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The nicotinic system plays an important role in cognitive control and is implicated in several neuropsychiatric conditions. However, the contributions of genetic variability in this system to individuals' cognitive control abilities are poorly understood and the brain processes that mediate such genetic contributions remain largely unidentified. In this first large-scale neuroimaging genetics study of the human nicotinic receptor system (two cohorts, males and females, fMRI total= 1586, behavioral total= 3650), we investigated a common polymorphism of the high-affinity nicotinic receptor α4β2 (rs1044396 on thegene) previously implicated in behavioral and nicotine-related studies (albeit with inconsistent major/minor allele impacts).
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The complex processing architecture underlying attentional control requires delineation of the functional role of different control-related brain networks. A key component is the cingulo-opercular (CO) network composed of anterior insula/operculum, dorsal anterior cingulate cortex, and thalamus. Its function has been particularly difficult to characterize due to the network's pervasive activity and frequent co-activation with other control-related networks.

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Multiple-demand (MD) regions of the human brain show coactivation during many different kinds of task performance. Previous work based on resting-state functional magnetic resonance imaging (fMRI) has shown that MD regions may be divided into two closely coupled subnetworks centered around the lateral frontoparietal (FP) and cingulo-opercular cortex. Here, we used on-task fMRI to test whether this division is apparent during the performance of an executive task.

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Drawing on converging behavioral, electrophysiological, and imaging evidence, we advance an hypothesis for a cognitive phenotype of a SNP in the CHRNA4 gene encoding the α(4) subunit of α(4)β(2) nicotinic receptors. First, we review evidence that visuospatial attention can be decomposed into several component processes. Secondly, we consider evidence that one component, redirection of attention, is modulated by the nicotinic cholinergic system.

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Recognizing speech in difficult listening conditions requires considerable focus of attention that is often demonstrated by elevated activity in putative attention systems, including the cingulo-opercular network. We tested the prediction that elevated cingulo-opercular activity provides word-recognition benefit on a subsequent trial. Eighteen healthy, normal-hearing adults (10 females; aged 20-38 years) performed word recognition (120 trials) in multi-talker babble at +3 and +10 dB signal-to-noise ratios during a sparse sampling functional magnetic resonance imaging (fMRI) experiment.

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