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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: Autism Spectrum Disorders (ASD) are characterised by social and communication impairment, yet evidence for deficits in the ability to recognise facial expressions of basic emotions is conflicting. Many studies reporting no deficits have used stimuli that may be too simple (with associated ceiling effects), for example, 100% ‘full-blown’ expressions. In order to investigate subtle deficits in facial emotion recognition, 21 adolescent males with high-functioning Austism Spectrum Disorders (ASD) and 16 age and IQ matched typically developing control males completed a new sensitive test of facial emotion recognition which uses dynamic stimuli of varying intensities of expressions of the six basic emotions (Emotion Recognition Test; Montagne et al., 2007). Participants with ASD were found to be less accurate at processing the basic emotional expressions of disgust, anger and surprise; disgust recognition was most impaired – at 100% intensity and lower levels, whereas recognition of surprise and anger were intact at 100% but impaired at lower levels of intensity. [ABSTRACT FROM AUTHOR]

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]

Abstract: Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1–9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in children with HFA. [Copyright &y& Elsevier]

Abstract: Response time (RT) variability is a common finding in ADHD research. RT variability may reflect frontal cortex function and may be related to deficits in sustained attention. The existence of a sustained attention deficit in ADHD has been debated, largely because of inconsistent evidence of time-on-task effects. A fixed-sequence Sustained Attention to Response Task (SART) was given to 29 control, 39 unimpaired and 24 impaired-ADHD children (impairment defined by the number of commission errors). The response time data were analysed using the Fast Fourier Transform, to define the fast-frequency and slow-frequency contributions to overall response variability. The impaired-ADHD group progressively slowed in RT over the course of the 5.5min task, as reflected in this group''s greater slow-frequency variability. The fast-frequency trial-to-trial variability was also significantly greater, but did not differentially worsen over the course of the task. The higher error rates of the impaired-ADHD group did not become differentially greater over the length of the task. The progressive slowing in mean RT over the course of the task may relate to a deficit in arousal in the impaired-ADHD group. The consistently poor performance in fast-frequency variability and error rates may be due to difficulties in sustained attention that fluctuate on a trial-to-trial basis. [Copyright &y& Elsevier]

Abstract: Susceptibility genes for schizophrenia have been hypothesised to mediate liability for the disorder at least partly by influencing cognitive performance. We investigated the association between genotype and cognitive performance for a Dysbindin risk haplotype which is associated with schizophrenia in our sample. Fifty-two patients with schizophrenia or schizoaffective disorder (24 risk haplotypes carriers versus 28 non-risk haplotype carriers) were assessed in areas of cognition showing evidence of familial deficits in schizophrenia. Verbal and spatial memory, working memory, and attentional control was assessed using selected measures from the Weschler memory scale (WMS), Cambridge automated test battery (CANTAB), continuous performance test (CPT), and a simple go/no-go task. Pre-morbid IQ was also assessed using the Weschler Test of Adult Reading (WTAR). Patients carrying the Dysbindin risk haplotype showed significantly lower spatial working memory performance than patients who were non-risk carriers, with genotype explaining 12% of variance in performance. Our study suggests that the increased risk for schizophrenia associated with dysbindin may be partly mediated by its influence on pre-frontal function. [Copyright &y& Elsevier]

Abstract: ADHD is a childhood-onset behavioural disorder with a heterogeneous profile of neuropsychological impairment. Neuropsychological heterogeneity may, in part, reflect underlying genetic differences. Here we examined sustained attention, response variability and spatial attentional asymmetries in a sample of children and adolescents with ADHD (n =22) in relation to dopamine transporter genotype (DAT1) and also controls (n =20). Participants performed the sustained attention to response task (SART) (testing sustained attention and response variability) and the greyscales task (a perceptual measure of attentional bias). The latter has previously been shown to yield a robust leftward attentional asymmetry in healthy subjects. The 10-repeat allele of the DAT1 gene has been associated with ADHD in a number of studies and appears to have biological significance. The ADHD group was sub-divided into those individuals with two copies of the “high-risk” 10-repeat allele (high-risk DAT1) versus those with one or no copies of this allele (low-risk DAT1). The high-risk DAT1 ADHD group displayed greater response variability on the SART than either the low-risk DAT1 group or healthy controls, whereas the latter two groups did not differ. Further, the high-risk DAT1 group showed an attenuated spatial asymmetry, relative to the low-risk DAT1 ADHD group, who showed the typical leftward attentional asymmetry. Our results suggest that the 10-repeat DAT1 allele may mediate neuropsychological impairment in ADHD. The application of molecular genetics may help to define neuropsychological impaired subgroups of ADHD. [Copyright &y& Elsevier]