A dopaminergic basis of behavioral control

Area of Science:

• Neuroscience
• Cognitive Science
• Behavioral Economics

Background:

• Human behavior results from competing goal-directed and automatic processes.
• Behavioral control, the selection of which process guides actions, is crucial for adaptive decision-making but its neural basis is poorly understood.
• It remains unclear if distinct neural mechanisms support behavioral control versus goal-relevant knowledge acquisition.

Purpose of the Study:

• To investigate the distinct neural mechanisms underlying behavioral control and knowledge formation within the dopamine system.
• To determine the specific roles of ventral striatal dopamine D2/3 receptor availability and dopamine synthesis capacity in regulating goal-directed and automatic behaviors.

Main Methods:

• Deep phenotyping of individual dopamine system function using PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design.
• Subjects performed a rule-based response time task to operationalize goal-directed (model-based) and automatic (model-free) decision-making influences.
• Analysis focused on dissociating the effects of D2/3 receptor availability and dopamine synthesis capacity on behavior and neural activity.

Main Results:

• A double dissociation was observed between ventral striatal D2/3 receptor availability and dopamine synthesis capacity.
• D2/3 receptor availability causally regulated behavioral control by enhancing model-based and reducing model-free influences, without impacting knowledge formation.
• Dopamine synthesis capacity was associated with model-based knowledge formation but not directly with behavioral control.
• D2/3 receptors modulated frontostriatal functional connectivity, suggesting a mechanism for gating prefrontal inputs to the striatum.

Conclusions:

• Striatal dopamine D2/3 receptors are central to behavioral control, mediating the balance between goal-directed and automatic processes.
• Dopamine synthesis capacity supports the acquisition of goal-relevant knowledge, separate from the control of behavior.
• These findings identify specific dopaminergic mechanisms underlying individual differences in behavioral control and suggest D2/3 receptors as therapeutic targets for enhancing goal-directed behavior.