The role of the dopamine transporter DAT1 genotype on the neural correlates of cognitive flexibility

Abstract

Cognitive flexibility, the ability to adapt goal-oriented behaviour in response to changing environmental demands, varies widely amongst individuals, yet its underlying neural mechanisms are not fully understood. Neuropharmacological and human clinical studies have suggested a critical role for striatal dopaminergic function mediated by the dopamine transporter (DAT). The present study aimed at revealing the role of the DAT in the individual brain response stereotypy underlying cognitive flexibility. A task-switching protocol was administered to a sample divided according to the presence or absence of the 9-repeat (9R) allele of the DAT1 polymorphism, while registering behavioural and electrophysiological novelty-P3 responses. The absence of the 9R (higher gene expression) is related to less striatal DA availability. Individuals lacking the 9R (9R-) showed specific response time (RT) increases for sensory change and task-set reconfiguration, as well as brain modulations not observed in participants with the 9R allele (9R+), suggesting that task performance of the former group depended on immediate local context. In contrast, individuals displaying high striatal DA showed larger RT costs than 9R- individuals to any sensory change, with no further increase for task-set reconfiguration, and a larger early positive brain response irrespective of the task condition, probably reflecting larger inhibition of any previous interference as well as stronger activation of the current task set. However, the polymorphic groups did not differ in their mean RTs in trials requiring task-set reconfiguration. This distinct stereotypy of cerebral responses reveals different patterns of cognitive control according to the DAT1 gene polymorphism.

COMT and ANKK1 gene–gene interaction modulates contextual updating of mental representations

“…This crucial function involves the DA system (Cools, 2008;Garcia-Garcia et al, 2010a;Garcia-Garcia et al, 2010b;Kaplan and Oudeyer, 2007;DA Lewis et al, 2001;Mehta et al, 2000;Sawaguchi and Goldman-Rakic, 1994) putatively through a reciprocal relationship between PFC and striatal DA (Akil et al, 2003;Meyer-Lindenberg et al, 2002). This interplay is thought to regulate the stability and flexibility of mental representations, maybe through the modulation of the firing of prefrontal pyramidal neurons, which is enhanced during maintenance in the delay period of a memory task (Durstewitz et al, 2000) and is modulated by the DA neurotransmitter through stimulation of D1 receptors at the PFC (Durstewitz et al, 2000;Durstewitz and Seamans, 2002;Sawaguchi and Goldman-Rakic, 1994).…”

The Effects of Foreknowledge and Task-Set Shifting as Mirrored in Cue- and Target-Locked Event-Related Potentials

“…On the contrary, if non-informatively cued switches influenced processing at a strictly sensory level, then target-locked brain activity should not be modulated by the interaction of the Cue type and Task condition factors. Several previous studies have shown that the mean amplitude of the cue-locked P3 component in the ERPs are modulated by both sensory updating and task switching, at least in the auditory modality [15], [19], [21]. Even though less well studied than the P3, the endogenous and fronto-centrally distributed P2 component has also been shown to be sensitive to change detection [22], [23].…”

Developmental imaging genetics: Linking dopamine function to adolescent behavior

“…FMRI research most consistently associates the 9R allele with increased reward reactivity in the striatum (Yacubian, Sommer et al 2007; Dreher, Kohn et al 2009; Forbes, Brown et al 2009). Although DAT is primarily expressed in striatum, evidence associates the 9-repeat allele with increased ventral striatal and dorsomedial PFC activation during working memory updating and task switching (Aarts, Roelofs et al 2010; Garcia-Garcia, Barcelo et al 2010), and increased PFC activation during inhibitory control, which was interpreted as supporting improved inhibitory control (Congdon, Lesch et al 2008; Congdon, Constable et al 2009). Developmental studies using the DAT1 polymorphism suggest that typically developing adolescents with the 9-repeat allele demonstrate reduced activation of prefrontal and striatal regions during inhibitory control (Braet, Johnson et al 2011), and reward prediction (Paloyelis, Mehta et al 2012).…”