The role of GABA in semantic memory and its neuroplasticity

The role of GABA in semantic memory and its neuroplasticity | 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 The role of GABA in semantic memory and its neuroplasticity JeYoung Jung, Stephen Williams, Matthew Lambon Ralph This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3026480/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract A fundamental aspect of neuroscience is understanding neural functioning and plasticity of the brain. The anterior temporal lobe (ATL) is a hub for semantic memory, which generates coherent semantic representations about the world. GABAergic inhibition plays a crucial role in shaping human cognition and plasticity, but it is unclear how this inhibition relates to human semantic memory and its plasticity. Here, we employed a combination of continuous theta burst stimulation (cTBS), MR spectroscopy and fMRI to investigate the role of GABA in semantic memory and its neuroplasticity. Our results demonstrated that the inhibitory cTBS increased regional GABA levels in the ATL and decreased ATL blood-oxygen level-dependent (BOLD) activity during semantic processing. Importantly, changes in GABA levels were strongly associated with changes in regional activity induced by cTBS. These results suggest that GABAergic activity may be the mechanism by which cTBS induces after effects on cortical excitability. Furthermore, individuals with better semantic performance exhibited selective activity in the ATL, attributable to higher concentrations of inhibitory GABA, which can sharpen distributed semantic representations, leading to more precise semantic processing. Our results revealed a non-linear, inverted-U-shape relationship between GABA levels in the ATL and semantic performance, thus offering an explanation for the individual differences in the cTBS effect on task performance. These results provide neurochemical and anatomical specificity in shaping task-related cortical activity and behaviour. Understanding the link between neurochemistry and semantic memory has important implications for understanding individual differences in semantic behaviour and developing therapeutic interventions for patients with semantic impairments. Biological sciences/Neuroscience/Learning and memory/Long-term memory Biological sciences/Psychology/Human behaviour Biological sciences/Neuroscience/Cognitive neuroscience/Language GABA Semantic memory anterior temporal lobe TMS neuroplasticity Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Supplementaryinformation.docx Supplementary material Cite Share Download PDF Status: Posted Version 3 posted You are reading this latest preprint version Show more versions 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-3026480","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":381534131,"identity":"6e9d226f-efa3-4b2d-9150-77c5ae82a91c","order_by":0,"name":"JeYoung Jung","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-3739-7331","institution":"University of Nottingham","correspondingAuthor":true,"prefix":"","firstName":"JeYoung","middleName":"","lastName":"Jung","suffix":""},{"id":381534132,"identity":"8a4b19a8-4f2c-4a52-83df-a87cf86d2cfc","order_by":1,"name":"Stephen Williams","email":"","orcid":"https://orcid.org/0000-0001-5940-1675","institution":"University of Manchester","correspondingAuthor":false,"prefix":"","firstName":"Stephen","middleName":"","lastName":"Williams","suffix":""},{"id":381534133,"identity":"23ec668a-c7e6-4c82-9759-543fe11825ed","order_by":2,"name":"Matthew Lambon Ralph","email":"","orcid":"https://orcid.org/0000-0001-5907-2488","institution":"MRC Cognition and Brain Sciences Unit","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"Lambon","lastName":"Ralph","suffix":""}],"badges":[],"createdAt":"2023-06-05 23:45:37","currentVersionCode":3,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3026480/v3","doiUrl":"https://doi.org/10.21203/rs.3.rs-3026480/v3","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78913385,"identity":"ebbc6fd9-a363-4ea5-a094-16fc389d0077","added_by":"auto","created_at":"2025-03-20 17:38:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1164218,"visible":true,"origin":"","legend":"","description":"","filename":"JungATLMRSTMSfMRI2ndrevisionclean.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3026480/v3_covered_062988db-e9ea-488e-8673-7ff9ea97a902.pdf"},{"id":78912399,"identity":"ac63877f-0ee5-4dc2-8fcf-8886e870f639","added_by":"auto","created_at":"2025-03-20 17:22:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38557,"visible":true,"origin":"","legend":"Supplementary material","description":"","filename":"Supplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-3026480/v3/b1ac846b09a289673ef4f57c.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"The role of GABA in semantic memory and its neuroplasticity","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":false,"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":"GABA, Semantic memory, anterior temporal lobe, TMS, neuroplasticity","lastPublishedDoi":"10.21203/rs.3.rs-3026480/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3026480/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA fundamental aspect of neuroscience is understanding neural functioning and plasticity of the brain. 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