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，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是S的“热手谬误”，即人们错误地将随机的成功视为连胜，认为自己有一只“热手”。这些近乎普遍的现象可能反映了决策的神经基础的基本方面。包括精神分裂症和双相情感障碍在内的精神障碍患者的决策能力会受到干扰。对大脑在决策过程中如何表示概率的电路水平的理解对人类健康有很大的影响。 最近，我使用高通量行为训练来开发行为范式，用于研究大鼠的概率扭曲，使强大的工具能够应用于监测和操纵神经回路。在这项任务中，老鼠在概率回报和保证回报之间做出选择。在这种行为过程中，我对大脑的两个区域--后顶叶皮质(PPC)和眶前叶皮质--进行了四极管记录。我对这些区域进行了光遗传扰动，虽然这些并没有扰乱老鼠的概率扭曲，但它们产生了一个有趣的效果。老鼠表现出一种“热手偏向”，即它们更有可能在做出有回报的高风险选择后赌博。光发生抑制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，这种偏差明显影响人们在金融、赌博和职业体育方面的行为。到目前为止，我正在准备和提交关于这项工作的两份手稿。我已经接受了完成该奖项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物微扰实验，以描绘概率扭曲背后的功能因果电路。我还将使用投射特异性的光发生和记录方法来探索OFC中特定的神经元亚路是否优先负责调节热手偏向。总之，这些实验将建立大鼠作为研究决策偏差的神经基础的具有成本效益的、易处理的哺乳动物模型，并将产生动物计算、表示和扭曲概率估计的电路和机制的信息丰富的工作模型。 我已经获得了纽约大学神经科学中心助理教授的终身教职。在00阶段，我将使用我在K99阶段学到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

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