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Abstract: Asymmetries of spatial attention are observed in both clinical and non-clinical populations. While lesions of the right hemisphere frequently result in symptoms of left neglect (right bias), the opposite pattern is often observed in healthy subjects, a phenomenon known as pseudoneglect. Pharmacological and animal studies have suggested a critical role for the catecholamines, in particular dopamine and noradrenaline, in modulating the direction and magnitude of spatial attentional bias. In the present study we investigated the effect of two catecholaminergic genes, DBH and DAT1, on performance in the Landmark task, a perceptual measure of spatial bias. 204 healthy participants performed the Landmark task and were genotyped for the DBH C-1021T and DAT1 3′UTR variants. Homozygosity for the DBH T allele, which is associated with relatively increased dopamine and decreased noradrenaline levels, resulted in a significant increase in rightwards spatial bias relative to the C allele. Similarly, homozygosity for the DAT1 9-repeat allele, which is associated with reduced dopamine transporter density, and consequently increased dopamine availability relative to the 10-repeat allele, was found to result in a greater degree of rightward bias. An additive effect of the two markers was also observed, such that the greatest degree of rightward spatial bias was observed in participants who possessed the ‘high dopamine’ alleles of both genes and the lowest degree in those without these alleles. These results provide the first evidence of genetic modulation of spatial bias in healthy adults. [ABSTRACT FROM AUTHOR]

Abstract: Sustained attention is modulated by the neurotransmitter noradrenaline. The balance of dopamine and noradrenaline in the cortex is controlled by the DBH gene. The principal variant in this gene is a C/T change at position −1021, and the T allele at this locus is hypothesised to result in a slower rate of dopamine to noradrenaline conversion than the C allele. Two hundred participants who were genotyped for the DBH C−1021T marker performed the Sustained Attention to Response Task (SART). DBH genotype was found to significantly predict performance; participants with more copies of the T allele made more errors of commission, indicative of lapses in sustained attention. A significant negative correlation was also observed for all participants between errors of commission and mean reaction time. The decrease in noradrenaline occasioned by the T allele may impair sustained attention by reducing participants’ ability to remain alert throughout the task and by increasing their susceptibility to distractors. [Copyright &y& Elsevier]

Abstract: The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as well as problems with response inhibition. In the present study we used fMRI to investigate the role of dopaminergic genetic variation on executive functioning by comparing how activation associated with successful and unsuccessful inhibitions differs based on DAT1-genotype and ADHD-diagnosis in adolescents performing a go/nogo task. The results identify regional specificity concerning which functional differences can be attributed to the possession of the high risk DAT1 genotype, the clinical condition or an interaction between the two. During response inhibition, individuals with two copies of the 10-repeat allele showed increased activation in frontal, medial, and parietal regions, which may indicate that inhibition is more effortful for this group. Conversely, this group displayed a reduced error response in the parahippocampal gyrus, suggestive of reduced learning from errors. There were also a number of frontal, parietal, medial and occipital regions, where the relationship between genotype and fMRI-activation differed between the ADHD group and the typically developing adolescents. Finally, the ADHD group displayed decreased activation in parietal and (pre)frontal regions during response inhibition, and in frontal and medial brain regions on error trials. [Copyright &y& Elsevier]

Abstract: Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to dopamine signaling is suggested in ADHD that may be ameliorated by methylphenidate (MPH). This study investigated the effects of MPH administration on the variability in RT and error performance on a sustained attention task of a group of 31 medication naïve children with ADHD, compared with 22 non-ADHD, non-medicated, control children. All children performed the fixed-sequence sustained attention to response task (SART) at two time-points: at baseline and after six weeks. The children with ADHD were tested when medication naive at baseline and after six weeks of treatment with MPH and whilst on medication. The medication naïve children with ADHD performed the SART with greater errors of commission and omission when compared with the control group. They demonstrated greater standard deviation of RT and fast moment-to-moment variability. They did not differ significantly from the control group in terms of slow variability in RT. MPH administration resulted in reduced and normalised levels of commission errors and fast, moment-to-moment variability in RT. MPH did not affect the rate of omission errors, standard deviation of RT or slow frequency variability in RT. MPH administration may have a specific effect on those performance components that reflect sustained attention and top–down control rather than arousal. [Copyright &y& Elsevier]