Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study

Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the nucleus accumbens, within the mesolimbic pathway. Although dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown whether alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in 27 participants including healthy volunteers and psychiatric patients with schizophrenia, depression, or cocaine addiction, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) multimodal imaging with a voxel-based statistical approach. Dopamine transporter (DAT) availability was assessed with PET and [¹¹C]PE2I as a marker of presynaptic dopamine function, and reward-related neural response was assessed using fMRI with a modified Monetary Incentive Delay task. Across all the participants, DAT availability in the midbrain correlated positively with the neural response to anticipation of reward in the nucleus accumbens. Moreover, this relationship was conserved in each clinical subgroup, despite the heterogeneity of mental illnesses examined. For the first time, a direct link between DAT availability and reward anticipation was detected within the mesolimbic pathway in healthy and psychiatric participants, and suggests that dopaminergic dysfunction is a common mechanism underlying the alterations of reward processing observed in patients across diagnostic categories. The findings support the use of a dimensional approach in psychiatry, as promoted by the Research Domain Criteria project to identify neurobiological signatures of core dysfunctions underling mental illnesses.