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Lesion\u2010symptom mapping (LSM) techniques can relate lesion location to cognitive performance. However, a limitation of current LSM approaches is that they can only evaluate one cognitive outcome at a time, without considering interdependencies between different cognitive tests. To overcome this challenge, we implemented canonical correlation analysis (CCA) as combined multivariable and multioutcome LSM approach. We performed a proof\u2010of\u2010concept study on 1075 patients with acute ischemic stroke to explore whether addition of CCA to a multivariable single\u2010outcome LSM approach (support vector regression) could identify infarct locations associated with deficits in three well\u2010defined verbal memory functions (encoding, consolidation, retrieval) based on four verbal memory subscores derived from the Seoul Verbal Learning Test (immediate recall, delayed recall, recognition, learning ability). We evaluated whether CCA could extract cognitive score patterns that matched prior knowledge of these verbal memory functions, and if these patterns could be linked to more specific infarct locations than through single\u2010outcome LSM alone. Two of the canonical modes identified with CCA showed distinct cognitive patterns that matched prior knowledge on encoding and consolidation. In addition, CCA revealed that each canonical mode was linked to a distinct infarct pattern, while with multivariable single\u2010outcome LSM individual verbal memory subscores were associated with largely overlapping patterns. In conclusion, our findings demonstrate that CCA can complement single\u2010outcome LSM techniques to help disentangle cognitive functions and their neuroanatomical correlates.<\/jats:p>","DOI":"10.1002\/hbm.26208","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T11:59:20Z","timestamp":1674215960000},"page":"2266-2278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Disentangling poststroke cognitive deficits and their neuroanatomical correlates through combined multivariable and multioutcome lesion\u2010symptom mapping"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8425-8436","authenticated-orcid":false,"given":"Nick A.","family":"Weaver","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery UMC Utrecht Brain Center  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Hasnain","family":"Mamdani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine, McConnell Brain Imaging Centre, School of Computer Science Montreal Neurological Institute (MNI), McGill University  Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6157-2908","authenticated-orcid":false,"given":"Jae\u2010Sung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-2148","authenticated-orcid":false,"given":"Johannes Matthijs","family":"Biesbroek","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery UMC Utrecht Brain Center  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-2496","authenticated-orcid":false,"given":"Geert Jan","family":"Biessels","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery UMC Utrecht Brain Center  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene M. C.","family":"Huenges Wajer","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery UMC Utrecht Brain Center  Utrecht The Netherlands"},{"name":"Experimental Psychology Helmholtz Institute, Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeonwook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine  Anyang Republic of Korea"},{"name":"Department of Psychology Hallym University  Chuncheon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beom Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung\u2010Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine  Anyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keon\u2010Joo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Korea University Guro Hospital  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010Ho","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine  Anyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0051-1997","authenticated-orcid":false,"given":"Hee\u2010Joon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3466-6620","authenticated-orcid":false,"given":"Danilo","family":"Bzdok","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine, McConnell Brain Imaging Centre, School of Computer Science Montreal Neurological Institute (MNI), McGill University  Montreal Canada"},{"name":"Mila\u2014Quebec Artificial Intelligence Institute  Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6997-9059","authenticated-orcid":false,"given":"Hugo J.","family":"Kuijf","sequence":"additional","affiliation":[{"name":"Image Sciences Institute University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2014.00014"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-7421(08)60452-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1050"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3791\/59653"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2021.06.019"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22702"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-015-1033-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041071"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-019-0069-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.04.061"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz272"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2017.10.021"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.07.033"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.10123"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/28.3-4.321"},{"volume-title":"Seoul neuropsychological screening battery (SNSB)","year":"2003","author":"Kang Y.","key":"e_1_2_8_17_1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.10.028"},{"volume-title":"Neuropsychological assessment","year":"2012","author":"Lezak M. 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