Non-invasive stimulation reveals ventromedial prefrontal cortex function in reward prediction and reward processing.

Introduction: Studies suggest an involvement of the ventromedial prefrontal cortex (vmPFC) in reward prediction and processing, with reward-based learning relying on neural activity in response to unpredicted rewards or non-rewards (reward prediction error, RPE). Here, we investigated the causal role of the vmPFC in reward prediction, processing, and RPE signaling by transiently modulating vmPFC excitability using transcranial Direct Current Stimulation (tDCS). Methods: Participants received excitatory or inhibitory tDCS of the vmPFC before completing a gambling task, in which cues signaled varying reward probabilities and symbols provided feedback on monetary gain or loss. We collected self-reported and evaluative data on reward prediction and processing. In addition, cue-locked and feedback-locked neural activity via magnetoencephalography (MEG) and pupil diameter using eye-tracking were recorded. Results: Regarding reward prediction (cue-locked analysis), vmPFC excitation (versus inhibition) resulted in increased prefrontal activation preceding loss predictions, increased pupil dilations, and tentatively more optimistic reward predictions. Regarding reward processing (feedback-locked analysis), vmPFC excitation (versus inhibition) resulted in increased pleasantness, increased vmPFC activation, especially for unpredicted gains (i.e., gain RPEs), decreased perseveration in choice behavior after negative feedback, and increased pupil dilations. Discussion: Our results support the pivotal role of the vmPFC in reward prediction and processing. Furthermore, they suggest that transient vmPFC excitation via tDCS induces a positive bias into the reward system that leads to enhanced anticipation and appraisal of positive outcomes and improves reward-based learning, as indicated by greater behavioral flexibility after losses and unpredicted outcomes, which can be seen as an improved reaction to the received feedback.