Reduced REM sleep fast theta power suggests early circuit vulnerability in a GBA1 mouse model of prodromal synucleinopathy

Reduced REM sleep fast theta power suggests early circuit vulnerability in a GBA1 mouse model of prodromal synucleinopathy | 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 Reduced REM sleep fast theta power suggests early circuit vulnerability in a GBA1 mouse model of prodromal synucleinopathy Veronica Munday, Cigdem Gelegen, Gemma Deegan, Katarina Ilic, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7794342/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 Sleep disturbance is a salient harbinger of synucleinopathies and is conspicuous in idiopathic REM sleep behaviour disorder. Variants in GBA1 confer substantial risk for iRBD and Parkinson’s disease, yet early electrophysiological correlates remain uncertain. We recorded 24‑h EEG/EMG in adult male D409V/WT GBA1 knock‑in and wild‑type mice. A priori, REM fast‑theta (8–10 Hz) relative power was the primary endpoint, tested in an epoch‑level linear mixed‑effects model with a random intercept per animal and fixed effects of genotype, light phase, and their interaction. Secondary bands were slow‑theta (5–7 Hz), total theta (5–10 Hz) and delta (1–4 Hz). Aperiodic components (offset, exponent) were parameterised with FOOOF (fixed mode, 2.5–40 Hz). Fast‑theta during REM was lower in GBA1 heterozygotes (β≈−0.013; p ≈ 0.032), though the genotype effect did not survive Benjamini–Hochberg false‑discovery control across the REM‑band family (q ≈ 0.127). Sensitivity analyses aligned in direction: clustered‑SE OLS and a non‑parametric Bayesian bootstrap on per‑animal values both supported a fast‑theta reduction, while slow‑theta, total theta and delta showed no group differences. Sleep macroarchitecture and aperiodic activity were similar between genotypes. This indicates a frequency‑specific attenuation of REM fast‑theta early in GBA1 heterozygotes, with preserved aperiodic background and architecture. Selective fast-theta attenuation may signal early microphysiological circuit vulnerability. Biological sciences/Genetics Health sciences/Neurology Biological sciences/Neuroscience REM sleep fast theta aperiodic spectral parameters synucleinopathy idiopathic REM sleep behaviour disorder EEG Full Text Additional Declarations No competing interests reported. Supplementary Files Mundayetalsupplement.docx MundayetalSupplementaryData.xlsx 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-7794342","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":587571588,"identity":"ea0c56d8-fcad-4376-a6ae-346c07e9beaf","order_by":0,"name":"Veronica Munday","email":"","orcid":"","institution":"King's College London (KCL)","correspondingAuthor":false,"prefix":"","firstName":"Veronica","middleName":"","lastName":"Munday","suffix":""},{"id":587571589,"identity":"2a001963-25d8-40ff-866c-1f8e1f0b2725","order_by":1,"name":"Cigdem Gelegen","email":"","orcid":"","institution":"King's College London 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behaviour disorder, EEG","lastPublishedDoi":"10.21203/rs.3.rs-7794342/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7794342/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSleep disturbance is a salient harbinger of synucleinopathies and is conspicuous in idiopathic REM sleep behaviour disorder. Variants in GBA1 confer substantial risk for iRBD and Parkinson\u0026rsquo;s disease, yet early electrophysiological correlates remain uncertain. We recorded 24‑h EEG/EMG in adult male D409V/WT GBA1 knock‑in and wild‑type mice. A priori, REM fast‑theta (8\u0026ndash;10 Hz) relative power was the primary endpoint, tested in an epoch‑level linear mixed‑effects model with a random intercept per animal and fixed effects of genotype, light phase, and their interaction. Secondary bands were slow‑theta (5\u0026ndash;7 Hz), total theta (5\u0026ndash;10 Hz) and delta (1\u0026ndash;4 Hz). Aperiodic components (offset, exponent) were parameterised with FOOOF (fixed mode, 2.5\u0026ndash;40 Hz). Fast‑theta during REM was lower in GBA1 heterozygotes (β\u0026asymp;\u0026minus;0.013; p\u0026thinsp;\u0026asymp;\u0026thinsp;0.032), though the genotype effect did not survive Benjamini\u0026ndash;Hochberg false‑discovery control across the REM‑band family (q\u0026thinsp;\u0026asymp;\u0026thinsp;0.127). Sensitivity analyses aligned in direction: clustered‑SE OLS and a non‑parametric Bayesian bootstrap on per‑animal values both supported a fast‑theta reduction, while slow‑theta, total theta and delta showed no group differences. Sleep macroarchitecture and aperiodic activity were similar between genotypes. This indicates a frequency‑specific attenuation of REM fast‑theta early in GBA1 heterozygotes, with preserved aperiodic background and architecture. Selective fast-theta attenuation may signal early microphysiological circuit vulnerability.\u003c/p\u003e","manuscriptTitle":"Reduced REM sleep fast theta power suggests early circuit vulnerability in a GBA1 mouse model of prodromal synucleinopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 20:48:22","doi":"10.21203/rs.3.rs-7794342/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":"80195bad-2cca-4a94-9174-3d34232fbb0c","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":62516938,"name":"Biological sciences/Genetics"},{"id":62516939,"name":"Health sciences/Neurology"},{"id":62516940,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-04-10T09:13:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 20:48:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7794342","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7794342","identity":"rs-7794342","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}