{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:55:41Z","timestamp":1791582941129,"version":"4.3.4"},"reference-count":95,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biogen Idec Ltd Insurance","award":["SMS_IC010"],"award-info":[{"award-number":["SMS_IC010"]}]},{"DOI":"10.13039\/501100000589","name":"Chief Scientist Office","doi-asserted-by":"publisher","award":["SMS_IC010"],"award-info":[{"award-number":["SMS_IC010"]}],"id":[{"id":"10.13039\/501100000589","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000381","name":"MS Society UK","doi-asserted-by":"crossref","award":["133"],"award-info":[{"award-number":["133"]}],"id":[{"id":"10.13039\/501100000381","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000589","name":"Chief Scientist Office","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000589","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anne Rowling Regenerative Neurology Clinic"},{"DOI":"10.13039\/100012164","name":"Row Fogo Charitable Trust","doi-asserted-by":"crossref","award":["BROD.FID3668413"],"award-info":[{"award-number":["BROD.FID3668413"]}],"id":[{"id":"10.13039\/100012164","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer's Society UK"},{"name":"Alzheimer's Research UK"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104916\/Z\/14\/Z"],"award-info":[{"award-number":["104916\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000377","name":"Dunhill Medical Trust","doi-asserted-by":"publisher","award":["R380R\/1114"],"award-info":[{"award-number":["R380R\/1114"]}],"id":[{"id":"10.13039\/501100000377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010898","name":"Edinburgh and Lothians Health Foundation","doi-asserted-by":"publisher","award":["2012\/17"],"award-info":[{"award-number":["2012\/17"]}],"id":[{"id":"10.13039\/100010898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019741","name":"Muir Maxwell Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019741","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edinburgh Imaging"},{"DOI":"10.13039\/501100000848","name":"University of Edinburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N = 354) underwent 3T structural MRI &lt;6 months after diagnosis and 1-year follow-up, as part of the Scottish multicentre \u2018FutureMS\u2019 study. MRI data were processed using FreeSurfer to derive volumetrics, and FSL for VBM (grey matter (GM) only), to establish regional patterns of change in GM and normal-appearing white matter (NAWM) over time throughout the brain. Volumetric analyses showed a decrease over time (q&lt;0.05) in bilateral cortical GM and NAWM, cerebellar GM, brainstem, amygdala, basal ganglia, hippocampus, accumbens, thalamus and ventral diencephalon. Additionally, NAWM and GM volume decreased respectively in the following cortical regions, frontal: 14 out of 26 regions and 16\/26; temporal: 18\/18 and 15\/18; parietal: 14\/14 and 11\/14; occipital: 7\/8 and 8\/8. Left GM and NAWM asymmetry was observed in the frontal lobe. GM VBM analysis showed three major clusters of decrease over time: 1) temporal and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex; and four smaller clusters within the occipital lobe. Widespread GM and NAWM atrophy was observed in this large recently-diagnosed RRMS cohort, particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions; indicative of neurodegeneration across tissue types, and in accord with limited previous studies in early disease. Volumetric and VBM results emphasise different features of longitudinal lobar and loco-regional change, however identify consistent atrophy patterns across individuals. Atrophy measures targeted to specific brain regions may provide improved markers of neurodegeneration, and potential future imaging stratifiers and endpoints for clinical decision making and therapeutic trials.<\/jats:p>","DOI":"10.1371\/journal.pone.0288967","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T17:32:27Z","timestamp":1690565547000},"page":"e0288967","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Patterns of brain atrophy in recently-diagnosed relapsing-remitting multiple sclerosis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-260X","authenticated-orcid":true,"given":"Rozanna","family":"Meijboom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4310-8607","authenticated-orcid":true,"given":"Elizabeth N.","family":"York","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agniete","family":"Kampaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew A.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-6546","authenticated-orcid":true,"given":"Maria del C.","family":"Vald\u00e9s Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Thrippleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-5538","authenticated-orcid":true,"given":"N. J. J.","family":"MacDougall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-8037","authenticated-orcid":true,"given":"Peter","family":"Connick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P. J.