The dopaminergic mechanisms that control reward-motivated
behavior are the subject of intense study, but it is yet unclear how, in humans,
neural activity in mesolimbic reward-circuitry and its functional neuroimaging
correlates are related to dopamine release. To address this question, we
obtained functional magnetic resonance imaging (fMRI) measures of reward-related
neural activity and [(11)C]raclopride positron emission tomography measures of
dopamine release in the same human participants, while they performed a delayed
monetary incentive task. Across the cohort, a positive correlation emerged
between neural activity of the substantia nigra/ventral tegmental area (SN/VTA),
the main origin of dopaminergic neurotransmission, during reward anticipation
and reward-related [(11)C]raclopride displacement as an index of dopamine
release in the ventral striatum, major target of SN/VTA dopamine neurons. Neural
activity in the ventral striatum/nucleus accumbens itself also correlated with
ventral striatal dopamine release. Additionally, high-reward-related dopamine
release was associated with increased activation of limbic structures, such as
the amygdala and the hippocampus. The observed correlations of reward-related
mesolimbic fMRI activation and dopamine release provide evidence that
dopaminergic neurotransmission plays a quantitative role in human mesolimbic
reward processing. Moreover, the combined neurochemical and hemodynamic imaging
approach used here opens up new perspectives for the investigation of molecular
mechanisms underlying human cognition.