Neuronal Mechanisms of Good-Based Economic Decisions

基于良好的经济决策的神经机制

• 批准号: 10211215
• 负责人: Camillo Padoa-Schioppa
• 金额: $ 49.67万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10211215
• 关键词: Address; Affect; Amygdaloid structure; Anatomy; Animals; Area; Attention; Behavior; Behavior Control; Brain; Brain region; Cells; Choice Behavior; Clinical; Clinical Data; Computational Technique; Decision Making; Disease; Drug Addiction; Economics; Electric Stimulation; Emotions; Foundations; Frontotemporal Dementia; Functional Imaging; Goals; Individual; Intuition; Juice; Lesion; Light; Link; Major Depressive Disorder; Mental disorders; Modality; Monkeys; Neurons; Outcome; Output; Pharmaceutical Preparations; Population; Process; Productivity; Psyche structure; Records; Role; Sensory; Signal Transduction; Testing; Visual; Work; base; classical conditioning; experimental study; inferotemporal cortex; mental function; nervous system disorder; neural circuit; neurophysiology; nonhuman primate; operation; relating to nervous system; success; visual stimulus

ABSTRACT Economic choice behavior is specifically disrupted in mental disorders such as frontotemporal dementia, major depression and drug addiction. To shed light on these diseases and to pave the way for treatments, it is critical to understand the neural underpinnings of this behavior. In this respect, the past 15 years witnessed very significant progress. Evidence from clinical data, lesion studies, functional imaging and neurophysiology links economic choice to the orbitofrontal cortex (OFC). In particular, work in my lab examined the activity of OFC neurons in monkeys choosing between different juices. We thus identified three populations of cells intimately related to choices: offer value cells encoding individual offer values, chosen juice cells encoding the binary choice outcome, and chosen value cells. In a recent breakthrough, we used electrical stimulation to show that offer values encoded in OFC are causal to choices. Together with work from other labs, our results lay the foundations for a satisfactory understanding of economic choices. However, at least three major questions remain open. (1) It is unclear where in the brain and how value comparisons (i.e., decisions) take place. (2) It is unclear where and how offer values are first computed (or “constructed”). (3) It is unclear whether offer values represented in other brain regions – such as the amygdala – are also causal to choices. The overarching goal of this proposal is to address these fundamental questions. All the experiments will be conducted in non- human primates. Using a combination of behavioral manipulation, neuronal recordings, electrical stimulation and computational techniques, we will pursue two Specific Aims. Under Aim 1, two experiments will examine whether neurons in the OFC participate in value comparison. The cell groups identified in this area represent both the input (offer value) and the output (chosen juice, chosen value) of the decision process, suggesting that they constitute the building blocks of a decision circuit. Exp.1 will assess whether the three cell groups are stable across choice conditions. In parallel, Exp.2 will use electrical stimulation to assess whether neuronal activity in OFC is necessary for value comparison. Under Aim 2, we will examine whether and how three brain regions interconnected with OFC – gustatory cortex (GC), inferotemporal cortex (IT) and basolateral amygdala (BLA) – are involved in the choice process. A working hypothesis is that GC and/or IT might participate in the construction of offer values. Two experiments will test this hypothesis by recording neuronal activity from these two areas. Work conducted in the previous cycle found that neurons in BLA encode the same variables represented in OFC, with some differences. In the last experiment, we will use electrical stimulation to assess (a) whether offer values encoded in BLA are causal to choices and (b) whether BLA participates in the decision process. Fulfilling these Aims will significantly advance our understanding of the neural circuits that underlie economic choices and that malfunction in mental illness. Our track record and substantial preliminary results indicate a high likelihood of success.

摘要 经济选择行为在精神障碍中尤其受到干扰，如额颞叶痴呆症 抑郁症和毒瘾。要阐明这些疾病并为治疗铺平道路，至关重要的是 来理解这种行为的神经基础。在这方面，过去15年见证了非常多 取得了重大进展。来自临床数据、病变研究、功能成像和神经生理学联系的证据 眼眶额叶皮质(OFC)的经济选择。特别是，我实验室的工作检查了OFC的活动 猴子的神经元在不同的果汁之间进行选择。因此，我们密切地鉴定了三种细胞群 与选择相关：提供值单元编码单个提供值，选择的果汁单元编码二进制 选择结果和选择的值单元格。在最近的一项突破中，我们使用电刺激来证明 在OFC中编码的报价价值是选择的因果关系。与其他实验室的工作一起，我们的结果奠定了 令人满意地理解经济选择的基础。然而，至少有三个主要问题 保持开放。(1)不清楚价值比较(即决策)在大脑的什么位置以及如何发生。(2)它是 不清楚首次计算(或“构建”)要约价值的地点和方式。(3)尚不清楚出价是否有价值 大脑的其他区域--比如杏仁核--也是选择的原因。首要目标是 这项提案的目的是解决这些根本问题。所有的实验都将在非 人类灵长类动物。使用行为操作、神经元记录、电刺激的组合 和计算技术，我们将追求两个具体目标。 在目标1中，两个实验将检验OFC中的神经元是否参与价值比较。这个 此区域中标识的单元组代表输入(提供值)和输出(选择的果汁、选择的果汁 值)，这表明它们构成了决策电路的构建块。Exp.1 将评估这三组细胞在不同的选择条件下是否稳定。同时，Exp2将使用 电刺激以评估OFC的神经元活动是否是价值比较所必需的。在……下面 目的2，我们将研究三个大脑区域是否以及如何与OFC-味觉皮质(GC)相互联系， 颞下皮质(IT)和基底外侧杏仁核(BLA)参与了选择过程。一名工作人员 假设GC和/或IT可能参与报价价值的构建。两个实验将测试 这一假设是通过记录这两个区域的神经元活动来实现的。上一个周期中进行的工作 发现BLA中的神经元编码的变量与OFC中的相同，但有一些不同。在最后一次 实验中，我们将使用电刺激来评估(A)编码在BLA中的提供值是否导致 (B)BLA是否参与决策过程。实现这些目标将极大地 加深我们对经济选择背后的神经回路和心理障碍的理解 生病了。我们的记录和大量的初步结果表明，成功的可能性很高。