Inter-individual differences in decision-making, flexible and goal-directed behaviors: novel insights within the prefronto-striatal networks

Inflexible behavior is a hallmark of several decision-making-related disorders such as ADHD and addiction. As in humans, a subset of healthy rats makes poor decisions and prefers immediate larger rewards despite suffering large losses in a rat gambling task (RGT). They also display a combination of traits reminiscent of addiction, notably inflexible behavior and perseverative responses. The goal of the present work was twofold: (1) to elucidate if behavioral inflexibility of poor decision-makers could be related to a lower quality of goal-directed behavior (action–outcome associations); (2) to uncover the neural basis of inter-individual differences in goal-directed behavior. We specifically assessed inter-individual differences in decision-making in the RGT, flexibility in the RGT-reversed version and goal-directed behavior in a contingency degradation test, i.e., response adaptation when dissociating reward delivery from the animal’s action. The contributions of the medial prefrontal cortex and the dorsal striatum to action–outcome associations were assessed using Zif268 immunodetection. Inflexible behavior was related to a lower sensitivity to contingency degradation in all poor decision-makers and only in a few good decision-makers. This poorer sensitivity was associated with a lower immunoreactivity in prelimbic and infralimbic cortices and a higher one in the dorsomedial and dorsolateral striatum. These findings suggest that an imbalanced prefronto-striatal activity could underlie inaccurate goal representation in changing environments and may promote maladaptive habit formation among poor decision-makers. These data strengthen our previous work identifying biomarkers of vulnerability to develop psychiatric disorders and demonstrate the relevance of inter-individual differences to model maladaptive behaviors.