Incentive Processing and Learning in Anorexia Nervosa and Bulimia Nervosa

神经性厌食症和神经性贪食症的激励处理和学习

基本信息

批准号：
10573214
负责人：
CHRISTINA E WIERENGA
金额：
$ 75.51万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10573214
关键词：
Address Adopted Adult Anorexia Nervosa Association Learning Behavior Behavioral Binge Eating Biological Markers Body Weight decreased Brain Bulimia Caring Chronic Classification Clinical Clinical Treatment Complex Computer Models Consumption Corpus striatum structure Coupled Dangerousness Data Decision Making Diagnosis Diagnostic Dimensions Disease Dopamine Eating Eating Disorders Etiology Exhibits Failure Functional Magnetic Resonance Imaging Functional disorder Heterogeneity Impairment Incentives Learning Machine Learning Magnetic Resonance Imaging Maintenance Measures Mental disorders Modality Modeling Motivation Operant Conditioning Outcome Participant Patients Performance Positive Valence Process Psychological reinforcement Psychopathology Punishment Research Domain Criteria Rewards Role Signal Transduction Stimulus Substantia nigra structure Sucrose Symptoms System Taste Perception Tea Testing Time Vomiting Woman aged approach behavior avoidance behavior clinical predictors diagnostic criteria diagnostic strategy dietary restriction disorder subtype effective therapy experience financial incentive food restriction hedonic improved incentive salience innovation medical complication mortality neural neural circuit neural correlate neuromelanin new therapeutic target novel physical symptom precision medicine predictive marker psychosocial purge response reward processing targeted treatment therapy development

项目摘要

PROJECT SUMMARY/ABSTRACT The etiology of eating disorders (ED) is complex, yet largely unknown, resulting in a profound lack of effective treatments and a “crisis in care”. Common to EDs are alterations in the motivation to eat, ranging from extreme food restriction and weight loss, to binge eating coupled with compensatory strategies like self-induced vomiting. Despite the traditional emphasis on diagnostic differentiation based on these physical symptoms, they often overlap, and, along with significant diagnostic crossover (e.g., from anorexia nervosa to bulimia nervosa) over time, suggest shared features that are not well captured by current diagnostic criteria. Persistence of restricted eating, binge eating and/or purging despite negative consequences, along with evidence of altered reward and punishment sensitivity in ED, raise the question of whether a failure to appropriately process and/or learn from rewarding and/or punishing experiences might contribute to repeated engagement in maladaptive approach and avoidance behavior and illness maintenance. This is the first study to apply a multi-dimensional framework of reward processing to ED, by examining how the interplay of RDoC-based Positive Valence measures of `liking' (i.e., the hedonic impact of reward consumption), `wanting' or incentive salience (i.e., motivation to pursue a reward), and learning (i.e., the acquisition of reward-outcome contingencies), which are associated with distinct frontostriatal neurocircuitry, differ across ED subtype and correspond to clinical symptoms at baseline and one year later. We will study 150 demographically-matched women with ED (50 AN-restricting type (AN-R), 50 AN- binge eating/purging type (AN-BP), 50 bulimia nervosa (BN)) and 50 healthy controls (HC) aged 18-35. During fMRI, participants will complete 1) a modified monetary incentive delay (MID) task to assess group differences in both neural anticipation (`wanting') and receipt (`liking') of rewarding and aversive disorder-specific (taste) and generalized (money) stimuli (Aim 1), and 2) a probabilistic associative learning task to assess decision-making and instrumental learning from monetary wins and losses (Aim 2). Aim 3 will examine interactions between `liking', `wanting' and learning and associations with symptoms at study entry and 1 year later. An Exploratory Aim will examine associations of dopamine function, as measured by neuromelanin MRI (NM-MRI), with ED diagnosis and brain response to `liking', `wanting', and learning to further inform mechanistic models of reward in ED. This study is innovative and significant in several ways: 1) it adopts a multi-dimensional framework of reward processing to examine independent and interactive contributions of understudied, yet critically important constructs (e.g., `liking', `wanting', learning) in ED, 2) it assesses the role of stimulus modality (taste, money) and valence in `liking' and `wanting', and 3) relates these constructs to actual symptoms and behavior at study entry and 1 year later to understand what drives shared and divergent symptoms and predicts symptom change, which has potential for substantial clinical impact. Identification of dimensional constructs underlying symptoms and their neural correlates is critical to improve a mechanistic understanding of ED and advance precision medicine.

项目摘要/摘要饮食失调（ED）的病因很复杂，但在很大程度上未知，导致严重缺乏有效性治疗和“护理危机”。 ED的共同点是进食动机的改变，从极端食物限制和体重减轻，以暴饮暴食，再加上诸如自我引起的呕吐之类的补偿策略。尽管基于这些身体症状的传统强调诊断性分化，但他们经常重叠，并与明显的诊断交叉（例如，从厌食症神经到贪食症神经紧张）时间，建议共享的功能，这些功能无法通过当前的诊断标准很好地捕获。限制的持久性进食，暴饮暴食和/或清除欲望的负面后果，以及奖励改变的证据 ED的惩罚敏感性，提出一个问题，即是否无法适当处理和/或向奖励和/或惩罚经历可能有助于反复参与适应不良的方法和避免行为和疾病维持。这是第一个应用多维框架的研究通过检查基于RDOC的正价衡量“喜欢”的相互作用如何通过研究奖励处理。（即奖励消费的享乐影响），“想要”或激励显着性（即购买动机奖励）和学习（即获得奖励成果意外情况），这与独特的相关额叶神经记录，在ED亚型中不同，对应于基线时的临床符号，一个一年后。我们将研究150名具有ED的人口统计学匹配的女性（50个限制性（AN-R），50个AN- 暴饮暴食/清除类型（AN-BP），50个贪食症神经（BN）和50个健康对照（HC）18-35岁。期间 fMRI，参与者将完成1）修改的货币激励延迟（中），以评估小组差异在神经元期望（“想要”）和收据（“喜欢”）中，有回报和厌恶障碍特异性（口味）和广义（金钱）刺激（AIM 1）和2）评估决策的概率关联学习任务以及从货币胜利和亏损中学习的乐器学习（AIM 2）。 AIM 3将检查之间的互动 “喜欢”，``想要''，学习和与症状的学习以及1年后的症状有关。探索性 AIM将检查由Neuromelanin MRI（NM-MRI）与ED测量的多巴胺功能的关联诊断和大脑对“喜欢”，“想要”和学习进一步为机械奖励模型提供信息的反应在ed。这项研究在几种方面具有创新性和重要性：1）它采用了一个多维框架奖励处理以检查理解的独立和互动贡献，但至关重要在Ed中的结构（例如，“喜欢”，“想要”，学习），2）它评估了刺激方式（品味，金钱）和 “喜欢”和“想要”中的价，3）将这些结构与研究进入时的实际符号和行为联系起来 1年后，以了解共享和不同症状的驱动器并预测症状的变化，这具有重大临床影响的潜力。识别尺寸构造符号的尺寸构造和他们的神经自我反合对于提高对ED的机械理解和预先精确药物至关重要。