Abstract
Both goal-directed and automatic processes shape human behavior. These processes often conflict, and behavioral control is the decision about which determines behavior. Behavioral control, or deciding how to decide, is critical for adaptive behavior. However, the neural mechanisms underlying behavioral control remain unclear. We performed deep phenotyping of individual dopamine system function by combining PET measures of dopamine physiology, functional MRI, and administration of dopaminergic drugs in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task in which we operationalized goal-directed and automatic decision-making as model-based and model-free contributions to behavior, respectively. We found convergent and causal evidence that dopamine D2/3 receptors in the striatum regulate behavioral control by enhancing model-based and blunting model-free influences on behavior. In contrast, we found a double dissociation whereby presynaptic dopamine synthesis capacity in the striatum was linked to acquiring model-based knowledge but not behavioral control. Neuroimaging analysis suggested that striatal D2/3 receptors influence behavioral control by adjusting frontostriatal functional connectivity. This multimodal study establishes a specific role of D2/3 receptors in regulating behavioral control and could contribute to an improved understanding of dysregulated behavioral control in clinical disorders affecting dopamine neurotransmission.Both goal-directed and automatic processes shape human behavior. These processes often conflict, and behavioral control is the decision about which determines behavior. Behavioral control, or deciding how to decide, is critical for adaptive behavior. However, the neural mechanisms underlying behavioral control remain unclear. We performed deep phenotyping of individual dopamine system function by combining PET measures of dopamine physiology, functional MRI, and administration of dopaminergic drugs in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task in which we operationalized goal-directed and automatic decision-making as model-based and model-free contributions to behavior, respectively. We found convergent and causal evidence that dopamine D2/3 receptors in the striatum regulate behavioral control by enhancing model-based and blunting model-free influences on behavior. In contrast, we found a double dissociation whereby presynaptic dopamine synthesis capacity in the striatum was linked to acquiring model-based knowledge but not behavioral control. Neuroimaging analysis suggested that striatal D2/3 receptors influence behavioral control by adjusting frontostriatal functional connectivity. This multimodal study establishes a specific role of D2/3 receptors in regulating behavioral control and could contribute to an improved understanding of dysregulated behavioral control in clinical disorders affecting dopamine neurotransmission.