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Explainable AI (XAI) analysis revealed that brain features associated with the default mode network, striatum, and limbic network consistently exhibited significant sex differences (effect sizes &gt; 1.5) across sessions and independent cohorts. Furthermore, XAI-derived brain features accurately predicted sex-specific cognitive profiles, a finding that was also independently replicated. Our results demonstrate that sex differences in functional brain dynamics are not only highly replicable and generalizable but also behaviorally relevant, challenging the notion of a continuum in male-female brain organization. Our findings underscore the crucial role of sex as a biological determinant in human brain organization, have significant implications for developing personalized sex-specific biomarkers in psychiatric and neurological disorders, and provide innovative AI-based computational tools for future research.<\/jats:p>","DOI":"10.1073\/pnas.2310012121","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T13:55:21Z","timestamp":1708437321000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Deep learning models reveal replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-0381","authenticated-orcid":false,"given":"Srikanth","family":"Ryali","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9157-5544","authenticated-orcid":false,"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"de los Angeles","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaustubh","family":"Supekar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305"},{"name":"Stanford Institute for Human-Centered Artificial Intelligence, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305"},{"name":"Stanford Institute for Human-Centered Artificial Intelligence, Stanford University, Stanford, CA 94305"},{"name":"Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1909"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0106"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1390-16.2016"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-279554"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5372-11.2012"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)30348-0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-7610.00194"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2022.13"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001081"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23872"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpp.12337"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835ee548"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0920-9964(96)00023-0"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64123-6.00001-1"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0857"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1919091117"},{"key":"e_1_3_4_17_2","first-page":"3","article-title":"Sex differences in brain anatomy","volume":"186","author":"Luders E.","year":"2010","unstructured":"E. 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