Effects of pharmacological modulation of corticalexcitability on resting-state EEG PAC in humans

Effects of pharmacological modulation of corticalexcitability on resting-state EEG PAC in humans | 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 Effects of pharmacological modulation of corticalexcitability on resting-state EEG PAC in humans Alper Er, Paolo Belardinelli, Véronique Marchand-Pauvert, Ulf Ziemann, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8539670/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Electroencephalography (EEG) signal is driven by oscillations arising from the synchronized activity of cortical neuronal populations. Phase-amplitude coupling (PAC) refers to the interaction whereby the amplitude of higher- frequency oscillations is systematically modulated by the phase of slower rhythms. It has been suggested that the excitation/inhibition (E/I) balance, which is often disrupted in neuropsychiatric and neurodegenerative disorders, plays a critical role in shaping PAC, although direct evidence in humans remains limited. In this study, we investigated the effects of pharmacologically modulated E/I balance on PAC using resting-state EEG (rs- EEG) data. Specifically, we analyzed the impact of anti-glutamatergic drugs, dextromethorphan (NMDA receptor antagonist) and perampanel (AMPA receptor antagonist), as well as nimodipine (L-type voltage-gated calcium channel blocker) on PAC in a double blind, placebo-controlled experiment. Analysis revealed a significant decrease in PAC following administration of dextromethorphan and perampanel, while nimodipine and placebo showed no effects. By showing that PAC reliably reflects pharmacological shifts in cortical E/I balance, this study confirms its physiological relevance and supports its use as a biomarker of excitability disturbances and cortical dysfunction across neurological and psychiatric disorders. Health sciences/Neurology Biological sciences/Neuroscience Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Feb, 2026 Reviews received at journal 03 Feb, 2026 Reviews received at journal 30 Jan, 2026 Reviewers agreed at journal 23 Jan, 2026 Reviewers agreed at journal 22 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor assigned by journal 13 Jan, 2026 Editor invited by journal 13 Jan, 2026 Submission checks completed at journal 09 Jan, 2026 First submitted to journal 09 Jan, 2026 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-8539670","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":575162773,"identity":"e8d8cb42-bb9f-4ad5-b1b5-0d713a1a6e62","order_by":0,"name":"Alper Er","email":"","orcid":"","institution":"Sorbonne Université, Inserm, CNRS","correspondingAuthor":false,"prefix":"","firstName":"Alper","middleName":"","lastName":"Er","suffix":""},{"id":575162774,"identity":"877357ce-1c66-460b-8dc0-8fefa1921467","order_by":1,"name":"Paolo Belardinelli","email":"","orcid":"","institution":"Universita di 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humans","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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8539670/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8539670/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Electroencephalography (EEG) signal is driven by oscillations arising from the synchronized activity of cortical\nneuronal populations. Phase-amplitude coupling (PAC) refers to the interaction whereby the amplitude of higher-\nfrequency oscillations is systematically modulated by the phase of slower rhythms. It has been suggested\nthat the excitation/inhibition (E/I) balance, which is often disrupted in neuropsychiatric and neurodegenerative\ndisorders, plays a critical role in shaping PAC, although direct evidence in humans remains limited. In this study,\nwe investigated the effects of pharmacologically modulated E/I balance on PAC using resting-state EEG (rs-\nEEG) data. Specifically, we analyzed the impact of anti-glutamatergic drugs, dextromethorphan (NMDA receptor\nantagonist) and perampanel (AMPA receptor antagonist), as well as nimodipine (L-type voltage-gated calcium\nchannel blocker) on PAC in a double blind, placebo-controlled experiment. Analysis revealed a significant decrease\nin PAC following administration of dextromethorphan and perampanel, while nimodipine and placebo showed no\neffects. 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