Decision confidence: neural coding and causal circuit mechanisms in behavior

决策信心：行为中的神经编码和因果回路机制

• 批准号: 8695880
• 负责人: Adam Kepecs
• 金额: $ 45.03万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695880
• 关键词: Affect; Animals; Anxiety; Architecture; Area; Attention; Autistic Disorder; Behavior; Behavioral; Brain; Brain region; Code; Computer Simulation; Data; Decision Making; Disease; Electrophysiology (science); Environment; Gambling; Goals; Heart; Heterogeneity; Human; Impairment; Investigation; Judgment; Lead; Learning; Left; Light; Link; Mediating; Mental Depression; Mental disorders; Methods; Modeling; Motor; Neural Pathways; Neurons; Neurosciences; Obsessive-Compulsive Disorder; Odors; Optics; Organism; Outcome; Pathway interactions; Play; Population; Prefrontal Cortex; Primates; Probability; Process; Property; Psychometrics; Psychophysics; Rattus; Reporting; Rewards; Rodent; Role; Route; Schizophrenia; Signal Transduction; Source; Staging; System; Task Performances; Testing; Time; Uncertainty; Viral; Virus; Work; addiction; base; cell cortex; cell type; computer framework; improved; indexing; information seeking behavior; insight; loss of function; neural circuit; neuromechanism; neuropsychiatry; novel; operation; optogenetics; public health relevance; relating to nervous system; response; tool

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.

描述(申请人提供)：我们研究的长期目标是了解前额叶皮质的神经回路是如何支持决策的。在人类和其他动物中，眼眶前额叶皮质(OFC)是在不确定性条件下进行决策的关键脑区。我们的中心假设是，OFC代表信心信息，并在向大脑其他区域报告决策信心方面发挥因果作用，从而影响行为。学习 在这个问题上，我们开发了啮齿动物的定量心理物理方法，改编自人类和灵长类动物的工作，这使得在一个良好控制的决策任务中能够读取信心的行为读数。简而言之，在每一次试验中，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港后，老鼠等待可能来也可能不来的延迟奖励。如果没有，老鼠最终会离开港口，开始另一次试验。老鼠愿意等待奖励的持续时间可以被认为是对感知决定结果的赌博，因此它提供了一个信心的量化指标。因此，在每个审判中，都有一个感性的决定(左/右)和一个决定后的置信度报告(离开决定)。如果OFC在这一离开决定中是因果的，神经活动应该在逐个试验的基础上预测大鼠在离开之前等待的时间(相关性)我们还将使用药理学失活来测试OFC活动对于这一过程的必要性。这些结果将在一个将神经和行为数据与决策信心联系起来的计算框架中进行解释。接下来，我们将测试这样一个假设，即确定了 投射到不同靶区的OFC神经元携带不同类型的信息，从而调节不同的行为功能。使用逆行病毒传递光敏激活物(ChR2)和抑制物(HALO)，我们将光学微刺激或阻断OFC神经元的子集，这一子集不是由空间接近而是由投射靶点定义的。结合电生理学，我们将确定不同投射神经元的神经相关性，并确定它们是否是试验对试验基础上的置信度报告所必需的和充分的。在完成这些目标后，我们期望确定OFC在决策信心中的作用，并确定它发挥其行动的神经回路。通过记录属于不同长程投射的神经元，我们也期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，我们希望提供一个改进的框架，以了解单个前额叶大脑区域的损伤如何导致如此广泛的精神障碍，包括成瘾、抑郁、焦虑、强迫症、精神分裂症和自闭症。