Probing the causal role of the frontopolar cortex in cognitive effort based decision-making using transcranial direct current stimulation in healthy participants and Parkinson patients with apathy

灵活的、目标导向的行为需要分配认知控制。然而，激发人们何时、为何以及如何选择应用于一项任务的认知资源数量的因素仍然难以捉摸。假设施加认知控制是费力的、令人厌恶的和昂贵的，有影响力的神经经济学研究表明，参与者参与认知要求行为的意愿是基于成本-收益决策过程的，该决策过程计算了应用认知努力的成本与预期回报的价值之间的权衡。事实上，个人倾向于通过获得金钱奖励所需的努力来贬低金钱奖励。然而，关于基于认知努力的决策的计算和神经基础的关键问题仍然没有得到回答，限制了该领域的普遍性和解释力。更具体地说，虽然与努力相关的奖励折扣主要是在允许参与者直接比较两种行为选项的成本效益命题的选择问题中进行研究，但仍然不清楚努力是否同样影响依赖于不同计算机制的其他形式的决策，例如学习一个行动的平均奖励率。此外，哪些大脑区域参与整合努力和奖励信息仍然存在很大争议。尽管令人鼓舞的研究结果表明，额极皮质（FPC）的活动与成本效益决策中减少的努力厌恶有关，但FPC是否在不同类型的选择问题中激发努力行为方面发挥了普遍作用，尚未得到检验。最后，由于以努力为基础的决策的改变可能是冷漠的潜在因素，冷漠是许多临床疾病（包括帕金森病）中常见的一种严重动机综合征，因此确定努力相关过程及其神经基础是否以及如何在这种情况下受损至关重要。拟议的项目旨在彻底解决这些问题。我们将进行两个平行实验，研究如何通过经颅直流电刺激（tDCS）调节FPC活动，对健康成人和PD患者在两种不同类型的选择问题（基于成本效益和平均奖励率的决策）中基于努力的决策产生因果影响。项目的两个部分都将采用为期两天，完全交叉，双盲的受试者设计，所有参与者将在积极和虚假刺激下进行测试。这个项目的结果将通过揭示认知努力如何影响基本的日常决策过程以及它是如何在大脑中实现的，从而大大扩展先前在认知努力方面的发现。此外，它将使我们了解这些过程的故障如何导致PD的冷漠，以及tDCS是否可以用于改善这些患者的冷漠症状。

Flexible, goal-directed behavior requires allocation of cognitive control. Yet, the factors that motivate when, why and how humans choose the amount of cognitive resources applied to a task remain elusive. Assuming that exerting cognitive control is effortful, aversive and costly, influential neuroeconomic research suggests that the participants’ willingness to engage in cognitively demanding behavior is based on a cost-benefit decision-making process that calculates the trade-off between the costs of applying cognitive effort against the value of the anticipated rewards. Indeed, individuals tend to discount monetary rewards by the amount of effort required to obtain them. However, critical questions regarding the computational and neural underpinnings of cognitive effort-based decision-making remain unanswered, limiting the generalizability and explanatory power of the field. More specifically, while effort-related discounting of rewards has been mostly studied in choice problems that allow participants to directly compare cost-benefit propositions of two behavioral options, it is still unknown whether effort similarly affects other forms of decision-making that rely on different computational mechanisms, such as learning the average reward rate of an action. Further, which brain regions are involved in integrating effort and reward information is still highly debated. Although promising findings showed that activity in the frontopolar cortex (FPC) is associated with reduced effort aversion in cost-benefit decisions, it is untested whether the FPC may play a general role in invigorating effortful behavior across different classes of choice problems. Finally, as alterations in effort-based decision-making may present an underlying factor in apathy, a syndrome of severe amotivation that is common in many clinical disorders, including Parkinson’s disease (PD), it is crucial to identify if and how effort-related processes and their neural basis are impaired in the conditions. The proposed project sets out to thoroughly address these questions. We will conduct two parallel experiments to investigate how modulating FPC activity with transcranial direct current stimulation (tDCS) causally affects effort-based decision-making in two distinct classes of choice problems (cost-benefit vs. average reward rate-based decisions) in healthy adults and PD patients with apathy. Both parts of the project will make use of a two-day, fully crossed, double-blinded within-subject design in which all participants will be tested under both active and sham stimulation. The results of this project will substantially extend previous finding on cognitive effort by shedding light on how it affects fundamental every-day-decision-making processes and how it is implemented in the brain. Furthermore, it will allow us to understand how malfunctioning of these processes may contribute to apathy in PD as well as whether tDCS may be used to improve apathy symptoms in these patients.