Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse
AbstractBackgroundRelapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex (DLPFC) is crucially involved in numerous cognitive and affective processes that are implicated in phenotypes of addiction, and is one of the most frequently reported brain regions with aberrant functionality in substance use disorders. However, the DLPFC is an anatomically large and functionally heterogeneous region, and the specific DLPFC-based circuits that contribute to drug relapse remain unknown.MethodsWe systematically investigated the relationship of cocaine relapse with 98 DLPFC functional circuits defined by evenly sampling the entire bilateral DLPFC in a cohort of cocaine dependent patients (n=43, 5F) following a psychosocial treatment intervention. A Cox regression model was utilized to predict relapse likelihood based on DLPFC functional connectivity strength.ResultsFunctional connectivity from 3 of the 98 DLPFC loci, one on the left and two on the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.7% and 85.4%, respectively. Combining all three significantly improved prediction validity to 87.5%. Protective and risk circuits related to these DLPFC loci were identified that are known to support “bottom up” drive to use drug and “top down” control over behavior together with social emotional, learning and memory processing.ConclusionThree DLPFC-centric circuits were identified that predict relapse to cocaine use with high accuracy. These functionally distinct DLPFC-based circuits provide insights into the multiple roles played by the DLPFC in cognitive and affective functioning that affects treatment outcome. The identified DLPFC loci may serve as potential neuromodulation targets for addiction treatment and as clinically relevant biomarkers of its efficacy.