Genetic and electrophysiological mechanisms of visuospatial attention bias in attention-deficit/hyperactivity disorder

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood with negative lifetime outcomes. Although subjective ratings of attention problems are diagnostic for the disorder, an objective attention deficit has proven hard to isolate. An emerging body of work suggests that a reliable attentional phenotype in ADHD is a subtle, “neglect-like” performance deficit for stimuli presented in the left hemifield. In comparison, healthy subjects tend to exhibit a subtle bias or asymmetry of visual attention favouring left space, termed ‘pseudoneglect’, that is thought to arise from right hemisphere lateralised attention processing in neurotypical individuals. An absence or reversal of the left hemifield advantage appears to mark neurological vulnerability across a number of disorders of attention, including ADHD. Previous research has found associations between spatial attention biases, asymmetries in hemispheric dominance for EEG markers, and genetic variants in genes associated with attentional systems such as the gene encoding the dopamine transporter (DAT1). However, no studies to date have examined the implications of these factors in combination in an ADHD sample. As such, the current study aims to understand the electrophysiological and genetic substrates of visuospatial attention in children with ADHD in comparison to typically developing controls. In addition to the collection of a saliva sample for genotyping, EEG was recorded from 22 children diagnosed with ADHD and 29 typically developing control children while they performed a visuospatial attention task. Behavioural data confirmed the existence of a significant leftward advantage for target detection in typically developing children that is consistent with pseudoneglect. This RT advantage for left targets was lost in ADHD subjects and tended to be reversed, favouring target detections in the right hemifield. EEG analysis confirmed the existence of group differences in the N2pc-like component that differed as a function of hemisphere and, across all subjects, a relationship between hemispheric asymmetry in pre-target alpha power and RT asymmetry was observed. Evidence for an earlier onset decision-making signal in ADHD and control participants was observed for right and left hemifield targets, respectively. Further, there was a significant relationship across all participants in the expected direction between the onset asymmetry of this decision variable and RT asymmetry. Although no differences in electrophysiological measures or RT asymmetry were found between the two DAT1 groups, there was a significant difference between the genotype groups in ADHD symptom scores irrespective of ADHD diagnosis, and also reading ability such that participants in the high-risk DAT1 group tended to have more severe ADHD symptomatology and poorer reading ability. The results of this study provide some of the first evidence for abnormal hemispheric activation patterns and perceptual decision-making processes in ADHD during the performance of a visuospatial task. These findings advance the knowledge in the field of ADHD towards the identification of objective biomarkers for the disorder that may aid clinical decision-making and result in more reliable diagnosis and treatment.