Dopamine transporter genotype is associated with a lateralized resistance to distraction during attention selection

Although lateral asymmetries in orienting behavior are evident across species and have been linked to interhemispheric asymmetries in dopamine signaling, the relative contribution of attentional versus motoric processes remains unclear. Here we took a cognitive genetic approach to adjudicate between roles for dopamine in attentional versus response selection. A sample of nonclinical adult humans (N = 518) performed three cognitive tasks (spatial attentional competition, spatial cueing, and flanker tasks) that varied in the degree to which they required participants to resolve attentional or response competition. All participants were genotyped for two putatively functional tandem repeat polymorphisms of the dopamine transporter gene (DAT1; SLC6A3), which are argued to influence the level of available synaptic dopamine and confer risk to disorders of inattention. DAT1 genotype modulated the task-specific effects of the various task-irrelevant stimuli across both the spatial competition and spatial cueing but not flanker tasks. Specifically, compared with individuals carrying one or two copies of the 10-repeat DAT1 allele, individuals without this allele demonstrated an immunity to distraction, such that response times were unaffected by increases in the number of distractor stimuli, particularly when these were presented predominantly in the left hemifield. All three genotype groups exhibited uniform costs of resolving leftward response selection in a standard flanker task. None of these significant effects could be explained by speed–accuracy trade-offs, suggesting that participants without the 10-repeat allele of the DAT1 tandem repeat polymorphism possess an enhanced attentional ability to suppress task-irrelevant stimuli in the left hemifield

Theta power is reduced in healthy cognitive aging

The effects of healthy cognitive aging on electroencephalographic (EEG) theta (4.9-6.8 Hz) power were examined during performance of a modified Stemberg, S., 1966. High-speed scanning in human memory. Science 153, 652-654.) word recognition task. In a sample of fourteen young (mean age 21.9 years, range = 18-27) and fourteen older (mean age 68.4 years, range = 60-80) participants, theta power was foundto be significantly lower in older adults during both the retention and recognition intervals. This theta power difference was greatest at the fronto-central midline electrode and occurred in parallel with a small, non-significant decrease in recognition accuracy in the older sample. A significant decrease in older adults' mean theta power was also observed in resting EEG, however, it was of substantially smaller magnitude than the task-related theta difference. It is proposed that a neurophysiological measure(s), such as task-specific frontal midline theta (W) power, may be a more sensitive marker of cognitive aging than task performance measures. Furthermore, as recent research indicates that W is generated primarily in the anterior cingulate cortex, the current findings support evidence that the function of brain networks incorporating this structure may be affected in cognitive aging. (C) 2007 Elsevier B.V. All rights reserved

Theta oscillations are affected by amnestic mild cognitive impairment and cognitive load

Amnestic mild cognitive impairment (aMCI) is classified primarily via substantial episodic memory deficits in the absence of a dementia diagnosis. To investigate the potential neurophysiological correlates of such deficits we compared QEEG power between 12 participants with aMCI and 12 healthy matched controls. EEG was acquired during performance of a modified Sternberg word recognition task with low and high memory load conditions. While recognition accuracy of aMCI participants was lower than that of controls, this difference was not significant. Nevertheless the aMCI group demonstrated significantly lower theta power at a number of electrode sites and significant correlations were observed between power at these sites and neuropsychological assessment scores. Furthermore in the aMCI sample only, theta power was significantly lower under high versus low memory load. Given current interpretations of the neural generator(s), as well as the role(s), of theta oscillations in cognitive processes, the present data indicate that aMCI may be associated with disruptions in the operation of neurocognitive networks (e.g., MTL-neocortical), particularly under high cognitive load. (C) 2008 Elsevier B.V. All rights reserved

Transcranial magnetic stimulation as a tool for understanding neurophysiology in Huntington's disease: a review.

Structural and functional magnetic resonance imaging modalities have been critical in advancing our understanding of the neuroanatomical and pathophysiological changes that emerge during the premanifest and symptomatic stages of Huntington's disease (HD). However, the relationship between underlying neuropathology and the motor, cognitive and behavioural changes associated with the disorder still remain poorly understood. Less conventional technologies, such as transcranial magnetic stimulation (TMS) and electroencephalography (EEG), provide a unique opportunity to further investigate the causal relationships between targeted neural circuits and objective neurophysiological responses together with overt behaviours. In this review, we discuss previous successful applications of TMS in other neurological disorders and its prospective use in HD. We also address the added value of multimodal TMS techniques, such as TMS-EEG, in investigating the integrity of neural networks in non-motor regions in HD. We conclude that neurophysiological outcome measures are likely to contribute towards characterising further the trajectory of decline across functional domains in HD, enhance understanding of underlying neural mechanisms, and offer new avenues for elucidating sensitive endophenotypic biomarkers of disease progression

Norepinephrine transporter –3081(A/T) and alpha-2A-adrenergic receptor MspI polymorphisms are associated with cardiovascular side effects of OROSmethylphenidate treatment

