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Following years of pharmacological treatment, high-frequency stimulation (HFS) of the subthalamic nucleus (STN), a key hub in goal-directed behaviors, can be proposed. While HFS-STN reliably improves motor symptoms, it does not specifically address non-motor symptoms. Clarifying how STN dysfunction contributes to these symptoms could improve stimulation strategies. Here, we longitudinally recorded STN local field potentials in two macaques performing a demanding task during chronic low-dose MPTP treatment. This progressive model, evolving from an asymptomatic stage to motivational, cognitive, and motor deficits, enabled detailed characterization of non-motor stages preceding motor impairment. Each stage was associated with distinct electrophysiological alterations, including early loss of reward-related theta activity, followed by disappearance of decision-related theta oscillations and later reduction of movement-related beta rebound. In the stable parkinsonian stage, stimulation of different STN territories produced complementary behavioral effects: dorsal HFS improved motor performance, whereas ventral low-frequency stimulation alleviated motivational deficits. These findings reveal a temporal relationship between STN dysfunction and symptom onset and support site- and frequency-specific stimulation strategies to address motor and non-motor symptoms in PD.<\/jats:p>","DOI":"10.1038\/s41531-026-01498-2","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:46:31Z","timestamp":1785469591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Behavioral changes preceded by subthalamic nucleus activity alterations in a progressive macaque model of Parkinson\u2019s disease"],"prefix":"10.1038","volume":"12","author":[{"given":"Mathilde","family":"Bertrand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Chabardes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessy","family":"Hugues Dit Ciles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"De Leiris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Bastin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Piallat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"1498_CR1","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/mds.22868","volume":"25","author":"KR Chaudhuri","year":"2010","unstructured":"Chaudhuri, K. 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