The Dorsomedial Prefrontal Cortex Uses Reward Predictions to Regulate How Rewards Are Pursued

Reward-predictive cues regulate not only whether but how rewards are pursued, and their influence depends on the strength of their predictive relationship with reward. Whereas weak cues signaling sparse or uncertain reward invigorate instrumental reward seeking, cues signaling imminent reward produce little net invigoration of instrumental behavior and instead promote conditioned goal-approach. We propose that this reflects two opposing influences: an automatic motivational impulse to seek reward, and a top-down, expectancy-dependent control process that constrains it. On this view, the muted or even suppressive effect of imminent-reward cues on instrumental reward seeking reflects an active constraint on motivation rather than its absence. Consistent with this account, we found that selectively devaluing the predicted reward unmasked a latent motivational influence. Cues for imminent reward now invigorated rather than constrained instrumental seeking, suggesting the involvement of a goal-directed regulatory process. Separately, shifting rats from hunger to general satiety abolished the cue-specific regulation of instrumental seeking. We then tested whether the dorsomedial prefrontal cortex (dmPFC) mediates this control. Bulk calcium recordings revealed phasic dmPFC activity that encoded predicted reward probability, dipped when reward was omitted, and covaried with instrumental performance in a cue-dependent manner. Moreover, chemogenetic dmPFC inhibition disrupted the cue-specific regulation of instrumental seeking, leaving rats unable to use these predictions to determine how vigorously to press. These findings identify the dmPFC as a substrate for top-down, expectancy-dependent control over reward pursuit and suggest that its dysfunction may contribute to impulsive or maladaptive reward seeking.

Cues for imminent reward availability normally suppress the impulse to perform instrumental reward-seeking actions, redirecting behavior toward goal-approach responses that facilitate reward retrieval. This flexible regulatory process depends on a real-time appraisal of predicted reward value and is lifted when that reward is devalued, allowing such cues to invigorate instrumental behavior. Here we identify the dorsomedial prefrontal cortex (dmPFC) as a critical substrate for this process. Using fiber photometry and chemogenetic inhibition, we show that dmPFC activity tracks these cue-elicited reward predictions and is required for their regulatory influence over instrumental reward seeking, but not over conditioned goal-approach. These findings illuminate a prefrontal mechanism for top-down motivational control with potential relevance to impulsive reward seeking.