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Although structural and functional connectivity abnormalities are well recognized, their potential interaction and neurobiological mechanisms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to identify potential biomarkers for\n                      <jats:styled-content style=\"fixed-case\">SCA3<\/jats:styled-content>\n                      by linking structural connectivity\u2013functional connectivity (\n                      <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\n                      \u2013\n                      <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content>\n                      ) coupling to mitochondrial function, neurotransmitter distribution, and gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This dual\u2010center study included discovery (117 SCA3, 163 healthy controls [HC]) and independent validation (24 SCA3, 48 HC) cohorts. [Correction added after first online publication on 8 July 2026: The number of healthy controls has been updated in the previous sentence.] Participants underwent multimodal 3\u2009T magnetic resonance imaging (MRI) and clinical assessments (Scale for the Assessment and Rating of Ataxia [SARA]; International Cooperative Ataxia Rating Scale [ICARS]; Montreal Cognitive Assessment [MoCA]; Hamilton Depression Rating Scale [HAMD]). Regional and network\u2010level SC\u2013FC coupling was quantified using multiple regression and compared across disease\u2010duration strata. Coupling alterations were spatially mapped to biological atlases (Allen Human Brain Atlas, MitoBrainMap, and positron emission tomography [PET]\u2010based neurotransmitter receptor atlases) using bootstrapped Spearman's correlations (false discovery rate [FDR]\u2010corrected). Gene enrichment analysis was implemented to characterize enriched biological pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SCA3 patients exhibited significant, atrophy\u2010independent SC\u2013FC decoupling in the bilateral dorsolateral putamen (dlPu), which correlated with ICARS scores. This decoupling pattern spatially aligned with mitochondrial complex II, 5\u2010HT2A\/5\u2010HT4 receptors densities, and genes enriching for synaptic regulation and cellular homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>By integrating SC\u2013FC coupling with biological atlases, this study reveals the pathological underpinnings of clinico\u2010radiological dissociation in SCA3 and identifies dlPu decoupling as a promising early\u2010stage candidate imaging marker, providing an early and objective target for future neuroprotective trials.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.chictr.org.cn\/\">Chinese Clinical Trial Registry<\/jats:ext-link>\n                      (ChiCTR): 1800019901, 2000039434. \u00a9 2026 International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70402","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:04:53Z","timestamp":1782803093000},"page":"2650-2661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Putamen Structural\u2013Functional Decoupling as an Early\u2010Stage Candidate Imaging Marker for Motor Severity in Spinocerebellar Ataxia Type 3"],"prefix":"10.1002","volume":"41","author":[{"given":"Lan","family":"Ou","sequence":"first","affiliation":[{"name":"7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology, Southwest Hospital Army Medical University (Third Military Medical University)  Chongqing 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