Neural mechanisms of probability estimation during decision-making

行为经济学描述了选择偏离规范（即最优）行为的许多方式。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，低估大概率。当个人决定购买保险或购买彩票时，这些决定受到他们认为低概率结果的可能性的影响。另一种普遍存在的决策偏差被称为“热手谬误”（hot - hand Fallacy），即人们错误地将随机的成功视为连胜，认为自己有一手热手。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。包括精神分裂症和双相情感障碍在内的精神疾病患者的决策被打乱。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有重大影响。我最近使用高通量行为训练来开发研究大鼠概率扭曲的行为范式，使应用强大的工具来监测和操纵神经回路成为可能。在这个任务中，老鼠在概率奖励和保证奖励之间做出选择。在这种行为中，我用四极电极记录了大脑的两个区域，后顶叶皮层（PPC）和眼窝额叶皮层。我对这些区域进行了光遗传扰动，虽然这些并没有干扰老鼠的概率扭曲，但它们产生了一个有趣的效果。老鼠表现出热手偏见，在这种情况下，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对热手偏向无影响。因此，到目前为止，我们已经确定了一个大脑区域，OFC，作为普遍存在的决策偏差的原因，它明显影响着人类在金融、赌博和职业体育中的行为。到目前为止，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R00阶段奖项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扰动实验，以描述概率扭曲背后的功能因果电路。我还将使用投影特异性光遗传学和记录方法来探索OFC神经元的特定亚回路是否优先负责介导热手偏倚。总之，这些实验将使大鼠成为研究决策偏差的神经基础的一种具有成本效益的、易于处理的哺乳动物模型，并将为动物计算、表示和扭曲概率估计的电路和机制提供信息充分的工作模型。我已获得纽约大学神经科学中心的终身职位，担任助理教授。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，并建立一个实验室，专注于使用创新的行为，电生理，计算和光遗传学方法研究概率扭曲和决策。

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.