Neural mechanisms of probability estimation during decision-making

决策过程中概率估计的神经机制

基本信息

批准号：
9894590
负责人：
Christine Marie Constantinople
金额：
$ 2.06万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-05 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9894590
关键词：
Address African American Amaze Amygdaloid structure Attitude Authorship Award Behavior Behavioral Behavioral Paradigm Biological Models Biology Bipolar Disorder Brain region Chicago Cognitive Collaborations Data Analyses Decision Making Discipline Doctor of Philosophy Ecology Economics Electrophysiology (science)Evolution Exhibits Faculty Fiber Funding Gambling Grant Hand Human Impairment Individual Intelligence Left Medial Medial Dorsal Nucleus Mental Health Mental disorders Methods Monitor Motivation NCI Scholars Program Neurons Neurosciences Outcome Overweight Phase Photometry Population Prefrontal Cortex Probability Process Psychology Publications Rattus Recording of previous events Research Research Project Grants Resolution Rewards Risk Rodent Schizophrenia Schools Soccer Sports Thalamic structure Time Training Transcript Underrepresented Minority Underweight Universities Update Wild Animals Woman Work base behavioral economics college experience experimental study graduate student improved interest neural circuit neuromechanism nonhuman primate novel optogenetics parent grant preference programs relating to nervous system skills student mentoring success theories tool undergraduate student

项目摘要

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” 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 disorder. A circuit-level understanding of how the brain represents probabilities 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 the R00 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 of probability distortion and decision-making using innovative behavioral, electrophysiological, computational, and optogenetic approaches.

行为经济学已经描述了许多方法，可以选择与正常（即最佳）行为偏差。例如，人类决策的普遍特征是概率扭曲：人类倾向于超重的小可能性和体重不足的大可能性。当个人决定购买保险或播放彩票时，这些决定会受到他们认为低概率结果的可能性的影响。另一个无处不在的决定偏见被称为“热手谬论”，在这种谬论中，人们错误地将随机的成功视为胜利的连胜，并认为他们有热手。这些近乎普遍的现象可能反映了决策神经底物的基本方面。在包括精神分裂症和躁郁症在内的精神疾病中，决策受到了破坏。对大脑在决策过程中如何代表可能性的电路级别的理解对人类健康产生了重大影响。我最近使用了高通量行为训练来开发行为范式来研究大鼠的概率失真，从而可以应用强大的工具来监测和操纵中性电路。在此任务中，大鼠在概率和保证的奖励之间进行选择。在这种行为期间，我从两个大脑区域，后顶层皮层（PPC）和眶额皮层进行了四极管记录。我对这些区域进行了光遗传学扰动，尽管这些区域没有扰动大鼠的概率失真，但它们产生了有趣的效果。大鼠暴露了一种热偏见，在这种偏见中，他们更有可能跟随得到奖励的风险选择。 OFC的光遗传学抑制消除了13只大鼠的热偏见； PPC的抑制对热手偏置没有影响。因此，到目前为止，我们已经确定了一个大脑区域，即OFC，是无处不在的决策偏见的因果关系，这显然是我正在准备和提交有关这项工作的两个手稿的过程。我已经接受了完成奖项R00阶段所需的所有技术的培训。在R00阶段，我将执行光遗传学和药理扰动实验，以描绘概率失真的功能性因果电路。我还将使用投影特异性的光遗传学和记录方法来探索OFC中神经元的特定亚电路是否更有可能响应介导热手偏见。总之，这些实验将把大鼠建立为一种具有成本效益的，可牵引的哺乳动物模型，用于研究决策偏见的神经元基础，并将产生良好的动物计算，代表和扭曲概率估计的电路和机制的良好工作模型。我担任纽约大学神经科学中心助理教授的任期职位。在R00阶段，我将使用我在K99阶段获得的技能来完成提出的目标，并建立一个专注于研究概率失真和决策的实验室，使用创新的行为，电生理，计算和光遗传学方法。