cross-modal generalization. Our results identify and comprehensively describe a cortical circuit organization that underlies an essential cognitive function, providing a structural and functional basis for abstract reasoning in the mammalian brain. Biological sciences/Neuroscience/Cognitive neuroscience Biological sciences/Neuroscience/Learning and memory/Cortex Biological sciences/Neuroscience/Sensorimotor processing/Decision Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 26 May, 2025 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. 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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-4518375","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":328060356,"identity":"f4808caf-314d-4404-baa7-ae1ba9b7d7f9","order_by":0,"name":"Sami El-Boustani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIie2RMUsDMRiG3yLoEuj6FQr3F1ICV4WCf+Xc7xzlhgMPhOtSdPVnHHRyyxG4xbhncHZSSFGk02HOliKFgN1E8kzJSx7yfgkQCPxRJHAKvt2w4SbBLvEotDngVmxU/kLBTwVcbjOfEs0fLyRywvRkId5t8TwWJmuajxzR1KNwndUSmnC20DHJ9oXF5jJRY43JQ+lR4JRBRde1SWPIY+WUlKtRhWTXcL/Y3ZtTOjeLSYWVnWLivlc6vwLT31J+K5yaSjFOKW9WpV/hxt2StP0s7RU93SpG+pUrtDSpvcWypbXFzL3YzdLmn+p8OE/Fal3MIm+xnmQ/OGLupw5jsD5QCAQCgX/NFylbY1pWPCgsAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-1733-4341","institution":"University of Geneva","correspondingAuthor":true,"prefix":"","firstName":"Sami","middleName":"","lastName":"El-Boustani","suffix":""},{"id":328060357,"identity":"171fe357-7c52-4aca-a824-3856d50ab877","order_by":1,"name":"Maëlle Guyoton","email":"","orcid":"","institution":"University of Geneva","correspondingAuthor":false,"prefix":"","firstName":"Maëlle","middleName":"","lastName":"Guyoton","suffix":""},{"id":328060358,"identity":"62c2d432-575b-4ecc-8e18-6c4585c2987a","order_by":2,"name":"Giulio Matteucci","email":"","orcid":"","institution":"University of Geneva","correspondingAuthor":false,"prefix":"","firstName":"Giulio","middleName":"","lastName":"Matteucci","suffix":""},{"id":328060359,"identity":"6ccf170d-5f62-4524-a892-62d4d55541ba","order_by":3,"name":"Charlie Foucher","email":"","orcid":"","institution":"University of Geneva","correspondingAuthor":false,"prefix":"","firstName":"Charlie","middleName":"","lastName":"Foucher","suffix":""},{"id":328060360,"identity":"266bdf25-27cd-480b-a653-229fcb4d28a1","order_by":4,"name":"Matthew Getz","email":"","orcid":"","institution":"Technical University of Munich","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Getz","suffix":""},{"id":328060361,"identity":"1f5f7463-619d-4aa9-9c05-320b8f408b88","order_by":5,"name":"Julijana Gjorgjieva","email":"","orcid":"https://orcid.org/0000-0001-7118-4079","institution":"Technical University of Munich","correspondingAuthor":false,"prefix":"","firstName":"Julijana","middleName":"","lastName":"Gjorgjieva","suffix":""}],"badges":[],"createdAt":"2024-06-02 21:50:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4518375/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4518375/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-025-59342-9","type":"published","date":"2025-05-26T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83481566,"identity":"fb9d1a60-48a5-4f19-b5d0-0ff85c08501e","added_by":"auto","created_at":"2025-05-27 07:07:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5348140,"visible":true,"origin":"","legend":"","description":"","filename":"GuyotonetalManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4518375/v1_covered_c21a269e-d9be-4c92-a0cb-7736cde32455.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"\u003cp\u003eCortical Circuits for Cross-Modal Generalization\u003c/p\u003e","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-4518375/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4518375/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Adapting goal-directed behaviors to changing sensory conditions is a fundamental aspect of intelligence. 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