Deciphering the Neural Mechanisms of Restrictive Eating in Anorexia Nervosa Using Repetitive Transcranial Magnetic Stimulation

使用重复经颅磁刺激破译神经性厌食症限制饮食的神经机制

• 批准号: 10525743
• 负责人: Alexandra Felicia Muratore
• 金额: $ 19.55万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525743
• 关键词: Adult; Anorexia Nervosa; Award; Behavior; Behavior Therapy; Behavioral; Biological; Brain; Brain region; Caloric Restriction; Clinical; Corpus striatum structure; Data; Decision Making; Development; Dietary Fats; Disease; Dorsal; Double-Blind Method; Eating Behavior; Eating Disorders; Electromagnetics; Energy Intake; Exhibits; Fatty acid glycerol esters; Food; Frequencies; Functional Magnetic Resonance Imaging; Goals; Individual; Inpatients; Intake; Intervention; Knowledge; Life; Magnetic Resonance Imaging; Measures; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Methodology; Morbidity - disease rate; Neuronavigation; Neurons; Patients; Pharmacological Treatment; Physiologic pulse; Prefrontal Cortex; Preparation; Procedures; Psychophysiology; Randomized; Recovery; Relapse; Research; Research Personnel; Resistance; Rest; Role; Self-control as a personality trait; Symptoms; Testing; Training; Transcranial magnetic stimulation; Woman; authority; base; behavioral outcome; behavioral response; biobehavior; brain behavior; career development; computerized; design; dietary restriction; food restriction; functional MRI scan; mortality; neural circuit; neuroimaging; neuromechanism; neuroregulation; novel; programs; relating to nervous system; repetitive transcranial magnetic stimulation; restrictive eating

PROJECT SUMMARY Anorexia nervosa (AN) is a devastating illness with morbidity and mortality rates among the highest associated with any psychiatric disorder. Treatments for adults with AN have limited efficacy due to an inadequate understanding of the mechanisms underlying AN's core symptoms. The salient feature of AN is extreme restriction of food, particularly dietary fat intake, a behavior both highly resistant to change and central to relapse. There is a pressing need to understand the neural bases of restrictive eating and use this knowledge to develop novel, mechanism-based treatments. Neuroimaging research of food restriction in AN has found that compared to healthy controls, patients with AN exhibit greater choice-related dorsal striatum activation, suggesting that activity in this region may underlie maladaptive eating behavior. To confirm the significance of these brain regions, a critical next step is to extend correlational findings by directly probing this region using repetitive transcranial magnetic stimulation (rTMS) and evaluating its effects on brain and behavior. TMS is a non-invasive form of neuromodulation that delivers an electromagnetic pulse to the cortex and modulates neuronal activity of both targeted cortical regions and subcortical regions within related circuits. Previous research indicates the DLPFC may be a cortical TMS target through which to engage the dorsal striatum. Preliminary data from our group shows that compared to sham, high-frequency rTMS (HF-rTMS) to a specific region of the right DLPFC previously implicated in AN significantly increases selection of high-fat foods among inpatients with AN. The goal of this Mentored Patient-Oriented Research Career Development Award is to examine the neural mechanisms underlying restrictive food choice in AN using HF-rTMS as an experimental manipulation of neural activation. The proposed study will combine neuronavigation-guided rTMS, individualized functional TMS targets, fMRI and a computerized food-choice task to test the effects of HF-rTMS on brain and behavior. The study will utilize a double-blinded randomized parallel design: adult inpatients with AN will receive either HF-rTMS (n=36) or sham (n=36) to the DLPFC. We will compare group changes in brain and behavior to test whether activity in the dorsal striatum underlies restrictive eating behavior in AN (Aim 1) and test the effects of HF-rTMS to the DLPFC on restrictive eating behavior (Aim 2). Our use of individualized TMS targets will enable us to identify whether resting-state functional connectivity predicts neural or behavioral response to HF-rTMS (Exploratory Aim). Data yielded from the proposed study will enable the field to generate causal inferences about the role of brain regions underlying maladaptive eating behavior in AN, and will support the preparation of an R01 application to develop novel treatments for this disorder. Together, the expertise developed through this K23 award will support the applicant's transition to research independence as a leading authority in the neural underpinnings of AN.

项目摘要 神经性厌食症（AN）是一种毁灭性疾病，发病率和死亡率最高 患有任何精神疾病。由于不足，针对成年人的治疗有限 了解AN核心症状的基础机制。 AN的显着特征是极端的 食物的限制，尤其是饮食脂肪的摄入，这种行为既对变化具有很高的抵抗力，又具有 复发。迫切需要了解限制性饮食的神经基础并使用这些知识 开发新颖的基于机制的治疗方法。发现食物限制的神经影像学研究发现 与健康对照相比，患有更大选择相关的背纹状体激活的患者， 表明该地区的活动可能是适应不良的饮食行为的基础。确认的意义 这些大脑区域，下一步的关键是通过直接使用该区域探测该区域的关键发现 重复的经颅磁刺激（RTMS），并评估其对大脑和行为的影响。 TMS是 神经调节的非侵入性形式，将电磁脉冲传递给皮层并调节 相关电路内靶向皮质区域和皮层下区域的神经元活性。以前的 研究表明，DLPFC可能是与背纹状体接合的皮质TMS靶标。 来自我们组的初步数据表明，与假，高频RTMS（HF-RTMS）相比 右DLPFC的区域以前涉及大量提高高脂食品的选择 带有An的住院患者。这个受过指导的以患者为导向的研究职业发展奖的目标是 检查使用HF-RTMS作为实验的限制性食物选择的神经机制 操纵神经激活。拟议的研究将结合神经驱动引导的RTMS， 个性化功能性TMS目标，fMRI和计算机化食品选择任务，以测试HF-RTMS的影响 关于大脑和行为。该研究将利用双盲随机平行设计：成人住院患者 一个将向DLPFC接收HF-RTMS（n = 36）或假（n = 36）。我们将比较大脑的群体变化 和测试背纹状体活动的行为是否是AN中限制性饮食行为的基础（AIM 1） 并测试HF-RTMS对DLPFC对限制性饮食行为的影响（AIM 2）。我们对个性化的使用 TMS目标将使我们能够确定静止状态的功能连通性是否预测神经或行为 对HF-RTMS的响应（探索目的）。拟议的研究产生的数据将使该领域能够生成 关于在AN中适应不良饮食行为的大脑区域作用的因果推论，并将 支持准备R01应用以开发该疾病的新疗法。在一起， 通过该K23奖开发的专业知识将支持申请人向研究独立的过渡 An神经基础的领先权威。