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）是一种毁灭性的疾病，发病率和死亡率是最高的相关疾病之一。 有任何精神障碍成人AN的治疗效果有限，因为 了解AN核心症状的潜在机制。AN的显著特征是极端的 限制食物，特别是饮食中的脂肪摄入，这种行为对改变具有高度抵抗力， 复发我们迫切需要了解限制性饮食的神经基础，并利用这些知识 来开发新的、基于机制的治疗方法。神经影像学研究发现， 与健康对照组相比，AN患者表现出更大的选择相关背侧纹状体激活， 这表明该区域的活动可能是适应不良饮食行为的基础。为了证实 这些大脑区域，关键的下一步是通过直接探测这个区域来扩展相关的发现， 重复经颅磁刺激（rTMS）并评估其对大脑和行为的影响。TMS是 一种非侵入性的神经调节形式，将电磁脉冲传递到皮层并调节 相关回路内的靶向皮质区域和皮质下区域的神经元活动。先前 研究表明，DLPFC可能是皮质TMS靶点，通过该靶点与背侧纹状体接合。 我们小组的初步数据显示，与假手术相比，高频rTMS（HF-rTMS）对特定的 先前与AN有关的右侧DLPFC区域显著增加了高脂肪食物的选择， AN患者。这个指导病人为导向的研究职业发展奖的目标是 使用HF-rTMS作为实验研究AN中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联合收割机神经导航引导的rTMS， 个性化的功能性TMS目标，fMRI和计算机化的食物选择任务，以测试HF-rTMS的效果 对大脑和行为的影响本研究将采用双盲、随机、平行设计： AN将接受HF-rTMS（n=36）或假手术（n=36）至DLPFC。我们将比较大脑中的组变化 和行为，以测试背侧纹状体的活动是否是AN中限制性进食行为的基础（目的1） 并测试HF-rTMS对限制性进食行为的DLPFC的影响（目的2）。我们使用个性化 TMS目标将使我们能够确定静息状态功能连接是否预测神经或行为 对HF-rTMS的反应（探索性目的）。从拟议的研究中获得的数据将使该领域能够产生 因果推理的作用，大脑区域的基础适应不良的饮食行为在AN，将 支持R 01申请的准备，以开发针对这种疾病的新疗法。统称 通过这个K23奖开发的专业知识将支持申请人向研究独立性的过渡， 他是AN神经基础方面的权威