{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:13:22Z","timestamp":1792102402510,"version":"4.4.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071910"],"award-info":[{"award-number":["82071910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601478"],"award-info":[{"award-number":["81601478"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Spinocerebellar ataxia type 3 (SCA3) is a rare movement disorder characterized with ataxia. Previous studies on movement disorders show that the whole-brain functional network tends to be more regular, and these reconfigurations correlate with genetic and clinical variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test whether the brain network in patients with SCA3 follows a similar reconfiguration course to other movement disorders, we recruited 41 patients with SCA3 (mean age = 40.51 \u00b1 12.13 years; 23 male) and 41 age and sex-matched healthy individuals (age = 40.10 \u00b1 11.56 years; 24 male). In both groups, the whole-brain network topology of resting-state functional magnetic resonance imaging (rs-fMRI) was conducted using graph theory, and the relationships among network topologies, cytosine-adenine-guanine (CAG) repeats, clinical symptoms, and functional connectivity were explored in SCA3 patients using partial correlation analysis, controlling for age and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The brain networks tended to be more regular with a higher clustering coefficient, local efficiency, and modularity in patients with SCA3. Hubs in SCA3 patients were reorganized as the number of hubs increased in motor-related areas and decreased in cognitive areas. At the global level, small-worldness and normalized clustering coefficients were significantly positively correlated with clinical motor symptoms. At the nodal level, the clustering coefficient and local efficiency increased significantly in the visual (bilateral cuneus) and sensorimotor (right cerebellar lobules IV, V, VI) networks and decreased in the cognitive areas (right middle frontal gyrus). The clustering coefficient and local efficiency in the bilateral cuneus gyrus were negatively correlated with clinical motor symptoms. The functional connectivity between right caudate nucleus and bilateral calcarine gyrus were negatively correlated with disease duration, while connectivity between right posterior cingulum gyrus and left cerebellar lobule III, left inferior occipital gyrus and right cerebellar lobule IX was positively correlated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that a more regular brain network occurred in SCA3 patients, with motor and visual-related regions, such as, cerebellar lobules and cuneus gyrus, both forayed neighbor nodes as \u201cresource predators\u201d to compensate for normal function, with motor and visual function having the higher priority comparing with other high-order functions. This study provides new information about the neurological mechanisms underlying SCA3 network topology impairments in the resting state, which give a potential guideline for future clinical treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>[<jats:ext-link>www.ClinicalTrials.gov<\/jats:ext-link>], identifier [ChiCTR1800019901].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.773119","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T07:26:52Z","timestamp":1649662012000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Network Reconfiguration Among Cerebellar Visual, and Motor Regions Affects Movement Function in Spinocerebellar Ataxia Type 3"],"prefix":"10.3389","volume":"14","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limeng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1093\/ije\/dyy094","article-title":"Comparison of cognitive and physical functioning of europeans in 2004-05 and 2013.","volume":"47","author":"Ahrenfeldt","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1002\/mds.26713","article-title":"Levodopa modulates small-world architecture of functional brain networks in Parkinson\u2019s disease.","volume":"31","author":"Berman","year":"2016","journal-title":"Mov. Disord."},{"key":"B3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1037\/h0047235","article-title":"Revised administration and scoring of the digit span test.","volume":"21","author":"Blackburn","year":"1957","journal-title":"J. Consult. Psychol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s12311-011-0318-6","article-title":"Cerebellar cognitive affective syndrome in machado joseph disease: core clinical features.","volume":"11","author":"Braga-Neto","year":"2012","journal-title":"Cerebellum"},{"key":"B5","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.nbd.2012.07.009","article-title":"Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors.","volume":"48","author":"Bruno","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nrn2575","article-title":"Complex brain networks: graph theoretical analysis of structural and functional systems.","volume":"10","author":"Bullmore","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2010.00013","article-title":"DPARSF: a matlab toolbox for \u201cPipeline\u201d.","volume":"4","author":"Chao-Gan","year":"2010","journal-title":"Front. Syst. Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"MINI-Mental State - practical method for grading cognitive state of patients for clinician.","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatric. