Taste reward circuits and prediction error define eating disorder psychopathology

描述(申请人提供)：进食障碍(EDS)、神经性厌食症(AN)和神经性暴食症(BN)是严重的精神疾病，死亡率很高。虽然AN的主要特征是严重体重不足，BN患者处于正常到高体重，并定期暴饮暴食和排泄，但这两种疾病都有许多重叠的症状，如食物限制、间歇性暴食、排泄或过度运动。人们对ED的神经生物学以及特定的ED行为如何与特定的生物机制联系在一起知之甚少。NIMH的资助机会“通过生物学和行为的维度研究推进饮食障碍研究”直接回应了这种知识的缺乏。在目前的应用中，使用NIMH的研究领域标准(RDoC)项目中的“预测误差”结构，我们研究了大脑功能和结构如何成为与ED相关的行为维度的生物学机制。这一结构与特定的大脑奖赏回路反应有关，这可能与特定的ED相关行为有关。目的1.利用RDoC结构预测误差，研究功能性神经奖赏回路是如何构成ED病理维度的。这项应用将研究所有16-29岁接受ED治疗的人，以捕捉ED的全部病理(符合RDoC要求)，研究AN死亡率最高的年龄范围，并通过在有限的年龄范围内研究青少年和年轻人来确定潜在的发育因素。这项研究将包括详细的临床评估以及味觉奖励预测错误反应的功能磁共振脑成像(FMRI)。通过前腹侧纹状体(尾状核/壳核)和脑岛预测错误反应来预测ED相关行为。此外，ED受试者较低的体重指数(BMI)将与较高的奖励值激活相关，以预测前扣带回皮质的条件刺激，该区域对于比较包括奖赏在内的刺激的行为反应选项很重要。目的2.进行灰质和白质体积的结构磁共振脑成像(SMRI)，以及白质完整性的扩散张量成像。我们预计，更严重的ED行为将预示尾状核和脑岛体积的降低。此外，岛叶和腹侧纹状体的灰质体积将从目标1开始预测功能性脑奖励激活的强度。目的3.根据预测误差反应而不是传统的DSM标准对ED个体进行分类，并将基于这种新分类的ED相关行为与年龄匹配的健康青少年和成人对照进行比较。在对显著刺激的敏感度方面，预测误差反应在ED受试者的聚集性上优于DSM，并且与对照相比。这将表明，EDS是显著反应改变的障碍。

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.