Schweighofer Nicolas, Bertin Mathieu, Shishida Kazuhiro, Okamoto Yasumasa, Tanaka Saori C, Yamawaki Shigeto, Doya Kenji
Department of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90089, USA.
J Neurosci. 2008 Apr 23;28(17):4528-32. doi: 10.1523/JNEUROSCI.4982-07.2008.
Previous animal experiments have shown that serotonin is involved in the control of impulsive choice, as characterized by high preference for small immediate rewards over larger delayed rewards. Previous human studies under serotonin manipulation, however, have been either inconclusive on the effect on impulsivity or have shown an effect in the speed of action-reward learning or the optimality of action choice. Here, we manipulated central serotonergic levels of healthy volunteers by dietary tryptophan depletion and loading. Subjects performed a "dynamic" delayed reward choice task that required a continuous update of the reward value estimates to maximize total gain. By using a computational model of delayed reward choice learning, we estimated the parameters governing the subjects' reward choices in low-, normal, and high-serotonin conditions. We found an increase of proportion in small reward choices, together with an increase in the rate of discounting of delayed rewards in the low-serotonin condition compared with the control and high-serotonin conditions. There were no significant differences between conditions in the speed of learning of the estimated delayed reward values or in the variability of reward choice. Therefore, in line with previous animal experiments, our results show that low-serotonin levels steepen delayed reward discounting in humans. The combined results of our previous and current studies suggest that serotonin may adjust the rate of delayed reward discounting via the modulation of specific loops in parallel corticobasal ganglia circuits.
先前的动物实验表明,血清素参与了冲动选择的控制,其特征是相较于更大的延迟奖励,对小的即时奖励有更高的偏好。然而,先前关于血清素操纵的人体研究,要么对冲动性的影响尚无定论,要么显示出对行动-奖励学习速度或行动选择最优性有影响。在此,我们通过饮食中色氨酸的消耗和补充来操纵健康志愿者的中枢血清素水平。受试者执行一项“动态”延迟奖励选择任务,该任务要求持续更新奖励价值估计以最大化总收益。通过使用延迟奖励选择学习的计算模型,我们估计了在低血清素、正常血清素和高血清素条件下控制受试者奖励选择的参数。我们发现,与对照和高血清素条件相比,在低血清素条件下,小奖励选择的比例增加,同时延迟奖励的折扣率也增加。在估计的延迟奖励价值的学习速度或奖励选择的变异性方面,各条件之间没有显著差异。因此,与先前的动物实验一致,我们的结果表明低血清素水平会使人类的延迟奖励折扣变陡。我们先前和当前研究的综合结果表明,血清素可能通过调节平行皮质基底神经节回路中的特定环路来调整延迟奖励折扣率。