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: 9982435
• 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/9982435
• 关键词: Adult; Alcohol or Other Drugs use; 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; 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.

项目总结/摘要 神经性贪食症（BN）是一种慢性进食障碍， 死亡有一个关键的需要，以确定大脑为基础的因素，使BN症状永久化， 作为新疗法的机制靶点。大多数研究都集中在暴饮暴食和净化行为上 并将这些症状与抑制性控制缺陷和额纹状体激活减少联系起来。 然而，患有BN的个体通常在有问题的控制不足和过度控制状态之间振荡， 过度进食和限制摄入/禁食。迄今为止的神经生物学研究未能解释这一点 振荡这个指导性的以病人为导向的研究职业发展奖的目标是更好地 理解BN中这两种状态下抑制控制的计算基础。具体而言是 这项研究将功能性磁共振成像（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女性的大脑如何准备和发挥 抑制控制本研究将比较30名BN妇女的神经反应与30组- 在16小时禁食后和标准餐后的抑制控制范例中匹配对照。这 一个良好的对照设计将测试以下假设：1）在BN中，额纹状体信号的预期需要 为了抑制，贝叶斯预测错误信号和反应抑制期间的激活会异常减弱， 进食状态，并在禁食状态下异常增强（目的1）; 2）对进食状态的反应改变促进 失控的进食和排泄，而对禁食状态的反应改变使长期的 限制暴饮暴食/清除发作之间的间隔（目标2）。本项目的数据将证实一个解释性模型 BN症状，查明BN中抑制过程的哪些成分发生了变化，并确定BN中的状态。 哪些以控制为重点的干预措施可能最有效。这项工作最终将告知精确的目标 以及可以更有效地中断暴饮暴食，净化， 限制.这项研究还将作为概念和技能方面的指导和实践培训的工具 对候选人的下一步至关重要具体而言，在资源丰富的环境中，拟议的培训将 在三个领域给予候选人新的专业知识：1）重复测量神经成像方法， 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 全方位的饮食失调症。这个项目和培训的完成 目标将启动候选人在饮食失调的转化神经科学的独立职业生涯， 为高影响力的研究奠定基础，这些研究结合了联合收割机神经成像和复杂的分析方法， 改善进食障碍诊断和治疗。