Haas School of Business and Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720;Department of Economics, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
Haas School of Business and Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720;
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9615-20. doi: 10.1073/pnas.1316259111. Epub 2014 Jun 16.
Game theory describes strategic interactions where success of players' actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance--catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase--modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function--dopamine transporter and D2 receptors--was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.
博弈论描述了策略性互动，其中参与者的成功取决于其他合作者的行动。在人类中，在刻画介导这种行为的多巴胺能和额纹状体机制的神经水平上已经取得了很大进展。在这里，我们将策略性学习的计算建模与通路方法相结合，以刻画策略性行为与多巴胺通路变化之间的关联。具体来说，我们使用基因集分析，系统地研究了不同的多巴胺基因对多策略竞争游戏变化的贡献，该游戏由(i)参与者预期和对他人行为做出反应的程度（信念学习）和(ii) 发生这种适应的速度（学习率）来捕捉。我们发现，主要调节前额叶多巴胺清除的基因——儿茶酚-O-甲基转移酶（COMT）和两种单胺氧化酶同工型——的变异调节了个体之间的信念学习程度。相比之下，我们没有发现多巴胺通路中其他基因的显著关联。此外，主要调节纹状体多巴胺功能的基因——多巴胺转运体和 D2 受体——的变异与学习率显著相关。我们发现 COMT 也是如此，但多巴胺能基因则不然。这些发现共同强调了额纹状体系统在策略性学习中的分离作用，并支持了这样一种观点，即沿着特定途径组织的遗传变异是复杂表型（如策略性行为）变化的重要来源。
