NEURONAL MECHANISMS OF GOOD-BASED ECONOMIC DECISIONS

 描述(由申请人提供)：许多精神和神经障碍--包括额-颞叶痴呆、强迫症和毒瘾--广泛地表现为患者做出“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，就会观察到赤字--这种行为被称为“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元基础至关重要。这一建议建立在最近的结果基础上，该结果显示，灵长类眼眶前额叶皮质(OFC)中的神经元编码与这一决定密切相关的三个变量。在实验中，猴子在不同的果汁之间进行选择，提供的果汁数量不同。不同的细胞组编码了供给值(两种果汁中一种的价值，与动物的选择无关)、选择的值(选择的果汁的价值，与其身份无关)和选择的果汁(选择的果汁的身份，与其值无关)。原则上，这些细胞群足以产生一个决定。此外，已有文献表明，OFC病变选择性地损害经济选择。因此，我们提出了一个假设，即基于良好基础的决定发生在OFC内部。我们将追求三个具体目标。在目标1中，我们将评估是否以及如何在整个行为环境中保持单个神经元的“同一性”。猴子将在第一个试验区中选择两种果汁(A和B)，在第二个试验区中选择不同的果汁(C和D)。初步结果表明，给定的单元格通常对两个块中的相同变量进行编码。同时，细胞被重新分配给任何给定区块中可用的果汁。在目标2中，我们将研究选择可变性的神经元起源。我们最近发现了几种现象，这些现象与动物在任何给定试验中所做的决定有关，与OFC中单个神经元活动的逐次试验波动有关。理论方面的考虑表明，这些现象关键取决于不同神经元活动的逐次试验波动是如何相互关联的。在目标2下，我们将使用高密度U探头测量OFC中的噪声相关性。此外，我们将评估不同的细胞组在解剖上是以簇状还是迷你柱的形式组织起来的。在目标3中，我们将研究杏仁核(AMY)的作用。对于OFC，AMY是唯一一个病变扰乱增强剂贬值任务执行的区域。以前的工作表明，与价值相关的信息从AMY流向OFC。然而，AMY在经济决策中的确切作用仍不清楚。虽然病变研究长期以来一直认为OFC与选择行为有关，但经济决策发生在OFC内部的假设是高度创新的，并具有潜在的变革性。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为理解经济决策背后的神经机制而进行的最先进的研究。

 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.