Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

神经性厌食症膳食相关内感受功能障碍的神经基础

• 批准号: 9295323
• 负责人: SAHIB KHALSA
• 金额: $ 19.99万
• 依托单位: LAUREATE INSTITUTE FOR BRAIN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295323
• 关键词: Address; Anorexia Nervosa; Anxiety; Attention; Behavior; Behavioral; Bipolar Disorder; Body Image; Body Weight decreased; Bolus Infusion; Brain; Bulimia; Calories; Clinical Trials; Cues; Data; Development; Dorsal; Eating; Eating Disorders; Epinephrine; Esthesia; Extinction (Psychology); Food; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Growth; Heart Rate; Image; Individual; Infusion procedures; Insula of Reil; Isoproterenol; K-Series Research Career Programs; Knowledge; Learning; Magnetic Resonance Imaging; Maintenance; Measures; Mediating; Mentors; Mentorship; Methodology; Negative Valence; Neurobiology; Neuronal Dysfunction; Patients; Perfusion; Peripheral; Pharmacology; Physiology; Postdoctoral Fellow; Procedures; Process; Protocols documentation; Public Health; Recruitment Activity; Reporting; Research; Research Institute; Research Personnel; Response to stimulus physiology; Role; Saline; Schizophrenia; Severities; Severity of illness; Signal Transduction; Source; Starvation; Stomach; Sympathomimetics; Symptoms; System; Time; Training; Training Activity; Unipolar Depression; Weight; Weight Gain; attentional bias; avoidance behavior; base; brain circuitry; career; computerized data processing; experience; improved; neural circuit; neuroimaging; novel; novel strategies; patient oriented; programs; reduced food intake; relating to nervous system; response; restoration; sex; statistics

PROJECT SUMMARY Dr. Sahib Khalsa is applying for the Mentored Patient-Oriented Career Development Award (K23) to support his growth as an independent researcher to delineate the pathophysiology of interoception (the brain body connection) in eating disorders. Anorexia nervosa (AN) is two to three-times deadlier than schizophrenia, bipolar disorder, and unipolar depression, yet the underlying pathophysiology and associated neural dysfunctions are poorly understood. Anticipating eating a meal makes individuals with AN fearful, which induces a state of Biased Interoceptive Anticipatory Signaling (BIAS) marked by a discrepancy between the actual interoceptive state and the subjective interoceptive experience. BIAS interferes with AN patients' ability to accurately sense what is happening in their bodies, which in turn reinforces fears of eating, food avoidance behaviors, and weight loss. To determine the neural basis of BIAS in AN, the candidate has developed a protocol that employs (a) interoceptive modulation using isoproterenol, a rapid peripherally acting sympathomimetic drug akin to adrenaline, (b) direct experimental manipulation of meal anticipation, which heightens anxiety in AN, and (c) functional magnetic resonance imaging to examine the brain's response to these manipulations. Weight-restored individuals with AN (to avoid the potentially confounding effects of starvation on measures of brain function) and sex and BMI matched healthy comparisons will undergo multi- level assessments focused on the negative valence domain and interoception. This proposal investigates the basic question “how does the state of anticipating a meal induce fear and dysregulate the processing of body- relevant information in AN?” Addressing it will help to clarify the behavioral and brain processes that reinforce starvation in the presence of food availability, and will enable the development of specific food-focused fear extinction procedures. Dr. Khalsa's long-term career goal is to understand the neural sources of interoceptive dysregulation in eating disorders, and to develop novel treatments. The proposed research will accomplish first steps towards this goal by evaluating the role of interoception across levels of behavior, physiology and neural circuits in AN. The training activities of this project will allow Dr. Khalsa to develop expertise in pharmacological fMRI methodology, increased knowledge of advanced statistics, and enhanced expertise in eating disorder treatment. Dr. Khalsa has assembled a team of mentors uniquely suited to provide the required diversity of expertise. Dr. Paulus (LIBR Scientific Director and primary mentor) will provide expertise in psychiatric and pharmacological neuroimaging using interoceptive probes. Dr. Walter Kaye will provide mentorship in AN neurobiology and treatment. Dr. Jerzy Bodurka, LIBR Neuroimaging Core Director, will provide mentorship in fMRI data processing and structural/functional connectivity analyses. Dr. Danny JJ Wang will provide mentorship in perfusion MRI and the combination of pharmaco-imaging with ASL. The training and associated research will take place at LIBR, a psychiatric research institute with state-of-the-art neuroimaging facilities.

项目摘要 Sahib Khalsa博士正在申请指导的以患者为导向的职业发展奖（K23）来支持 他作为独立研究人员的成长来描述拦截的病理生理学（大脑身体 连接）饮食失调。厌食症（AN）比精神分裂症的近三倍， 躁郁症和单极抑郁症，但基本的病理生理和相关神经 功能障碍知之甚少。预计吃饭会使人有可怕的人，这 引起偏见的互感性预期信号传导（偏见），该状态以差异为标志 实际的际观察状态和主题的跨感受经验。偏见干扰患者的能力 准确地感觉到他们体内正在发生的事情，从而加剧了人们对饮食的恐惧，避免食物 行为和体重减轻。为了确定AN中偏见的神经基础，候选人已经开发了 员工（a）使用异丙肾上腺素的互感调制的协议，这是一种快速的外围表演 类似类似肾上腺素的交感神经药物，（b）直接对饮食预期的实验操纵，这 增加AN和（c）功能磁共振成像的焦虑，以检查大脑对 这些操纵。重量成员的人（以避免 对脑功能的测量的饥饿）和性别和BMI匹配的健康比较将经历多种多样 级别评估集中在负价域和际观察范围内。该提案调查了 基本问题：“预期一餐的状态如何引起恐惧和失调的身体处理 - 相关信息？ 在粮食可用性的情况下饥饿，并将能够发展特定的以食物为中心的恐惧 灭绝程序。 Khalsa博士的长期职业目标是了解互感的神经来源 饮食失调的失调，并开发新的治疗方法。拟议的研究将首先完成 通过评估跨行为，生理和神经元的拦截作用来实现这一目标的步骤 电路该项目的培训活动将使Khalsa博士能够在药理学方面发展专业知识 fMRI方法论，对先进统计数据的了解增加以及饮食失调方面的专业知识增强 治疗。 Khalsa博士召集了一个非常适合提供所需多样性的导师团队 专业知识。 Paulus博士（图书馆科学主任兼主要导师）将提供精神科专业知识， 使用互感问题的药理神经影像学。沃尔特·凯（Walter Kaye）博士将在 神经生物学和治疗。图书馆神经影像核心主任Jerzy Bodurka博士将在 fMRI数据处理和结构/功能连接分析。 Danny JJ Wang博士将提供 灌注MRI的遗传和药剂师成像与ASL的结合。培训和相关的 研究将在具有最先进的神经影像机构的精神病学研究所Libr。