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We previously reported that <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>+ youths have elevated activity in the supplementary motor area (<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and dorsal striatum while performing go\/no\u2010go tasks and have reduced frontal white matter integrity. A better understanding of relationships between these variables would provide insight into how frontostriatal circuitry is altered in <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>+ youths, which may be an important contributor to their elevated risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we used structural equation modeling (<jats:styled-content style=\"fixed-case\">SEM<\/jats:styled-content>) to test interactions between activity in the <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and dorsal striatum in 72 <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>+ and 32 <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>\u2212 youths during go\/no\u2010go task performance and to determine whether increased activity in these regions in <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>+ youths can be at least partially explained by reduced frontal white matter integrity, as indexed by anterior corona radiata fractional anisotropy and N\u2010acetylaspartate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased dorsal striatum activity explained most (~75%) of the elevated <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> activity in <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>+ youths, and the combined contributions of increased dorsal striatal activity, and decreased white matter integrity fully explained the elevated <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest the elevated frontal cortical activity in <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>+ youths is driven both by their increased striatal activity via downstream projections and reduced white matter integrity in frontal cortical projections, the latter likely increasing frontal cortical activity due to increased energy demands required for action potential propagation. As part of our ongoing longitudinal studies we will examine how\u00a0these frontostriatal alterations relate to risk for developing substance\u2010use disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.352","type":"journal-article","created":{"date-parts":[[2015,5,28]],"date-time":"2015-05-28T14:40:11Z","timestamp":1432824011000},"source":"Crossref","is-referenced-by-count":9,"title":["Striatal activity and reduced white matter increase frontal activity in youths with family histories of alcohol and other substance\u2010use disorders performing a go\/no\u2010go task"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3843-5726","authenticated-orcid":false,"given":"Ashley","family":"Acheson","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Texas Health Science Center at San Antonio San Antonio Texas"},{"name":"Research Imaging Institute University of Texas Health Science Center at San Antonio San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malle A.","family":"Tagamets","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Maryland Psychiatric Research Center University of Maryland School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anderson","family":"Winkler","sequence":"additional","affiliation":[{"name":"Oxford Centre for Functional MRI of the Brain University of Oxford Oxford UK"},{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Rowland","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Maryland Psychiatric Research Center University of Maryland School of Medicine Baltimore Maryland"},{"name":"Russell H. 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