Delta-Beta and Beta-Gamma Coupling as Biomarkers of Medication Efficacy in Parkinson's Disease

Delta-Beta and Beta-Gamma Coupling as Biomarkers of Medication Efficacy in Parkinson's Disease | 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 Delta-Beta and Beta-Gamma Coupling as Biomarkers of Medication Efficacy in Parkinson's Disease Tanvir Hasib, Parameswari Shunmugam, Kalai Arasu Muthusamy, Kannan Ramakrishnan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6476008/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 Parkinson’s disease (PD) is marked by neural synchronization, with cross-frequency interactions such as phase-amplitude coupling (PAC) believed to underpin its motor and non-motor symptoms. While invasive studies implicate beta-gamma PAC in PD pathophysiology, the feasibility of detecting and characterizing these dynamics non-invasively and their modulation by therapy remains underexplored. This pilot study investigates nested PAC across delta, beta, and gamma bands in PD using scalp EEG, aiming to identify PD-specific coupling patterns and evaluate their responsiveness to dopaminergic medication. EEG data from PD patients and healthy controls were analyzed using PAC metrics. We examined interactions between delta (0.5–4 Hz), beta (13–30 Hz), and gamma (30–110 Hz) bands pre- and post-medication, with rigorous artifact rejection to confirm coupling specificity. Unmedicated PD patients exhibited delta-beta and beta-gamma PAC which were attenuated following dopaminergic therapy. Notably, delta-beta coupling persisted in the majority of patients, suggesting that delta oscillations may play an underrecognized role in sustaining pathological interactions. These findings reveal a sequential hierarchy in which delta-phase organizes beta activity, which subsequently modulates gamma amplitude, a cascading mechanism disrupted by medication. This work provides preliminary evidence that non-invasive EEG can capture PD-specific PAC dynamics, linking delta-band activity to motor dysfunction. The suppression of pathological couplings post-therapy highlights delta-beta PAC’s potential as a biomarker for treatment efficacy. While further validation is required, these results advocate for expanded investigations into nested cross-frequency interactions, paving the way for neuromodulatory strategies that target oscillatory network dysfunction in PD. Biological sciences/Neuroscience Health sciences/Biomarkers Health sciences/Medical research Health sciences/Neurology Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryPACImages.zip 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-6476008","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":454680666,"identity":"5150f8e7-df5e-4f1c-a51f-c4e04b09b68d","order_by":0,"name":"Tanvir Hasib","email":"","orcid":"","institution":"Multimedia University","correspondingAuthor":false,"prefix":"","firstName":"Tanvir","middleName":"","lastName":"Hasib","suffix":""},{"id":454680667,"identity":"49a71a73-58e2-4d0c-8098-6271b9a5076b","order_by":1,"name":"Parameswari Shunmugam","email":"","orcid":"","institution":"Sultan Salahuddin Abdul Aziz Shah Polytechnic","correspondingAuthor":false,"prefix":"","firstName":"Parameswari","middleName":"","lastName":"Shunmugam","suffix":""},{"id":454680668,"identity":"ad732079-c53c-4a02-9fb6-5017c9d0fa6a","order_by":2,"name":"Kalai Arasu Muthusamy","email":"","orcid":"","institution":"University of Malaya","correspondingAuthor":false,"prefix":"","firstName":"Kalai","middleName":"Arasu","lastName":"Muthusamy","suffix":""},{"id":454680669,"identity":"8cae31f1-3b94-44b9-94f5-10d6e6d968ad","order_by":3,"name":"Kannan Ramakrishnan","email":"","orcid":"","institution":"Multimedia University","correspondingAuthor":false,"prefix":"","firstName":"Kannan","middleName":"","lastName":"Ramakrishnan","suffix":""},{"id":454680670,"identity":"19cd629a-68f8-4e13-aa58-395c2237d2e8","order_by":4,"name":"Vijayakumar Vengadasalam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYDACZoYEIGkD4fCQoCWNFC0QcJgELQbHGR5+5qk5H607I4Hxwds2hmiDA4S0HGZIluY5djt3240EZsO5bQy5GwhpkWxmSJDmYQNrYZPmJVJL8m+ef+dAWth/E6WFn5khDWj4AbAtzERrsZzbl5y77czDZsk55yRyZxLSwsZ/JvnGm292uduOJx/88KbMJrePkBZgXCQwQaKDsQFISDAoENbCfoDxBzJfvoGgllEwCkbBKBhhAAABikRfvyHDHAAAAABJRU5ErkJggg==","orcid":"","institution":"Multimedia University","correspondingAuthor":true,"prefix":"","firstName":"Vijayakumar","middleName":"","lastName":"Vengadasalam","suffix":""}],"badges":[],"createdAt":"2025-04-18 04:53:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6476008/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6476008/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86675602,"identity":"7e03a7cb-0513-4875-b67f-49fc878c4523","added_by":"auto","created_at":"2025-07-14 12:02:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1176736,"visible":true,"origin":"","legend":"","description":"","filename":"ScientificReports.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6476008/v1_covered_eacc7c24-cb92-4ed2-bfc4-19f2aed94f87.pdf"},{"id":82496758,"identity":"7433677d-d3da-41ba-a863-22e023096c88","added_by":"auto","created_at":"2025-05-12 07:58:47","extension":"zip","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":8426629,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryPACImages.zip","url":"https://assets-eu.researchsquare.com/files/rs-6476008/v1/03822082436bc8688563fa34.zip"}],"financialInterests":"No competing interests reported.","formattedTitle":"Delta-Beta and Beta-Gamma Coupling as Biomarkers of Medication Efficacy in Parkinson's Disease","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-6476008/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6476008/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Parkinson’s disease (PD) is marked by neural synchronization, with cross-frequency interactions such as phase-amplitude coupling (PAC) believed to underpin its motor and non-motor symptoms. While invasive studies implicate beta-gamma PAC in PD pathophysiology, the feasibility of detecting and characterizing these dynamics non-invasively and their modulation by therapy remains underexplored. This pilot study investigates nested PAC across delta, beta, and gamma bands in PD using scalp EEG, aiming to identify PD-specific coupling patterns and evaluate their responsiveness to dopaminergic medication. EEG data from PD patients and healthy controls were analyzed using PAC metrics. We examined interactions between delta (0.5–4 Hz), beta (13–30 Hz), and gamma (30–110 Hz) bands pre- and post-medication, with rigorous artifact rejection to confirm coupling specificity. Unmedicated PD patients exhibited delta-beta and beta-gamma PAC which were attenuated following dopaminergic therapy. Notably, delta-beta coupling persisted in the majority of patients, suggesting that delta oscillations may play an underrecognized role in sustaining pathological interactions. 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