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，激励人类何时、为何以及如何选择应用于任务的认知资源量的因素仍然难以捉摸。有影响力的神经经济学研究表明，假设施加认知控制是费力的，令人厌恶的和昂贵的，参与者参与认知要求行为的意愿是基于成本效益决策过程，该过程计算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，人们往往会根据获得金钱奖励所需的努力程度来低估金钱奖励。然而，关于认知努力为基础的决策的计算和神经基础的关键问题仍然没有答案，限制了该领域的概括性和解释力。更具体地说，虽然与努力相关的奖励折扣主要是在选择问题中研究的，这些问题允许参与者直接比较两种行为选项的成本效益主张，但仍然不知道努力是否同样影响其他依赖于不同计算机制的决策形式，例如学习行动的平均奖励率。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。虽然有希望的研究结果表明，在额极皮层（FPC）的活动与减少努力厌恶成本效益的决定，它是未经测试的FPC是否可能在激励努力的行为在不同类别的选择问题的一般作用。最后，由于基于努力的决策的改变可能是冷漠的一个潜在因素，冷漠是一种在许多临床疾病中常见的严重失动综合征，包括帕金森病（PD），因此确定与努力相关的过程及其神经基础是否以及如何受损至关重要。拟议项目着手彻底解决这些问题。我们将进行两个平行的实验，以调查如何调制FPC活动与经颅直流电刺激（tDCS）因果影响的努力为基础的决策在两个不同类别的选择问题（成本效益与平均奖励率为基础的决策）在健康成人和PD患者的冷漠。该项目的两个部分将使用为期两天的、完全交叉的、双盲的受试者内设计，其中所有参与者将在主动和假刺激下接受测试。该项目的结果将大大扩展先前关于认知努力的发现，揭示它如何影响基本的日常决策过程以及它如何在大脑中实施。此外，它将使我们能够了解这些过程的故障如何导致PD中的冷漠，以及tDCS是否可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.