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharthan","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Waldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the FutureMS Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"pone.0288967.ref001","doi-asserted-by":"crossref","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple Sclerosis Pathology","volume":"8","author":"H. Lassmann","year":"2018","journal-title":". Cold Spring Harb Perspect Med"},{"key":"pone.0288967.ref002","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis.","volume":"378","author":"DS Reich","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0288967.ref003","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1474-4422(18)30443-5","article-title":"Global, regional, and national burden of multiple sclerosis 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"MT Wallin","year":"2019","journal-title":"Lancet Neurol"},{"key":"pone.0288967.ref004","doi-asserted-by":"crossref","first-page":"146","DOI":"10.7224\/1537-2073.2012-053","article-title":"Natural history of multiple sclerosis symptoms","volume":"15","author":"I Kister","year":"2013","journal-title":"Int J MS Care"},{"key":"pone.0288967.ref005","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: The 2013 revisions","volume":"83","author":"FD Lublin","year":"2014","journal-title":"Neurology"},{"key":"pone.0288967.ref006","unstructured":"MS Trust. Types of MS. https:\/\/www.mstrust.org.uk\/about-ms\/what-ms\/types-ms. 2018."},{"key":"pone.0288967.ref007","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"AJ Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"pone.0288967.ref008","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and Treatment of Multiple Sclerosis","volume":"325","author":"MP McGinley","year":"2021","journal-title":"JAMA"},{"key":"pone.0288967.ref009","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s13311-019-00781-w","article-title":"Effects of Natalizumab and Fingolimod on Clinical, Cognitive, and Magnetic Resonance Imaging Measures in Multiple Sclerosis.","volume":"17","author":"P Preziosa","year":"2020","journal-title":"Neurotherapeutics"},{"key":"pone.0288967.ref010","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/brain\/awf025","article-title":"Brain atrophy in clinically early relapsing\u2013remitting multiple sclerosis","volume":"125","author":"DT Chard","year":"2002","journal-title":"Brain"},{"key":"pone.0288967.ref011","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/brain\/awy088","article-title":"Progression of regional grey matter atrophy in multiple sclerosis","volume":"141","author":"A Eshaghi","year":"2018","journal-title":"Brain"},{"key":"pone.0288967.ref012","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1177\/1352458514543811","article-title":"Cortical thickness and surface area relate to specific symptoms in early relapsing\u2013remitting multiple sclerosis.","volume":"21","author":"GO Nygaard","year":"2015","journal-title":"Mult Scler J"},{"key":"pone.0288967.ref013","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1007\/s00415-006-0503-6","article-title":"Cortical atrophy is relevant in multiple sclerosis at clinical onset","volume":"254","author":"M Calabrese","year":"2007","journal-title":"J Neurol"},{"key":"pone.0288967.ref014","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1136\/jnnp.70.6.773","article-title":"A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis","volume":"70","author":"R. Zivadinov","year":"2001","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0288967.ref015","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13317-019-0117-5","article-title":"Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options.","volume":"10","author":"A Andravizou","year":"2019","journal-title":"Autoimmun Highlights."},{"key":"pone.0288967.ref016","doi-asserted-by":"crossref","first-page":"102550","DOI":"10.1016\/j.nicl.2020.102550","article-title":"The sequence of structural, functional and cognitive changes in multiple sclerosis.","volume":"29","author":"I Dekker","year":"2021","journal-title":"NeuroImage Clin"},{"key":"pone.0288967.ref017","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/hbm.24849","article-title":"Gray matter integrity predicts white matter network reorganization in multiple sclerosis","volume":"41","author":"A Radetz","year":"2020","journal-title":"Hum Brain Mapp"},{"key":"pone.0288967.ref018","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.nicl.2017.11.002","article-title":"Gray matter atrophy patterns in multiple sclerosis: A 10-year source-based morphometry study.","volume":"17","author":"N Bergsland","year":"2018","journal-title":"NeuroImage Clin."},{"key":"pone.0288967.ref019","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.nicl.2014.02.012","article-title":"Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis.","volume":"6","author":"M Deppe","year":"2014","journal-title":"NeuroImage Clin"},{"key":"pone.0288967.ref020","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1191\/1352458503ms868oa","article-title":"Cerebral atrophy and disability in relapsing-remitting and secondary progressive multiple sclerosis over four years.","volume":"9","author":"B Turner","year":"2003","journal-title":"Mult Scler J"},{"key":"pone.0288967.ref021","first-page":"16","article-title":"Diffusion Tensor Imaging Revealed Microstructural Changes in Normal-Appearing White Matter Regions in Relapsing\u2013Remitting Multiple Sclerosis.","author":"J Bao","year":"2022","journal-title":"Front Neurosci."