DRD2/ANKK1 Polymorphism Modulates the Effect of Ventral Striatal Activation on Working Memory Performance

Abstract

Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n ¼ 1080, age 13-15 years) and BrainChild (nB300, age 6-27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (po0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (po0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission.

Childhood cognitive development as a skill

“…This polymorphism has previously been associated with reduced levels of striatal DRD2 [44], but increased striatal reactivity to DRD2 agonists [45]. In a follow-up study, the same SNP showed an interaction, with carriers of the A allele (previously associated with larger training improvement) demonstrating a positive correlation between ventral striatal activation and WM capacity in adolescents [46].…”

Dopamine Does Double Duty in Motivating Cognitive Effort

“…Also, systemic DA agonism by the indirect agonist d-amphetamine ameliorates physical effort deficits among individuals with Parkinson’s disease (Chong et al, 2015). In the cognitive domain, VS BOLD signal interacted with a genetic D2 receptor density marker to predict individual differences in working memory performance (Nymberg et al, 2014). …”

The Brain’s Response to Reward Anticipation and Depression in Adolescence: Dimensionality, Specificity, and Longitudinal Predictions in a Community-Based Sample

“…sourceforge.net) (24). Whole regions from the Automated Anatomical Labeling atlas (25) were used, with the exception of the ventral striatum, which we defined according to Martinez et al (26,27).…”