Modeling Causal Relationships among Brain Areas in the Mesocorticolimbic System during Resting-State in Cocaine Users Utilizing a Graph Theoretic Approach

OBJECTIVE: While effective connectivity (EC, causal interaction) between brain areas has been investigated in chronic users of cocaine as they view cocaine pictures cues, no study has examined EC while they take part in a resting-state scan. This resting-state fMRI study aims to investigate the causal interaction among brain areas in the mesocorticolimbic system (MCLS), which is involved in reward and motivation, in cocaine users (vs. controls). METHOD: Twenty cocaine users and 17 healthy controls finished a structural and a resting-state scan. Mean voxel-based time series data were obtained from brain regions of interest (ROIs) from the MCLS, and were input into a Bayesian search algorithm called IMaGES. RESULTS: The causal interaction pattern was different between the two groups. The feed-forward pattern found in cocaine smokers, between 7 ROIs of the MCLS during resting-state [ventral tegmental area (VTA)→hippocampus (HIPP)→ventral striatum (VenStri)→orbital frontal cortex (OFC), medial frontal cortex (MFC), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC)], was absent in controls. That is, the subcortical VenStri area had a causal influence on four cortical brain areas only in cocaine users. CONCLUSIONS: During the resting-state scan, the VTA of cocaine smokers abstinent for at least 72 hours, but not controls, begins causal connections to limbic, midbrain, and frontal regions in the MCLS in a feed-forward manner. Following replication, further studies may assess if changes over time in EC during resting-state predict cocaine treatment efficacy and outcome.