Taste reward circuits and prediction error define eating disorder psychopathology

味觉奖励回路和预测误差定义了饮食失调精神病理学

• 批准号: 8678582
• 负责人: Guido KW Frank
• 金额: $ 38.72万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8678582
• 关键词: Adolescent; Adolescent and Young Adult; Adult; Age; Anorexia Nervosa; Anterior; Area; Behavior; Binge Eating; Biological; Biology; Body mass index; Brain; Brain imaging; Bulimia; Categories; Classification; Clinical assessments; Corpus striatum structure; Data; Decision Making; Development; Diagnosis; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Dopamine; Eating Disorders; Emotional; Emotions; Funding Opportunities; Goals; Individual; Insula of Reil; Knowledge; Link; Magnetic Resonance; Measures; Mental disorders; Methods; Monitor; National Institute of Mental Health; Neurobiology; Neurosciences; Pathology; Patients; Pharmaceutical Preparations; Psychopathology; Punishment; Research; Research Domain Criteria; Rewards; Stimulus; Structure; Subgroup; Symptoms; System; Taste Perception; Testing; Underweight; Ventral Striatum; Weight; Youth; base; brain volume; cingulate cortex; dopaminergic neuron; effective therapy; excessive exercise; food restriction; gray matter; mortality; novel; public health relevance; purge; putamen; relating to nervous system; response; reward circuitry; white matter; young adult

Project Summary/Abstract 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.

项目摘要/摘要 进食障碍(EDS)、神经性厌食症(AN)和神经性暴食症(BN)都是严重的精神障碍 死亡率很高。而AN的主要特征是体重严重不足，BN个体处于正常状态 对于体重过高和经常暴饮暴食的人，这两种疾病都有许多重叠的症状， 例如食物限制、间歇性暴饮暴食、排便或过度运动。人们对此知之甚少 勃起功能障碍的神经生物学以及特定的勃起功能障碍行为如何与特定的生物机制相联系。NIMH 资助机会：通过生物学和维度研究推进饮食障碍研究 行为“是对这种知识缺乏的直接反应。在本申请中，使用”预测误差“ 从NIMH的研究领域标准(RDoC)项目构建，我们检查大脑功能和 结构可能是ED相关行为维度下的生物学机制。 这一结构与特定的大脑奖赏回路反应有关，这可能与 特别是与ED相关的行为。目的1.研究功能性神经奖赏回路是如何影响维度的。 使用RDoC结构预测误差对ED病理进行预测。这个应用程序将研究所有16岁的人- 29年来接受ED治疗以全面了解ED病理(符合RDoC 要求)，研究AN死亡率最高的年龄范围，并确定潜在的 通过研究青少年和年轻人的发展因素，同时保持在有限的年龄范围内。这个 研究将包括详细的临床评估以及功能磁共振脑成像(Fmri)。 对于味觉-奖赏预测的错误反应。前腹侧纹状体可预测ED相关行为 (尾状/壳核)以及脑岛预测误差响应。此外，ED的体重指数(BMI)较低 受试者对前部条件性刺激具有较高的奖励值预测能力 扣带回皮质，这是比较包括奖励在内的刺激的行为反应选项的重要区域。目标 2.是对灰质和白质体积进行结构磁共振脑成像(Smri)。 作为脑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 尾状核和脑岛体积较低。此外，脑岛和腹侧纹状体的灰质体积可以预测 脑功能奖赏激活的强度来自目标1.目标3.基于预测对ED个体进行分类 错误响应取代了传统的DSM标准，并基于此新标准比较了ED的相关行为 与年龄相匹配的健康青少年和成人对照。预测误差响应将为 在对显著刺激的敏感度方面，在ED受试者的聚集性方面优于DSM，与之相比 控制。这将表明，EDS是显著反应改变的障碍。