Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects

Cocaine addiction is characterized by persistent decision-making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine-dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting-state activation. Ten cocaine-dependent subjects and 14 non-drug-using controls participated in the study. Cocaine-dependent subjects were carefully selected to discard potentially confounding co-morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting-state. During the moral dilemmas task, cocaine-dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting-state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine-dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.