Distinct Alteration Patterns of Resting-State Functional Connectivity of the Corticostriatal Circuits Effected by Cigarette Smoking in Mild Cognitive Impairment Patients and Cognitively Normal subjects | 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 Research Article Distinct Alteration Patterns of Resting-State Functional Connectivity of the Corticostriatal Circuits Effected by Cigarette Smoking in Mild Cognitive Impairment Patients and Cognitively Normal subjects Tiantian Qiu, Fei Xie, Qingze Zeng, Zhujing Shen, guijin Du, Xiaopei Xu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-959685/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 To explore the interaction effects of smoking status (non-smoking vs. smoking) and disease (cognitively normal (CN) vs. MCI) based on resting-state functional connectivity (rsFC) of the corticostriatal circuits. We included 304 CN non-smokers, 44 CN smokers, 130 MCI non-smokers, and 33 MCI smokers. The seed-based rsFC of striatal subregions (caudate, putamen, and nucleus accumbens [NAc]) with the whole-brain voxel was calculated. Furthermore, we performed mixed effect analysis to explore the interaction effects between smoking status and disease. Significant interaction effects were detected between: (1) right caudate and left inferior parietal lobule (IPL); (2) right putamen and bilateral cuneus; (3) bilateral NAc and bilateral anterior cingulate cortex (ACC). The post-hoc analyses revealed that the CN smokers showed increased rsFC between right caudate and left IPL compared to non-smokers; while the MCI smokers demonstrated decreased rsFC between right putamen and cuneus, and increased rsFC between bilateral NAc and ACC compared to non-smokers. In MCI smokers, the rsFC value between left NAc and ACC was positively correlated with Semantic Verbal Fluency (SVF, r = 0.387, p = 0.026), and the rsFC value between right NAc and ACC was positively correlated with SVF (r = 0.390, p = 0.025), Wechsler memory scale-logical memory (WMS-LM) immediate recall (r = 0.378, p = 0.03), and WMS-LM delayed recall (r = 0.367, p = 0.036). Our findings suggest that chronic nicotine exposure may lead to functional connectivity alterations of corticostriatal circuits in MCI patients, and the pattern is different from CN smokers. Nuclear Medicine & Medical Imaging Mild cognitive impairment cigarette smoking striatum corticostriatal circuits resting-state functional connectivity. Figures Figure 1 Figure 2 Figure 3 Full Text Supplementary Files AuthorChecklist.pdf supplementarymaterials.pdf 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-959685","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":56635909,"identity":"560478eb-0a68-4fe7-b49c-f6ff5bb0c8b4","order_by":0,"name":"Tiantian Qiu","email":"","orcid":"https://orcid.org/0000-0002-9428-4117","institution":"Linyi People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tiantian","middleName":"","lastName":"Qiu","suffix":""},{"id":56635910,"identity":"398153a4-799b-4ae8-b742-88d3cb51c4e2","order_by":1,"name":"Fei Xie","email":"","orcid":"","institution":"Linyi People's 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01:27:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-959685/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-959685/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":14617983,"identity":"c89625f2-d73b-451a-b1ae-4068b4ff3f5c","added_by":"auto","created_at":"2021-10-18 14:12:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2705205,"visible":true,"origin":"","legend":"The interaction effects of smoking status × disease on rsFC of the striatal subregions. (A) between right caudate and left IPL; (B) between right putamen and bilateral cuneus; (C) between left NAc and bilateral ACC; and (D) between right NAc and bilateral ACC. IPL, inferior parietal lobule; NAc, nucleus accumbens; ACC, anterior cingulate cortex. The statistical threshold was set at p \u003c 0.005 with a cluster-level of p \u003c 0.05 (two-tailed, GRF corrected).","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-959685/v1/a32bd8c26737d79087b939dd.png"},{"id":14617987,"identity":"2af610ea-7691-4d35-9890-94d32fc82b17","added_by":"auto","created_at":"2021-10-18 14:12:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":300651,"visible":true,"origin":"","legend":"The post-hoc analysis of rsFC values of the interaction regions. The CN smokers showed increased rsFC of right caudate to left IPL than other subgroups (A). The MCI smokers showed decreased rsFC of right putamen to cuneus (B) and increased rsFC of bilateral NAc to ACC (C and D) compared to other subgroups. IPL, inferior parietal lobule; NAc, nucleus accumbens; ACC, anterior cingulate cortex. *p \u003c 0.05, **p \u003c 0.01, ***p \u003c 0.005.","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-959685/v1/939f1922d38c92b21c67a7e4.png"},{"id":14617985,"identity":"4588531b-0ad9-44e9-a018-c6b6a67d8cf2","added_by":"auto","created_at":"2021-10-18 