NEURONAL MECHANISMS OF GOOD-BASED ECONOMIC DECISIONS

 描述（由申请人提供）：许多精神和神经系统疾病-包括额颞叶痴呆症，强迫症和药物成瘾-的广泛特征是患者做出“糟糕的选择”。更具体地说，当受试者根据主观偏好做出决定时，会观察到赤字-这种行为称为“经济选择”。因此，为了更好地了解这些疾病的起源，并为治疗铺平道路，了解经济选择的神经基础至关重要。这个建议建立在最近的结果表明，灵长类动物眶额皮质（OFC）的神经元编码三个变量密切相关的决定。在实验中，猴子在不同数量的果汁中做出选择。不同的细胞群分别编码了提供价值（两种果汁中的一种的价值，与动物的选择无关）、选择价值（所选果汁的价值，与其身份无关）和选择果汁（所选果汁的身份，与其价值无关）。原则上，这些细胞群可以被分类以产生决策。此外，一个既定的文献表明，OFC病变选择性损害经济选择。因此，我们提出假设，基于良好的决策发生在OFC。我们将追求三个具体目标。在目标1中，我们将评估单个神经元的“身份”是否以及如何在行为背景下保持。猴子将在第一个试验块中选择两种果汁（A和B），在第二个试验块中选择不同的果汁（C和D）。初步结果表明，一个给定的细胞通常在两个块中编码相同的变量。同时，细胞被重新分配给任何给定块中可用的果汁。在目标2中，我们将研究选择变异性的神经元起源。我们最近发现了几种现象，这些现象与动物在任何特定试验中所做的决定有关，这些决定与OFC中单个神经元活动的逐个试验波动有关。理论上的考虑表明，这些现象严重依赖于不同神经元活动的一次又一次的波动是如何相互关联的。在目标2下，我们将使用高密度U型探针测量OFC中的噪声相关性。此外，我们将评估不同的细胞群是否在解剖学上组织成簇或微柱。在目标3中，我们将研究杏仁核（AMY）的作用。对于眶额皮层，AMY是唯一一个病变会破坏大脑评价任务表现的区域。以前的研究表明，价值相关的信息流从AMY到OFC。然而，AMY在经济决策中的确切作用仍不清楚。虽然损伤研究长期暗示眶额皮层参与选择行为，但经济决策发生在眶额皮层内的假设是高度创新的，具有潜在的变革性。在整个提案中，实验和计算工作将齐头并进。据我们估计，这项研究是有史以来最先进的了解经济决策背后的神经机制的研究。

 DESCRIPTION (provided by applicant): Many mental and neurological disorders - including frontotemporal dementia, obsessive-compulsive disorder and drug addiction - are broadly characterized by patients making "poor choices". More specifically, deficits are observed when subjects make decisions based on subjective preferences - a behavior termed "economic choice". Thus to better understand the origins of these disorders, and to pave the way for treatments, it is critical to understand the neuronal underpinnings of economic choice. This proposal builds on recent results showing that neurons in the primate orbitofrontal cortex (OFC) encode three variables intimately related to the decision. In the experiments, monkeys chose between different juices offered in variable amounts. Different groups of cells encoded the offer value (the value of one of the two juices, independent of the animal choice), the chosen value (the value of the chosen juice, independent of its identity) and the chosen juice (the identity of the chosen juice, independent of its value). In principle, these groups of cells could be sufficien to generate a decision. Furthermore, an established literature shows that OFC lesions selectively impair economic choices. We thus put forth the hypothesis that good-based decisions take place within the OFC. We will pursue three specific aims. In Aim 1, we will assess whether and how the "identity" of individual neurons is maintained across behavioral contexts. Monkeys will choose between two juices (A and B) in a first trial block and between different juices (C and D) in a second trial block. Preliminary results indicate that a given cell typically encodes the same variable in the two blocks. At the same time, cells are re-assigned to the juices available in any given block. In Aim 2, we will examine the neuronal origins of choice variability. We recently discovered several phenomena relating the decision made by the animal in any given trial with trial-by-trial fluctuations in the activity of individual neurons in OFC. Theoretical considerations indicate that these phenomena critically depend on how trial-by-trial fluctuations in the activity of different neurons are correlated with each other. Under Aim 2, we will measure noise correlations in the OFC using high-density U-probes. In addition, we will assess whether different groups of cells are anatomically organized in clusters or mini-columns. In Aim 3, we will examine the role of the amygdala (AMY). With the OFC, the AMY is the only area where lesions disrupt performance in reinforcer devaluation tasks. Previous work suggests that value-relevant information flows from the AMY to the OFC. However, the precise role of the AMY in economic decisions remains unclear. While lesion studies long implicated the OFC in choice behavior, the hypothesis that economic decisions take place within the OFC is highly innovative and potentially transformative. Throughout this proposal, experiments and computational work will proceed hand-in-hand. In our estimation, this research is the most advanced ever conducted to understand the neuronal mechanisms underlying economic decisions.