The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A Computational Neuroimaging Study

饮食和禁食对神经性贪食症抑制控制的影响：一项计算神经影像学研究

• 批准号: 10447689
• 负责人: Laura A. Berner
• 金额: $ 19.19万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447689
• 关键词: Adult; Anterior; Base of the Brain; Bayesian Modeling; Bayesian Prediction; Behavior; Behavioral; Binge Eating; Biological Markers; Brain; Bulimia; Cessation of life; Characteristics; Chronic; Clinical Data; Clinical Investigator; Computer Models; Corpus striatum structure; Dangerousness; Data; Diagnosis; Diagnostic; Disease; Disinhibition; Eating; Eating Behavior; Eating Disorders; Environment; Fasting; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hyperphagia; Impairment; Individual; Intake; Interruption; Intervention; Knowledge; Lateral; Learning; Life; Link; Matched Group; Measurement; Measures; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic; Methodology; Methods; Modeling; Neurobiology; Neurocognitive; Obesity; Pattern; Performance; Perfusion; Periodicity; Persons; Phenotype; Prefrontal Cortex; Process; Psychiatry; Psychophysiology; Psychotherapy; Research; Research Training; Resistance; Resources; Rest; Risk; Satiation; Scanning; Severities; Signal Transduction; Standardization; Symptoms; Testing; Time; Training; Update; Woman; Work; base; career; clinically significant; cost; design; dietary restriction; disability; effective therapy; expectation; experience; ideal observer (Bayesian); improved; neurobiological mechanism; neuroimaging; neurotransmission; novel; outcome prediction; premature; psychologic; psychosocial; purge; purging behavior; relating to nervous system; response; skills; substance use; symptomatology; theories; tool; translational neuroscience; treatment optimization; treatment response

PROJECT SUMMARY/ABSTRACT Bulimia nervosa (BN) is an often-chronic eating disorder associated with high rates of disability and premature death. There is a critical need to identify brain-based factors that perpetuate BN symptoms and that may serve as mechanistic targets for novel treatments. Most studies have focused on binge eating and purging behaviors in BN and have linked these symptoms to inhibitory control deficits and reduced frontostriatal activation. However, individuals with BN typically oscillate between states of problematic under- and over-control— excessive eating and restricted intake/fasting. Neurobiological research to date has failed to account for this oscillation. The goal of this mentored patient-oriented research career development award is to better understand the computational underpinnings of inhibitory control in these two states in BN. Specifically, the proposed study combines functional magnetic resonance imaging (fMRI) with dynamic Bayesian modeling to examine whether eating and fasting abnormally impact how the brains of women with BN prepare for and exert inhibitory control. This study will compare neural responses of 30 women with BN to those of 30 group- matched controls during an inhibitory control paradigm after a 16-h fast and after a standardized meal. This well-controlled design will test the following hypotheses: 1) In BN, frontostriatal signals for the expected need to inhibit, Bayesian prediction error signals, and activation during response inhibition are abnormally blunted in a fed state, and abnormally enhanced in a fasted state (Aim 1); 2) Altered response to the fed state promotes out-of-control eating and purging, whereas altered response to the fasted state perpetuates prolonged restriction between binge/purge episodes (Aim 2). Data from this project will substantiate an explanatory model of BN symptoms, pinpoint which components of the inhibition process are altered in BN, and identify states in which control-focused interventions may be most effective. This work ultimately will inform precisely targeted and context-dependent interventions that can more effectively interrupt the cycle of binge eating, purging, and restriction. The study will also serve as a vehicle for mentorship and hands-on training in concepts and skills critical to the candidate’s next steps. Specifically, within a resource-rich environment, the proposed training will give the candidate new expertise in three domains: 1) repeated-measures neuroimaging methods and associated analyses, 2) neurocomputational modeling and computational psychiatry, and 3) the neurobiology of the full spectrum of disordered eating symptomatology in BN. This project and the completion of training goals will launch the candidate’s independent career in the translational neuroscience of eating disorders and lay groundwork for high-impact studies that combine neuroimaging and sophisticated analytic approaches to improve eating disorder diagnosis and treatment.

项目概要/摘要 神经性贪食症 (BN) 是一种慢性饮食失调症，与高残疾率和早产率相关 迫切需要确定导致 BN 症状持续存在并可能起作用的大脑因素。 作为新型治疗的机制目标，大多数研究都集中在暴食和清除行为上。 BN 并将这些症状与抑制控制缺陷和额纹状体激活减少联系起来。 然而，患有 BN 的人通常会在有问题的控制不足和过度控制之间摇摆不定—— 迄今为止，过度饮食和限制摄入/禁食尚未解释这一点。 这个以患者为导向的研究职业发展奖的目标是更好地发展。 了解 BN 中这两种状态的抑制控制的计算基础。 拟议的研究将功能磁共振成像（fMRI）与动态贝叶斯建模相结合 检查饮食和禁食是否异常影响 BN 女性的大脑准备和发挥的方式 这项研究将比较 30 名 BN 女性与 30 名对照组的神经反应。 禁食 16 小时和标准化膳食后的抑制控制范式中的对照。 良好控制的设计将测试以下假设：1）在 BN 中，额纹状体信号满足预期需求 抑制，贝叶斯预测误差信号和响应抑制期间的激活异常钝化 进食状态，并且在禁食状态异常增强（目标 2）对进食状态的改变反应促进 失控的饮食和净化，而对禁食状态的反应改变则使长期持续 狂欢/清除事件之间的限制（目标 2）。 BN 症状，查明 BN 中抑制过程的哪些组成部分发生改变，并识别 BN 中的状态 这项工作最终将提供精确的针对性指导。 以及与环境相关的干预措施，可以更有效地中断暴食、通便和暴饮暴食的循环 该研究还将作为概念和技能方面的指导和实践培训的工具。 具体来说，在资源丰富的环境中，拟议的培训将对候选人的下一步至关重要。 为候选人提供三个领域的新专业知识：1）重复测量神经影像方法和 相关分析，2) 神经计算建模和计算精神病学，以及 3) 神经生物学 BN 的全面饮食失调症状学并完成培训。 目标将开启候选人在饮食失调和转化神经科学领域的独立职业生涯 为结合神经影像学和复杂分析方法的高影响力研究奠定基础 改善饮食失调的诊断和治疗。