Reward processing in humans has been extensively studied by examining brain activity during reward anticipation or outcome in relation to psychopathology. However, animal models reveal distinct phenotypes when both phases are considered, showing unique behavioral and neural patterns. Sign-tracking (ST) and goal-tracking (GT) behaviors in animals reflect different responses to reward cues, with ST focusing on the cue and GT on the outcome, mediated by distinct neural circuits—ST linked to the ventral striatum and GT to the prefrontal cortex. This study aimed to test the presence of these phenotypes in humans using a modified version of the monetary incentive delay (MID) task. BOLD signals extracted from regions of interest (ROIs) derived from meta-analytic reward anticipation and outcome maps were analyzed through K-means clustering, revealing two groups of individuals across independent cohorts (N = 934 and N = 127): one showing extended activation in the reward anticipation network (ST), and the other in the reward outcome network (GT). Trial-by-trial analyses showed that ST, compared to GT, did not habituate to reward (vs. control) trials in the ventral striatum, consistent with animal studies showing no dopaminergic habituation in GT. This supports the hypothesis that ST continues to attribute incentive salience to reward-predicting stimuli, even after repeated exposure. Altogether, we demonstrated the existence of ST-GT phenotypes in humans and confirmed the mechanism of incentive salience, extending animal model insights to human reward processing and highlighting distinct neural patterns in reward anticipation and outcome.
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