{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:53:22Z","timestamp":1793303602042,"version":"4.5.0"},"posted":{"date-parts":[[2026,2,26]]},"group-title":"Neuroscience","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01MH136248"],"award-info":[{"award-number":["R01MH136248"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K23MH121657"],"award-info":[{"award-number":["K23MH121657"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01MH140916"],"award-info":[{"award-number":["R01MH140916"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01MH113929"],"award-info":[{"award-number":["R01MH113929"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21MH126271"],"award-info":[{"award-number":["R21MH126271"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UM1NS132358"],"award-info":[{"award-number":["UM1NS132358"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lesion network mapping (LNM) and related techniques have been used in over 200 studies, primarily to test whether anatomically distributed lesions that cause the same symptom fall within a common brain network. A recent article\n                  <jats:sup>1<\/jats:sup>\n                  challenges the specificity and validity of this technique, suggesting that lesion network maps primarily reflect intrinsic properties of the normative connectome rather than lesion\u2013symptom relationships. However, the data and procedures in van den Heuvel et al. do not reflect those used in most LNM studies. Further, the main conclusions were based on similarity between maps, but similarity does not imply the absence of meaningful differences. In contrast, LNM provides evidence for meaningful differences using specificity testing. Exemplary analyses of 1090 lesion locations from 34 prior LNM studies do not support van den Heuvel\u2019s concerns and confirm the lesion-deficit specificity of LNM. While we encourage further methodological investigation, the analyses of van den Heuvel et al. do not invalidate prior LNM findings or future applications.\n                <\/jats:p>","DOI":"10.64898\/2026.02.24.707529","type":"posted-content","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:45:20Z","timestamp":1772138720000},"source":"Crossref","is-referenced-by-count":12,"title":["The methodological foundations of lesion network mapping remain sound"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0967-9289","authenticated-orcid":false,"given":"Shan","family":"Siddiqi","sequence":"first","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"},{"name":"Dauten Behavioral Health Institute & Stephen Stahl Center for Psychiatric Neuroscience, Department of Psychiatry, Northwestern University Feinberg School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0695-6025","authenticated-orcid":false,"given":"Andreas","family":"Horn","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"},{"name":"Institute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic L.W.V.J.","family":"Schaper","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2469-5325","authenticated-orcid":false,"given":"Sanaz","family":"Khosravani","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-5866","authenticated-orcid":false,"given":"Alexander Li","family":"Cohen","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"},{"name":"Department of Neurology, Boston Children\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-9415","authenticated-orcid":false,"given":"Juho","family":"Joutsa","sequence":"additional","affiliation":[{"name":"Turku Brain and Mind Center, Clinical Neurosciences, University of Turku; Neurocenter, Turku University Hospital, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-5468","authenticated-orcid":false,"given":"John D.","family":"Rolston","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-0082","authenticated-orcid":false,"given":"Michael A.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-7890","authenticated-orcid":false,"given":"Samuel B.","family":"Snider","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4169-9781","authenticated-orcid":false,"given":"Anderson M.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2899-628X","authenticated-orcid":false,"given":"Harith","family":"Akram","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8166-069X","authenticated-orcid":false,"given":"Stephen M.","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-5103","authenticated-orcid":false,"given":"Thomas E.","family":"Nichols","sequence":"additional","affiliation":[{"name":"University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-8909","authenticated-orcid":false,"given":"Karl","family":"Friston","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7865-9257","authenticated-orcid":false,"given":"Aaron D.","family":"Boes","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neurology, Psychiatry, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-6399","authenticated-orcid":false,"given":"Michael D.","family":"Fox","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, Neurosurgery, and Radiology, Brigham & Women\u2019s Hospital, Harvard Medical School, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026030120250837000_2026.02.24.707529v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02196-7"},{"key":"2026030120250837000_2026.02.24.707529v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/ANA.25285"},{"key":"2026030120250837000_2026.02.24.707529v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac009"},{"key":"2026030120250837000_2026.02.24.707529v1.4","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/s41562-021-01161-1","article-title":"Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease","volume":"5","year":"2021","journal-title":"Nat Hum Behav"},{"key":"2026030120250837000_2026.02.24.707529v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60089-6"},{"key":"2026030120250837000_2026.02.24.707529v1.6","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1001\/jamaneurol.2023.1988","article-title":"Mapping Lesion-Related Epilepsy to a Human Brain Network","volume":"80","year":"2023","journal-title":"JAMA Neurol"},{"key":"2026030120250837000_2026.02.24.707529v1.7","unstructured":"Taylor, J. et al. 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