{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T19:18:06Z","timestamp":1793819886976,"version":"4.6.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aimed to assess functional connectivity (FC) differences in (i) persons with MS compared to healthy controls (HC), (ii) persons with both MS and CI (MS-CI) compared to HC, (iii) persons with MS that are cognitively preserved (MS-CP) compared to HC, (iv) MS-CI compared to MS-CP, and (v) in relation to cognition within the MS group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 107 participants with MS (age 49.5\u2009\u00b1\u200912.9, 82% women), and 94 controls (age 37.9\u2009\u00b1\u200915.4, 66% women). Each participant was administered the Symbol Digit Modalities Test (SDMT) and underwent a resting state fMRI scan. The MS-CI group was created by applying a <jats:italic>z<\/jats:italic>-score cut-off of <jats:inline-formula><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mo>\u2264<\/mml:mo><\/mml:math><\/jats:inline-formula>\u22121.5 to locally normalized SDMT scores. The MS-CP group was created by applying a <jats:italic>z<\/jats:italic>-score of \u22650. Control groups (HC<jats:sub>MS-CI<\/jats:sub> and HC<jats:sub>MS-CP<\/jats:sub>) were based on the nearest age-matched HC participants. A whole-brain ROI-to-ROI analysis was performed followed by specific contrasts and a regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Individuals with MS showed FC differences compared to HC that involved the cerebellum, visual and language-associated brain regions, and the thalamus, hippocampus, and basal ganglia. The MS-CI showed FC differences compared to HC<jats:sub>MS-CI<\/jats:sub> that involved the cerebellum, visual and language-associated areas, thalamus, and caudate. SDMT scores were correlated with FC between the cerebellum and lateral occipital cortex in MS. No differences were observed between the MS-CP and HC<jats:sub>MS-CP<\/jats:sub> or MS-CI and MS-CP groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings emphasize FC changes of cerebellar, visual, and language-associated areas in persons with MS. These differences were apparent for (i) all MS participants compared to HC, (ii) MS-CI subgroup and their matched controls, and (iii) the association between FC and SDMT scores within the MS group. Our findings strongly suggest that future work that examines the associations between FC and IPS impairments in MS should focus on the involvement of these regions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1250894","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T08:37:30Z","timestamp":1697704650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed"],"prefix":"10.3389","volume":"14","author":[{"given":"Sean L.","family":"Carter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronak","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Fisk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chase R.","family":"Figley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Ann","family":"Marrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin L.","family":"Mazerolle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Nasir","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaihim","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley A.","family":"Graff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Bolton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Marriott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kornelsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","article-title":"Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues","volume":"19","author":"Benedict","year":"2020","journal-title":"Lancet Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1007\/s00415-012-6705-1","article-title":"Cognitive impairment, health-related quality of life and vocational status at early stages of multiple sclerosis: a 7-year longitudinal study","volume":"260","author":"Ruet","year":"2013","journal-title":"J Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"828","DOI":"10.3389\/fneur.2018.00828","article-title":"Functional connectivity in multiple sclerosis: recent findings and future directions","volume":"9","author":"Tahedl","year":"2018","journal-title":"Front Neurol"},{"key":"ref4","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511895029","volume-title":"Handbook of functional MRI data analysis","author":"Poldrack","year":"2011"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"671894","DOI":"10.3389\/fneur.2021.671894","article-title":"Structural and functional connectivity substrates of cognitive impairment in multiple sclerosis","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"103076","DOI":"10.1016\/j.nicl.2022.103076","article-title":"Task- and resting-state fMRI studies in multiple sclerosis: from regions to systems and time-varying analysis. 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