Individual differences in the mechnistic control of the dopaminergic midbrain

The dopaminergic midbrain is associated with elementary brain functions, such as reward processing, reinforcement learning, motivation and decision-making that are often disturbed in neuropsychiatric disease. Previous research has shown that activity in the dopaminergic midbrain can be endogenously modulated via neurofeedback, suggesting potential for non-pharmacological interventions. However, the robustness of endogenous modulation, a requirement for clinical translation, is unclear. Here, we used non-invasive modulation of the dopaminergic midbrain activity by real-time neurofeedback to examine how self-modulation capability affects transfer and correlated activation across the brain. In addition, to further elucidate potential mechanisms underlying successful self-regulation, we studied individual prediction error coding during neurofeedback training, and, during a completely independent monetary incentive delay (MID) task, individual reward sensitivity. Fifty-nine participants underwent neurofeedback training either in a veridical or inverted feedback group. Post-training activity within the cognitive control network was increased only in those individuals with successful self-regulation of the dopaminergic midbrain during neurofeedback training. Successful learning to regulate was accompanied by decreasing prefrontal prediction error signals and increased prefrontal reward sensitivity in the MID task. Our findings suggest that the cognitive control network contributes to successful transfer of the capability to upregulate the dopaminergic midbrain. The link of dopaminergic self-regulation with individual differences in prefrontal prediction error and reward sensitivity indicates that reinforcement learning contributes to successful top-down control of the midbrain. Our findings therefore provide new insights in the cognitive control of dopaminergic midbrain activity and pave the way to improving neurofeedback training in neuropsychiatric patients