Resting State fMRI Functional and Effective Connectivity in Opioid and Cocaine Use Disorders

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Project Summary and Abstract Substance use disorders represent a major public health problem, and improved therapies are needed. To-date, pre-clinical models of addiction have not translated well into improved therapy options. An improved understanding of the clinical neurobiology of addictions can help refine preclinical neurocircuit models of addiction which may help inform the development of future therapies. One tool that can help improve the understanding of the neurobiology of substance use disorders is resting state brain functional magnetic resonance imaging (fMRI). fMRI measurements taken at rest allow for the assessment of functional connectivity, or correlations in activity patterns between spatially distinct brain regions. Dynamic Causal Modeling-estimated effective (directional) connectivity further estimates the direction of connectivity between brain regions. As opposed to preclinical models focused on specific brain regions acting as independent modules, human research has emphasized the analysis of the brain as functional networks of brain regions (Bressler & Menon, 2010). Functional and effective connectivity can provide insight into how the brain is organized into networks and how those networks may be altered in substance use disorders. The study of how brain networks interact opens a new avenue of research on the neurobiology of substance use disorders and other related brain disorders. However, published studies assessing functional or effective connectivity between whole brain networks in substance use disorders compared to healthy controls are lacking. In particular, there has been a relative lack of studies assessing functional or effective connectivity of the executive control network, despite well documented executive control deficits in substance use disorders. Robust and replicable within- and between-network connectivity differences in substance use disorders could help refine preclinical models of addiction helping to inform future pharmacotherapy development. The present study aims to assess between-network brain functional connectivity and effective connectivity among three key brain networks (Salience Network, Default Mode Network, and Executive Control Network) in opioid and cocaine use disorder subjects compared to non-drug using controls. The completion of this project will determine the extent to which functional and effective connectivity among the Default Mode Network, Salience Network, and Executive Control Network differs in opioid and cocaine use disorders compared to non-drug using controls, providing neurocircuit targets for preclinical and clinical models of substance use disorders.