Genetic variation in nicotinic receptors affects brain networks involved in reorienting attention

Prior evidence suggests that a genetic variation in nicotinic receptors modulates visuospatial attention in humans. Brain areas contributing to this modulation are largely unknown. Here we investigate the influence of the nicotinic receptor gene CHRNA4 (rs 1044396) on brain networks involved in detecting unattended events. Subjects were genotyped and studied with functional magnetic resonance imaging while performing a cued target detection task with valid, neutral and invalid trials. Two brain areas within a core region of the attention network, the right temporoparietal junction, showed a genotype dependent modulation. CHRNA4 C/C homozygotes showed differentially higher neural activity in the right middle temporal gyrus when reorienting attention was required in invalid trials. In contrast, T/T homozygotes had stronger activations within the right superior temporal gyrus. An analysis of functional connectivity further revealed that these temporoparietal regions have a distinct connectivity pattern. The superior temporal gyrus recruited by T/T homozygotes shows stronger connections to temporal and parietal brain regions, which are primarily involved in shifting attention, independent of stimulus frequency. In contrast, the middle temporal gyrus exhibits stronger connections to the caudate nucleus, which is involved in detecting violations of expectations. These findings suggest that, depending on genotype, detection of stimuli outside the focus of attention is more driven by reorienting or by expectation signals.