Dopamine has long been implicated in impulsivity, but the precise mechanisms linking human variability in dopamine signaling to differences in impulsive traits remain largely unknown. Using a dual PET scan approach in healthy human volunteers with amphetamine and the D2/D3 ligand 18F-fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal dopamine release.
Psychopathy is a personality disorder that is strongly linked to criminal behavior. Using [18F]fallypride PET and BOLD fMRI, we show that impulsive-antisocial psychopathic traits selectively predict nucleus accumbens dopamine release and reward anticipation-related neural activity in response to pharmacological and monetary reinforcers, respectively. These findings suggest that neurochemical and neurophysiological hyperreactivity of the dopaminergic reward system may comprise a neural substrate for impulsivity, antisocial behavior and substance abuse in psychopathy.
Preferences for different combinations of costs and benefits are a key source of variability in economic decision-making. However, the neurochemical basis of individual differences in these preferences is poorly understood. Studies in both animals and humans have demonstrated that direct manipulation of the neurotransmitter dopamine (DA) significantly impacts cost/benefit decision-making, but less is known about how naturally occurring variation in DA systems may relate to individual differences in economic behavior. In the present study, 25 healthy volunteers completed a dual-scan PET imaging protocol with [18F]fallypride and d-amphetamine to measure DA responsivity, and separately completed the Effort Expenditure for Rewards Task, a behavioral measure of cost/benefit decision-making in humans. We found that individual differences in DA function in the left striatum and ventromedial prefrontal cortex were correlated with a willingness to expend greater effort for larger rewards, particularly when probability of reward receipt was low. Additionally, variability in DA responses in the bilateral insula was negatively correlated with willingness to expend effort for rewards, consistent with evidence implicating this region in the processing of response costs. These findings highlight the role of DA signaling in striatal, prefrontal and insular regions as key neurochemical mechanisms underlying individual differences in cost/benefit decision-making.
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