Patients with stimulant use disorder (SUD) experience high rates of relapse. While a large body of research has advanced our understanding of the neural mechanisms involved in addiction, treatment options are still not effective in the majority of patients. One reason for this is that mechanistic studies of addiction are typically performed in animal models, where translatability to human relapse is unknown. My dissertation research aims to establish a translational bridge between the mechanistic understanding afforded by genetic and molecular tools available in animal models, and the behavioral sophistication afforded by human neuroimaging and psychophysics. To achieve this, we have taken several steps as part of this dissertation: (1) used human neuroimaging to identify the anterior insula (AIns) and nucleus accumbens (NAcc) as key regulators of relapse in abstaining SUD patients; (2) established the role of AIns as a robust neural predictor of risk-avoidance and NAcc as neural predictor of risk-seeking behavior in healthy humans; (3) combining multiple cutting-edge techniques of neuroscience in rodents and developing novel analysis pipelines, we are now poised to characterize the anatomical and functional properties of the AIns-NAcc circuitry and establish its causal role on risky behaviors across species.
