{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:28:43Z","timestamp":1783366123756,"version":"3.54.6"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Accumulating evidences indicate regional gray matter (GM) morphology atrophy in spinocerebellar ataxia type 3 (SCA3); however, whether large\u2010scale morphological brain networks (MBNs) undergo widespread reorganization in these patients remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the topological organization of large\u2010scale individual\u2010based MBNs in SCA3 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The individual\u2010based MBNs were constructed based on the inter\u2010regional morphological similarity of GM regions. Graph theoretical analysis was taken to assess GM structural connectivity in 76 symptomatic SCA3, 24 pre\u2010symptomatic SCA3, and 54 healthy normal controls (NCs). Topological parameters of the resulting graphs and network\u2010based statistics analysis were compared among symptomatic SCA3, pre\u2010symptomatic SCA3, and NCs groups. The inner association between network properties and clinical variables was further analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to NCs and pre\u2010symptomatic SCA3 patients, symptomatic SCA3 indicated significantly decreased integration and segregation, a shift to \u201cweaker small\u2010worldness\u201d, characterized by decreased <jats:italic>C<\/jats:italic><jats:sub>p<\/jats:sub>, lower <jats:italic>E<\/jats:italic><jats:sub>loc,<\/jats:sub> and <jats:italic>E<\/jats:italic><jats:sub>glob<\/jats:sub> (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005). Regarding nodal properties, symptomatic SCA3 exhibited significantly decreased nodal profiles in the central executive network (CEN)\u2010related left inferior frontal gyrus, limbic regions involving the bilateral amygdala, left hippocampus, and bilateral pallidum, thalamus; and increased nodal degree, efficiency in bilateral caudate (all <jats:italic>p<\/jats:italic><jats:sub>FDR<\/jats:sub>\u2009&lt;0.05). Meanwhile, clinical variables were correlated with altered nodal profiles (<jats:italic>p<\/jats:italic><jats:sub>FDR<\/jats:sub>\u2009\u22640.029). SCA3\u2010related subnetwork was closely interrelated with dorsolateral cortico\u2010striatal circuitry extending to orbitofrontal\u2010striatal circuits and dorsal visual systems (lingual gyrus\u2010striatal).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Symptomatic SCA3 patients undergo an extensive and significant reorganization in large\u2010scale individual\u2010based MBNs, probably due to disrupted prefrontal cortico\u2010striato\u2010thalamo\u2010cortical loops, limbic\u2010striatum circuitry, and enhanced connectivity in the neostriatum. This study highlights the crucial role of abnormal morphological connectivity alterations beyond the pattern of brain atrophy, which might pave the way for therapeutic development in the future.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14332","type":"journal-article","created":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T06:55:46Z","timestamp":1688194546000},"page":"4102-4112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Altered large\u2010scale individual\u2010based morphological brain network in spinocerebellar ataxia type 3"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8704-9752","authenticated-orcid":false,"given":"Shu","family":"Su","sequence":"first","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 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Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Engineering Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manshi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald L.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Spin Imaging Technology Co., Ltd  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-5593","authenticated-orcid":false,"given":"Yingqian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9270-3250","authenticated-orcid":false,"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 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