Criticality emerges within coherent functional organization in human forebrain organoids

Criticality emerges within coherent functional organization in human forebrain organoids | 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 Criticality emerges within coherent functional organization in human forebrain organoids Naoya Itatani, Melissa Zavaglia This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8640242/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 Critical dynamics optimise information processing in neural systems, yet two-dimensional cortical cultures require structured external input to approach the critical point. Whether three-dimensional organoids achieve criticality autonomously, and whether this criticality reflects genuine functional organization, has not been systematically examined. Here we analyse spontaneous activity in 45 human forebrain organoids, revealing robust near-critical dynamics (branching ratio = 1.099 ± 0.052) that emerge without external input. Branching ratio correlates strongly with single-channel firing regularity (r = -0.816), functional connectivity, and network clustering, while small-world topology (σ = 8.26) co-emerges with near-critical dynamics. These results demonstrate that naive organoids self-organise to a computationally favourable state with coherent functional architecture, providing a validated baseline and identifying candidate biomarkers for organoid intelligence applications. Biological sciences/Neuroscience/Computational neuroscience/Dynamical systems Biological sciences/Neuroscience/Neural circuits Biological sciences/Systems biology/Criticality Full Text Additional Declarations There is NO Competing Interest. Supplementary Files CriticalityinOrganoidSupplementarySubmit.docx Criticality emerges within coherent functional organization in human forebrain organoids: Supplementary materials 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. 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. 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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-8640242","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":584848930,"identity":"49fb722d-79f8-4880-a697-41b30ea592ff","order_by":0,"name":"Naoya Itatani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYPACCQiVUAGmDIjSIsHABtJyxoBoLQwQLYxtRGgxZz98TOIHg0Ud//zmZw8ezvuTuLaBeeMDfFose9LSJHuADpM4xmZukLgNiA6wFeO1xuBAjpkED8gvxxjMJCBaeMwk8Go5/8ZM8g9Qi/wx9m8SiXPAWsx/4NVyI8dMGmSLwTGg4YkNEFvw6QBqeZZsLWMgIbnxWE6ZRMIxY+Nth9mKCTgs+eDNNxV1/HKHj2+T/FEjJ7vtePPGD3itYWBgkUCNCGYC6kFKCJk5CkbBKBgFIx0AAMc3RROJGiEDAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-3662-3499","institution":"Technical University of Munich","correspondingAuthor":true,"prefix":"","firstName":"Naoya","middleName":"","lastName":"Itatani","suffix":""},{"id":584848931,"identity":"a95466e6-fe6b-4c5d-862d-6c412a68bc88","order_by":1,"name":"Melissa Zavaglia","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Melissa","middleName":"","lastName":"Zavaglia","suffix":""}],"badges":[],"createdAt":"2026-01-19 14:16:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8640242/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8640242/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102312477,"identity":"66f96dfb-7fb3-4818-b6ba-1d4a6e9aa352","added_by":"auto","created_at":"2026-02-10 12:02:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":935255,"visible":true,"origin":"","legend":"","description":"","filename":"CriticalityinOrganoidSubmit.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8640242/v1_covered_76573d50-c2ae-4923-83ea-4fac27f3b89d.pdf"},{"id":102312430,"identity":"ded8368b-a746-4015-ad30-d939bd4877f2","added_by":"auto","created_at":"2026-02-10 12:01:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":449030,"visible":true,"origin":"","legend":"Criticality emerges within coherent functional organization in human forebrain organoids: Supplementary materials","description":"","filename":"CriticalityinOrganoidSupplementarySubmit.docx","url":"https://assets-eu.researchsquare.com/files/rs-8640242/v1/776689d89b8c2f0c08003577.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Criticality emerges within coherent functional organization in human forebrain organoids","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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-8640242/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8640242/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCritical dynamics optimise information processing in neural systems, yet two-dimensional cortical cultures require structured external input to approach the critical point. 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