Neuronal Mechanisms of Good-Based Economic Decisions

摘要 经济选择行为在精神疾病中特别受到干扰，如额颞叶痴呆，主要是 抑郁症和毒瘾为了阐明这些疾病并为治疗铺平道路， 来理解这种行为的神经基础。在这方面，过去15年见证了 重大进展。来自临床数据、病变研究、功能成像和神经生理学链接的证据 眶额皮质（OFC）的经济选择。特别是，我的实验室研究了OFC的活性， 猴子的神经元在不同的果汁之间进行选择。因此，我们确定了三个群体的细胞密切 与选择相关：提供值单元格编码个人提供值，选择汁单元格编码二进制 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， OFC中编码的报价值是选择的原因。与其他实验室的工作一起，我们的结果奠定了 对经济选择的满意理解的基础。然而，至少有三个主要问题 保持开放。(1)目前还不清楚大脑中的何处以及如何进行比较（即，决定）发生。(2)是 不清楚在哪里以及如何首先计算（或“构造”）报价值。(3)目前还不清楚报价是否 大脑其他区域--如杏仁核--也是选择的原因。总体目标 这项建议的目的是解决这些基本问题。所有实验将在非- 人类灵长类动物使用行为控制，神经记录，电刺激 和计算技术，我们将追求两个具体目标。 在目标1下，两个实验将检查OFC中的神经元是否参与价值比较。的 在该区域中标识的单元格组既表示输入（报价值），又表示输出（选择的果汁、选择的 值），这表明它们构成了决策电路的构建块。实验1 将评估这三个细胞群在选择条件下是否稳定。同时，实验2将使用 电刺激以评估OFC中的神经元活动对于值比较是否是必要的。下 目的2，我们将研究是否以及如何三个大脑区域与OFC -味觉皮层（GC）， 下颞叶皮层（IT）和基底外侧杏仁核（BLA）-参与选择过程。一个工作 假设是GC和/或IT可能参与构建要约价值。两个实验将测试 通过记录这两个区域的神经元活动来证实这一假设。上一周期开展的工作 发现BLA中的神经元编码与OFC中相同的变量，但存在一些差异。在过去 在实验中，我们将使用电刺激来评估（a）BLA中编码的报价值是否与 选择和（B）BLA是否参与决策过程。实现这些目标将大大 推进我们对经济选择背后的神经回路和心理障碍的理解。 病我们的跟踪记录和大量的初步结果表明，成功的可能性很大。

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.