14:12:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":396058,"visible":true,"origin":"","legend":"Correlation between rsFC of the striatal subregions and neuropsychological scores. In MCI smokers, the rsFC value between left NAc and ACC was positively correlated with language (SVF, r = 0.387, p = 0.026); the rsFC value between right NAc and ACC was positively associated with language (SVF, r = 0.390, p = 0.025) and memory (WMS-LM immediate recall, r = 0.378, p = 0.03; delayed recall, r = 0.367, p = 0.036). NAc, nucleus accumbens; ACC, anterior cingulate cortex; WMS-LM, Wechsler memory scale-logical memory; SVF, Semantic Verbal Fluency.","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-959685/v1/d718971aec540ebd8ea11096.png"},{"id":14618551,"identity":"d63f89b9-0abb-4436-b765-cab95d1cd1ae","added_by":"auto","created_at":"2021-10-18 14:15:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":752466,"visible":true,"origin":"","legend":"","description":"","filename":"BrainImagingandBehaviormanuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-959685/v1_covered.pdf"},{"id":14618407,"identity":"7f33292b-1765-4ca7-b78c-336a4e2511ad","added_by":"auto","created_at":"2021-10-18 14:15:39","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":197557,"visible":true,"origin":"","legend":"","description":"","filename":"AuthorChecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-959685/v1/b51149295dea90f73a92dc3f.pdf"},{"id":14617984,"identity":"9e336420-d7d4-4374-a18a-91216aa0092e","added_by":"auto","created_at":"2021-10-18 14:12:39","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":378046,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-959685/v1/2cda12af16431f7a6966f9ae.pdf"}],"financialInterests":"","formattedTitle":"Distinct Alteration Patterns of Resting-State Functional Connectivity of the Corticostriatal Circuits Effected by Cigarette Smoking in Mild Cognitive Impairment Patients and Cognitively Normal subjects","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-959685/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"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":false,"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":"Mild cognitive impairment, cigarette smoking, striatum, corticostriatal circuits, resting-state functional connectivity.","lastPublishedDoi":"10.21203/rs.3.rs-959685/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-959685/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTo explore the interaction effects of smoking status (non-smoking vs. smoking) and disease (cognitively normal (CN) vs. MCI) based on resting-state functional connectivity (rsFC) of the corticostriatal circuits. We included 304 CN non-smokers, 44 CN smokers, 130 MCI non-smokers, and 33 MCI smokers. The seed-based rsFC of striatal subregions (caudate, putamen, and nucleus accumbens [NAc]) with the whole-brain voxel was calculated. Furthermore, we performed mixed effect analysis to explore the interaction effects between smoking status\u0026nbsp;and disease. Significant interaction effects were detected\u0026nbsp;between:\u0026nbsp;(1) right caudate and left inferior parietal lobule (IPL); (2) right putamen and bilateral cuneus; (3) bilateral NAc and bilateral anterior cingulate cortex (ACC). The\u0026nbsp;\u003cem\u003epost-hoc\u003c/em\u003e\u0026nbsp;analyses revealed that the CN smokers showed increased rsFC between right caudate and left IPL compared to non-smokers; while the MCI smokers demonstrated decreased rsFC between right putamen and cuneus, and increased rsFC between bilateral NAc and ACC compared to non-smokers. In MCI smokers, the rsFC value between left NAc and ACC was positively correlated with Semantic Verbal Fluency (SVF, r = 0.387,\u0026nbsp;\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.026), and the rsFC value between right NAc and ACC was positively correlated with SVF (r = 0.390,\u0026nbsp;\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.025), Wechsler memory scale-logical memory (WMS-LM) immediate recall (r = 0.378,\u0026nbsp;\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.03), and WMS-LM delayed recall (r = 0.367,\u0026nbsp;\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.036).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eOur findings suggest that chronic nicotine exposure may lead\u0026nbsp;to functional connectivity alterations of corticostriatal circuits in MCI patients, and the pattern is different from CN smokers.\u003c/p\u003e","manuscriptTitle":"Distinct Alteration Patterns of Resting-State Functional Connectivity of the Corticostriatal Circuits Effected by Cigarette Smoking in Mild Cognitive Impairment Patients and Cognitively Normal subjects","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-18 14:12:37","doi":"10.21203/rs.3.rs-959685/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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