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: 8914714
• 负责人: Guido KW Frank
• 金额: $ 6.27万
• 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/8914714
• 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; Health; 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; purge; putamen; relating to nervous system; response; reward circuitry; white matter; young adult

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.

描述（由申请人提供）：饮食失调（EDS）神经性厌食症（AN）和神经性贪食症（BN）是严重的精神疾病，死亡率很高。虽然A的主要体重不足和BN个体的特征是正常重量到高体重，并经常暴饮暴食，但两种疾病中都有许多重叠的症状，例如食物限制，情节性暴饮暴食，清除或过度运动。关于ED的神经生物学以及特定的ED行为如何与特定的生物学机制联系在一起，知之甚少。 NIMH的资助机会“通过生物学和行为的维度研究来推进饮食失调研究”，这是对缺乏知识的直接回应。在本应用中，使用NIMH研究领域标准（RDOC）项目的“预测误差”构建体，我们研究了大脑功能和结构如何成为ED相关行为的基础生物学机制。该结构与特定的大脑奖励电路响应有关，这可能与特定的相关行为有关。目的1。是研究使用RDOC构造预测误差的功能神经奖励电路是ED病理学维度的基础。该应用将研究所有16至29岁年龄段的人，他们出席了ED治疗，以捕捉ED病理的全部范围（符合RDOC要求），以研究AN的年龄范围，并通过研究青少年和年轻人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展因素。该研究将包括详细的临床评估以及功能性磁共振脑成像（fMRI），以进行味觉奖励预测误差响应。 ED相关行为将通过前腹纹状体（尾状/壳虫）以及岛群预测误差响应来预测。此外，ED受试者中的低体重指数（BMI）将与较高的激活相关，以奖励预测前扣带回皮质中的条件刺激的价值，这对于比较包括奖励的刺激的行为反应选择的区域很重要。目标2是为灰质和白质体积执行结构磁共振脑成像（SMRI），以及用于白质完整性的扩散张量成像。我们预计更严重的ED行为将预测较低的尾状尾巴和岛素体积。此外，岛和腹侧纹状体中的灰质体积将预测AIM 1的功能性脑奖励激活的强度。AIM3。是基于预测错误响应而不是传统的DSM标准聚集ED的个体，并根据这种新分类与年龄相匹配的健康青少年和成人控制的新分类进行比较相关的行为。通过对显着刺激的敏感性以及与对照相反的敏感性，预测误差响应将优于DSM。这将表明ED是显着反应改变的疾病。