Individual differences in successful self-regulation of the dopaminergic midbrain

Abstract

The dopaminergic midbrain is associated with brain functions, such as 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 examined how self-modulation capability relates to regulation transfer. Moreover, to elucidate potential mechanisms underlying successful self-regulation, we studied individual prediction error coding, and, during an independent monetary incentive delay (MID) task, individual reward sensitivity. Fifty-nine participants underwent neurofeedback training either in a veridical or inverted feedback group. Successful selfregulation was associated with post-training activity within the cognitive control network and accompanied by decreasing prefrontal prediction error signals and increased prefrontal reward sensitivity in the MID task. The correlative link of dopaminergic self-regulation with individual differences in prefrontal prediction error and reward sensitivity suggests that reinforcement learning contributes to successful self-regulation. Our findings therefore provide new insights in the control of dopaminergic midbrain activity and pave the way to improve neurofeedback training in neuropsychiatric patients. Introduction 1The dopaminergic midbrain, including the ventral tegmental area (VTA) and substantia nigra (SN), plays 2 a crucial role in reward processing, reinforcement learning 1-4 , motivation 5,6 , and decision-making 7 .3 Dysfunctions of the reward system have far-reaching consequences and are associated with the 4 development of several severe psychiatric disease such as addiction 8 and schizophrenia 9,10 . Despite 5 decades of extensive neuroscience and imaging studies which have contributed to an impressive body 6 of knowledge of normal and abnormal reward system function, the neural mechanisms controlling 7 midbrain activity are still not fully understood 11 . One key issue that has received increasing attention 8 is whether humans are able to cognitively control brain activity within the reward system. It has already 9 been shown that both healthy controls 12,13 , and patients with cocaine addiction 14 can learn to regulate 10 SN/VTA activity during real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback 11 training. However, the outcome of primary interest in neurofeedback training is a transfer beyond 12 training itself, i.e., the ability to regulate activity also after training and without feedback. Such transfer 13 is critical for clinical applications, including those involving disorders of the reward system 15 . While 14MacInnes and colleagues 13 observed significant neural transfer effects in the form of increased neural 15 activity and connectivity of the VTA during transfer on the group level, the other two stud...