Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Victoria, Australia.
Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Brain. 2019 Mar 1;142(3):719-732. doi: 10.1093/brain/awy341.
Disorders of motivation, such as apathy, are common in Parkinson's disease, and a key feature of such disorders is a greater aversion to effort. In humans, the experience of cognitive effort is ubiquitous, and cognitive apathy has traditionally been considered distinct and separable from other subtypes. Surprisingly, however, the neurobiology of cognitive motivation is poorly understood. In particular, although dopamine has a well-characterized role in incentivizing physically effortful behaviour, a critical, unresolved issue is whether its facilitatory role generalizes to other domains. Here, we asked how dopamine modulates the willingness of patients with Parkinson's disease to invest cognitive effort in return for reward. We tested 20 patients with idiopathic Parkinson's disease across two counterbalanced sessions-ON and OFF their usual dopaminergic medication-and compared their performance to 20 healthy age-matched controls. We applied a novel task in which we manipulated cognitive effort as the number of rapid serial visual presentation streams to which participants had to attend. After training participants to ceiling performance, we then asked them to choose between a low-effort/low-reward baseline option, and a higher-effort/higher-reward offer. Computational models of choice behaviour revealed four key results. First, patients OFF medication were significantly less cognitively motivated than controls, as manifest by steeper cognitive effort discounting functions in the former group. Second, dopaminergic therapy improved this deficit, such that choices in patients ON medication were indistinguishable from controls. Third, differences in motivation were also accompanied by independent changes in the stochasticity of individuals' decisions, such that dopamine reduced the variability in choice behaviour. Finally, choices on our task correlated uniquely with the subscale of the Dimensional Apathy Scale that specifically indexes cognitive motivation, which suggests a close relationship between our laboratory measure of cognitive effort discounting and subjective reports of day-to-day cognitive apathy. Importantly, participants' choices were not confounded by temporal discounting, probability discounting, physical demand, or varying task performance. These results are the first to reveal the central role of dopamine in overcoming cognitive effort costs. They provide an insight into the computational mechanisms underlying cognitive apathy in Parkinson's disease, and demonstrate its amenability to dopaminergic therapy. More broadly, they offer important empirical support for prominent frameworks proposing a domain-general role for dopamine in value-based decision-making, and provide a critical link between dopamine and multidimensional theories of apathy.
动机障碍，如冷漠，在帕金森病中很常见，此类障碍的一个关键特征是对努力的更大厌恶。在人类中，认知努力的体验无处不在，认知冷漠传统上被认为是独特且可分离的。然而，令人惊讶的是，认知动机的神经生物学仍未被充分理解。特别是，尽管多巴胺在激励身体努力行为方面具有明确的作用，但一个关键的、未解决的问题是，它的促进作用是否普遍适用于其他领域。在这里，我们研究了多巴胺如何调节帕金森病患者为获得奖励而投入认知努力的意愿。我们在两个平衡的阶段——患者服用和未服用通常的多巴胺药物——测试了 20 名特发性帕金森病患者，并将他们的表现与 20 名年龄匹配的健康对照组进行了比较。我们应用了一种新的任务，通过操纵认知努力，即参与者必须关注的快速序列视觉呈现流的数量，来测试多巴胺的作用。在训练参与者达到最佳表现后，我们要求他们在低努力/低回报的基准选项和高努力/高回报的选项之间做出选择。选择行为的计算模型揭示了四个关键结果。首先，未服用药物的患者的认知动机明显低于对照组，前者的认知努力折扣函数更陡峭。其次，多巴胺治疗改善了这一缺陷，使得服用药物的患者的选择与对照组无法区分。第三，动机的差异也伴随着个体决策的随机性的独立变化，即多巴胺降低了选择行为的可变性。最后，我们任务的选择与专门索引认知动机的维度冷漠量表的子量表独特相关，这表明我们实验室对认知努力折扣的测量与日常认知冷漠的主观报告之间存在密切关系。重要的是，参与者的选择不受时间折扣、概率折扣、体力需求或不同任务表现的影响。这些结果首次揭示了多巴胺在克服认知努力成本方面的核心作用。它们为帕金森病中认知冷漠的计算机制提供了一个见解，并证明了它对多巴胺治疗的敏感性。更广泛地说，它们为多巴胺在基于价值的决策中具有普遍作用的主流框架提供了重要的经验支持，并为多巴胺与多维冷漠理论之间提供了关键联系。
