Dopamine, Corticostriatal Connectivity, and Intertemporal Choice
Dopamine, Corticostriatal Connectivity, and Intertemporal Choice
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DOI：
10.1523/jneurosci.1180-12.2012
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发表时间：
2012-07-04
影响因子：
5.3
通讯作者：
Fields, Howard L.
中科院分区：
文献类型：
--
作者：
Kayser, Andrew S.;Allen, Daicia C.;Fields, Howard L.
基于价值观的决策可以优化行为结果。因为延迟的奖励会被打折扣，所以选择较小的即时奖励的倾向会导致次优选择。延迟奖励的急剧折扣（冲动性）是额叶损伤和行为障碍（包括药物滥用）的特征。相应地，动物研究和人类的间接证据表明，额叶皮质中多巴胺的降低通过损害皮质纹状体功能而导致更陡峭的折扣。为了直接检验这一假设，我们进行了一项随机、双盲、平衡、安慰剂对照研究，在该研究中，我们向执行延迟折扣任务的健康受试者给予脑渗透剂儿茶酚-O-甲基转移酶抑制剂托卡朋或安慰剂。托卡朋显着增加延迟金钱奖励的选择，这种托卡朋诱导的增加与左腹侧壳核和前丘脑中BOLD活性增加共变。托卡朋也改变了皮质纹状体的连接：特别是，通过诱导腹侧壳核和前膝扣带皮层之间的连贯性减少。这些结果表明，提高皮质多巴胺水平减弱冲动的选择，通过改变皮质纹状体功能。
Value-based decisions optimize behavioral outcomes. Because delayed rewards are discounted, an increased tendency to choose smaller, immediate rewards can lead to suboptimal choice. Steep discounting of delayed rewards (impulsivity) characterizes subjects with frontal lobe damage and behavioral disorders including substance abuse. Correspondingly, animal studies and indirect evidence in humans suggest that lower dopamine in the frontal cortex contributes to steeper discounting by impairing corticostriatal function. To test this hypothesis directly, we performed a randomized, double-blind, counterbalanced, placebo-controlled study in which we administered the brain penetrant catechol-O-methyltransferase inhibitor tolcapone or placebo to healthy subjects performing a delay discounting task. Tolcapone significantly increased choice of delayed monetary rewards, and this tolcapone-induced increase covaried with increased BOLD activity in the left ventral putamen and anterior insula. Tolcapone also changed corticostriatal connectivity: specifically, by inducing a decrease in the coherence between ventral putamen and pregenual cingulate cortex. These results indicate that raising cortical dopamine levels attenuates impulsive choice by changing corticostriatal function.