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This study aimed to map alterations in structural and functional connectivity (SC and FC) in SCA3 using network\u2010based statistics (NBS) and to explore the potential of transcranial magnetic stimulation (TMS) for modulating these aberrant networks and identifying novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      NBS was used to compare SC and FC between a large cohort of 117 SCA3 patients and 163 healthy controls (HCs). Partial correlation analysis examined the associations between altered connectivity and clinical variables (CAG repeat length, disease duration, and clinical scale scores). Additionally, paired\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests were used to evaluate longitudinal brain connectivity changes in 58 patients before and after TMS intervention to assess therapeutic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SCA3 patients exhibited a distinct disconnection\u2013compensation pattern, characterized by significantly reduced SC and elevated FC within the subcortical (SUB), sensorimotor (SMN), and dorsal attention (DAN) networks. SC between the frontoparietal network (FPN) and SUB was abnormally increased and positively correlated with both disease duration and CAG repeat length, whereas intra\u2010SUB SC was negatively correlated with disease duration. Following TMS intervention, SC strength in two pathways that were abnormally enhanced at baseline was significantly attenuated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings reveal extensive connectome reorganization in SCA3. The correlations between SC abnormalities and clinical metrics, coupled with the modulatory effects of TMS, suggest that network\u2010based metrics can serve as biomarkers and guide the development of personalized neuromodulation strategies for SCA3.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      (ChiCTR) 1800019901, 2000039434, 2500095738.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71016","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:57:56Z","timestamp":1783328276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping the Disrupted Connectome in Spinocerebellar Ataxia Type 3: A Network\u2010Based Statistics Study Identifying Novel Therapeutic Targets for Neuromodulation"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8939-676X","authenticated-orcid":false,"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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology Southwest Hospital, Army Medical University (Third Military Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingang","family":"Wang","sequence":"additional","affiliation":[{"name":"7T Magnetic Resonance Imaging Translational Medical Center, Department of Radiology Southwest Hospital, Army Medical University (Third Military 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