Interictal Scale-Free Neural Dynamics Identify Epileptogenic Cortex

Interictal Scale-Free Neural Dynamics Identify Epileptogenic 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 Interictal Scale-Free Neural Dynamics Identify Epileptogenic Cortex Igor Belykh, Marrium Shamshad, Kelley Smith, Kevin Slote, Mukesh Dhamala This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9336143/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 Background: In epilepsy, clinically useful electrophysiological markers often depend on seizure capture or transient epileptiform events, whereas the broadband aperiodic ``background'' of intracranial recordings is commonly treated as noise. Yet, scale-free spectral structure may reflect an imbalance between excitation and inhibition and cortical instability. Methods: We analyzed interictal intracranial electroencephalography from 55 patients with drug-resistant focal epilepsy using spectral parameterization to quantify aperiodic slope and broadband offset across epileptogenic and non-epileptogenic cortex and across recording modalities. Results: Here, we show that epileptogenic cortex exhibits steeper aperiodic slopes and higher broadband offsets than non-epileptogenic tissue, with these effects remaining robust across stereoelectroencephalography and electrocorticography. These abnormalities are detectable during interictal periods, without seizure capture, indicating that the ongoing background organization of neural activity contains biologically and clinically meaningful information. The findings support a persistent alteration in scale-free cortical dynamics consistent with excitation--inhibition imbalance and identify a compact interictal signature of epileptic network dysfunction. Conclusions: By showing that the aperiodic component of human intracranial recordings is signal rather than noise, this study identifies a seizure-independent and mechanistically grounded marker of epileptic network instability with potential translational value for invasive monitoring. Health sciences/Neurology/Neurological disorders/Epilepsy Biological sciences/Neuroscience/Diseases of the nervous system/Epilepsy Full Text Additional Declarations There is NO Competing Interest. All analyses were conducted on retrospectively collected data. The study protocol was reviewed and approved by the Institutional Review Board of Georgia State University (IRB H25299) and complied with all relevant guidelines and regulations. Supplementary Files SupplementaryMaterialCommunicationMedicinesubmitted.pdf Supplementary Information for “Interictal Scale-Free Neural Dynamics Identify Epileptogenic Cortex” 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. 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-9336143","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":619538754,"identity":"3143df2f-29ab-4614-a529-84ddd14429f4","order_by":0,"name":"Igor Belykh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYBACNgkGxgMMBw7IQbnEaWEAaTEmXgsDVEtiA9Fa+KSbDxzmOXMnfb7/GQOGD2WHiXCYzLGEwzw3nuVuvJFjwDjjHDFaJHIMDvN8OJy7cQaPATNvG1Fa8j+AtKQb9p8xYP5LnJYcBqDDDifIM+QYMDMSpUXmmMHBOWcOG26QSCs42HMunbAW+dnNDx+8OXZYXr7/8MYHP8qsCWsBASYeIGFwABRBxALGHyDrGohWPwpGwSgYBSMNAACfyUN+gKvAPgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5683-0754","institution":"Georgia State University","correspondingAuthor":true,"prefix":"","firstName":"Igor","middleName":"","lastName":"Belykh","suffix":""},{"id":619538755,"identity":"c4225950-cd7f-4575-89b0-14b940868c20","order_by":1,"name":"Marrium Shamshad","email":"","orcid":"","institution":"Georgia State University","correspondingAuthor":false,"prefix":"","firstName":"Marrium","middleName":"","lastName":"Shamshad","suffix":""},{"id":619538756,"identity":"10e7ac39-84d7-4d9a-af0f-ade2a9ad380e","order_by":2,"name":"Kelley Smith","email":"","orcid":"","institution":"Georgia State University","correspondingAuthor":false,"prefix":"","firstName":"Kelley","middleName":"","lastName":"Smith","suffix":""},{"id":619538757,"identity":"c1cad3d2-71c5-4c28-8a15-978df3d478a3","order_by":3,"name":"Kevin Slote","email":"","orcid":"https://orcid.org/0009-0008-3167-3992","institution":"Georgia State University","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Slote","suffix":""},{"id":619538758,"identity":"0637f03d-5114-41a5-9036-7c41de30c39e","order_by":4,"name":"Mukesh Dhamala","email":"","orcid":"https://orcid.org/0009-0003-7765-0749","institution":"Georgia State University","correspondingAuthor":false,"prefix":"","firstName":"Mukesh","middleName":"","lastName":"Dhamala","suffix":""}],"badges":[],"createdAt":"2026-04-06 17:20:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9336143/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9336143/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106725738,"identity":"2cd3f1b5-88b2-427e-924b-d08b4ca77544","added_by":"auto","created_at":"2026-04-12 18:33:46","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":17811446,"visible":true,"origin":"","legend":"Article File","description":"","filename":"CommunicationMedicineSlopemainpapersubmitted.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9336143/v1_covered_4d2042c2-7779-4255-8449-2a5eb154bfd7.pdf"},{"id":106501950,"identity":"be5f6aed-8c63-47cf-909b-c0c0c1dc1f8b","added_by":"auto","created_at":"2026-04-09 09:19:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":6201067,"visible":true,"origin":"","legend":"Supplementary Information for \u0026#x201C;Interictal Scale-Free Neural Dynamics Identify Epileptogenic Cortex\u0026#x201D;","description":"","filename":"SupplementaryMaterialCommunicationMedicinesubmitted.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9336143/v1/fc10522fcf458e8a7b3ca499.pdf"}],"financialInterests":"\u003cp\u003eThere is \u003cstrong\u003eNO\u003c/strong\u003e Competing Interest.\u003c/p\u003e\n\u003cp\u003eAll analyses were conducted on retrospectively collected data. 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Yet, scale-free spectral structure may reflect an imbalance between excitation and inhibition and cortical instability.\r\n\r\nMethods: We analyzed interictal intracranial electroencephalography from 55 patients with drug-resistant focal epilepsy using spectral parameterization to quantify aperiodic slope and broadband offset across epileptogenic and non-epileptogenic cortex and across recording modalities.\r\n\r\nResults: Here, we show that epileptogenic cortex exhibits steeper aperiodic slopes and higher broadband offsets than non-epileptogenic tissue, with these effects remaining robust across stereoelectroencephalography and electrocorticography. These abnormalities are detectable during interictal periods, without seizure capture, indicating that the ongoing background organization of neural activity contains biologically and clinically meaningful information. The findings support a persistent alteration in scale-free cortical dynamics consistent with excitation--inhibition imbalance and identify a compact interictal signature of epileptic network dysfunction.\r\n\r\nConclusions: By showing that the aperiodic component of human intracranial recordings is signal rather than noise, this study identifies a seizure-independent and mechanistically grounded marker of epileptic network instability with potential translational value for invasive monitoring.","manuscriptTitle":"Interictal Scale-Free Neural Dynamics Identify Epileptogenic Cortex","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 09:19:26","doi":"10.21203/rs.3.rs-9336143/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-medicine","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsmed","sideBox":"Learn more about [Communications Medicine](http://www.nature.com/commsmed)","snPcode":"43856","submissionUrl":"https://mts-commsmed.nature.com/cgi-bin/main.plex","title":"Communications Medicine","twitterHandle":"@commsmedicine","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7aa4fb8c-cba5-4f27-b62f-6f79e1b13c35","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65925587,"name":"Health sciences/Neurology/Neurological disorders/Epilepsy"},{"id":65925588,"name":"Biological sciences/Neuroscience/Diseases of the nervous system/Epilepsy"}],"tags":[],"updatedAt":"2026-04-29T10:41:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 09:19:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9336143","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9336143","identity":"rs-9336143","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}