Asymmetric scaling of cerebellar cortex and deep nuclei reshapes input-output architecture across primates

Asymmetric scaling of cerebellar cortex and deep nuclei reshapes input-output architecture across primates | 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 Asymmetric scaling of cerebellar cortex and deep nuclei reshapes input-output architecture across primates Kadharbatcha Saleem, Alexandru Avram, Daniel Glen, Peter Basser This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9464995/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The cerebellum shapes distributed motor and association networks through precisely organized pathways linking the cerebellar cortex to the deep cerebellar nuclei (DCN), its principal output structures. Whether these cortical and nuclear compartments scale proportionally across primates, and how their relative expansion relates to cerebellar organization, remains unresolved. Here, we generate multimodal, high-resolution cross-species 3D cerebellar atlases in marmoset, macaque, and human by integrating iron-sensitive and diffusion MRI (MAP-MRI) with histological markers, enabling direct delineation of cerebellar lobules and DCN subdivisions within a unified framework. Comparative volumetric analyses reveal strikingly nonuniform scaling of cerebellar cortical-nuclear architecture: cortical expansion markedly outpaces DCN enlargement, indicating disproportionate growth of input relative to output systems. This divergence is accompanied by progressive reorganization of the DCN, with increasing dominance of the dentate nucleus. In contrast, cortical expansion is driven by posterior hemispheric territories, with lobules VI-IX and Crus I/II, linked to higher-order functions, showing the strongest scaling and largest absolute gains, whereas DCN subdivisions show selective rather than uniform scaling. Together, these findings establish nonuniform cortical-nuclear scaling as a systems-level organizational principle that reshapes cerebellar input-output architecture across primates. Biological sciences/Neuroscience/Motor control/Cerebellum Health sciences/Anatomy/Nervous system/Brain Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review 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. 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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-9464995","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":627979620,"identity":"cf4143e9-af0b-4140-afbd-c73ab019d1a3","order_by":0,"name":"Kadharbatcha Saleem","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYFAC5gYgkcDADyQPPGBg4DEgrIURokUSSB1IIEmLwQEwxcBAUIt8+8HGBx9z0uyNrx1+CLTljow5A/vFxzx4tBicSWw2nLktJ3Hb7TQDoJZnPJYNPMXGeLUwJLZJ826rSDC7nQDScpjH4ABPmuQMfA7rf9j++++2Cnvj2ekfiNPCcCOxjZlxWw7jBukcmC3sxyQ+4HPYjYfNkr3b0hJn3M4pOJBgANRymIfZAJ8W+f7kgx9+bku255+dvvnDh4rD9gbH2x8+SMDnMDRLgZiZmNhEA+wPSNYyCkbBKBgFwxoAAEPqVMjTpoY+AAAAAElFTkSuQmCC","orcid":"","institution":"National Institutes of Health","correspondingAuthor":true,"prefix":"","firstName":"Kadharbatcha","middleName":"","lastName":"Saleem","suffix":""},{"id":627979621,"identity":"b663eed7-9bb3-48e7-9e73-99a0fd46bab9","order_by":1,"name":"Alexandru Avram","email":"","orcid":"https://orcid.org/0000-0002-0295-601X","institution":"NIH","correspondingAuthor":false,"prefix":"","firstName":"Alexandru","middleName":"","lastName":"Avram","suffix":""},{"id":627979622,"identity":"4378d974-dffe-4d9a-9eae-41be2eac47e2","order_by":2,"name":"Daniel Glen","email":"","orcid":"","institution":"National Institutes of Mental Heatlh","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Glen","suffix":""},{"id":627979623,"identity":"12ee52ba-a2bc-4dc3-843f-66503c6d66e0","order_by":3,"name":"Peter Basser","email":"","orcid":"https://orcid.org/0000-0003-4795-6088","institution":"NIH","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Basser","suffix":""}],"badges":[],"createdAt":"2026-04-19 22:25:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9464995/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9464995/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108044122,"identity":"4f5ca7ac-0e11-4fab-90df-fc24d1335b07","added_by":"auto","created_at":"2026-04-28 18:57:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3191545,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9464995/v1_covered_b3d234fc-2b3b-4fc2-88c0-19c828c2f605.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Asymmetric scaling of cerebellar cortex and deep nuclei reshapes input-output architecture across primates","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"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":"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-9464995/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9464995/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The cerebellum shapes distributed motor and association networks through precisely organized pathways linking the cerebellar cortex to the deep cerebellar nuclei (DCN), its principal output structures. 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