Neuroimaging and Genetics Studies of the Role of Right Prefrontal Cortex in Controlled Attention.

[摘要] Maintaining goal-relevant behavior requires controlled attention, especially when attention is challenged by distraction. Deficits in controlled attention are characteristic of a number of disorders, including schizophrenia. Here I present three studies investigating the human neural correlates of successful attentional control, specifically those associated with stabilizing performance during distractor challenge. To optimize the translational potential of this work, the present studies used the Sustained Attention Task (SAT) and its distractor condition (dSAT) which has been validated for use in both humans and rodent models, and has been identified as a promising tool for understanding attention deficits in schizophrenia (Luck et al., 2012). The first study, using BOLD fMRI, found that a region in right inferior frontal gyrus approximating Broadmann’s Area (BA) 9 showed increased activation in response to the distractor. This right mid-dorsal/dorsolateral prefrontal cortex region is part of the frontoparietal cognitive control network, and multivariate analyses charting its functional connections to other regions revealed that increases in connectivity between BA 9 and posterior parietal cortex were associated with successful behavioral resistance to distraction. A second study using electrophysiological methods complemented these findings by showing a similar correlation between increases in theta phase-locking during distractor challenge and optimal performance. Finally, the third study used genetic variation to probe the role of the cholinergic system, which rodent studies employing SAT and dSAT suggest is critical for attention. Specifically, in rodents, the maintenance of performance during distraction is associated with increases in acetylcholine in right prefrontal cortex. Consistent with rodent findings, the present work in humans suggested a role of acetylcholine in distractor-related activation increases in right BA 9. Participants with a genetic polymorphism thought to limit cholinergic release capacity showed diminished distractor-evoked right BA 9 activation increases. Together, these findings further specify the neural correlates of controlled attention in humans, and take the first steps in linking these measures to the human cholinergic system. The ultimate goal of this research is to capitalize on the strengths of both human-based and animal model-based investigations of attention to contribute to the identification of therapeutic targets to treat deficits where they may exist.

[发布机构] University of Michigan

[效力级别] Science (General)

[关键词] Attention;Science (General);Science;Neuroscience