Sex Differences and Exogenous Estrogen Influence Learning and Brain Responses to Prediction Errors.
Sex Differences and Exogenous Estrogen Influence Learning and Brain Responses to Prediction Errors.
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DOI：
10.1093/cercor/bhab334
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发表时间：
2021-10
期刊：
影响因子：
3.7
通讯作者：
Gina Joue;Karima Chakroun;J. Bayer;J. Gläscher;Lei Zhang;J. Fuss;N. Hennies;T. Sommer
中科院分区：
文献类型：
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作者：
Gina Joue;Karima Chakroun;J. Bayer;J. Gläscher;Lei Zhang;J. Fuss;N. Hennies;T. Sommer
动物研究表明，在中皮质边缘多巴胺能(DA)通路中存在显著的性别差异以及雌激素(E2)的影响，DA通路在奖赏加工和强化学习中起关键作用，也与药物成瘾有关。在这项计算药理学功能磁共振研究中，我们研究了性别和雌激素两个因素对人类强化学习和多巴胺能系统的影响：67名男性和自然骑自行车的女性志愿者，后者处于低激素阶段，被随机分成两组，分别服用E2或安慰剂。他们在核磁共振扫描仪中完成了一项强化学习任务，我们之前已经显示，与奖励预测误差(RPE)相关的活动是多巴胺能的。我们发现，与男性相比，女性与RPE相关的大脑活动增强，而且在更大程度上，当雌二醇水平在两性中升高时。然而，两个因素，女性性别和雌激素，都减缓了对RPE的适应(较小的学习速度)。这种较大的RPE相关活动和较小的学习速率的差异可以用组织性别差异和循环E2的激活效应来解释，这两者对DA释放的影响与DA受体结合能力不同。
Animal studies show marked sex differences as well as effects of estrogen (E2) in the mesocorticolimbic dopaminergic (DA) pathways, which play a critical role in reward processing and reinforcement learning and are also implicated in drug addiction. In this computational pharmacological fMRI study, we investigate the effects of both factors, sex and estrogen, on reinforcement learning and the dopaminergic system in humans; 67 male and 64 naturally cycling female volunteers, the latter in their low-hormone phase, were randomly assigned, double-blind, to take E2 or placebo. They completed a reinforcement learning task in the MRI scanner for which we have previously shown reward prediction error (RPE)-related activity to be dopaminergic. We found RPE-related brain activity to be enhanced in women compared with men and to a greater extent when E2 levels were elevated in both sexes. However, both factors, female sex and E2, slowed adaptation to RPEs (smaller learning rate). This discrepancy of larger RPE-related activity yet smaller learning rates can be explained by organizational sex differences and activational effects of circulating E2, which both affect DA release differently to DA receptor binding capacities.