Neural Correlates of Reinforcement Learning Specific to Hyperactivityin Adolescent Anorexia Nervosa

青少年神经性厌食症多动症特有的强化学习的神经相关性

• 批准号: 10371149
• 负责人: Sasha Catherine Gorrell
• 金额: $ 16.95万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10371149
• 关键词: Adolescent; Age; Anhedonia; Anorexia Nervosa; Base of the Brain; Behavior; Behavior Control; Behavior Disorders; Behavioral; Brain; Brain region; Chronic; Compulsive Behavior; Cues; Dangerousness; Data; Eating Disorders; Emotions; Etiology; Exercise; Food; Functional Magnetic Resonance Imaging; Future; Goals; Heterogeneity; Impairment; Individual; Interruption; Intervention; Knowledge; Learning; Link; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentorship; Modeling; Negative Valence; Neurobiology; Nucleus Accumbens; Obsessive compulsive behavior; Participant; Pathway interactions; Performance; Phenotype; Population; Positive Valence; Precision therapeutics; Process; Psychological reinforcement; Psychopathology; Recording of previous events; Research; Research Design; Research Domain Criteria; Resistance; Rewards; Stimulus; Subgroup; Symptoms; System; Task Performances; Testing; Training; Treatment outcome; United States National Institutes of Health; Weight; Work; base; behavior measurement; behavioral response; biobehavior; burden of illness; career; cognitive neuroscience; computer framework; cost; experience; frontal lobe; improved; indexing; mortality; neural correlate; neuroimaging; novel; psychosocial; relapse risk; relating to nervous system; response; reward processing; skills; suicidal risk; therapy development; translational neuroscience

PROJECT SUMMARY/ABSTRACT Anorexia nervosa (AN) is an often-chronic eating disorder with the highest mortality rate of any mental illness, significant costs, and global disease burden. There is a critical need to identify brain-based factors that perpetuate AN symptoms and that may serve as mechanistic targets for existing and novel treatments. Most neurobiological studies in AN have focused on food-related behavior, and have specifically linked these symptoms to broad deficits in frontostriatal activation. However, biobehavioral research to date has failed to account for brain-based mechanisms that may maintain driven exercise, an alarming symptom experienced by a majority of adolescents with AN (59-80%). The goal of this K23 mentored patient-oriented research career development award is to better understand the neurocomputational underpinnings of reinforcement learning in adolescents with AN who engage in driven exercise (AN-DEx). Specifically, the proposed study leverages decision tasks to examine whether adolescents with AN-DEx demonstrate differences in reinforcement learning related to food or exercise reward stimuli. This study will compare task responses in 50 adolescents with AN-DEx, to those of 50 with AN, and 100 age-and activity-matched controls. As a secondary exploratory aim, this study will use functional magnetic resonance imaging (fMRI) to characterize neural activity substantiating task performance for a portion of each group (25 from each, 75 total). This study design will test the following hypotheses: Aim 1: H1a: Compared to controls, AN + AN-DEx will demonstrate deficits in model- based strategy (forward planning) in response to food and exercise stimuli. H1b: Compared to AN, AN-DEx will demonstrate deficits in model-based strategy in response to exercise stimuli; Aim 2: H2a: Compared to controls, AN + AN-DEx will demonstrate increased OFC - NAcc functional connectivity (frontal-limbic pathway, key brain regions implicated in inhibitory control). H2b: Compared to AN, AN-DEx will demonstrate increased OFC-NAcc functional connectivity in response to exercise stimuli. Data from this project will substantiate an explanatory model of DEx, pinpoint which components of reinforcement learning are altered in AN-DEx, and identify ways in which behavioral control-focused interventions may be most effective. This line of inquiry will ultimately inform targeted interventions that can more effectively interrupt DEx, and other compulsive AN symptoms. The current study will also serve as a vehicle for mentorship and training in concepts and skills that are critical to the candidate’s current project, and next steps. Specifically, the proposed training will allow the candidate to gain new knowledge in: (i) cognitive neuroscience and neural substrates specific to eating disorders, (ii) neurocomputational tasks and modeling, and (iii) preliminary training in fMRI. This project and fulfillment of the training goals will launch the candidate’s independent career in the translational neuroscience of AN and lay groundwork for future high-impact studies that combine sophisticated analytic approaches and neuroimaging to improve eating disorder treatment.

项目摘要/摘要 厌食症（AN）是一种经常会慢性饮食障碍，任何精神疾病的死亡率最高， 巨大的成本和全球疾病伯恩。迫切需要确定基于大脑的因素 使符号永久化，并可以作为现有和新颖治疗方法的机械目标。最多 A的神经生物学研究集中在与食物相关的行为上，并特别关联了这些行为 额叶激活中广泛定义的症状。但是，迄今为止的生物行为研究未能 考虑可能维持驱动运动的基于大脑的机制，这是一种令人震惊的症状 大多数具有（59-80％）的青少年。这个K23的目标是指导以患者为导向的研究职业 发展奖是为了更好地了解强化学习的神经计算基础 与参与驱动器运动的青少年（AN-DEX）。特别是拟议的研究利用 决策任务以检查具有AN-DEX的青少年是否显示强化差异 与食物或运动有关的学习奖励刺激。这项研究将比较50名青少年的任务响应 使用AN-DEX，到50个具有AN和100年龄匹配的对照的人。作为次要探索 目的，本研究将使用功能磁共振成像（fMRI）来表征神经活动 确定每组一部分的任务绩效（每组25，总共75个）。该研究设计将测试 以下假设：AIM 1：H1A：与对照组相比，AN + AN-DEX将证明在模型中定义 响应食物和运动刺激的基于策略（远期计划）。 H1b：与一个and-dex相比 在响应运动刺激的情况下，在基于模型的策略中表现出防御；目标2：H2A：与 控件， + AN-DEX将显示出增加的OFC-NACC功能连接性（额叶途径， 在抑制控制中实施的关键大脑区域）。 H2B：与An-Dex相比，AN-DEX将显示出增加 OFC-NACC功能连通性响应于运动刺激。该项目的数据将证实 DEX的解释模型，Pinpoint在AN-DEX中更改了强化学习的组成部分，以及 确定以行为控制干预措施最有效的方式。这条询问将 最终告知有针对性的干预措施，这些干预措施可以更有效地中断DEX，而其他强迫性的干预措施 症状。当前的研究还将作为概念和技能的心态和培训的工具 对于候选人的当前项目和下一步至关重要。具体而言，拟议的培训将允许 候选人获得新知识：（i）特定于饮食的认知神经科学和神经植物 疾病，（ii）神经计算任务和建模，以及（iii）fMRI的初步培训。这个项目和 实现培训目标将启动候选人在转化神经科学领域的独立职业 将来的高影响力研究的基础，结合了复杂的分析方法和 神经影像以改善饮食失调治疗。