},{"key":"pone.0288967.ref022","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1002\/hbm.23144","article-title":"Early silent microstructural degeneration and atrophy of the thalamocortical network in multiple sclerosis","volume":"37","author":"M Deppe","year":"2016","journal-title":"Hum Brain Mapp"},{"key":"pone.0288967.ref023","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1212\/WNL.0b013e318212a8be","article-title":"MRI predictors of cognitive outcome in early multiple sclerosis","volume":"76","author":"MSA Deloire","year":"2011","journal-title":"Neurology"},{"key":"pone.0288967.ref024","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jns.2008.12.005","article-title":"Gray matter atrophy and disability progression in patients with early relapsing\u2013remitting multiple sclerosis","volume":"282","author":"D Horakova","year":"2009","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref025","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jns.2008.11.018","article-title":"Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS","volume":"282","author":"RA Rudick","year":"2009","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref026","article-title":"A matter of atrophy: differential impact of brain and spine damage on disability worsening in multiple sclerosis","author":"S Ruggieri","year":"2021","journal-title":"J Neurol"},{"key":"pone.0288967.ref027","article-title":"Cortical involvement determines impairment 30 years after a clinically isolated syndrome","author":"L Haider","year":"2021","journal-title":"Brain"},{"key":"pone.0288967.ref028","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1111\/ene.14471","article-title":"Fatigue in multiple sclerosis patients with different clinical phenotypes: a clinical and magnetic resonance imaging study","volume":"27","author":"O Marchesi","year":"2020","journal-title":"Eur J Neurol"},{"key":"pone.0288967.ref029","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2018.01172","article-title":"The Contribution of Various MRI Parameters to Clinical and Cognitive Disability in Multiple Sclerosis.","volume":"9","author":"E T\u00f3th","year":"2019","journal-title":"Front Neurol."},{"key":"pone.0288967.ref030","first-page":"11","article-title":"Thalamic Atrophy Predicts 5-Year Disability Progression in Multiple Sclerosis.","author":"K H\u00e4nninen","year":"2020","journal-title":"Front Neurol."},{"key":"pone.0288967.ref031","first-page":"jnnp","article-title":"Linear brain atrophy measures in multiple sclerosis and clinically isolated syndromes: a 30-year follow-up","author":"L Haider","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0288967.ref032","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jns.2018.02.045","article-title":"Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year employment status in multiple sclerosis patients","volume":"388","author":"L Kadrnozkova","year":"2018","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref033","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jns.2011.08.034","article-title":"Effect of disease-modifying therapies on brain volume in relapsing\u2013remitting multiple sclerosis: Results of a five-year brain MRI study","volume":"312","author":"O Khan","year":"2012","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref034","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1177\/1352458519826364","article-title":"Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.","volume":"26","author":"ES Sotirchos","year":"2020","journal-title":"Mult Scler J"},{"key":"pone.0288967.ref035","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/jon.12518","article-title":"Fingolimod\u2019s Impact on MRI Brain Volume Measures in Multiple Sclerosis: Results from MS-MRIUS.","volume":"28","author":"R Zivadinov","year":"2018","journal-title":"J Neuroimaging"},{"key":"pone.0288967.ref036","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jns.2017.10.019","article-title":"A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis","volume":"383","author":"F Yousuf","year":"2017","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref037","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jns.2018.03.028","article-title":"Effect of teriflunomide on gray and white matter brain pathology in multiple sclerosis using volumetric and diffusion-tensor imaging MRI measures","volume":"388","author":"R Zivadinov","year":"2018","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref038","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jns.2019.06.011","article-title":"Relapse numbers and earlier intervention by disease modifying drugs are related with progression of less brain atrophy in patients with multiple sclerosis","volume":"403","author":"H Masuda","year":"2019","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref039","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41582-020-0314-x","article-title":"MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice","volume":"16","author":"J Sastre-Garriga","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"pone.0288967.ref040","article-title":"FutureMS Cohort Profile: A Scottish Multi-Centre Inception Cohort Study of Relapsing-Remitting Multiple Sclerosis.","author":"PKA Kearns","year":"2021","journal-title":"medRxiv. 