Genes of the dopaminergic system selectively modulate top-down but not bottom-up attention

Abstract

Cognitive performance is modulated by the neurotransmitter dopamine (DA). Recently, it has been proposed that DA has a strong impact on top-down but not on bottom-up selective visual attention. We tested this assumption by analyzing the influence of two gene variants of the dopaminergic system. Both the catechol O-methyltransferase (COMT) protein and the dopamine transporter (DAT) protein are crucial for the degradation and inactivation of DA. These metabolizing proteins modulate the availability of DA, especially in the prefrontal cortex and basal ganglia. The functional COMT Val158Met polymorphism of the COMT gene represents two coding variants, valine and methionine. In Met allele carriers, the COMT activity is reduced three- to fourfold. A variable number of tandem repeats (VNTR) polymorphism exists in the DAT1 gene, which encodes DAT. The DAT density was reported to be about 50% higher for the DAT1 10-repeat than the DAT1 9-repeat allele. We assessed attention via two experimental tasks that predominantly measure either top-down processing (the Stroop task) or bottom-up processing (the Posner-Cuing task). Carriers of the Met allele of the COMT Val158Met polymorphism displayed better performance in the Stroop task, but did not outperform the other participants in the Posner-Cuing task. The same result was noted for carriers of the DAT1 10-repeat allele. From these findings, we suggest that normal variations of the dopaminergic system impact more strongly on top-down than on bottom-up attention.

Association of COMT and SLC6A3 polymorphisms with impulsivity, response inhibition and brain function

“…Additionally, most previous studies selected only one response inhibition task, thereby failing to allow the assessment of the specificity of any observed associations within the domain of inhibitory function. Finally, the only response inhibition studies combining the two polymorphisms (Colzato, van den Wildenberg, Van der Does, & Hommel, 2010;Congdon et al, 2009;Gurvich & Rossell, 2014;Schneider et al, 2014;Stokes et al, 2011) did not investigate or report statistical interactions of the two polymorphisms with regards to inhibition performance, leaving open whether such geneegene interaction effects may exist.…”

“…However, opposing evidence has also been obtained (Kim, Kim, & Cho, 2006). In a recent study, 9R homozygotes performed worse on the incongruent condition of a Stroop task compared to 10R homozygotes and 9/10 heterozygotes (Schneider, Schote, Meyer, & Frings, 2014). A genetic imaging study of adolescents showed that during response inhibition, the homozygosity for the 10R allele may be associated with increased activation in frontal, medial, and parietal regions compared to non-10R carriers (Braet et al, 2011), although the opposite pattern was observed in adult ADHD patients (Dresler et al, 2010).…”

“…Whilst there is evidence of the val allele being associated with better inhibition in the antisaccade task (Haraldsson et al, 2010), the met allele has been associated with better performance in the Stroop task (Schneider et al, 2014). Other studies have failed to observe significant associations with go/no-go and stop-signal task performance (Gurvich & Rossell, 2014;Plewnia et al, 2013;Stokes, Rhodes, Grasby, & Mehta, 2011).…”

The negative priming paradigm: An update and implications for selective attention

“…The latter result fits with the missing influence of nicotine on NP as nicotine leads to a heightened acetylcholine transmission. However, studies that analyze the influence of dopamine on selective attention in humans are scarce (see Schneider, Schote, Meyer, & Frings, 2015, for an exception) but might prove quite useful to disentangle the different cognitive processes contributing to NP effects.…”

Individual response speed is modulated by variants of the gene encoding the alpha 4 sub-unit of the nicotinic acetylcholine receptor (CHRNA4)

“…This sample is part of a larger sample that has also been analyzed in regard to several polymorphisms (see[45,46])3 Recently,[47] have reported on the low extent of genetic heterogeneity in German samples. In their study, only a slight north-south gradient was detectible, though this difference was still several times smaller than those between samples drawn in Germany and samples in other Germanic populations, accounting for far less than 5 % of the total variance.…”