{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:47Z","timestamp":1786951547403,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DE240100327"],"award-info":[{"award-number":["DE240100327"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR302224"],"award-info":[{"award-number":["NIHR302224"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lesion\u2010symptom mapping results can vary substantially as a function of specific analysis parameters, but the extent to which individual methodological choices interact to modulate the sensitivity and specificity of results is not clear. Here, we employed a large\u2010scale simulation approach to inform practical recommendations for lesion\u2010symptom mapping studies. Routine clinical imaging from 959 stroke survivors (mean age\u2009=\u200972.5, 49.3% female) was used to conduct 384,780 lesion\u2010symptom mapping analyses based on simulated behavioural data. Each simulated analysis used different combinations of plausible sample inclusion criteria, analysis parameters (e.g., correction factors), analysis types (e.g., univariate vs. multivariate), and underlying target correlates. Simulated analysis accuracy (percent coverage of target correlates, Dice similarity coefficient, and false positives) was compared across designs. Overall, analysis accuracy varied widely and was substantially modulated by the specific design used. Analyses that maximised lesion coverage by including large and diverse samples reliably outperformed analyses using more restricted samples. Analyses using direct total lesion volume controls outperformed analyses using other (or no) volume corrections across all accuracy measures. False discovery rate corrections yielded the best performance in terms of target coverage, while permutation corrections yielded the best Dice coefficients. While multivariate approaches were more accurate than univariate analyses in terms of Dice coefficient, univariate analyses generated higher target hit rates and percent target coverage. These results identify specific analysis designs suitable for studies aiming to maximise their sensitivity and\/or specificity to underlying critical correlates, while highlighting the inferential strengths and weaknesses of these complementary approaches.<\/jats:p>","DOI":"10.1002\/hbm.70619","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:55:10Z","timestamp":1785416110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methodological Choices Strongly Modulate the Sensitivity and Specificity of Lesion\u2010Symptom Mapping Analyses"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-5978","authenticated-orcid":false,"given":"Margaret Jane","family":"Moore","sequence":"first","affiliation":[{"name":"Queensland Brain Institute, University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-6142","authenticated-orcid":false,"given":"Chris","family":"Rorden","sequence":"additional","affiliation":[{"name":"Department of Psychology University of South Carolina  Colombia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0078-0364","authenticated-orcid":false,"given":"Gail A.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, University of Queensland  St. Lucia Queensland Australia"},{"name":"School of Psychology, University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-9216","authenticated-orcid":false,"given":"Jason B.","family":"Mattingley","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, University of Queensland  St. Lucia Queensland Australia"},{"name":"School of Psychology, University of Queensland  Brisbane Queensland Australia"},{"name":"Canadian Institute for Advanced Research  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-5147","authenticated-orcid":false,"given":"Nele","family":"Demeyere","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Ashburner J. 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