The Human Neurocircuitry of Occasion Setting in Pavlovian Fear Conditioning

该奖项是作为NSF社会、行为和经济科学(SBE)博士后研究奖学金(SPRF)计划和SBE认知神经科学计划的一部分提供的。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职业生涯培养有前途的、早期职业博士水平的科学家。SPRF奖项包括在知名科学家的赞助下进行两年的培训，并鼓励博士后研究员进行独立研究。国家科学基金会致力于促进科学界所有阶层的科学家参与其研究方案和活动，包括那些来自代表性不足的群体的科学家；博士后阶段被认为是实现这一目标的专业发展的一个重要水平。每个博士后研究员都必须解决推动各自学科领域向前发展的重要科学问题。在加州理工学院博士迪恩·莫布斯的赞助下，这一博士后奖学金奖项支持一名早期职业科学家，研究焦虑对了解物体/情景之间的模糊关系以及潜在的神经回路的影响。人们在日常生活中需要学习的许多东西至少包含一定程度的模棱两可。例如，遇到一个新的人是一种模棱两可的情况，因为它不知道在多大程度上会出现积极的结果(例如，享受谈话、结交新朋友或浪漫的伴侣)或消极的结果(例如，无聊、拒绝)。模棱两可可能会在多种情况下对人们的学习和决策产生负面影响，包括财务、社会、职业或医疗决策。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了解始终如一的关系。在临床上，高度焦虑的人往往很难根据背景来辨别物体/情况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的含义的能力还不太清楚。例如，一个人可能会感到焦虑，因为在某些情况下，演讲可能会导致拒绝，比如当他们在一个特别雄辩和吸引人的演讲者之后发表演讲时。通过了解人们如何学习歧义，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焦虑症治疗的研究。巴甫洛夫情景是一种学习现象，在这种学习现象中，特定的刺激(即情景创建者)有助于解决歧义。当刺激(X)调节其他两个刺激之间的关系时，就会发生情景设置：通常是条件刺激(CS)和生物相关的刺激(即无条件刺激；美国)。例如，只有当呈现情景设定者X时，当CS预测美国时，才会发生积极情景设置。情景设定者可以是上下文提示(例如，时间、地点)或离散提示(例如，音调、光线)。例如，公开演讲是否会导致听众的拒绝可能是模棱两可的/不确定的。对于一个有时害怕这种情况发生的人来说，在一个特别能言善辩的演讲者(离散线索场合创建者)之后或在已知听众持批评态度的特定地点(语境情境创建者)发表演讲可能会消除情况的歧义，导致对拒绝的恐惧增加。在这项研究方案中，目的是更好地了解情景设置、其神经机制以及它与焦虑的关系。本项目由两个巴甫洛夫恐惧条件作用研究组成：第一个研究将评估焦虑在离散刺激情景下消除安全/危险歧义的效果，第二个研究将使用功能磁共振成像来研究离散刺激情景设置的神经机制。研究人员还将在这两项研究中测量自我报告和恐惧的生理反应。通过了解场合设置，该项目可能能够为旨在提高人们的生活质量和改善焦虑症患者治疗的研究做出贡献。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.