Recurrent code for working memory maintenance in the human frontal cortex

Recurrent code for working memory maintenance in the human frontal cortex | 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 Recurrent code for working memory maintenance in the human frontal cortex Ke Jia, Yuan Gao, Xin Hu, Yuhui Chai, Yinghua Xi, Bin Xu, Bolin Qin, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6398278/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Despite accumulating evidence for the involvement of frontal cortex in working memory, it remains debated whether frontal cortex stores stimulus-specific mnemonic information or coordinates mnemonic representations in sensory areas. Neurophysiological non-human primate studies at microcircuit level largely support the former view, while human neuroimaging findings at macroscale level remain inconsistent. Here, we leverage ultra-high-field (7T) functional magnetic resonance imaging (fMRI) to interrogate the nature of working memory representations in human frontal cortex at submillimeter resolution. Our results reveal decodable working memory contents in the superficial layers of superior precentral sulcus (sPCS), indicating recurrent working memory mechanisms. These mnemonic contents are represented in a continuous format, resembling those observed during encoding. Their fidelity depends on the spatial selectivity of individual voxels and the strength of persistent activity, and closely tracks working memory performance. Our findings highlight the recurrent code for working memory in human frontal cortex, reconciling cross-species controversy into a shared mechanistic framework of working memory. Biological sciences/Neuroscience/Learning and memory/Working memory Biological sciences/Psychology/Human behaviour Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Posted 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-6398278","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":449247278,"identity":"fc8fbe72-39f1-4bda-b7fe-84aa161f69fa","order_by":0,"name":"Ke Jia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYBACCYaDDQwfGNhAbAPitTDOIFELAwMzD4RNpBbJxsONn23+8CU2sDdvk2CouUNYizTDwWbpHB62xAaeY2USDMeeEdYiB/SLdI4EUItEjpkEY8NhorQ0/7YwAGqRf0OkFqDD2qQZEkC28BCpRbLhYJtlzwE24zaetGKLhGNEaJG4cfzxjR9/jsn2sx/eeONDDRFaGCQOgMhjkMhMIEIDAwN/A4isIUrtKBgFo2AUjFAAABgmN937JK6DAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0005-5498-8952","institution":"Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Ke","middleName":"","lastName":"Jia","suffix":""},{"id":449247279,"identity":"8bae2e12-ace7-4ff7-90b6-b5892f390313","order_by":1,"name":"Yuan Gao","email":"","orcid":"","institution":"Department of Psychology and Behavioral Sciences, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Gao","suffix":""},{"id":449247280,"identity":"d69f7aa1-05de-4948-92d0-88bae12839c0","order_by":2,"name":"Xin Hu","email":"","orcid":"","institution":"Department of Psychology and Behavioral Sciences, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Hu","suffix":""},{"id":449247281,"identity":"7a948846-9695-4d83-a69f-974b3ef63252","order_by":3,"name":"Yuhui Chai","email":"","orcid":"https://orcid.org/0000-0003-1523-3117","institution":"University of Illinois at Urbana-Champaign","correspondingAuthor":false,"prefix":"","firstName":"Yuhui","middleName":"","lastName":"Chai","suffix":""},{"id":449247282,"identity":"24e7812c-a084-4e9d-bd37-71670851d9d0","order_by":4,"name":"Yinghua Xi","email":"","orcid":"","institution":"Interdisciplinary Institute of Neuroscience and Technology，Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yinghua","middleName":"","lastName":"Xi","suffix":""},{"id":449247283,"identity":"ccd87098-2f3e-46a9-b5e9-b34942a43424","order_by":5,"name":"Bin Xu","email":"","orcid":"","institution":"Department of Neurosurgery of the Second Affiliated Hospital and Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Xu","suffix":""},{"id":449247284,"identity":"00d18cf2-f8bd-4960-80fb-1767ba609f03","order_by":6,"name":"Bolin Qin","email":"","orcid":"","institution":"Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University","correspondingAuthor":false,"prefix":"","firstName":"Bolin","middleName":"","lastName":"Qin","suffix":""},{"id":449247285,"identity":"5e4d5ff6-a361-43ef-a8a6-2faeeac01335","order_by":7,"name":"Jia-Hong Gao","email":"","orcid":"https://orcid.org/0000-0002-9311-0297","institution":"National Biomedical