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The aim of this explorative study was to investigate sex\u2010dependent differences in prefrontal cortex (PFC) functioning during a working memory (WM) functional magnetic resonance imaging (fMRI) task in regular cocaine users (CUs), as PFC deficits are implicated in the shift from recreational cocaine use to CUD. Neural activation was measured using fMRI during a standard WM task (n\u2010back task) in 27 male and 28 female CUs and in 26 male and 28 female non\u2010cocaine users (non\u2010CUs). Although there were no main or interaction effects of sex and group on n\u2010back task performance, WM\u2010related (2\u2010back\u00a0&gt;\u00a00\u2010back) PFC functioning was significantly moderated by sex and group: female compared with male CUs displayed higher WM\u2010related activation of the middle frontal gyrus (MFG), whereas female compared with male non\u2010CUs displayed lower WM\u2010related MFG activation. Additionally, WM\u2010related activation of the inferior frontal gyrus, insula, and putamen was negatively associated with cocaine use severity in female but not male CUs. These data support the hypothesis of sex\u2010dependent PFC differences in CUs and speculatively suggest that PFC deficits may be more strongly implicated in the development, continuation, and possibly treatment of CUD in females. Most importantly, the current data stress the importance of studying both males and females in psychiatry research as not doing so could greatly bias our knowledge of CUD and other psychiatric disorders.<\/jats:p>","DOI":"10.1111\/adb.13003","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T02:14:20Z","timestamp":1611886460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sex\u2010dependent prefrontal cortex activation in regular cocaine users: A working memory functional magnetic resonance imaging study"],"prefix":"10.1111","volume":"26","author":[{"given":"Janna","family":"Cousijn","sequence":"first","affiliation":[{"name":"Neuroscience of Addiction (NofA) Lab, Department of Psychology University of Amsterdam  Amsterdam The Netherlands"},{"name":"The Amsterdam Brain and Cognition Center (ABC) University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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