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：
9353881
负责人：
Christine Marie Constantinople
金额：
$ 13.01万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-16 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9353881
关键词：
Address Animals Behavior Behavioral Behavioral Paradigm Bipolar Disorder Brain Brain region Choice Behavior Cognitive Collaborations Cues Data Data Set Decision Making Development Environment Evaluation Event Exhibits Female Foundations Frequencies Gambling Goals Head Health Human Image Imaging Techniques Impairment Individual Institutes Insurance Laboratories Leadership Learning Light Mental Health Mental disorders Mentors Methods Modeling Monitor Neurons Neurosciences Noise Outcome Overweight Parietal Lobe Pharmacology Phase Play Population Population Dynamics Positioning Attribute Probability Procedures Psychophysics Rattus Research Resolution Rewards Risk Schizophrenia Side Statistical Data Interpretation Statistical Models Study models System Techniques Testing Time Training Transgenic Organisms Underweight Visual Cortex Water Work Writing base calcium indicator cognitive function collaborative environment cost effective experimental study high dimensionality imaging system improved innovation male neural circuit neuromechanism novel optogenetics relating to nervous system restraint skills symposium tool two-photon

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"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

行为经济学描述了选择偏离规范（即最优）行为的多种方式。例如，人类决策的一个普遍特征是概率扭曲：人类倾向于高估小概率而低估大概率。当个人决定购买保险或玩彩票时，这些决定会受到他们认为低概率结果的可能性的影响。另一种普遍存在的决策偏差被称为“热手谬误”，人们错误地将随机成功视为连胜，相信自己拥有“热手”。这些近乎普遍的现象可能反映了决策神经基础的基本方面。精神疾病（包括精神分裂症和双相情感障碍）的决策会受到干扰9-14。对大脑在决策过程中如何表示概率的电路级理解对人类健康具有重大影响。我最近使用高通量行为训练来开发用于研究大鼠概率扭曲的行为范例，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进行选择。在这种行为过程中，我对两个大脑区域进行了四极管记录，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，虽然这些扰动并没有扰乱老鼠的概率扭曲，但它们产生了有趣的效果。老鼠表现出“热手偏见”，即他们更有可能在做出有回报的冒险选择后进行赌博。 OFC 的光遗传学抑制消除了 13 只大鼠的热手偏差；抑制 PPC 对热手偏差没有影响。因此，到目前为止，我们已经确定了一个大脑区域，即 OFC，是导致普遍存在的决策偏差的原因，这种偏差明显影响着人类在金融、赌博和职业体育方面的行为。到目前为止，我正在准备并提交有关这项工作的两份手稿。我接受了完成该奖项 R00 阶段所需的所有技术培训。在 R00 阶段，我将进行光遗传学和药理学微扰实验，以描绘概率失真背后的功能因果回路。我还将使用投影特异性光遗传学和记录方法来探索 OFC 中神经元的特定子电路是否优先负责调节热手偏差。总之，这些实验将把大鼠建立为一种经济高效、易于处理的哺乳动物模型，用于研究决策偏差的神经基础，并将产生动物计算、表示和扭曲概率估计的电路和机制的消息灵通的工作模型。我已获得纽约大学神经科学中心助理教授的终身职位。在00阶段，我将利用我在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的实验室