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Frontostriatal involvement in task switching depends on genetic differences in d2 receptor density.

ABSTRACT: Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior frontal junction area, and increased functional connectivity in dorsal frontostriatal circuits, relative to A1 allele carriers. A DRD2 haplotype analysis in the same sample confirmed these results, indicating an association between high D2 density and increased task-switching effort. Our results provide evidence that converges with that from association studies relating increased D2 density to deficits in cognitive flexibility in schizophrenia. We suggest that individual differences in striatal D2 signaling in healthy humans modulate goal-directed gating to prefrontal cortex, thus leading to individual differences in switching intentionally to newly relevant behaviors.

SUBMITTER: Stelzel C

PROVIDER: S-EPMC6634769 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Frontostriatal involvement in task switching depends on genetic differences in d2 receptor density.

Stelzel Christine C Basten Ulrike U Montag Christian C Reuter Martin M Fiebach Christian J CJ

The Journal of neuroscience : the official journal of the Society for Neuroscience 20101001 42

Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior front ...[more]

PMID: 20962241

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Project description:Individuals differ in their tendencies to seek positive decision outcomes or to avoid negative ones. At the neurobiological level, our model suggests that phasic changes in dopamine support learning to reinforce good decisions via striatal D1 receptors, and to avoid maladaptive choices via striatal D2 receptors. Accordingly, in a previous study individual differences in positive and negative learning were strongly modulated by two genetic polymorphisms factors related to striatal D1 and D2 function, respectively. Nevertheless, whereas the role for dopamine in positive learning is relatively well accepted, that in learning to avoid negative outcomes is more controversial. Here we further explore D2-receptor-related genetic contributions to probabilistic avoidance in humans, in light of recent data showing that particular DRD2 polymorphisms are associated with functional modulation of receptor expression [Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee M-LT, Xiao T, Papp A, Wang D, Sadée W (2007) Polymorphisms in human dopamine d2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A 104(51):20552-20557]. We find that a promoter polymorphism rs12364283 associated with transcription and D2 receptor density was strongly and selectively predictive of avoidance-based decisions. Two further polymorphisms (rs2283265 and rs1076560) associated with relatively reduced presynaptic relative to postsynaptic D2 receptor expression were predictive of relative impairments in negative compared to positive decisions. These previously undocumented effects of DRD2 polymorphisms were largely independent of those we reported previously for the C957T polymorphism (rs6277) associated with striatal D2 density. In contrast, effects of the commonly studied Taq1A polymorphism on reinforcement-based decisions were due to indirect association with C957T. Taken together these findings suggest multiple D2-dependent genetic mechanisms contributing to avoidance. We discuss these effects in the context of neurocomputational models of reinforcement leaning in the basal ganglia.

Dataset Information

Frontostriatal involvement in task switching depends on genetic differences in d2 receptor density.

Publications

Frontostriatal involvement in task switching depends on genetic differences in d2 receptor density.

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