Role of basal ganglia in reward-biased visual decisions

项目摘要 基底神经节（BG）通路已被假设为在几个重要的方式来决定， 决策，包括积累证据，控制决策终止和承诺， 抽象的决定，以适当的运动反应，并提供评估和调整的机制， 决策绩效。然而，这些函数中的许多已经在计算建模中被提出 研究，但尚未在大脑中进行详细检查，留下重要的知识空白， 阻碍了我们理解健康大脑中正常BG功能以及诊断和治疗临床 影响BG功能的疾病。我们的长期目标是进行实验， BG途径对决策的因果贡献的确切性质。我们最初的项目审查 尾状核的因果作用，在BG的输入结构，在纳入奖励和视觉 做出扫视决策的证据。在这里，我们建议检查的因果作用，另外两个BG 结构，黑质网状部（SNr，眼球BG中的输出结构）和 丘脑底核（BG核，具有高度临床重要性），在决策。指导 几个突出的理论模型的预测，我们结合联合收割机计算，行为， 神经生理学技术，以检查SNr（目标1）和SNr（目标2）神经元如何有助于决策 考虑和承诺给予不确定的视觉输入，并在灵活的决策， 还必须考虑奖励期望的变化（目标3）。拟议项目的结果将 为这些特定的、临床相关的核团如何有助于 决策的这些发现将特别有助于约束和告知有关的理论 灵长类大脑中决策的神经执行。这些发现也将作为基础 用于研究与血糖功能障碍相关的认知障碍。

Project Summary The basal ganglia (BG) pathway has been hypothesized to contribute in several important ways to decision- making, including accumulating evidence, controlling decision termination and commitment, transforming abstract decisions to appropriate motor responses, and providing the machinery for evaluating and adjusting the decision performance. However, many of these functions have been proposed in computational modeling studies but have yet to be examined in detail in the brain, leaving important knowledge gaps that seriously impede our ability to understand normal BG function in healthy brains and to diagnose and treat clinical disorders that affect BG function. Our long-term goal is to conduct experiments that allow us to understand the exact nature of the BG pathway's causal contributions to decision-making. Our original project examined the causal roles of the caudate nucleus, an input structure in the BG, in incorporating reward and visual evidence to make saccade decisions. Here we propose to examine the causal roles of two other BG structures, the substantia nigra pars reticulata (SNr, the output structure in the oculomotor BG) and subthalamic nucleus (STN, a BG nucleus with high clinical importance), in decision-making. Guided by predictions of several prominent theoretical models, we combine computational, behavioral, and neurophysiological techniques to examine how SNr (Aim 1) and STN (Aim 2) neurons contribute to decision deliberation and commitment given uncertain visual input alone, and in the context of flexible decisions that must also take into account changes in reward expectation (Aim 3). Results from the proposed project will provide the first direct experimental evidence for how these specific, clinically relevant nuclei contribute to decision-making. These findings will be particularly useful for constraining and informing theories about the neural implementation of decision-making in the primate brain. These findings will also serve as a foundation for investigating the cognitive impairments associated with BG dysfunction.