Imaging Center","correspondingAuthor":false,"prefix":"","firstName":"Jia-Hong","middleName":"","lastName":"Gao","suffix":""},{"id":449247286,"identity":"9aa8ed4c-8bd8-49d8-98bd-55dacd634227","order_by":8,"name":"Xiaotong Zhang","email":"","orcid":"https://orcid.org/0000-0002-9197-1421","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xiaotong","middleName":"","lastName":"Zhang","suffix":""},{"id":449247287,"identity":"4d308b09-2efb-4d8a-980b-0e1960a73b7a","order_by":9,"name":"Sheng Li","email":"","orcid":"https://orcid.org/0000-0002-6258-3147","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Li","suffix":""},{"id":449247288,"identity":"c05c31e7-365f-48a5-a8e0-41a3c19eb383","order_by":10,"name":"Zoe kourtzi","email":"","orcid":"https://orcid.org/0000-0001-9441-7832","institution":"Univ of Cambridge","correspondingAuthor":false,"prefix":"","firstName":"Zoe","middleName":"","lastName":"kourtzi","suffix":""},{"id":449247289,"identity":"5230d7a9-45fd-4dc7-b01a-c71429f50c68","order_by":11,"name":"Mengyuan Gong","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Mengyuan","middleName":"","lastName":"Gong","suffix":""}],"badges":[],"createdAt":"2025-04-08 02:15:20","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6398278/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6398278/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102747408,"identity":"ae7f5797-ca42-4990-99cc-ae2e6a11f1bd","added_by":"auto","created_at":"2026-02-16 09:04:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1103039,"visible":true,"origin":"","legend":"","description":"","filename":"Gaoetalfinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6398278/v1_covered_170b73cb-34cc-47b8-ad3a-2c425c2cce11.pdf"},{"id":102625986,"identity":"72a503a3-4652-483d-b8df-b31019f0a6e0","added_by":"auto","created_at":"2026-02-13 17:51:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1103039,"visible":true,"origin":"","legend":"","description":"","filename":"Gaoetalfinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6398278/v1_covered_86028f0c-d363-4ce3-b8ee-558ad184628d.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Recurrent code for working memory maintenance in the human frontal cortex","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6398278/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6398278/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Despite accumulating evidence for the involvement of frontal cortex in working memory, it remains debated whether frontal cortex stores stimulus-specific mnemonic information or coordinates mnemonic representations in sensory areas. Neurophysiological non-human primate studies at microcircuit level largely support the former view, while human neuroimaging findings at macroscale level remain inconsistent. Here, we leverage ultra-high-field (7T) functional magnetic resonance imaging (fMRI) to interrogate the nature of working memory representations in human frontal cortex at submillimeter resolution. Our results reveal decodable working memory contents in the superficial layers of superior precentral sulcus (sPCS), indicating recurrent working memory mechanisms. These mnemonic contents are represented in a continuous format, resembling those observed during encoding. Their fidelity depends on the spatial selectivity of individual voxels and the strength of persistent activity, and closely tracks working memory performance. Our findings highlight the recurrent code for working memory in human frontal cortex, reconciling cross-species controversy into a shared mechanistic framework of working memory.","manuscriptTitle":"Recurrent code for working memory maintenance in the human frontal cortex","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-29 04:03:57","doi":"10.21203/rs.3.rs-6398278/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fda13a4b-3cd3-4b24-8d24-8d46a0e7733f","owner":[],"postedDate":"April 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47806458,"name":"Biological sciences/Neuroscience/Learning and memory/Working memory"},{"id":47806459,"name":"Biological sciences/Psychology/Human behaviour"}],"tags":[],"updatedAt":"2026-02-13T17:50:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-29 04:03:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6398278","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6398278","identity":"rs-6398278","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}