Department of Psychology, Biological Psychology, University of Cologne, Cologne 50969, Germany
Department of Systems Neuroscience, University-Medical-Center Hamburg-Eppendorf, Hamburg 20246, Germany.
J Neurosci. 2020 Oct 7;40(41):7936-7948. doi: 10.1523/JNEUROSCI.0592-20.2020. Epub 2020 Sep 18.
The neurotransmitter dopamine is implicated in diverse functions, including reward processing, reinforcement learning, and cognitive control. The tendency to discount future rewards over time has long been discussed in the context of potential dopaminergic modulation. Here we examined the effect of a single dose of the D2 receptor antagonist haloperidol (2 mg) on temporal discounting in healthy female and male human participants. Our approach extends previous pharmacological studies in two ways. First, we applied combined temporal discounting drift diffusion models to examine choice dynamics. Second, we examined dopaminergic modulation of reward magnitude effects on temporal discounting. Hierarchical Bayesian parameter estimation revealed that the data were best accounted for by a temporal discounting drift diffusion model with nonlinear trialwise drift rate scaling. This model showed good parameter recovery, and posterior predictive checks revealed that it accurately reproduced the relationship between decision conflict and response times in individual participants. We observed reduced temporal discounting and substantially faster nondecision times under haloperidol compared with placebo. Discounting was steeper for low versus high reward magnitudes, but this effect was largely unaffected by haloperidol. Results were corroborated by model-free analyses and modeling via more standard approaches. We previously reported elevated caudate activation under haloperidol in this sample of participants, supporting the idea that haloperidol elevated dopamine neurotransmission (e.g., by blocking inhibitory feedback via presynaptic D2 auto-receptors). The present results reveal that this is associated with an augmentation of both lower-level (nondecision time) and higher-level (temporal discounting) components of the decision process. Dopamine is implicated in reward processing, reinforcement learning, and cognitive control. Here we examined the effects of a single dose of the D2 receptor antagonist haloperidol on temporal discounting and choice dynamics during the decision process. We extend previous studies by applying computational modeling using the drift diffusion model, which revealed that haloperidol reduced the nondecision time and reduced impulsive choice compared with placebo. These findings are compatible with a haloperidol-induced increase in striatal dopamine (e.g., because of a presynaptic mechanism). Our data provide novel insights into the contributions of dopamine to value-based decision-making and highlight how comprehensive model-based analyses using sequential sampling models can inform the effects of pharmacological modulation on choice processes.
神经递质多巴胺与多种功能有关，包括奖励处理、强化学习和认知控制。长期以来，人们一直在讨论随着时间的推移，未来奖励的折扣倾向可能与多巴胺能调节有关。在这里，我们研究了单剂量 D2 受体拮抗剂氟哌啶醇（2 毫克）对健康女性和男性人类参与者的时间折扣的影响。我们的方法在两个方面扩展了以前的药理学研究。首先，我们应用结合时间折扣漂移扩散模型来检查选择动态。其次，我们研究了多巴胺能对奖励幅度对时间折扣的调节作用。分层贝叶斯参数估计表明，数据最好由一个具有非线性试验漂移率缩放的时间折扣漂移扩散模型来解释。该模型具有良好的参数恢复能力，后验预测检查表明，它准确地再现了个体参与者决策冲突与反应时间之间的关系。与安慰剂相比，氟哌啶醇下的时间折扣减少，非决策时间大大加快。对于低奖励和高奖励幅度，折扣更陡峭，但这种效果在很大程度上不受氟哌啶醇的影响。结果通过无模型分析和通过更标准的方法进行建模得到了证实。我们之前在这个参与者样本中报告了氟哌啶醇下尾状核的激活升高，支持氟哌啶醇升高多巴胺神经传递的想法（例如，通过阻断突触前 D2 自身受体的抑制性反馈）。本研究结果揭示，这与决策过程中较低水平（非决策时间）和较高水平（时间折扣）成分的增强有关。多巴胺与奖励处理、强化学习和认知控制有关。在这里，我们研究了单剂量 D2 受体拮抗剂氟哌啶醇对时间折扣和决策过程中选择动态的影响。我们通过应用漂移扩散模型的计算建模来扩展以前的研究，该模型揭示了氟哌啶醇与安慰剂相比降低了非决策时间并减少了冲动选择。这些发现与氟哌啶醇引起的纹状体多巴胺增加（例如，由于突触前机制）一致。我们的数据为多巴胺对基于价值的决策的贡献提供了新的见解，并强调了使用序列采样模型的综合基于模型的分析如何为药物调节对选择过程的影响提供信息。
