Abstract
Complex cognitive tasks such as visual working memory (WM) involve networks of interacting brain regions. Several neurotransmitters, including an appropriate dopamine concentration, are important for WM performance. A number of gene polymorphisms are associated with individual differences in cognitive task performance. COMT, for example, encodes catechol-o-methyl transferase the enzyme primarily responsible for catabolizing dopamine in the prefrontal cortex. Striatal dopamine function, linked with cognitive tasks as well as habit learning, is influenced by the Taq-Ia polymorphism of the DRD2/ANKK1 gene complex; this gene influences the density of dopamine receptors in the striatum. Here, we investigated the effects of these polymorphisms on a WM task requiring the maintenance of 4 or 6 items over delay durations of 1 or 5 seconds. We explored main effects and interactions between the COMT and DRD2/ANKK1-Taq-Ia polymorphisms on WM performance. Participants were genotyped for COMT (Val158Met) and DRD2/ANKK1-Taq-Ia (A1+, A1−) polymorphisms. There was a significant main effect of both polymorphisms. Participants' WM reaction times slowed with increased Val loading such that the Val/Val homozygotes made the slowest responses and the Met/Met homozygotes were the fastest. Similarly, WM reaction times were slower and more variable for the DRD2/ANKK1-Taq-Ia A1+ group than the A1− group. The main effect of COMT was only apparent in the DRD2/ANKK1-Taq-Ia A1− group. These findings link WM performance with slower dopaminergic metabolism in the prefrontal cortex as well as a greater density of dopamine receptors in the striatum.
Highlights
Working memory (WM) refers to the ability to maintain and manipulate information ‘on-line’ in the face of disruptions such as eye movements
The effects for longer stimuli could reflect a working memory (WM) deficit rather than the assumed effect of stimulus duration. To explore these issues we investigated the effects of COMT and DRD2/ANKK1-TAQ-Ia polymorphisms on WM performance in healthy adults
The reaction time data were subjected to repeated measures ANOVA with the within-subject factors of set size (4, 6), and delay (1 s, 5 s), and the between-subjects factors of genotype: COMT (Met/Met, Met/Val, Val/Val), and DRD2/ANKK1-Taq-Ia (A1+, A12)
Summary
Working memory (WM) refers to the ability to maintain and manipulate information ‘on-line’ in the face of disruptions such as eye movements. Examples include remembering the number you looked up to dial or the location of your coffee mug while you continue to look at your computer. WM is studied using the full experimental toolkit including neuroimaging, investigations in participants with brain lesions, brain stimulation and behavioral tasks in normal participants. In WM the focus has been on several genes that modulate the dopamine concentration. Successful WM is believed to depend on an optimal dopamine concentration and too much or too little dopamine is considered to be detrimental to executive function We investigated the effects on WM of two genes that affect dopamine activity through two single nucleotide polymorphisms that are common in the general population
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