Neural correlates of craving and impulsivity in abstinent former cocaine users: Towards biomarkers of relapse risk.

A significant hindrance to effective treatment of addiction is identifying those most likely to relapse. Cocaine addiction is characterized by deficits in inhibitory control and elevated reactivity to cocaine cues, both hypothesized to be integral to development of addiction and propensity to relapse. It follows that reduction of both impulsivity and cue-reactivity following abstinence is protective against relapse, and that persistence of these factors increases vulnerability. Using functional magnetic resonance imaging, we examined neural activation patterns in dorsal and ventral striatum in abstinent cocaine dependent (CD) individuals (N=20) and non-using controls (N=19) as they performed a cocaine craving task. We also examined activations in nodes of the response inhibition circuit (RIC) as they performed an inhibition task. At the between-groups level, no differences in RIC or striatal activation were seen in former users, in contrast to previous investigations in current users, suggesting large-scale functional recovery with abstinence. However, at the individual participant-level, abstinent CD individuals displayed an association between cocaine cue-related neural activations in the right ventral striatum and compulsive cocaine craving scores. Compulsive craving scores were also negatively correlated with duration of abstinence. Further, there was an association between motor impulsivity scores and inhibition-related activations in the right inferior frontal gyrus and pre-supplementary motor area in abstinent CD individuals. Thus, while former users as a group did not show deficits in inhibitory function or cocaine-cue reactivity, participant-level results pointed to activation patterns in a minority of these individuals that likely contributes to enduring relapse vulnerability.