Mesolimbic Functional Magnetic Resonance Imaging Activations during Reward Anticipation Correlate with Reward-Related Ventral Striatal Dopamine Release

TLDR

The dopaminergic mechanisms that control reward‑motivated behavior are intensely studied, but it remains unclear how human mesolimbic neural activity and its fMRI correlates relate to dopamine release. The study aimed to determine the relationship between reward‑related neural activity and dopamine release in humans. Participants performed a delayed monetary incentive task while undergoing simultaneous fMRI to measure reward‑related neural activity and PET with [(11)C]raclopride to quantify dopamine release. Across participants, reward anticipation activity in the substantia nigra/ventral tegmental area and ventral striatum/nucleus accumbens positively correlated with ventral striatal dopamine release, and higher dopamine release was linked to increased activation of limbic structures such as the amygdala and hippocampus, demonstrating that dopaminergic neurotransmission quantitatively influences human mesolimbic reward processing and highlighting the value of combined neurochemical and hemodynamic imaging.

Abstract

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.