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We assessed the topography of focused ultrasound subthalamotomy (\n            <jats:italic>n<\/jats:italic>\n            = 39) by voxel-based lesion-symptom mapping to identify statistically validated brain voxels with the optimal effect against each cardinal feature and their respective cortical connectivity patterns by diffusion-weighted tractography. Bradykinesia and rigidity amelioration were associated with ablation of the rostral motor STN subregion connected to the supplementary motor and premotor cortices, whereas antitremor effect was explained by lesioning the posterolateral STN projection to the primary motor cortex. These findings were corroborated prospectively in another PD cohort (\n            <jats:italic>n<\/jats:italic>\n            = 12). This work concurs with recent deep brain stimulation findings that suggest different corticosubthalamic circuits underlying each PD cardinal feature. Our results provide sound evidence in humans of segregated anatomy of subthalamic-cortical connections and their distinct role in PD pathophysiology and normal motor control.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adr9891","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T19:10:42Z","timestamp":1732302642000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Functional anatomy of the subthalamic nucleus and the pathophysiology of cardinal features of Parkinson\u2019s disease unraveled by focused ultrasound ablation"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-199X","authenticated-orcid":true,"given":"Rafael","family":"Rodriguez-Rojas","sequence":"first","affiliation":[{"name":"HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain."},{"name":"Facultad de Tecnolog\u00eda y Ciencia, Universidad Camilo Jos\u00e9 Cela, Madrid, Spain."},{"name":"Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, Madrid, Spain."},{"name":"CIBERNED, Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8995-8340","authenticated-orcid":true,"given":"Jorge U.","family":"M\u00e1\u00f1ez-Mir\u00f3","sequence":"additional","affiliation":[{"name":"HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain."},{"name":"PhD Program in Neuroscience, Aut\u00f3noma de Madrid University-Cajal Institute, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-0031","authenticated-orcid":true,"given":"Jos\u00e9 A.","family":"Pineda-Pardo","sequence":"additional","affiliation":[{"name":"HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain."},{"name":"Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, Madrid, Spain."},{"name":"CIBERNED, Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-4200","authenticated-orcid":true,"given":"Marta","family":"del \u00c1lamo","sequence":"additional","affiliation":[{"name":"HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-013X","authenticated-orcid":true,"given":"Ra\u00fal","family":"Mart\u00ednez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain."},{"name":"Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, Madrid, Spain."},{"name":"CIBERNED, Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-8613","authenticated-orcid":true,"given":"Jos\u00e9 A.","family":"Obeso","sequence":"additional","affiliation":[{"name":"HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain."},{"name":"Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, Madrid, Spain."},{"name":"CIBERNED, Instituto de Salud Carlos III, Madrid, Spain."},{"name":"Medical School, CEU-San Pablo University, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.2397"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27860"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4674-12.2013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2012.00014"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02671.1996"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13738"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28862"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.32.5.514"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2915"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.08.030"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurpsyc.1956.02330190052003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/83.2.337"},{"key":"e_1_3_2_14_2","unstructured":"H. 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