2021"},{"key":"pone.0288967.ref041","doi-asserted-by":"crossref","first-page":"94","DOI":"10.12688\/wellcomeopenres.17731.1","article-title":"Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland","volume":"7","author":"R Meijboom","year":"2022","journal-title":"Wellcome Open Res"},{"key":"pone.0288967.ref042","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1361-8415(01)00036-6","article-title":"A global optimisation method for robust affine registration of brain images","volume":"5","author":"M Jenkinson","year":"2001","journal-title":"Med Image Anal"},{"key":"pone.0288967.ref043","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1006\/nimg.2002.1132","article-title":"Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images","volume":"17","author":"M. Jenkinson","year":"2002","journal-title":". Neuroimage"},{"key":"pone.0288967.ref044","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hbm.10062","article-title":"Fast robust automated brain extraction","volume":"17","author":"SM Smith","year":"2002","journal-title":"Hum Brain Mapp"},{"key":"pone.0288967.ref045","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuroimage.2006.01.015","article-title":"User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability.","volume":"31","author":"PA Yushkevich","year":"2006","journal-title":"Neuroimage"},{"key":"pone.0288967.ref046","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1049\/iet-cvi.2014.0121","article-title":"Automatic method for white matter lesion segmentation based on T1-fluid-attenuated inversion recovery images.","volume":"9","author":"T Zhan","year":"2015","journal-title":"IET Comput Vis"},{"key":"pone.0288967.ref047","volume-title":"Medical Image Computing and Computer-Assisted Intervention -- MICCAI 2015 MICCAI 2015 Lecture Notes in Computer Science","author":"L Chen","year":"2015"},{"key":"pone.0288967.ref048","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.neuroimage.2012.02.084","article-title":"Within-subject template estimation for unbiased longitudinal image analysis.","volume":"61","author":"M Reuter","year":"2012","journal-title":"Neuroimage."},{"key":"pone.0288967.ref049","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"RS Desikan","year":"2006","journal-title":"Neuroimage"},{"key":"pone.0288967.ref050","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1093\/brain\/awm184","article-title":"Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia","volume":"130","author":"G Douaud","year":"2007","journal-title":"Brain"},{"key":"pone.0288967.ref051","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/nimg.2001.0786","article-title":"A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains.","volume":"14","author":"CD Good","year":"2001","journal-title":"Neuroimage."},{"issue":"1","key":"pone.0288967.ref052","doi-asserted-by":"crossref","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","article-title":"Advances in functional and structural MR image analysis and implementation as FSL.","volume":"23","author":"SM Smith","year":"2004","journal-title":"Neuroimage."},{"key":"pone.0288967.ref053","first-page":"805","article-title":"Voxel-based morphometry--the methods.","volume":"11","author":"J Ashburner","year":"2000","journal-title":"Neuroimage. 2000"},{"key":"pone.0288967.ref054","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; Available: https:\/\/www.r-project.org\/."},{"key":"pone.0288967.ref055","first-page":"82","article-title":"lmerTest Package: Tests in Linear Mixed Effects Models.","author":"A Kuznetsova","year":"2017","journal-title":"J Stat Softw."},{"key":"pone.0288967.ref056","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"H. Wickham","year":"2016"},{"key":"pone.0288967.ref057","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-75969-2","volume-title":"Lattice: Multivariate Data Visualization with R","author":"D. Sarkar","year":"2008"},{"key":"pone.0288967.ref058","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.neuroimage.2014.01.060","article-title":"Permutation inference for the general linear model.","volume":"92","author":"AM Winkler","year":"2014","journal-title":"Neuroimage"},{"key":"pone.0288967.ref059","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.neuroimage.2008.03.061","article-title":"Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference.","volume":"44","author":"SM Smith","year":"2009","journal-title":"Neuroimage."},{"key":"pone.0288967.ref060","unstructured":"National Institute for Health and Care Excellence. Multiple Sclerosis in adults: management. Available: https:\/\/www.nice.org.uk\/guidance\/ng220\/chapter\/Recommendations#ms-symptom-management-and-rehabilitation."