Taste reward circuits and prediction error define eating disorder psychopathology

描述（申请人提供）：进食障碍（ED）、神经性厌食症（AN）和神经性贪食症（BN）是严重的精神疾病，死亡率高。虽然AN的主要特征是体重严重不足，而BN个体处于正常至高体重并定期暴饮暴食和腹泻，但两种疾病之间存在许多重叠的症状，例如食物限制，间歇性暴饮暴食，腹泻或过度运动。关于ED的神经生物学以及特定的艾德行为如何与特定的生物学机制联系在一起，我们知之甚少。NIMH资助机会“通过生物学和行为的维度研究推进饮食失调研究”是对这种知识缺乏的直接回应。在本申请中，使用来自NIMH的研究领域标准（RDoC）项目的“预测误差”构造，我们研究脑功能和结构如何可能是艾德相关行为的基本维度的生物机制。这种结构与特定的大脑奖赏回路反应有关，这可能与特定的艾德相关行为有关。目标1.是使用RDoC结构预测误差来研究功能性神经奖励回路如何成为艾德病理学维度的基础。本申请将研究年龄在16- 29岁之间接受艾德治疗的所有个体，以获取艾德病理学的全部范围（符合RDoC要求），研究AN死亡率最高的年龄范围，并通过研究青少年和年轻人同时保持在有限的年龄范围内来识别潜在的发育因素。这项研究将包括详细的临床评估以及功能性磁共振脑成像（fMRI）的味觉奖励预测错误反应。艾德相关行为将通过前腹侧纹状体（尾状核/壳核）以及纹状体预测错误响应来预测。此外，艾德受试者中较低的体重指数（BMI）将与预测前扣带皮层中条件刺激的奖励值的较高激活相关，前扣带皮层是比较对包括奖励在内的刺激的行为反应选项的重要区域。目标二。是对灰色和白色物质体积进行结构磁共振脑成像（sMRI），以及对白色物质完整性进行扩散张量成像。我们预计更严重的艾德行为将预示更低的尾状核和小脑体积。此外，中脑和腹侧纹状体中的灰质体积将预测来自Aim 1的功能性大脑奖励激活的强度。目标3.基于预测误差响应而不是传统的DSM标准对艾德个体进行聚类，并将基于这种新分类的艾德相关行为与年龄匹配的健康青少年和成人对照进行比较。预测误差响应将是上级的DSM在聚类的艾德主题的维度的敏感性显着的刺激和对照。这将表明ED是改变的突显性反应的障碍。

DESCRIPTION (provided by applicant): The eating disorders (EDs) anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. While AN is mainly characterized by severe underweight and BN individuals are at normal to high weight and regularly binge and purge, there are many overlapping symptoms across both disorders, such as food restriction, episodic binge eating, purging or excessive exercise. Little is known about the neurobiology of EDs and how specific ED behaviors are linked to particular biological mechanisms. The NIMH Funding opportunity "Advancing Eating Disorders Research through Dimensional Studies of Biology and Behavior" is in direct response to this lack of knowledge. In the present application, using the "Prediction Error" construct from the NIMH's Research Domain Criteria (RDoC) project, we examine how brain function and structure could be biological mechanisms underlying dimensions of ED relevant behaviors. This construct has been associated with specific brain reward circuit responses, which could be related to particular ED relevant behaviors. Aim 1. is to study how functional neural reward circuits underlie dimensions of ED pathology using the RDoC construct prediction error. This application will study all individuals ages 16- 29 years who present for ED treatment to capture the full range of ED pathology (conforming with RDoC requirements), to study the age range with the highest mortality rate for AN, and to identify potential developmental factors by studying adolescents and young adults while staying within a limited age range. The study will include detailed clinical assessments as well as functional magnetic resonance brain imaging (fMRI) for taste-reward prediction error response. ED relevant behaviors will be predicted by anteroventral striatum (caudate/putamen) as well as insula prediction error response. In addition, lower body mass index (BMI) in ED subjects will be associated with higher activation to reward value predicting conditioned stimuli in the anterior cingulate cortex, an area important for comparing options of behavior response to stimuli including reward. Aim 2. is to perform structural magnetic resonance brain imaging (sMRI) for gray and white matter volume, as well as diffusion tensor imaging for white matter integrity. We expect that more severe ED behaviors will predict lower caudate and insula volumes. In addition, gray matter volume in insula and ventral striatum will predict strength of functional brain reward activation from Aim 1. Aim 3. is to cluster ED individuals based on prediction error response instead of traditional DSM criteria, and compare ED relevant behaviors based on this new classification with age matched healthy adolescent and adult controls. Prediction error response will be superior to DSM in clustering of ED subjects by dimensions of sensitivity to salient stimuli and in contrast to controls. This will suggest that EDs are disorders of altered salience response.