Cortical dopamine release during a behavioral response inhibition task

Abstract

Dopamine (DA) dysregulation within fronto-striatal circuitry may underlie impulsivity in alcohol and other substance use disorders. To date, no one has directly demonstrated DA release during a task requiring the control of impulsive behavior. The current study was conducted to determine whether a response inhibition task (stop signal task; SST) would elicit detectable extrastriatal DA release in healthy controls. We hypothesized that DA release would be detected in regions previously implicated in different aspects of inhibitory control. [(18) F]Fallypride (FAL) PET imaging was performed in nine healthy males (24.6 ± 4.1 y.o.) to assess changes in cortical DA during a SST relative to a baseline "Go" task. On separate days, subjects received one FAL scan during the SST, and one FAL scan during a "Go" control; task-order was counter-balanced across subjects. Parametric BPND images were generated and analyzed with SPM8. Voxel-wise analysis indicated significant SST-induced DA release in several cortical regions involved in inhibitory control, including the insula, cingulate cortex, orbitofrontal cortex, precuneus, and supplementary motor area. There was a significant positive correlation between stop signal reaction time and DA release in the left orbitofrontal cortex, right middle frontal gyrus, and right precentral gyrus. These data support the feasibility of using FAL PET to study DA release during response inhibition, enabling investigation of relationships between DA function and impulsive behavior.

Keywords: D2 receptor; dopamine; fallypride; impulsivity; positron emission tomography; stop signal task.

Fig. 1

Whole-brain voxel-wise paired t-test comparing BP_ND between baseline “Go” and SST scan conditions (n=9). The “hot” colorscale indicates voxels where BP_{ND, BL} was significantly higher than BP_{ND, SS} (increased DA during SST). Display threshold P<0.005, uncorrected, k>10. Significant clusters are listed in Table II.

Fig. 2

Whole-brain voxel-wise paired t test comparing BP_ND between baseline “Go” and SST scan conditions (n=9). The “cool” colorscale indicates voxels where BP_{ND, SS} was significantly higher than BP_{ND, BL} (indicating decreased DA during SST). Display threshold P<0.005, uncorrected, k>10. Significant clusters are listed in Table II.