Influence of Reward and Punishment on Goal-directed and Habit Learning in Adolescent Anorexia Nervosa

奖惩对青少年神经性厌食症目标导向和习惯学习的影响

• 批准号: 9899323
• 负责人: CHRISTINA E WIERENGA
• 金额: $ 23.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899323
• 关键词: Adolescence; Adolescent; Age; Anorexia Nervosa; Arbitration; Area; Behavior; Behavior Disorders; Behavioral; Behavioral Symptoms; Binge Eating; Biological Markers; Chronic; Clinical; Cognition; Cognitive; Complex; Compulsive Behavior; Computer Models; Corpus striatum structure; Data; Decision Making; Development; Diagnosis; Diagnostic; Dimensions; Disease; Eating; Eating Disorders; Ecological momentary assessment; Equilibrium; Etiology; Female Adolescents; Foundations; Frequencies; Future; Goals; Habits; Heterogeneity; Impulsivity; Individual; Intake; Learning; Link; Longitudinal Studies; MRI Scans; Measures; Medial; Mediating; Methodology; Modeling; Motor; Neurites; Neurobiology; Outcome; Participant; Protocols documentation; Psychological reinforcement; Punishment; Rest; Rewards; Scanning; Structure; Symptoms; System; Temperament; Testing; Time; Ventral Striatum; Weight; base; behavioral phenotyping; density; experience; flexibility; food restriction; frontal lobe; girls; habit learning; improved; innovation; neural correlate; neural network; neurodevelopment; neuroimaging; neuromechanism; new therapeutic target; novel; precision medicine; purge; purging behavior; putamen; recruit; therapy development

PROJECT SUMMARY/ABSTRACT Anorexia nervosa (AN) is a debilitating, often chronic, and sometimes fatal eating disorder (ED) that typically develops in adolescence. The etiology of AN is likely complex, yet remains unknown, and as a result, current treatments lack sufficient efficacy. Significant symptom heterogeneity exists, yet is not well captured by current diagnostic criteria. Thus, the identification of dimensional constructs underlying ED symptoms and their neural correlates is critical to improve our mechanistic understanding of ED and identify novel therapeutic targets to inform precision medicine. Behavioral symptoms of AN, such as food restriction (AN-R) and binge/purge episodes (AN-BP), arise from maladaptive decision-making. Decision-making is governed by two systems: 1) goal-directed learning reflects flexible and purposeful actions based on anticipated outcome, and 2) habit learning reflects automatic, efficient, and inflexible choices established by previous reinforcement. These learning systems are mediated by separate, yet overlapping, corticostriatal circuits and can be computationally modeled using a two-step sequential decision-making task. Difficulty arbitrating between these systems, resulting in an over-reliance on one strategy over the other, may contribute to divergent AN symptoms. This proposal tests the novel hypothesis that goal-directed and habit learning under conditions of reward and loss differs in AN and is uniquely associated with divergent symptoms and corticostriatal connectivity. Adolescent girls ages 14-17 with AN-R, AN-BP or who are healthy controls will undergo neuroimaging to assess resting state functional connectivity and microstructural integrity of corticostriatal networks, followed by performing the two-step learning task outside the scanner under conditions of reward and loss. For each participant, a weighting factor (ω), representing the relative balance between goal-directed and habit learning, will be calculated for gain and loss conditions. After scanning, AN participants will complete a 14-day ecological momentary assessment protocol to evaluate naturalistic, momentary experiences of ED symptoms. Aim 1 will determine the behavioral differences in goal-directed and habit learning under conditions of reward and punishment in individuals with AN- R, AN-BP and healthy controls. Aim 2 will examine the association of goal-directed and habit learning for reward and punishment with symptoms and real-world experiences in AN to determine whether learning differences contribute to divergent symptoms. Aim 3 will determine whether corticostriatal circuits associated with goal- directed and habit learning for reward and punishment differ by group and condition to inform neural mechanisms of altered reinforcement learning in AN. Data will support a future longitudinal R01 application to test a dimensional approach of behavioral phenotyping based on reinforcement learning in a wider spectrum of restricting and binge-type EDs to inform a neurodevelopmental model. Defining meaningful biomarkers in ED would be a major advance in the field, as it would allow the development of new treatment approaches to reduce poor outcome.

项目摘要/摘要 神经性厌食症(AN)是一种衰弱的、通常是慢性的、有时甚至是致命的进食障碍(ED)，通常 在青春期发展。AN的病因可能很复杂，但仍不清楚，因此，目前 治疗缺乏足够的疗效。存在显著的症状异质性，但不能很好地被当前 诊断标准。因此，识别ED症状及其神经的维度结构 相关性对于提高我们对勃起功能障碍的机制理解和确定新的治疗靶点是至关重要的 通知精准医疗。AN的行为症状，如食物限制(AN-R)和暴饮暴食/清洗 突发事件(AN-BP)是由不适应的决策引起的。决策由两个系统管理：1) 目标导向学习反映了基于预期结果的灵活和有目的的行动，以及2)习惯 学习反映了由先前强化建立的自动、高效和僵化的选择。这些 学习系统由分离但重叠的皮质纹状体回路调节，并且可以通过计算 使用两步连续决策任务进行建模。很难在这些系统之间进行仲裁， 导致过度依赖一种策略而不是另一种策略，可能会导致不同的AN症状。这 提案检验了目标导向和习惯学习在得失条件下的新假设 在AN方面有所不同，并与不同的症状和皮质纹状体连接独特地联系在一起。青少年 患有An-R、An-BP或健康对照的14-17岁女孩将接受神经成像以评估休息情况 说明皮质纹状体网络的功能连通性和微结构完整性，然后执行 在有奖赏和有损失的情况下，扫描仪外的两步学习任务。对于每个参与者，都有一个权重 代表目标导向学习和习惯学习之间相对平衡的因素(ω)将被计算为收益 和损失条件。扫描后，参与者将完成为期14天的生态瞬时评估 评估ED症状的自然的、短暂的体验的方案。目标1将决定行为 被试在奖惩条件下的目标定向和习惯学习的差异 R组、An-BP组和健康对照组。目标2将考察目标导向学习和习惯学习之间的关联，以获得奖励。 以及惩罚中的症状和现实世界的经验，以确定是否学习差异 会导致不同的症状。目标3将确定是否与目标相关的皮质纹状体回路- 奖励和惩罚的定向学习和习惯学习因群体和条件不同而不同，以告知神经机制 改变强化学习在一个。数据将支持未来的纵向R01应用程序以测试 基于强化学习的行为表型维分型方法 限制和狂欢类型的ED，以告知神经发育模型。在边缘定义有意义的生物标记物 这将是该领域的一大进步，因为它将使开发新的治疗方法能够减少 糟糕的结果。