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Here, a total of 97 drug\u2010na\u00efve patients, 43 patients under long\u2010term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting\u2010state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test. Whole\u2010brain functional connectivity (FC) matrices were constructed. Network\u2010based statistics were performed to assess FC difference between drug\u2010na\u00efve patients and NC, and these significant FCs were defined as disease\u2010related connectomes, which were used for further statistical analyses. Patients showed better motor performances after both long\u2010term DRT and levodopa challenge test. Two disease\u2010related connectomes were observed with distinct patterns. The FC of the increased connectome, which mainly consisted of the motor, visual, subcortical, and cerebellum networks, was higher in drug\u2010na\u00efve patients than that in NC and was normalized after long\u2010term DRT (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value &lt;.050). The decreased connectome was mainly composed of the motor, medial frontal, and salience networks and showed significantly lower FC in all patients than NC (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value &lt;.050). The global FC of both increased and decreased connectome was significantly enhanced after levodopa challenge test (\n                    <jats:italic>q<\/jats:italic>\n                    \u2010value &lt;0.050, false discovery rate\u2010corrected). The global FC of increased connectome in ON\u2010state was negatively associated with levodopa equivalency dose (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u2212.496,\n                    <jats:italic>q<\/jats:italic>\n                    \u2010value\u2009=\u20090.007). Higher global FC of the decreased connectome was related to better motor performances (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u2212.310,\n                    <jats:italic>q<\/jats:italic>\n                    \u2010value\u2009=\u20090.022). Our findings provided insights into brain functional alterations under dopaminergic medication and its benefit on motor symptoms.\n                  <\/jats:p>","DOI":"10.1002\/hbm.26316","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T14:14:25Z","timestamp":1682950465000},"page":"3845-3858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Normalization effect of dopamine replacement therapy on brain functional connectome in Parkinson's disease"],"prefix":"10.1002","volume":"44","author":[{"given":"Chenqing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengye","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmei","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Duanmu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baorong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital, Zhejiang University School of 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