Decision confidence: neural coding and causal circuit mechanisms in behavior

描述（由申请人提供）：我们研究的长期目标是了解前额叶皮层中的神经回路如何支持决策。眶额皮层（orbitofrontalcortex，OFC）是人类和其他动物在不确定条件下进行决策的关键脑区.我们的中心假设是，眶额皮层代表信心信息，并在向其他脑区报告决策信心方面发挥因果作用，从而影响行为。 研究 这个问题，我们已经开发了定量的心理物理学方法的啮齿动物，改编自人类和灵长类动物的工作，这使得行为读出的信心，在一个良好的控制决策任务。简单地说，在每次试验中，动物必须决定两种气味成分中哪一种占多数。在移动到相应的选择端口后，大鼠等待可能会或可能不会到来的延迟奖励。如果没有，老鼠最终会离开港口，开始另一次试验。大鼠愿意等待奖励的持续时间可以被认为是对知觉决定结果的赌博，因此它提供了信心的定量指标。因此，在每次试验中，都有一个感知决策（左/右）和一个决策后置信度报告（离开决策）。如果OFC在这个离开的决定是因果关系，神经活动应该是预测多久大鼠等待之前离开的一个试验的基础上（相关性），我们还将测试OFC活动的必要性，这个过程中使用药理学失活。这些结果将在一个计算框架中解释，该框架将神经和行为数据与决策信心联系起来。接下来，我们将测试的假设，确定子集的 投射到不同靶区的眶额皮层神经元携带不同类型的信息，从而介导不同的行为功能。使用逆行病毒传递光敏激活剂（ChR 2）和抑制剂（Halo），我们将光学微刺激或阻断一个不是由空间接近度而是由投射靶点定义的OFC神经元子集。结合电生理学，我们将确定不同的投射神经元的神经相关性，并确定它们是否是必要的和足够的信心报告的试验到试验的基础上。 在完成这些目标后，我们期望建立OFC在决策信心中的作用，并确定它发挥作用的神经回路。通过记录属于不同长程投射的神经元，我们也希望有助于解释观察到的OFC神经表征的异质性。除了这些机制研究之外，我们希望为理解单个前额叶脑区的损伤如何导致如此广泛的精神疾病提供改进的框架，包括成瘾，抑郁症，焦虑症，强迫症，精神分裂症和自闭症。

DESCRIPTION (provided by applicant): The long-term goal of our investigation is to understand how neural circuits in the prefrontal cortex support decision-making. Orbitofrontal cortex (OFC) is a key brain region for decision- making under uncertainty in humans and other animals. Our central hypothesis is that OFC represents confidence information and plays causal role in reporting decision confidence to other brain regions, thereby affecting behavior. To study this issue, we have developed quantitative psychophysical methods for rodents, adapted from human and primate work, which enables the behavioral readout of confidence in a well-controlled decision task. Briefly, in each trial the animal has to decide which of two odor components is in the majority. After moving to the corresponding choice port, the rat waits for a delayed reward that may or may not come. If it doesn't, the rat eventually leaves the port and initiates another trial. The duration rats are willing to wait for a reward can be thought of as a gamble on the outcome of the perceptual decision, and hence it provides a quantitative index for confidence. Thus in each trial there is a perceptual decision (left/right) and a post-decision confidence report (leaving decision). If OFC is causal in this leaving decision, neural activity should be predictive of how long a rat waits before leaving on a trial-by-trial basis (correlation) We will also test the necessity of OFC activity for this process using pharmacological inactivation. These results will be interpreted in a computational framework that links neural and behavioral data to decision confidence. Next we will test the hypothesis that identified subsets of OFC neurons projecting to distinct target areas carry different types of information and thus mediate distinct behavioral functions. Using retrograde viruses to deliver light-sensitive activators (ChR2) and suppressors (Halo), we will optically microstimulate or block a subset of OFC neurons defined not by spatial proximity but by projection target. In combination with electrophysiology we will identify the neural correlates of distinct projection neurons and determine whether they are necessary and sufficient for confidence reports on a trial-to-trial basis. Upon completion of these aims, we expect to establish the role of OFC in decision confidence and determine the neural circuits through which it exerts its actions. By recording from neurons belonging to different long-range projections we also expect to help explain the observed heterogeneity in OFC neural representations. Beyond these mechanistic studies, we hope to inform an improved framework for understanding how impairments in a single prefrontal brain area can lead to such a wide range of psychiatric disorders, including addiction, depression, anxiety, obsessive-compulsive disorder, schizophrenia, and autism.