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.neuroimage.2013.12.008","article-title":"Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.","volume":"94","author":"Gamboa","year":"2014","journal-title":"Neuroimage"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e3036","DOI":"10.1212\/wnl.0000000000010986","article-title":"Gray matter atrophy patterns within the cerebellum-neostriatum-cortical network in SCA3.","volume":"95","author":"Guo","year":"2020","journal-title":"Neurology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3699","DOI":"10.1093\/brain\/aws281","article-title":"Resting state functional connectivity of the striatum in Parkinson\u2019s disease.","volume":"135","author":"Hacker","year":"2012","journal-title":"Brain"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1093\/brain\/awy222","article-title":"Basal ganglia and cerebellar pathology in X-linked dystonia-parkinsonism.","volume":"141","author":"Hanssen","year":"2018","journal-title":"Brain"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1002\/mds.26320","article-title":"Functional connectivity changes related to cognitive and motor performance in spinocerebellar ataxia type 2.","volume":"30","author":"Hernandez-Castillo","year":"2015","journal-title":"Mov. Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.tics.2017.03.003","article-title":"Injured brains and adaptive networks: the benefits and costs of hyperconnectivity.","volume":"21","author":"Hillary","year":"2017","journal-title":"Trends Cogn. Sci."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040709","article-title":"GAT: a graph-theoretical analysis toolbox for analyzing between-group differences in large-scale structural and functional brain networks.","volume":"7","author":"Hosseini","year":"2012","journal-title":"PLoS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.neuroimage.2013.04.032","article-title":"Comparing connectivity pattern and small-world organization between structural correlation and resting-state networks in healthy adults.","volume":"78","author":"Hosseini","year":"2013","journal-title":"Neuroimage"},{"key":"B17","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.nicl.2016.11.007","article-title":"CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3.","volume":"13","author":"Huang","year":"2017","journal-title":"Neuroimage Clin."},{"key":"B18","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/ng1194-221","article-title":"CAG expansions in a novel gene for Machado-joseph disease at chromosome 14q32.1.","volume":"8","author":"Kawaguchi","year":"1994","journal-title":"Nat. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1093\/cercor\/bhx267","article-title":"Network structure and function in parkinson\u2019s disease.","volume":"28","author":"Ko","year":"2018","journal-title":"Cereb. Cortex"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3428","DOI":"10.1093\/brain\/awz270","article-title":"Dynamic modular-level alterations of structural-functional coupling in clinically isolated syndrome.","volume":"142","author":"Koubiyr","year":"2019","journal-title":"Brain"},{"key":"B21","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1001\/archpsyc.1981.01780260035003","article-title":"Depressed outpatients treated with cognitive therapy or pharmacotherapy.","volume":"38","author":"Kovacs","year":"1981","journal-title":"Arch. Gen. Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1136\/jnnp-2014-309180","article-title":"Disrupted small world topology and modular organisation of functional networks in late-life depression with and without amnestic mild cognitive impairment.","volume":"86","author":"Li","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/srep34156","article-title":"Simulating the evolution of functional brain networks in alzheimer\u2019s disease: exploring disease dynamics from the perspective of global activity.","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1111\/adb.12155","article-title":"Altered brain functional networks in heavy smokers.","volume":"20","author":"Lin","year":"2015","journal-title":"Addict. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1076\/jcen.20.2.194.1173","article-title":"Mayo\u2019s older Americans normative studies: category fluency norms.","volume":"20","author":"Lucas","year":"1998","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1109\/EMBC.2016.7590637","article-title":"Resting-state EEG network change in alpha and beta bands after upper limb amputation","author":"Lyu","year":"2016","journal-title":"Proceedings of the 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.nicl.2018.03.038","article-title":"The cerebral metabolic topography of spinocerebellar ataxia type 3.","volume":"19","author":"Meles","year":"2018","journal-title":"Neuroimage Clin."},{"key":"B28","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1093\/brain\/awt290","article-title":"Aberrant topology of striatum\u2019s connectivity is associated with the number of episodes in depression.","volume":"137","author":"Meng","year":"2014","journal-title":"Brain"},{"key":"B29","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1093\/brain\/awv399","article-title":"Cerebellar atrophy in Parkinson\u2019s disease and its implication for network connectivity.","volume":"139","author":"O\u2019Callaghan","year":"2016","journal-title":"Brain"},{"key":"B30","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/s0022-510x(96)00231-6","article-title":"International cooperative ataxia rating scale for pharmacological assessment of the cerebellar syndrome the ataxia neuropharmacology committee of the world federation of neurology.","volume":"145","author":"Trouillas","year":"1997","journal-title":"J. Neurol. Sci."