Effective Connectivity within the Mesocorticolimbic System during Resting-State in Cocaine Users

Objective: Although effective connectivity between brain regions has been examined in cocaine users during tasks, no effective connectivity study has been conducted on cocaine users during resting-state. In the present functional magnetic resonance imaging study, we examined effective connectivity in resting-brain, between the brain regions within the mesocorticolimbic dopamine system, implicated in reward and motivated behavior, while the chronic cocaine users and controls took part in a resting-state scan by using a spectral Dynamic causal modeling (spDCM) approach. Method: As part of a study testing cocaine cue reactivity in cocaine users (Ray et al., 2015b), 20 non-treatment seeking cocaine-smoking (abstinent for at least 3 days) and 17 control participants completed a resting state scan and an anatomical scan. A mean voxel-based time series data extracted from four key brain areas (ventral tegmental area, VTA; nucleus accumbens, NAc; hippocampus, medial frontal cortex) within the mesocorticolimbic dopamine system during resting-state from the cocaine and control participants were used as input to the spDCM program to generate spDCM analysis outputs. Results: Compared to the control group, the cocaine group had higher effective connectivity from the VTA to NAc, hippocampus and medial frontal cortex. In contrast, the control group showed a higher effective connectivity from the medial frontal cortex to VTA, from the NAc to medial frontal cortex, and on the hippocampus self-loop. Conclusions: The present study is the first to show that during resting-state in abstaining cocaine users compared to controls, the VTA initiates an enhanced effective connectivity to NAc, hippocampus and medial frontal cortex areas within the mesocorticolimbic dopamine system, the brain's reward system. Future studies of effective connectivity analysis during resting-state may eventually be used to monitor treatment outcome.