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McManus Charitable Trust Grant","award":["#P50 DA009262"],"award-info":[{"award-number":["#P50 DA009262"]}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse (NIDA)","doi-asserted-by":"crossref","award":["K02 DA00403"],"award-info":[{"award-number":["K02 DA00403"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p>Although reduced working memory brain activation has been reported in several brain regions of cocaine\u2010dependent subjects compared with controls, very little is known about whether there is altered connectivity of working memory pathways in cocaine dependence. This study addresses this issue by using functional magnetic resonance imaging\u2010based stochastic dynamic causal modeling (DCM) analysis to study the effective connectivity of 19 cocaine\u2010dependent subjects and 14 healthy controls while performing a working memory task. Stochastic DCM is an advanced method that has recently been implemented in SPM8 that can obtain improved estimates, relative to deterministic DCM, of hidden neuronal causes before convolution with the hemodynamic response. Thus, stochastic DCM may be less influenced by the confounding effects of variations in blood oxygen level\u2010dependent response caused by disease or drugs. Based on the significant regional activation common to both groups and consistent with previous working memory activation studies, seven regions of interest were chosen as nodes for DCM analyses. Bayesian family level inference, Bayesian model selection analyses, and Bayesian model averaging (BMA) were conducted. BMA showed that the cocaine\u2010dependent subjects had large differences compared with the control subjects in the strengths of prefrontal\u2013striatal modulatory (<jats:italic>B<\/jats:italic> matrix) DCM parameters. These findings are consistent with altered cortical\u2013striatal networks that may be related to reduced dopamine function in cocaine dependence. As far as we are aware, this is the first between\u2010group DCM study using stochastic methodology. 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