DOPAMINE-REGULATING GENES, EXECUTIVE CONTROL, AND THE NETWORK STRUCTURE OF THE HUMAN BRAIN
Gordon, Evan Moss
Vaidya, Chandan J
Executive control processes, including working memory (WM), attention, and impulse control, rely on brain networks centered in the prefrontal cortex, and especially on dopaminergic signaling in these networks. The function of networks supporting executive processes may thus depend on genetic factors which influence dopaminergic signaling, such as polymorphisms in the dopamine transporter (DAT1) gene. To investigate this possibility, this dissertation describes four studies conducted using functional connectivity magnetic resonance imaging (fcMRI) to examine relationships between WM function, connectivity, DAT1 genotype, and other executive processes. The first study bridges the gap between studies of brain activation during WM and studies of network function at rest. This study demonstrated that networks delineated at rest were the same networks activated during WM, and that the degree of network activation predicted WM accuracy and reaction time. The second study investigated how these networks were persistently altered during WM performance. Results indicated that WM altered functional connectivity within the Task-positive network engaged by the task, as well as between this network and the Default network suppressed by the task. Further, altered connectivities persisted after task completion, suggesting a post-task period of recovery from cognitive effort, and this recovery period obscured relationships between Default connectivity and trait-level inattentiveness. The third study investigated how DAT1 genotype affected functional connectivities between striatum and the prefrontal cortex at rest. Results indicated that individuals with one copy of the 9-repeat allele (9/10) had stronger connectivity between caudate and a cingulo-opercular network than those homozygous for the 10-repeat allele (10/10), and that these connectivity differences predicted WM ability and trait-level impulsivity. The fourth study investigated how DAT1 genotype affected functional connectivities between Task-positive and Default networks, both at rest and during WM performance. Results indicated that 9/10 individuals had more negative connectivities between Default and Task-positive networks during WM, but not at rest, and that the differences between resting and WM connectivities predicted
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Breeden, Andrew (Georgetown University, 2016)Executive control, the goal directed deployment of cognitive resources, depends critically on a class of neurotransmitters called catecholamines. One such catecholamine, norepinephrine, is theorized to facilitate cognition ...