The purpose of this study was to investigate a possible association between norepinephrine genes and cardiovascular side effects of the Osmotic Controlled-Release Oral Delivery System–methylphenidate (OROS-MPH) in Korean children with attention-deficit/hyperactivity disorder (ADHD). One hundred and one children with ADHD (8.71.7 years) were recruited from child psychiatric centers at six university hospitals in South Korea. All participants were drug-naive ADHD children treated with OROS-MPH for 12 weeks. During the treatment period the investigators titrated the OROS-MPH dosage on the basis of symptom severity and side effects. Resting heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were examined before and after treatment. The percentage change score (post-treatment – pretreatment/pretreatment100) of each parameter was calculated. Genotyping of SLC6A2 –3081(A/T) and G1287A, and alpha-2A-adrenergic receptor (ADRA2A) MspI and DraI polymorphisms was performed. Clinically significant changes were not found in cardiovascular monitoring during the course of treatment. An increase of HR after OROS-MPH treatment was found to be statistically significant (t¼3.54, p¼0.001). Changes in SBP and DBP were not significant and no specific change was found in the ECGs. However, an additive regression analysis demonstrated a significant association between SLC6A2 –3081(A/T) and percentage change in HR post-treatment (p¼0.01) after controlling for age, gender, dosage of MPH and response and baseline pulse rate. Children with ADHD having the T/T genotype of SLC6A2 showed a 12.5% increase in HR compared to baseline, whereas children with the A/T or A/A genotype showed a 3.5% and 2.5% increase after OROS-MPH treatment, respectively. There was also a significant association between the ADRA2A MspI genotype and percentage change of DBP post-treatment after controlling for age, gender, dosage of MPH and response and baseline DBP (p¼0.009). Children with ADHD having the C/C genotype of ADRA2A MspI showed an 18.5% increase in DBP compared to baseline, but children with the G/G or G/C genotype showed a 0.2% decrease after OROS-MPH treatment. The overall cardiovascular effects of OROS-MPH were modest. However, our findings show a positive association between norepinephrine-related gene polymorphisms and cardiovascular response induced by MPH in Korean children with ADHD. Consideration must be given to such children or adults with specific norepinephrine-related genotypes, especially if they show significant changes in HR or DBP after OROS-MPH administration

BRIEF REPORT Attentional asymmetries in a visual orienting task are related to temperament

Spatial asymmetries are an intriguing feature of directed attention. Recent observations indicate an influence of temperament upon the direction of these asymmetries. It is unknown whether this influence generalises to visual orienting behaviour. The aim of the current study was therefore to explore the relationship between temperament and measures of spatial orienting as a function of target hemifield. An exogenous cueing task was administered to 92 healthy participants. Temperament was assessed using Carver and White's (1994) Behavioural Inhibition System and Behavioural Activation System (BIS/BAS) scales. Individuals with high sensitivity to punishment and low sensitivity to reward showed a leftward asymmetry of directed attention when there was no informative spatial cue provided. This asymmetry was not present when targets were preceded by spatial cues that were either valid or invalid. The findings support the notion that individual variations in temperament influence spatial asymmetries in visual orienting, but only when lateral targets are preceded by a non-directional (neutral) cue. The results are discussed in terms of hemispheric asymmetries and dopamine activity

Attentional asymmetries in a visual orienting task are related to temperament

Spatial asymmetries are an intriguing feature of directed attention. Recent observations indicate an influence of temperament upon the direction of these asymmetries. It is unknown whether this influence generalises to visual orienting behaviour. The aim of the current study was therefore to explore the relationship between temperament and measures of spatial orienting as a function of target hemifield. An exogenous cueing task was administered to 92 healthy participants. Temperament was assessed using Carver and White's (1994) Behavioural Inhibition System and Behavioural Activation System (BIS/BAS) scales. Individuals with high sensitivity to punishment and low sensitivity to reward showed a leftward asymmetry of directed attention when there was no informative spatial cue provided. This asymmetry was not present when targets were preceded by spatial cues that were either valid or invalid. The findings support the notion that individual variations in temperament influence spatial asymmetries in visual orienting, but only when lateral targets are preceded by a non-directional (neutral) cue. The results are discussed in terms of hemispheric asymmetries and dopamine activity

Allelic variation in dopamine D2 receptor gene is associated with attentional impulsiveness on the Barratt Impulsiveness Scale (BIS-11)

Objectives: Previous studies have postulated that noradrenergic and/or dopaminergic gene variations are likely to underlie individual differences in impulsiveness, however, few have shown this. The current study examined the relationship between catecholamine gene variants and self-reported impulsivity, as measured by the Barratt Impulsiveness Scale (Version 11; BIS-11) Methods: Six hundred and seventy-seven non-clinical adults completed the Barratt Impulsiveness Scale (BIS-11). DNA was analysed for a set of 142 single-nucleotide polymorphisms (SNPs) across 20 autosomal catecholamine genes. Association was tested using an additive regression model with permutation testing used to control for the influence of multiple comparison. Results: Analysis revealed an influence of rs4245146 of the dopamine D2 receptor (DRD2) gene on the BIS-11 attention first-order factor, such that self-reported attentional impulsiveness increased in an additive fashion with each copy of the T allele. Conclusions: These findings provide preliminary evidence that allelic variation in DRD2 may influence impulsiveness by increasing the propensity for attentional lapses