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.