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01025","article-title":"Gene-Related cerebellar neurodegeneration in SCA3\/MJD: a case-controlled imaging-genetic study.","volume":"10","author":"Peng","year":"2019","journal-title":"Front. Neurol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3476","DOI":"10.1093\/cercor\/bhw128","article-title":"Disrupted network topology in patients with stable and progressive mild cognitive impairment and alzheimer\u2019s disease.","volume":"26","author":"Pereira","year":"2016","journal-title":"Cereb. Cortex"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1002\/mds.28113","article-title":"A 5-year longitudinal clinical and magnetic resonance imaging study in spinocerebellar ataxia type 3.","volume":"135","author":"Piccinin","year":"2020","journal-title":"Mov. Disord."},{"key":"B34","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1002\/ana.25297","article-title":"Structural signature of SCA3: from presymptomatic to late disease stages.","volume":"84","author":"Rezende","year":"2018","journal-title":"Ann. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.neuroimage.2009.10.003","article-title":"Complex network measures of brain connectivity: uses and interpretations.","volume":"52","author":"Rubinov","year":"2010","journal-title":"Neuroimage"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013788","article-title":"Loss of \u2018small-world\u2019 networks in alzheimer\u2019s disease: graph analysis of fmri resting-state functional connectivity.","volume":"5","author":"Sanz-Arigita","year":"2010","journal-title":"PLoS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1212\/01.wnl.0000219042.60538.92","article-title":"Scale for the assessment and rating of ataxia: development of a new clinical scale.","volume":"66","author":"Schmitz-Hubsch","year":"2006","journal-title":"Neurology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S1474-4422(04)00737-9","article-title":"Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis.","volume":"5","author":"Sch\u00f6ls","year":"2004","journal-title":"Lancet Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1212\/wnl.0000000000001285","article-title":"Thalamus structure and function determine severity of cognitive impairment in multiple sclerosis.","volume":"84","author":"Schoonheim","year":"2015","journal-title":"Neurology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1093\/brain\/awz034","article-title":"Dopamine depletion alters macroscopic network dynamics in parkinson\u2019s disease.","volume":"142","author":"Shine","year":"2019","journal-title":"Brain"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1007\/s00415-015-7807-3","article-title":"Psychiatric disorders, spinocerebellar ataxia type 3 and CAG expansion.","volume":"262","author":"Silva","year":"2015","journal-title":"J. Neurol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nrn1474","article-title":"Pathways to motor incoordination: the inherited ataxias.","volume":"5","author":"Taroni","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1097\/j.pain.0000000000001507","article-title":"Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain.","volume":"160","author":"Tu","year":"2019","journal-title":"Pain"},{"key":"B44","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1006\/nimg.2001.0978","article-title":"Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.","volume":"15","author":"Tzourio-Mazoyer","year":"2002","journal-title":"Neuroimage"},{"key":"B45","doi-asserted-by":"publisher","first-page":"123","DOI":"10.4088\/JCP.14m09344","article-title":"Altered topolotical patterns of brain networks in remitted late-onset depression: a resting-state fMRI study.","volume":"77","author":"Wang","year":"2016","journal-title":"J. Clin. Psychiatry"},{"key":"B46","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/30918","article-title":"Collective dynamics of \u2018small-world\u2019 networks.","volume":"393","author":"Watts","year":"1998","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.neuroimage.2010.11.074","article-title":"Effective connectivity of brain networks during self-initiated movement in Parkinson\u2019s disease.","volume":"55","author":"Wu","year":"2011","journal-title":"Neuroimage"},{"key":"B48","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2019.00110","article-title":"Extra-Cerebellar signs and non-motor features in chinese patients with spinocerebellar ataxia type 3.","volume":"10","author":"Yuan","year":"2019","journal-title":"Front. Neurol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.biopsych.2011.05.018","article-title":"Disrupted Brain connectivity networks in Drug-Naive.","volume":"70","author":"Zhang","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.101619","article-title":"Abnormal topological organization of structural covariance networks in amyotrophic lateral sclerosis.","volume":"21","author":"Zhang","year":"2019","journal-title":"Neuroimage Clin."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.773119\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T07:26:57Z","timestamp":1649662017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.773119\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,11]]},"references-count":50,"alternative-id":["10.3389\/fnagi.2022.773119"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.773119","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,11]]},"article-number":"773119"}}