Role of basal ganglia in reward-biased visual decisions

项目摘要 基底节(BG)通路被假设在几种重要的方式中对决策做出贡献。 作出，包括收集证据，控制决定终止和承诺，转化 抽象适当的运动响应决策，并提供评估和调整的机制 决策表现。然而，这些函数中有许多是在计算建模中提出的 研究但尚未在大脑中进行详细检查，留下了严重的知识空白 妨碍我们了解健康大脑中正常的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，让我们能够理解 BG通路对决策的因果贡献的确切性质。我们最初的项目被检查了 BG的输入结构--尾状核在整合奖赏和视觉方面的因果作用 作出扫视决定的证据。在这里，我们建议研究另外两个BG的因果作用 结构，黑质网状部(SNR，动眼神经的输出结构)和 丘脑底核(STN，一种具有很高临床意义的BG核)，参与决策。指导原则 几个重要理论模型的预测，我们结合了计算、行为和 研究SNR(Aim 1)和STN(Aim 2)神经元如何参与决策的神经生理学技术 仅在不确定的视觉输入的情况下，以及在灵活决策的背景下，进行审议和承诺 还必须考虑到奖励预期的变化(目标3)。拟议项目的结果将 提供了第一个直接的实验证据，说明这些特定的、临床相关的核是如何参与 决策。这些发现将特别有助于约束和告知有关 灵长类动物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BG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.