THE ROLE OF PREFRONTAL REGIONS IN ECONOMIC CHOICE AND CHOICE-GUIDED BEHAVIOR

摘要 精神和神经障碍，如额颞叶痴呆和吸毒成瘾，可以被描述为 因为病人做出了“糟糕的选择”。特别受影响的是基于主观偏好的选择，也 被称为“经济选择”。从而更好地了解这些疾病的起源，并为 对于治疗方法，了解这种行为的神经基础是至关重要的。经济选择是 被认为涉及两个心理阶段--价值被分配给可用选项，而决策是由 比较值。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)的经济决定。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，我们确定了三个密切相关的种群 对于决策：提供编码单个果汁的值的单元格；选择编码该值的值单元格 以及编码与数量无关的所选果汁的身份的所选果汁细胞。 值得注意的是，这些单元组同时捕获输入(提供值)和输出(选择的果汁、选择的值) 这表明，决定可能是在OFC内部产生的。这件事的首要目标是 该提案旨在阐明这一神经回路的组织和机制。使用以下组合 行为、计算和神经生理学技术，我们将追求两个特定的目标。目标1重点 关于连续报价下的选择。以前的绝大多数研究都考察了商品之间的选择 同时提供。Exp.1将确定当前的概念是否适用于顺序选择 报价，可以说，这与现实生活中的决定更相关。此外，通过解离数值计算 从数值比较来看，Exp1将解决判决电路上的未决问题。目标2侧重于 因果关系的根本问题。尽管近年来取得了巨大的进步，但我们对 经济决策背后的机制仍处于试探性阶段。这主要是因为 OFC的活动和决定尚未确定。原则上，可以使用以下方法演示此类链接 电刺激以可预测的方式偏向选择，但OFC中没有柱状组织 使这种方法变得更加困难。为了避免这个问题，我们设计了三个实验协议。在实验2中， 猴子会在连续提供的条件下进行选择。通过在其中一次报价中注入电流，我们将偏向 这是动物的决定。Exp.3和Exp.4将侧重于特定的单元组。这些实验将需要 我实验室最近发现的现象的优势，即报价价值单元的范围适应 (实验3)，所选果汁细胞的预测活性和选择滞后(实验4)。 这笔赠款的第一个周期已经产生了多项突破，目前的具体目标建立在我们的 之前的结果。通过实现它们，这里描述的研究将极大地促进我们对 经济决策背后的神经机制，以及精神疾病中的故障。

ABSTRACT Mental and neurological disorders such as frontotemporal dementia and drug addiction can be characterized as patients making “poor choices.” Specifically affected are choices based on subjective preferences, also referred to as "economic choices". Thus to better understand the origins of these disorders and to pave the way for treatments, it is critical to understand the neural underpinnings of this behavior. Economic choices are thought to involve two mental stages – values are assigned to the available options and a decision is made by comparing values. Evidence from clinical data, lesion studies, functional imaging and neurophysiology links economic decisions 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 intimately related to the decision: offer value cells encoding the value of individual juices; chosen value cells encoding the value of the chosen juice; and chosen juice cells encoding the identity of the chosen juice independent of quantity. Notably, these groups of cells capture both the input (offer value) and the output (chosen juice, chosen value) of the decision process, suggesting that decisions might be generated within OFC. The overarching goal of this proposal is to shed light onto the organization and mechanisms of this neural circuit. Using a combination of behavioral, computational and neurophysiology techniques, we will pursue two Specific Aims. Aim 1 focuses on choices under sequential offers. The vast majority of previous studies examined choices between goods offered simultaneously. Exp.1 will establish whether current notions generalize to choices under sequential offers, which are arguably more relevant to real-life decisions. Furthermore, by dissociating value computation from value comparison, Exp.1 will address outstanding questions on the decision circuit. Aim 2 focuses on the fundamental question of causality. Despite the enormous advances of recent years, our understanding of the mechanisms underlying economic decisions remains tentative. This is primarily because causal links between OFC activity and decisions have not yet been established. In principle, such links may be demonstrated using electrical stimulation to bias choices in a predictable way, but the absence of columnar organization in OFC makes this approach more difficult. To obviate this issue, we designed three experimental protocols. In Exp.2, monkeys will perform choices under sequential offers. By injecting current during one of the offers, we will bias the animal's decision. Exp.3 and Exp.4 will focus on specific groups of cells. The experiments will take advantage of phenomena recently discovered in my lab, namely the range adaptation of offer value cells (Exp.3), the predictive activity of chosen juice cells and choice hysteresis (Exp.4). The first cycle of this grant has generated multiple breakthroughs, and the current Specific Aims build on our previous results. By fulfilling them, the research described here will significantly advance our understanding of the neural mechanisms that underlie economic decisions and that malfunction in mental illness.