Nicotinic Receptor Gene CHRNA4 Interacts with Processing Load in Attention

BACKGROUND Pharmacological studies suggest that cholinergic neurotransmission mediates increases in attentional effort in response to high processing load during attention demanding tasks [1]. METHODOLOGY/PRINCIPAL FINDINGS In the present study we tested whether individual variation in CHRNA4, a gene coding for a subcomponent in α4β2 nicotinic receptors in the human brain, interacted with processing load in multiple-object tracking (MOT) and visual search (VS). We hypothesized that the impact of genotype would increase with greater processing load in the MOT task. Similarly, we predicted that genotype would influence performance under high but not low load in the VS task. Two hundred and two healthy persons (age range  =  39-77, Mean  =  57.5, SD  =  9.4) performed the MOT task in which twelve identical circular objects moved about the display in an independent and unpredictable manner. Two to six objects were designated as targets and the remaining objects were distracters. The same observers also performed a visual search for a target letter (i.e. X or Z) presented together with five non-targets while ignoring centrally presented distracters (i.e. X, Z, or L). Targets differed from non-targets by a unique feature in the low load condition, whereas they shared features in the high load condition. CHRNA4 genotype interacted with processing load in both tasks. Homozygotes for the T allele (N  =  62) had better tracking capacity in the MOT task and identified targets faster in the high load trials of the VS task. CONCLUSION The results support the hypothesis that the cholinergic system modulates attentional effort, and that common genetic variation can be used to study the molecular biology of cognition.