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

摘要 精神和神经系统疾病，如额颞叶痴呆和药物成瘾， 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， 被称为“经济选择”。因此，为了更好地了解这些疾病的起源， 治疗的方法，关键是要了解这种行为的神经基础。经济选择是 被认为涉及两个心理阶段-价值被分配给可用的选项，并作出决定， 比较值。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）。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，我们确定了三个密切相关的人群 提供编码单个果汁的值的值单元格;选择编码值的值单元格 所选择的汁液的标识;以及所选择的汁液细胞，其编码所选择的汁液的标识而与数量无关。 值得注意的是，这些单元格组同时捕获输入（提供值）和输出（选择果汁，选择值） 的决策过程中，这表明，决定可能产生的OFC。这个项目的首要目标是 这个提议是为了阐明这种神经回路的组织和机制。结合使用 行为，计算和神经生理学技术，我们将追求两个具体目标。目标1侧重于 在顺序提供下的选择。绝大多数以前的研究考察了商品之间的选择 同时提供。实验1将确定当前的概念是否可以推广到序列下的选择 报价，可以说与现实生活中的决策更相关。此外，通过分离值计算， 通过数值比较，实验1将解决决策电路中的突出问题。目标2侧重于 因果关系的基本问题。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然是试验性的。这主要是因为， 竞争事务办公室的活动和决定尚未确定。原则上，这种联系可以用 电刺激以可预测的方式使选择偏向，但OFC中缺乏柱状组织 使得这种方法更加困难。为了解决这个问题，我们设计了三个实验方案。在实验2中， 猴子会在顺序提供的条件下进行选择。通过在其中一个要约期间注入电流，我们将偏置 动物的决定。实验3和实验4将集中于特定的细胞群。这些实验需要 最近在我的实验室发现的现象的优点，即提供价值单元的范围适应性 （实验3），所选汁液细胞的预测活性和选择滞后（实验4）。 该赠款的第一个周期产生了多个突破，目前的具体目标建立在我们的基础上， 以前的结果。通过实现这些目标，这里描述的研究将大大促进我们对 经济决策的神经机制和精神疾病的神经机制。

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.