},{"key":"pone.0288967.ref061","article-title":"Deep grey matter injury in multiple sclerosis: A NAIMS consensus statement","author":"D Ontaneda","year":"2021","journal-title":"Brain"},{"key":"pone.0288967.ref062","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1212\/WNL.0b013e31827b910b","article-title":"The thalamus and multiple sclerosis: Modern views on pathologic, imaging, and clinical aspects","volume":"80","author":"A Minagar","year":"2013","journal-title":"Neurology"},{"key":"pone.0288967.ref063","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jns.2016.04.054","article-title":"Subcortical grey matter volumes predict subsequent walking function in early multiple sclerosis","volume":"366","author":"B Nourbakhsh","year":"2016","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref064","first-page":"9","article-title":"Identification of Cortical and Subcortical Correlates of Cognitive Performance in Multiple Sclerosis Using Voxel-Based Morphometry.","author":"JA Mat\u00edas-Guiu","year":"2018","journal-title":"Front Neurol."},{"key":"pone.0288967.ref065","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00415-011-6147-1","article-title":"Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis","volume":"259","author":"S Batista","year":"2012","journal-title":"J Neurol"},{"key":"pone.0288967.ref066","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1007\/s10072-020-04395-5","article-title":"Early putamen hypertrophy and ongoing hippocampus atrophy predict cognitive performance in the first ten years of relapsing-remitting multiple sclerosis.","volume":"41","author":"ME Morelli","year":"2020","journal-title":"Neurol Sci"},{"key":"pone.0288967.ref067","first-page":"9","article-title":"Differential Gray Matter Vulnerability in the 1 Year Following a Clinically Isolated Syndrome.","author":"I Koubiyr","year":"2018","journal-title":"Front Neurol."},{"key":"pone.0288967.ref068","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1177\/1352458518760716","article-title":"The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis.","volume":"25","author":"KA Koenig","year":"2019","journal-title":"Mult Scler J."},{"key":"pone.0288967.ref069","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1002\/hbm.23970","article-title":"Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA 1","volume":"39","author":"V Planche","year":"2018","journal-title":"Hum Brain Mapp"},{"key":"pone.0288967.ref070","doi-asserted-by":"crossref","first-page":"102785","DOI":"10.1016\/j.msard.2021.102785","article-title":"Event-related potentials and deep grey matter atrophy in multiple sclerosis: Exploring the possible associations with cognition.","volume":"49","author":"L Lorefice","year":"2021","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0288967.ref071","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1177\/1352458516680750","article-title":"Impairment of social cognition in multiple sclerosis: Amygdala atrophy is the main predictor.","volume":"23","author":"D Batista S","year":"2017","journal-title":"Mult Scler J"},{"key":"pone.0288967.ref072","first-page":"11","article-title":"Patterns of cortical grey matter thickness reduction in multiple sclerosis","author":"J Fujimori","year":"2021","journal-title":"Brain Behav"},{"key":"pone.0288967.ref073","article-title":"Dual-Task Performance in Multiple Sclerosis\u2019 Patients: Cerebellum Matters?","author":"O Argento","year":"2020","journal-title":"Arch Clin Neuropsychol."},{"key":"pone.0288967.ref074","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12311-020-01190-y","article-title":"White Matter Microstructure of the Cerebellar Peduncles Is Associated with Balance Performance during Sensory Re-Weighting in People with Multiple Sclerosis.","volume":"20","author":"AD Odom","year":"2021","journal-title":"The Cerebellum"},{"key":"pone.0288967.ref075","first-page":"11","article-title":"A Comprehensive Approach to Disentangle the Effect of Cerebellar Damage on Physical Disability in Multiple Sclerosis.","author":"S Ruggieri","year":"2020","journal-title":"Front Neurol."},{"key":"pone.0288967.ref076","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/ene.14119","article-title":"Is the walk ratio a window to the cerebellum in multiple sclerosis? A structural magnetic resonance imaging study","volume":"27","author":"A Kalron","year":"2020","journal-title":"Eur J Neurol"},{"key":"pone.0288967.ref077","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1177\/1352458508101934","article-title":"MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction.","volume":"15","author":"V Anderson","year":"2009","journal-title":"Mult Scler J"},{"key":"pone.0288967.ref078","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.nicl.2018.04.028","article-title":"Non-lesional cerebellar damage in patients with clinically isolated syndrome: DTI measures predict early conversion into clinically definite multiple sclerosis.","volume":"19","author":"V. Kugler A","year":"2018","journal-title":"NeuroImage Clin"},{"key":"pone.0288967.ref079","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1136\/jnnp-2019-322439","article-title":"Two-year regional grey and white matter volume changes with natalizumab and fingolimod","volume":"91","author":"P Preziosa","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0288967.ref080","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jns.2008.12.034","article-title":"Extent of cerebellum, subcortical and cortical atrophy in patients with MS","volume":"282","author":"DP Ramasamy","year":"2009","journal-title":"J Neurol Sci"},{"key":"pone.0288967.ref081","first-page":"10","article-title":"Temporal Dynamics of Diffusion Metrics in Early Multiple Sclerosis and Clinically Isolated Syndrome: A 2-Year Follow-Up Tract-Based Spatial Statistics Study.","author":"R Schneider","year":"2019","journal-title":"Front Neurol."