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However, non\u2010motor outcomes are more variable, and it remains unclear which specific brain circuits need to be modulated or avoided to improve them. Since numerous non\u2010motor symptoms potentially respond to DBS, it is challenging to independently identify the circuits mediating each one of them. Data compression algorithms such as principal component analysis (PCA) may provide a powerful alternative. This study aimed at providing a proof of concept for this approach by mapping changes along extensive score batteries to a few anatomical fiber bundles and, in turn, estimating changes in individual scores based on stimulation of these tracts. Retrospective data from 56 patients with PD and bilateral STN\u2010DBS was included. The patients had undergone comprehensive clinical assessments covering changes in appetitive behaviors, mood, anxiety, impulsivity, cognition, and empathy. PCA was implemented to identify the main dimensions of neuropsychiatric and neuropsychological outcomes. Using DBS fiber filtering, we identified the structural connections whose stimulation was associated with change along these dimensions. Then, estimates of individual symptom outcomes were derived based on the stimulation of these connections by inverting the PCA. Finally, changes along a specific non\u2010motor score were estimated in an independent validation dataset (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200968) using the tract model. Four principal components were retained, which could be interpreted to reflect (i) general non\u2010motor improvement; (ii) improvement of mood and cognition and worsening of trait impulsivity; (iii) improvement of cognition; and (iv) improvement of empathy and worsening of impulsive\u2010compulsive behaviors. Each component was associated with the stimulation of spatially segregated fiber bundles connecting regions of the frontal cortex with the subthalamic nucleus. The extent of stimulation of these tracts was able to explain significant amounts of variance in outcomes for individual symptoms in the original cohort (circular analysis), as well as in the rank of depression outcomes in the independent validation cohort. Our approach represents an innovative concept for mapping changes along extensive score batteries to a few anatomical fiber bundles and could pave the way toward personalized deep brain stimulation.\n                  <\/jats:p>","DOI":"10.1002\/hbm.70207","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T17:00:56Z","timestamp":1744045256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Subthalamic Deep Brain Stimulation: Mapping Non\u2010Motor Outcomes to Structural Connections"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-6070","authenticated-orcid":false,"given":"Garance M.","family":"Meyer","sequence":"first","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology Brigham &amp; Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkem Aysu","family":"Sahin","sequence":"additional","affiliation":[{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin School of Mind and Brain, Humboldt\u2010Universit\u00e4t Zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-6927","authenticated-orcid":false,"given":"Barbara","family":"Hollunder","sequence":"additional","affiliation":[{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin School of Mind and Brain, Humboldt\u2010Universit\u00e4t Zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Butenko","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology Brigham &amp; Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanditha","family":"Rajamani","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology Brigham &amp; Women's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin School of Mind and Brain, Humboldt\u2010Universit\u00e4t Zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Neudorfer","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology Brigham &amp; Women's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurosurgery Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Hart","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology Brigham &amp; Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Niklas","family":"Petry\u2010Schmelzer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and University Hospital University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-4233","authenticated-orcid":false,"given":"Haidar S.","family":"Dafsari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and University Hospital University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Barbe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and University Hospital University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Visser\u2010Vandewalle","sequence":"additional","affiliation":[{"name":"Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-3419","authenticated-orcid":false,"given":"Philip E.","family":"Mosley","sequence":"additional","affiliation":[{"name":"Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute  Brisbane Queensland Australia"},{"name":"Neurosciences Queensland, St Andrew's War Memorial Hospital  Brisbane Queensland Australia"},{"name":"Queensland Brain Institute, University of Queensland  Brisbane Queensland Australia"},{"name":"Australian eHealth Research Centre, CSIRO Health and Biosecurity  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Horn","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology Brigham &amp; 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