Resting-state brain activation patterns and network topology distinguish human sign and goal trackers

The Sign-Tracking/Goal-tracking (ST/GT) is an animal model of individual differences in cue-reward learning offering a translational approach to investigate the vulnerability to impulse control disorders. In the present study, we mapped such model onto humans, on the one hand by adopting a new translational relevant Pavlovian paradigm and on the other by investigating resting state functional magnetic resonance imaging correlates in individuals categorized as more disposed to ST or GT. To do so, eyetracking was used to classify humans as prone to STs (n = 36) or GTs (n = 35) or as intermediates (n = 33), depending on their eye-gaze towards the reward-related cue versus the reward location. Using both connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in the ST phenotype, and a more cortical involvement in the GT phenotype. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder.