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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,5,5]]},"abstract":"<jats:p>One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g\/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.<\/jats:p>","DOI":"10.1073\/pnas.1919048117","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T20:26:58Z","timestamp":1587414418000},"page":"10035-10044","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5557-6048","authenticated-orcid":false,"given":"Xiaojie","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &amp; Science University, Beaverton, OR 97006;"},{"name":"Advanced Imaging Research Center, Oregon Health &amp; Science University, Portland, OR 97214;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verginia C.","family":"Cuzon Carlson","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &amp; Science University, Beaverton, OR 97006;"},{"name":"Department of Behavioral Neuroscience, Oregon Health &amp; Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-6906","authenticated-orcid":false,"given":"Colin","family":"Studholme","sequence":"additional","affiliation":[{"name":"Biomedical Image Computing Group, Department of Pediatrics, University of Washington, Seattle, WA 98105;"},{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98105;"},{"name":"Department of Radiology, University of Washington, Seattle, WA 98105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-9673","authenticated-orcid":false,"given":"Natali","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &amp; Science University, Beaverton, OR 97006;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Ford","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &amp; Science University, Beaverton, OR 97006;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-7219","authenticated-orcid":false,"given":"Kathleen A.","family":"Grant","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &amp; Science University, Beaverton, OR 97006;"},{"name":"Department of Behavioral Neuroscience, Oregon Health &amp; Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-3632","authenticated-orcid":false,"given":"Christopher D.","family":"Kroenke","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &amp; Science University, Beaverton, OR 97006;"},{"name":"Advanced Imaging Research Center, Oregon Health &amp; Science University, Portland, OR 97214;"},{"name":"Department of Behavioral Neuroscience, Oregon Health &amp; Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,4,20]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"657","volume-title":"The Corsini Encyclopedia of Psychology","author":"Moore T. 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Rehm, Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder. Biochem. Cell Biol. 96, 237\u2013240 (2018).","journal-title":"Biochem. Cell Biol."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1001\/jamapediatrics.2017.1919","article-title":"Global prevalence of fetal alcohol spectrum disorder among children and youth: A systematic review and meta-analysis","volume":"171","author":"Lange S.","year":"2017","unstructured":"S. Lange ., Global prevalence of fetal alcohol spectrum disorder among children and youth: A systematic review and meta-analysis. JAMA Pediatr. 171, 948\u2013956 (2017).","journal-title":"JAMA Pediatr."},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1056\/NEJMsa1506575","article-title":"Declines in unintended pregnancy in the United States, 2008\u20132011","volume":"374","author":"Finer L. B.","year":"2016","unstructured":"L. B. Finer, M. R. Zolna, Declines in unintended pregnancy in the United States, 2008\u20132011. N. Engl. J. Med. 374, 843\u2013852 (2016).","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_4_6_2","volume-title":"Behavioral Risk Factor Surveillance System User\u2019s Guide","author":"CDC","year":"2019","unstructured":"CDC, Behavioral Risk Factor Surveillance System User\u2019s Guide (US Centers for Disease Control and Prevention, Atlanta, GA, 2019)."},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.15585\/mmwr.mm6816a1","article-title":"Consumption of alcohol beverages and binge drinking among pregnant women aged 18\u201344 years\u2013United States, 2015\u20132017","volume":"68","author":"Denny C. H.","year":"2019","unstructured":"C. H. Denny, C. S. Acero, T. S. Naimi, S. Y. Kim, Consumption of alcohol beverages and binge drinking among pregnant women aged 18\u201344 years\u2013United States, 2015\u20132017. MMWR Morb. Mortal. Wkly. 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Acta Neuropsychiatr. 27, 197\u2013205 (2015).","journal-title":"Acta Neuropsychiatr."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1002\/hbm.22785","article-title":"White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning","volume":"36","author":"Fan J.","year":"2015","unstructured":"J. Fan ., White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning. Hum. Brain Mapp. 36, 2470\u20132482 (2015).","journal-title":"Hum. Brain Mapp."},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1002\/hbm.23218","article-title":"White matter deficits mediate effects of prenatal alcohol exposure on cognitive development in childhood","volume":"37","author":"Fan J.","year":"2016","unstructured":"J. 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