The Human Neurocircuitry of Occasion Setting in Pavlovian Fear Conditioning

该奖项是美国国家科学基金会社会、行为和经济科学（SBE）博士后研究奖学金（SPRF）项目和SBE认知神经科学项目的一部分。SPRF计划的目标是为学术界、工业界或私营部门和政府的科学事业准备有前途的早期职业博士级科学家。SPRF奖励包括在知名科学家的赞助下进行为期两年的培训，并鼓励博士后进行独立研究。美国国家科学基金会寻求促进科学界各阶层的科学家，包括那些未被充分代表的群体的科学家，参与其研究项目和活动；博士后阶段被认为是实现这一目标的一个重要的专业发展阶段。每个博士后必须解决各自学科领域的重要科学问题。在加州理工学院（California Institute of Technology）的Dean Mobbs博士的赞助下，这个博士后奖学金奖支持一位早期职业科学家，研究焦虑对学习物体/情境之间模糊关系的影响，以及潜在的神经回路。人们在日常生活中需要学习的很多东西至少都有一定程度的模糊性。例如，遇到一个新朋友是一种模棱两可的情况，因为不知道会出现多大程度的积极结果（例如，享受谈话，结交新朋友或浪漫伴侣）或消极结果（例如，无聊，拒绝）。歧义可能在多种情况下对人们的学习和决策产生潜在的负面影响，包括财务、社会、专业或医疗决策。然而，研究人员对人们如何学习减少歧义的了解远远少于他们如何学习一致的关系。临床上，高度焦虑的个体往往难以根据上下文来判断物体/情境是危险的还是安全的，但焦虑如何影响我们学习一个离散刺激如何消除另一个离散刺激意义的能力却不太清楚。例如，一个人可能会感到焦虑，因为只有在某些时候，他的演讲可能会被拒绝，比如当他在一个特别雄辩和迷人的演讲者之后发表演讲时。通过了解人们如何了解模棱两可，这个项目的结果可能最终有助于旨在提高人们的生活质量和治疗焦虑症的研究。巴甫洛夫情境设置是一种学习现象，在这种现象中，特定的刺激（即情境设置者）有助于消除模糊性。场合设置发生在一个刺激(X)调节另外两个刺激之间的关系时：通常是条件刺激（CS）和生物相关刺激（即无条件刺激；US）。例如，当情境设定者X出现时，CS才会预测美国。场合设置可以是上下文线索（如时间、地点）或离散线索（如语气、光线）。例如，公开演讲是否会导致听众的拒绝可能是模糊的/不确定的。对于一个有时害怕这种情况发生的人来说，在一个特别雄辩的演讲者（离散提示场合设置者）之后发表演讲，或者在一个特定的地方，听众是众所周知的挑剔的（语境场合设置者），可能会消除情况的模糊性，导致对被拒绝的恐惧增加。本研究旨在了解情境设定、情境设定的神经机制，以及情境设定与焦虑的关系。本项目包括两项巴甫洛夫恐惧条件反射研究：第一项研究将评估焦虑在离散刺激情境设置下对安全/危险消歧化的影响，第二项研究将使用功能磁共振成像（fMRI）研究离散刺激情境设置的神经机制。研究人员还将在两项研究中测量恐惧的自我报告和生理反应。通过了解情境设置，本项目可能有助于旨在改善人们生活质量和改善焦虑症治疗的研究。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award was provided as part of NSF's Social, Behavioral and Economic Sciences (SBE) Postdoctoral Research Fellowships (SPRF) program and SBE's Cognitive Neuroscience program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from underrepresented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. Under the sponsorship of Dean Mobbs, PhD at California Institute of Technology, this postdoctoral fellowship award supports an early career scientist investigating the effects of anxiety on learning about ambiguous relationships between objects/situations, as well as the underlying neurocircuitry. Much of what people need to learn about in everyday life contains at least some degree of ambiguity. For example, meeting someone new is an ambiguous situation since it is unknown to what degree positive outcomes (e.g., enjoying the conversation, making a new friend or romantic partner) or negative outcomes (e.g., boredom, rejection) will occur. Ambiguity can potentially negatively affect people's learning and decision making in multiple situations, including financial, social, professional, or medical decision making. However, researchers know far less about how people learn to reduce ambiguity than how they learn about consistent relationships. Clinically, highly anxious individuals tend to have difficulty disambiguating whether objects/situations are dangerous or safe based on context, but it is less clear how anxiety affects our ability to learn how one discrete stimulus disambiguates the meaning of another discrete stimulus. For example, a person may feel anxious that giving a speech may lead to rejection only some of the time, such as when they give their speech after a particularly eloquent and engaging speaker. By understanding how people learn about ambiguity, the results of this project may ultimately contribute to research aiming to improve people's quality of life and the treatment of anxiety disorders.Pavlovian occasion setting is a learning phenomenon in which specific stimuli (i.e., occasion setters) help resolve ambiguity. Occasion setting occurs when a stimulus (X) modulates the relationship between two other stimuli: usually a conditional stimulus (CS) and a biologically relevant stimulus (i.e., unconditional stimulus; US). For example, positive occasion setting occurs when the CS predicts the US only if the occasion setter, X, is presented. Occasion setters can be contextual cues (e.g., time, place) or discrete cues (e.g., tone, light). For example, whether giving public speeches leads to rejection from the audience may be ambiguous/uncertain. For a person who is sometimes afraid of this happening, giving a speech after a particularly eloquent speaker (discrete cue occasion setter) or in a particular location where the audience is known to be critical (contextual occasion setter) may disambiguate the situation, leading to increased fear of rejection. In this research proposal, the goal is to better understand occasion setting, its neural mechanism, and its relation to anxiety. This project consists of two Pavlovian fear conditioning studies: the first study will assess the effects of anxiety on disambiguating safety/danger with discrete stimulus occasion setting, and the second will be conducted using fMRI to investigate the neural mechanisms of discrete stimulus occasion setting. The researchers will also measure self-report and physiological responses of fear in both studies. By understanding occasion setting, this project may be able to contribute to research aimed at improving people's quality of life and improve the treatment of anxiety disorders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.