title: Resting-state striato-frontal functional connectivity is sensitive to DAT1 genotype and predicts executive function.
abstract: Individual differences in striatal dopamine (DA) signaling have been associated both with individual differences in executive function in healthy individuals and with risk for psychiatric disorders defined by executive dysfunction. We used resting-state functional connectivity in 50 healthy adults to examine whether a polymorphism of the dopamine transporter gene (DAT1), which regulates striatal DA function, affects striatal functional connectivity in healthy adults, and whether that connectivity predicts executive function. We found that 9/10 heterozygotes, who are believed to have higher striatal DA signaling, demonstrated stronger connectivity between dorsal caudate (DC) and insular, dorsal anterior cingulate, and dorsolateral prefrontal regions, as well as between ventral striatum and ventrolateral prefrontal cortex, than 10/10 homozygotes. Across subjects, stronger DC-seeded connectivity predicted superior N-back working memory performance, while stronger ventral striatum-seeded connectivity predicted reduced impulsivity in everyday life. Further, mediation analysis suggested that connectivity strength mediated relationships between DAT1 genotype and behavior. These findings suggest that resting-state striato-frontal connectivity may be an endophenotype for executive function in healthy individuals.
authors: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
authors: Evan M
authors: EM
authors: Gordon
authors: Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20310, USA.
authors: Joseph M
authors: JM
authors: Devaney
authors: Department of Psychology, Georgetown University, Washington, DC 20057, USA and.
authors: Stephanie
authors: S
authors: Bean
authors: Department of Psychology, Georgetown University, Washington, DC 20057, USA and Children's Research Institute, Children's National Medical Center, Washington, DC 20310, USA.
authors: Chandan J
authors: CJ
authors: Vaidya
mesh_terms: D001931:Brain Mapping; D003342:Corpus Striatum / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D056344:Executive Function; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D007175:Impulsive Behavior; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009434:Neural Pathways / Q000502:physiology; D011110:Polymorphism, Genetic; D011581:Psychological Tests; D012146:Rest; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
keywords: DAT1; fMRI; functional connectivity; impulsivity; working memory
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