Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release

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.

Figures

Figure 1.

Schematic illustration of the experimental paradigm. Top, Both the PET and the fMRI experiment consisted of a rewarded (135 rewarded trials, 45 neutral trials) and a neutral condition (135 neutral trials and 45 bogus reward trials), which were conducted on 2 consecutive days, counterbalanced across participants. The “reward” trials in the neutral condition consisted of reward-predicting cue pictures, followed by a neutral feedback. Bottom, The trials consisted of a cue picture indicating the possibility of a reward (indoor or outdoor scenes, counterbalanced across participants), followed by a target number and a feedback after a variable delay ranging from 1000 to 6000 ms. The feedback was positive or negative in the rewarded trials (arrow up or down) and neutral (“?”) in the neutral trials.

Figure 2.

Reward-related [11C]raclopride displacement. A, Coronal section of the striatal ROIs in the left hemisphere. The corresponding ROIs in the right hemisphere were also segmented. B, Time–activity curves of a representative single subject. Total binding in the NAcc, unspecific binding in the cerebellum, and specific binding in the NAcc as the difference NAcc-cerebellum are shown. The x-axis depicts the time of PET scanning, starting with the injection of [11C]raclopride. The y-axis displays local radioactivity in the NAcc and cerebellum and the difference of NAcc and cerebellum activity, in MBq/mm3.

Figure 3.

Dopamine release and fMRI activations in the ventral striatum (results from the voxel-based analysis). Left, [11C]raclopride displacement in the left nucleus accumbens. Right, Activation of the ventral striatum during reward anticipation in the fMRI study. Coordinates are given in MNI space; p < 0.005, uncorrected; extent threshold k = 15 voxels.

Figure 4.

Correlation of dopamine release and fMRI activations. Top, Left, Location of the ROI for the left midbrain. Right, Across the study cohort, fMRI response in the left midbrain (segmented area) during reward anticipation was significantly correlated with [11C]raclopride displacement in the rewarded relative to the neutral condition. Bottom, Left, Representative ROI from a single subject. Six-millimeter spheres were centered at the local maxima of the reward anticipation response closest to [x y z] = [−6 10 −6] (the coordinate of maximal reward-related BPND decrease in PET), individually for each subject. Right, A significant correlation was observed between [11C]raclopride displacement and the fMRI response in the left nucleus accumbens.