},{"key":"pone.0288967.ref082","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1093\/brain\/awaa162","article-title":"Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability","volume":"143","author":"A Kerbrat","year":"2020","journal-title":"Brain"},{"key":"pone.0288967.ref083","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00415-019-09595-4","article-title":"Patterns of regional brain volume loss in multiple sclerosis: a cluster analysis","volume":"267","author":"J Fujimori","year":"2020","journal-title":"J Neurol"},{"key":"pone.0288967.ref084","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.msard.2015.04.003","article-title":"Cervical cord area is associated with infratentorial grey and white matter volume predominantly in relapsing\u2013remitting multiple sclerosis: A study using semi-automated cord volumetry and voxel-based morphometry.","volume":"4","author":"B Bellenberg","year":"2015","journal-title":"Mult Scler Relat Disord."},{"key":"pone.0288967.ref085","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/brain\/awg175","article-title":"Focal thinning of the cerebral cortex in multiple sclerosis","volume":"126","author":"M. Sailer","year":"2003","journal-title":"Brain"},{"key":"pone.0288967.ref086","doi-asserted-by":"crossref","first-page":"798","DOI":"10.3390\/brainsci10110798","article-title":"Localised Grey Matter Atrophy in Multiple Sclerosis and Clinically Isolated Syndrome\u2014A Coordinate-Based Meta-Analysis, Meta-Analysis of Networks, and Meta-Regression of Voxel-Based Morphometry Studies","volume":"10","author":"S Singh","year":"2020","journal-title":"Brain Sci"},{"key":"pone.0288967.ref087","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4161\/pri.22580","article-title":"Grey matter lesions in MS.","volume":"7","author":"M Calabrese","year":"2013","journal-title":"Prion"},{"key":"pone.0288967.ref088","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1002\/hbm.23755","article-title":"Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5-year study","volume":"38","author":"P Preziosa","year":"2017","journal-title":"Hum Brain Mapp"},{"key":"pone.0288967.ref089","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.neuroimage.2005.08.034","article-title":"Grey matter loss in relapsing\u2013remitting multiple sclerosis: A voxel-based morphometry study.","volume":"29","author":"A Prinster","year":"2006","journal-title":"Neuroimage"},{"key":"pone.0288967.ref090","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00429-012-0440-3","article-title":"Superior temporal gyrus thickness correlates with cognitive performance in multiple sclerosis","volume":"218","author":"A Achiron","year":"2013","journal-title":"Brain Struct Funct"},{"key":"pone.0288967.ref091","doi-asserted-by":"crossref","first-page":"101899","DOI":"10.1016\/j.msard.2019.101899","article-title":"Low CSF \u03b2-amyloid levels predict early regional grey matter atrophy in multiple sclerosis.","volume":"39","author":"AM Pietroboni","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"pone.0288967.ref092","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1016\/j.ejrad.2012.09.006","article-title":"Iron deposition in the precentral grey matter in patients with multiple sclerosis: A quantitative study using susceptibility-weighted imaging.","volume":"82","author":"R Rumzan","year":"2013","journal-title":"Eur J Radiol"},{"key":"pone.0288967.ref093","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.neuroimage.2017.02.082","article-title":"A critical analysis of neuroanatomical software protocols reveals clinically relevant differences in parcellation schemes.","volume":"170","author":"S Mikhael","year":"2018","journal-title":"Neuroimage."},{"key":"pone.0288967.ref094","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/B978-012372560-8\/50020-6","volume-title":". Statistical Parametric Mapping.","author":"K. Nichols","year":"2007"},{"key":"pone.0288967.ref095","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neurobiolaging.2019.05.010","article-title":"Lifespan normative data on rates of brain volume changes","volume":"81","author":"M Battaglini","year":"2019","journal-title":"Neurobiol Aging"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288967","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T17:33:58Z","timestamp":1690565638000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288967"}},"subtitle":[],"editor":[{"given":"Niels","family":"Bergsland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,28]]},"references-count":95,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0288967","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,28]]}}}