Gordon Evan M, Devaney Joseph M, Bean Stephanie, Vaidya Chandan J
Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20310, USA.
Cereb Cortex. 2015 Feb;25(2):336-45. doi: 10.1093/cercor/bht229. Epub 2013 Aug 22.
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.
纹状体多巴胺（DA）信号的个体差异既与健康个体执行功能的个体差异有关，也与由执行功能障碍定义的精神疾病风险有关。我们对50名健康成年人进行静息态功能连接研究，以检验调节纹状体DA功能的多巴胺转运体基因（DAT1）的多态性是否影响健康成年人的纹状体功能连接，以及这种连接是否能预测执行功能。我们发现，与10/10纯合子相比，被认为具有较高纹状体DA信号的9/10杂合子在背侧尾状核（DC）与岛叶、背侧前扣带回和背外侧前额叶区域之间，以及腹侧纹状体与腹外侧前额叶皮层之间表现出更强的连接。在所有受试者中，更强的以DC为种子点的连接预示着更好的N-回溯工作记忆表现，而更强的以腹侧纹状体为种子点的连接预示着日常生活中冲动性的降低。此外，中介分析表明连接强度介导了DAT1基因型与行为之间的关系。这些发现表明，静息态纹状体-额叶连接可能是健康个体执行功能的一种内表型。
