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Most studies of PDE effects on the brain are based on animal models. In this study, based on a large sample of 133 human neonates and leveraging a novel linear mixed\u2010effect model designed for intersubject variability analyses, we studied the effects of six prenatally exposed drugs (i.e., nicotine, alcohol, selective serotonin reuptake inhibitor, marijuana, cocaine, and opioids) on neonatal whole\u2010brain functional organization and compared them with five other critical nondrug variables (i.e., gestational age at birth\/scan, sex, birth weight, and maternal depression). The behavioral implications were also examined. Magnitude\u2010wise, through summing across individual drug effects, our results highlighted ~5% of whole\u2010brain functional connections (FCs) affected by PDE, which was highly comparable with the combined effects of the five nond rug variables. Spatially, the detected PDE effects featured drug\u2010specific patterns with a common bias in higher\u2010order brain regions\/networks. Regarding brain\u2013behavioral relationships, the detected connections showing significant drug effects also demonstrated significant correlations with 3\u2010month behavioral outcomes. Further mediation analyses supported a mediation role of the detected brain FCs between PDE status and cognitive\/language outcomes. Our findings of widespread, and spatially biased PDE effect patterns coupled with significant behavioral implications may hopefully stimulate more human\u2010based studies into effects of PDE on long\u2010term developmental outcomes.<\/jats:p>","DOI":"10.1002\/hbm.25158","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T22:30:38Z","timestamp":1597185038000},"page":"4789-4803","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Functional dissection of prenatal drug effects on baby brain and behavioral development"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-3879","authenticated-orcid":false,"given":"Andrew","family":"Salzwedel","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Imaging, and Biomedical Imaging Research Institute (BIRI) Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2960-089X","authenticated-orcid":false,"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Scientific and Statistical Computing Core National Institute of Mental Health, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Imaging, and Biomedical Imaging Research Institute (BIRI) Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Grewen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurobiology, and Psychology University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-2601","authenticated-orcid":false,"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Imaging, and Biomedical Imaging Research Institute (BIRI) Cedars\u2010Sinai Medical Center  Los Angeles California USA"},{"name":"Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"issue":"6","key":"e_1_2_7_2_1","first-page":"506","article-title":"Heroin addiction and pregnancy","volume":"134","author":"Bashore R. 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