Neural Bases of Disgust Conditioning in Anorexia Nervosa

项目总结/摘要 此K23应用程序旨在支持丽莎安德森博士实现她的首要目标， 独立的，以病人为导向的研究生涯，将（a）阐明生物和心理机制 与进食障碍的风险和维持相关，以及（B）使用该信息来开发和优化 精确有效的饮食失调治疗方法拟议中的申请将加强安德森博士的 通过提供高级培训，提高其实现职业目标的能力，这些培训旨在：（a）发展理论方面的专门知识 和评估的厌恶条件反射机制涉及transdiagnosis模型精神病理学 以回避行为为特征，并将这些知识转化为饮食失调的研究;（B） 获得进行独立研究所需的神经影像学方法的知识和技能 饮食失调的神经基础;以及（c）获得神经成像分析（fMRI）的高级培训 独立检查各种饮食失调的维持机制所需的数据 测量单位（即，心理、行为、生理和神经生物学水平变量）。博士 安德森已经组建了一个专家团队，他们将提供培训，以完成拟议的培训目标 科学的目的。核心导师团队由Scott Crow博士（翻译饮食培训 Dr. Kathryn Cullen（神经影像学培训），Dr. Mark Fiecas（生物统计学），Dr. Shmuel Lissek（厌恶学习的交叉诊断模型）和托马斯希尔德布兰特博士（厌恶的翻译 学习模型，厌食症的厌恶强化学习的计算建模 nervosa [AN]）。Kelvin Lim博士将为神经影像学研究设计和R 01应用准备提供咨询。博士 卡罗尔彼得森将咨询情绪调节模型和情绪为基础的机制研究吃 紊乱乔希·西斯勒博士将咨询厌恶为基础的任务设计和计算模型的厌恶 强化学习作为培训的一部分，安德森博士将完成一项由两部分组成的研究。研究1a将 比较在特定食物的厌恶概括和灭绝任务期间， 与AN和非进食障碍比较参与者的个体，以建立神经系统的程度， 食物特异性厌恶泛化和消退的底物具体涉及食物回避， 限制性饮食的严重性。在纵向臂中，研究1b将确定神经系统 与厌恶泛化和消退相关的激活模式预测了后来的AN维持。总的来说， 除了支持安德森博士的培训目标外，该项目还将通过确定 可能是食物回避症状严重程度和障碍的基础的厌恶条件反射机制 在AN的维护。这些知识最终将为新型生物治疗的开发提供信息（例如， 精神药理学，神经调节）和心理干预的优化（例如，强化- 基于心理疗法），促进这种持续性精神障碍的长期恢复。

PROJECT SUMMARY/ABSTRACT This K23 application aims to support Dr. Lisa Anderson to achieve her overarching goal of establishing an independent, patient-oriented research career that will (a) elucidate biological and psychological mechanisms associated with risk and maintenance of eating disorders, and (b) use this information to develop and optimize precise, efficacious treatments for eating disorders. The proposed application will strengthen Dr. Anderson’s abilities to meet her career goals by providing advanced training designed to: (a) develop expertise in theory and assessment of disgust conditioning mechanisms involved in transdiagnostic models psychopathology characterized by avoidance behaviors, and to translate this knowledge to research for eating disorders; (b) gain knowledge and skills in neuroimaging methods necessary to conduct independent research investigating the neural substrates of disordered eating; and (c) obtain advanced training in analysis of neuroimaging (fMRI) data required to independently examine maintenance mechanisms underlying eating disorders across various units of measurement (i.e., psychological-, behavioral-, physiological-, and neurobiological-level variables). Dr. Anderson has assembled a team of experts who will provide training to accomplish the proposed training goals and scientific aims. The core mentorship team consists of Dr. Scott Crow (training in translational eating disorders research), Dr. Kathryn Cullen (neuroimaging training), Dr. Mark Fiecas (biostatistics), Dr. Shmuel Lissek (cross-diagnostic models of disgust learning), and Dr. Thomas Hildebrandt (translation of disgust learning models to eating disorders, computational modeling of aversive reinforcement learning in anorexia nervosa [AN]). Dr. Kelvin Lim will consult on neuroimaging study design and R01 application preparations. Dr. Carol Peterson will consult on emotion regulation models and emotion-based mechanisms research for eating disorders. Dr. Josh Cisler will consult on disgust-based task design and computational models of aversive reinforcement learning. As part of her training, Dr. Anderson will complete a two-part study. Study 1a will compare patterns in neural activation during a food-specific disgust generalization and extinction task between individuals with AN and non-eating-disorder comparison participants to establish the extent to which the neural substrates of food-specific disgust generalization and extinction specifically relate to food avoidance and restrictive eating severity in AN. In a longitudinal arm, Study 1b will determine the extent to which neural activation patterns associated with disgust generalization and extinction predict later AN maintenance. Overall, in addition to supporting Dr. Anderson’s training goals, this project will meet a critical need by identifying disgust conditioning mechanisms that may underlie food avoidance symptom severity and disorder maintenance in AN. This knowledge will ultimately inform the development of novel biological treatments (e.g., psychopharmacology, neuromodulation) and optimization of psychological interventions (e.g., reinforcement- based psychotherapies) that promote long-term recovery from this persistent psychiatric disorder.