Neural Bases of Disgust Conditioning in Anorexia Nervosa

项目摘要/摘要 此K23应用程序旨在支持Lisa Anderson博士实现她的首要目标，即建立 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 与饮食失调的风险和维持有关，以及(B)使用这些信息来开发和优化 精确、有效的饮食失调治疗。拟议中的申请将加强安德森博士的 通过提供高级培训来实现其职业目标的能力，旨在：(A)在理论上发展专门知识 和评估跨诊断模型中涉及的厌恶条件作用机制 以回避行为为特征，并将这一知识转化为饮食失调研究；(B) 获得进行独立研究调查所需的神经成像方法方面的知识和技能 饮食失调的神经基础；以及(C)接受神经成像分析(FMRI)方面的高级培训 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的变量)。Dr。 安德森组建了一个专家团队，他们将提供培训，以实现拟议的培训目标 和科学目标。核心指导团队由Scott Crow博士(翻译进食培训 障碍研究)，Kathryn Cullen博士(神经成像培训)，Mark Fiecas博士(生物统计学)，Shmuel博士 LISSEK(厌恶学习的交叉诊断模型)和Thomas Hildebrandt博士(厌恶的翻译 进食障碍的学习模型，厌食症患者厌恶强化学习的计算模型 神经质的，神经质的Kelvin Lim博士将就神经成像研究设计和R01应用准备提供咨询。Dr。 Carol Peterson将就情绪调节模型和基于情绪的进食机制研究提供咨询 精神错乱。乔希·西斯勒博士将为厌恶者的任务设计和计算模型提供咨询 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 比较食物特异性厌恶概括和消退任务中的神经激活模式 将患有进食障碍的个体与非进食障碍的参与者进行比较，以确定神经功能的程度 食物特有的厌恶泛化和消亡的底物具体涉及食物避免和 限制进食的严重程度。在纵向臂中，研究1b将确定神经的程度 与厌恶、泛化和消亡相关的激活模式预示着后来的维持。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 厌恶的条件反射机制可能是食物回避症状严重和紊乱的基础 维护在一个。这一知识最终将为开发新的生物治疗方法(例如， 精神药理学、神经调节)和心理干预的优化(例如，强化- 以心理疗法为基础)，促进这种持续性精神障碍的长期康复。

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.