The ability to represent and respond to uncertainty is fundamental to human cognition and decision-making. Noradrenaline (NA) is hypothesized to play a key role in coordinating the sensory, learning, and physiological states necessary to adapt to a changing world, but direct evidence for this is lacking in humans. Here, we tested the effects of attenuating noradrenergic neurotransmission on learning under uncertainty. We probed the effects of the β-adrenergic receptor antagonist propranolol (40 mg) using a between-subjects, double-blind, placebo-controlled design. Participants performed a probabilistic associative learning task, and we employed a hierarchical learning model to formally quantify prediction errors about cue-outcome contingencies and changes in these associations over time (volatility). Both unexpectedness and noise slowed down reaction times, but propranolol augmented the interaction between these main effects such that behavior was influenced more by prior expectations when uncertainty was high. Computationally, this was driven by a reduction in learning rates, with people slower to update their beliefs in the face of new information. Attenuating the global effects of NA also eliminated the phasic effects of prediction error and volatility on pupil size, consistent with slower belief updating. Finally, estimates of environmental volatility were predicted by baseline cardiac measures in all participants. Our results demonstrate that NA underpins behavioral and computational responses to uncertainty. These findings have important implications for understanding the impact of uncertainty on human biology and cognition.

表示和应对不确定性的能力是人类认知和决策的基础。据推测，去甲肾上腺素（NA）在协调适应不断变化的世界所必需的感觉、学习和生理状态方面发挥着关键作用，但人类缺乏这方面的直接证据。在这里，我们测试了减弱去甲肾上腺素能神经传递对不确定性下学习的影响。我们采用受试者间、双盲、安慰剂对照设计探讨了 β-肾上腺素能受体拮抗剂普萘洛尔（40 mg）的作用。参与者执行概率关联学习任务，我们采用分层学习模型来正式量化有关提示结果意外事件以及这些关联随时间变化（波动性）的预测误差。意外事件和噪音都会减慢反应时间，但普萘洛尔增强了这些主要效应之间的相互作用，使得当不确定性较高时，行为更多地受到先前预期的影响。从计算角度来看，这是由于学习率下降造成的，人们在面对新信息时更新信念的速度变慢。减弱 NA 的全局影响还消除了预测误差和波动性对瞳孔大小的阶段性影响，这与较慢的信念更新一致。最后，通过所有参与者的基线心脏测量来预测环境波动的估计。我们的结果表明，NA 支撑着对不确定性的行为和计算反应。这些发现对于理解不确定性对人类生物学和认知的影响具有重要意义。