Title : Neuroimaging markers of drug addiction From preclinical models to substance use disorder patients
ompulsive drug use is a cardinal feature of substance use disorder (SUD). Using a forward- and backward-translational strategy, we investigated cortical-striatal circuits underpinning compulsive drug use in human drug addicts and preclinical models. We started with a cross-sectional human study, comparing cocaine users and healthy controls, to identify cortical-striatal circuits altered in cocaine users. We then demonstrated that the impaired circuits were associated with compulsive drug taking behaviors characterized by symptoms of loss-of-control over drug use described in the Diagnostic and Statistical Manual. For mechanistic understanding of the circuit alterations at various addiction phases, we “backwardtranslated” the findings from the human study to a compulsive drug taking model of rats. We found that cortical-striatal circuits in rats homologous to those of humans were disrupted and the severity of circuit disruption was associated with the level of compulsive drug taking in these animals. We further evaluate therapeutic potentials of these circuits in the rat model. We expect that findings from the preclinical model would then “forward-translate” to clinical studies for developing effective therapeutic treatments by restoring these altered brain circuits. In this presentation, identification of imaging biomarkers that underlie compulsive drug taking behaviors in humans and preclinical models will be presented. Potential treatment strategies based on neuromodulation, such as transcranial magnetic stimulation, will be discussed.