Measuring extrastriatal dopamine release during a reward learning task

Objectives: Reward learning is critical for survival. Animal research emphasizes the role of dopaminergic (DA) mesocorticolimbic pathways in reward learning, but few studies have evaluated extrastriatal DA functioning in humans. The purpose of this study was to examine presynaptic DA release in extrastriatal regions of the reward circuit by measuring displacement of the high affinity D(2) /D(3) radioligand [(18) F]Fallypride during a reward task.

Design: Ten healthy volunteers underwent a [(18) F]Fallypride positron emission tomography protocol while performing a reward task, allowing us to assess participants' ability to modulate behavior as a function of reward. DA receptor ligand displacement was correlated with task performance and self-reported anhedonia.

Observations: Parametric t-maps revealed significant decrease in [(18) F]Fallypride binding in the medial orbitofrontal cortex (mOFC), ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC), indicating endogenous DA release in these regions. Increasing anhedonic symptoms correlated with DA release in the left vmPFC, left dACC, and right dACC emerged (all r's > 0.65, P's < 0.05). Similarly, reduced reward learning correlated with higher DA release in left vmPFC, right vmPFC, and left dACC (all r's < -0.64, P's < 0.05). Left dACC (r = 0.66, P = 0.04) and left vmPFC (r = 0.74, P = 0.01) DA release showed a significant positive correlation with impaired tendency to modulate behavior as a function of prior positive reinforcements.

Conclusions: These findings support the hypothesis that DA release in mOFC, vmPFC, and dACC regions plays an important role in reinforcement learning in the human brain.