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However, QoL outcomes after deep brain stimulation (DBS) of the subthalamic nucleus (STN) vary considerably. Current approaches lack integration of demographic, patient-reported, neuroimaging, and neurophysiological data to understand this variability. This study used explainable machine learning to analyze multimodal factors affecting QoL changes, measured by the Parkinson\u2019s Disease Questionnaire (PDQ-39) in 63 patients, and quantified each variable\u2019s contribution. Results showed that preoperative PDQ-39 scores and upper beta band activity (&gt;20\u2009Hz) in the left STN were key predictors of QoL changes. Lower initial QoL burden predicted worsening, while improvement was associated with higher beta activity. Additionally, electrode positions along the superior-inferior axis, especially relative to the <jats:italic>z<\/jats:italic>\u2009=\u2009\u22127 coordinate in standard space, influenced outcomes, with improved and worsened QoL above and below this marker. This study emphasizes a tailored, data-informed approach to optimize DBS treatment and improve patient QoL.<\/jats:p>","DOI":"10.1038\/s41746-024-01253-y","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:02:02Z","timestamp":1727827322000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Machine learning explains response variability of deep brain stimulation on Parkinson\u2019s disease quality of life"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1352-4789","authenticated-orcid":false,"given":"Enrico","family":"Ferrea","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-7177","authenticated-orcid":false,"given":"Farzin","family":"Negahbani","sequence":"additional","affiliation":[]},{"given":"Idil","family":"Cebi","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Weiss","sequence":"additional","affiliation":[]},{"given":"Alireza","family":"Gharabaghi","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"1253_CR1","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/mds.26885","volume":"32","author":"P Martinez\u2010Martin","year":"2017","unstructured":"Martinez\u2010Martin, P. 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