Neural mechanisms of probability estimation during decision-making

决策过程中概率估计的神经机制

• 批准号: 9816021
• 负责人: Christine Marie Constantinople
• 金额: $ 24.9万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-12 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9816021
• 关键词: Address; Affect; Animals; Award; Behavior; Behavioral; Behavioral Paradigm; Bipolar Disorder; Brain; Brain region; Choice Behavior; Cues; Data; Data Set; Decision Making; Environment; Evaluation; Event; Exhibits; Female; Foundations; Frequencies; Gambling; Hand; Health; Human; Image; Imaging Techniques; Impairment; Individual; Insurance; Laboratories; Light; Manuscripts; Mediating; Mental Health; Mental disorders; Mentors; Methods; Modeling; Monitor; Neurons; New York; Noise; Outcome; Overweight; Parietal Lobe; Pharmacology; Phase; Play; Population; Population Dynamics; Positioning Attribute; Probability; Procedures; Process; Psychophysics; Rattus; Rewards; Risk; Schizophrenia; Science; Secure; Side; Sports; Statistical Data Interpretation; Statistical Models; Study models; System; Techniques; Testing; Time; Training; Transgenic Organisms; Underweight; Universities; Visual Cortex; Water; Work; base; behavioral economics; cognitive function; cost effective; experimental study; high dimensionality; improved; male; neural circuit; neuromechanism; novel; optogenetics; professor; relating to nervous system; skills; success; tenure track; tool; two-photon

Behavioral economics has described many ways in which choice deviates from normative (i.e., optimal) behavior. For example, a pervasive feature of human decision-making is probability distortion: humans tend to overweight small probabilities and underweight large probabilities. When individuals decide to purchase insurance or play the lottery, these decisions are influenced by how likely they perceive low probability outcomes to be. Another ubiquitous decision bias is called the "Hot-Hand Fallacy"S in which people mistakenly perceive random successes as winning streaks, believing that they have a "hot hand." These near universal phenomena may reflect fundamental aspects of the neural substrates of decision-making. Decision-making is disrupted in psychiatric disorders including schizophrenia and bipolar disorder9-14. A circuit-level understanding of how the brain represents probabilisties during decision-making has great consequences for human health. I have recently used high-throughput behavioral training to develop behavioral paradigms for studying probability distortion in rats, enabling application of powerful tools to monitor and manipulate neural circuits. In this task, rats chose between probabilistic and guaranteed rewards. I have performed tetrode recordings from two brain regions during this behavior, posterior parietal cortex (PPC) and orbitofrontal cortex. I performed optogenetic perturbations of these regions, and while these did not perturb rats' probability distortion, they produced an intriguing effect. Rats exhibited a "Hot-Hand Bias," in which they were more likely to gamble following risky choices that were rewarded. Optogenetic inhibition of OFC eliminated the hot-hand bias in 13 rats; inhibition of PPC had no effect on the hot-hand bias. Therefore, thus far, we have identified a brain region, the OFC, as causal to a ubiquitous decision bias that demonstrably affects human behavior in finance, gambling, and professional sports. I am in the process of preparing and submitting two manuscripts about this work so far. I have been trained in all of the techniques required to complete the R00 phase of the award. In the R00 phase, I will perform optogenetic and pharmacological perturbation experiments to delineate the functional causal circuits underlying probability distortion. I will also use projection-specific optogenetic and recording methods to explore whether specific subcircuits of neurons in OFC are preferentially responsible for mediating the hot-hand bias. Together, these experiments will establish the rat as a cost-effective, tractable mammalian model for studying the neural basis of decision biases and will produce well-informed working models of the circuits and mechanisms by which animals compute, represent, and distort probability estimates. I have secured a tenure-track position as an Assistant Professor in the Center for Neural Science at New York University. In 00 phase, I will use the skills I have acquired during the K99 phase to complete the proposed aims and build a laboratory focused on the study

行为经济学描述了许多选择偏离规范的方式（即，最佳）行为。例如，人类决策的一个普遍特征是概率失真：人类倾向于高估小概率，低估大概率。当个人决定购买保险或玩彩票时，这些决定受到他们认为低概率结果的可能性的影响。另一个普遍存在的决策偏见被称为“手气热谬误“，即人们错误地将随机的成功视为连胜，认为自己有一个“手气热”。“这些近乎普遍的现象可能反映了决策的神经基质的基本方面。精神疾病包括精神分裂症和双相情感障碍的决策中断9 -14。从回路层面理解大脑在决策过程中如何表现概率，对人类健康有着重大影响。 我最近使用高通量行为训练来开发研究大鼠概率失真的行为范式，从而能够应用强大的工具来监测和操纵神经回路。在这项任务中，老鼠在概率奖励和保证奖励之间做出选择。在这个行为过程中，我对两个大脑区域进行了四极记录，即后顶叶皮层（PPC）和眶额皮层。我对这些区域进行了光遗传学扰动，虽然这些并没有扰乱老鼠的概率失真，但它们产生了一种有趣的效果。老鼠表现出一种“热手偏见”，即它们更有可能在有回报的冒险选择后赌博。光遗传抑制OFC消除了13只大鼠的热手偏向;抑制PPC对热手偏向没有影响。因此，到目前为止，我们已经确定了一个大脑区域，眶额皮层，作为一个普遍存在的决策偏见的因果关系，这显然会影响人类在金融，赌博和职业运动中的行为。目前我正在准备和提交两份关于这项工作的手稿。我已经接受了完成R 00阶段奖励所需的所有技术培训。 在R 00阶段，我将进行光遗传学和药理学扰动实验，以描绘概率失真背后的功能因果回路。我还将使用投射特异性光遗传学和记录方法来探索OFC中神经元的特定子回路是否优先负责介导热手偏置。总之，这些实验将建立大鼠作为一个具有成本效益的，易于处理的哺乳动物模型，用于研究决策偏差的神经基础，并将产生良好的工作模型的电路和机制，动物计算，代表，并扭曲概率估计。 我已经在纽约大学神经科学中心获得了一个终身助理教授的职位。在00阶段，我将使用我在K99阶段获得的技能来完成拟议的目标，并建立一个专注于研究的实验室