Neural Dysfunction of Interoception in Adolescents Diagnosed with Anorexia Nervos

描述（申请人提供）：神经性厌食症（AN）患者有异常的进食行为，情绪和冲动控制障碍，体重恢复后复发率高1,2。目前还没有证实的治疗方法可以逆转症状。尽管对AN康复个体的影像学研究表明，这些症状与纹状体、岛状体和前额叶区功能障碍有关，但对当前患者这些核心症状的生物学知之甚少。本应用将使用血氧水平依赖（BOLD）功能磁共振成像（fMRI）来检查AN病中食欲、奖励和认知失调的神经基质。我们将研究20名患有AN的青春期妇女和20名健康的青春期对照妇女（CW），她们都是14至18岁。目的1：脑岛前部（AI）、眼窝额叶皮层（OFC）和相关区域整合味觉和内感受意识的感觉/享乐方面，为内稳态服务。我们假设限制饮食和体重减轻发生在AN中，因为美味的食物引起的奖励很少。目标2：对于AN患者来说，除了减肥之外，生活中几乎没有什么值得奖励的，他们往往过于关注未来的后果。我们预测，患病的AN将表现出无法区分反映异常前腹侧纹状体（AVS）边缘功能的正反馈和负反馈。目标3:AN倾向于僵化，不灵活和行为抑制。我们将使用停止任务3-5来表征抑制性运动控制的神经基质。我们假设，相对于神经性脑炎，患有神经性脑炎的人会表现出对运动抑制所必需的额-丘脑下回路的需求特异性改变6。最后，在探索性目标中，我们建议研究临床、认知和人格/气质测量如何与BOLD反应和/或使用扩散张量成像（DTI）确定的额纹状体连通性的完整性相关。综上所述，这些目标将使我们能够更好地表征这些人群的认知和边缘功能障碍。了解AN的生物脆弱性对于开发有效的治疗干预措施至关重要，这通常是慢性和致命的疾病。此外，还缺乏对适当的方法的理解，这些方法是解决疾病的研究中固有的独特问题所必需的。因此，本R21应用程序还将表征混杂因素，如脑容量、能量代谢、发育阶段和性腺类固醇，目的是未来的R01应用程序将纳入严格调查这一人群所需的方法。公共卫生相关性：有大量证据表明，大脑功能的改变有助于神经性厌食症的食欲、情绪和冲动控制紊乱。该应用程序将使用功能性脑磁成像来表征神经元回路及其与行为的关系。了解神经性厌食症的病理生理学是必要的，以便为这种经常是慢性和致命的疾病设计新的和更有效的治疗干预措施。

DESCRIPTION (provided by applicant): Individuals with anorexia nervosa (AN) have aberrant feeding behavior, disturbances of emotionality and impulse control, and have high rates of relapse after weight restoration1, 2. There is no proven treatment that reverses symptoms. Although imaging studies in individuals recovered from AN suggest that these symptoms are related to dysfunction of the striatal, insular, and prefrontal areas, less is known about the biology of these core symptoms in currently ill individuals. This application will use blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine neural substrates underlying appetitive, reward, and cognitive dysregulation in ill AN. We will study 20 adolescent women currently ill with AN and 20 healthy adolescent control women (CW), all of whom are 14 to 18 years old. AIM 1: The anterior insula (AI), orbitofrontal cortex (OFC), and associated regions integrate sensory/hedonic aspects of taste and interoceptive awareness in the service of homeostasis. We hypothesize that restricted eating and weight loss occur in AN because a palatable food elicits little reward. AIM 2: Little in life is rewarding to individuals with AN aside from weight loss, and they tend to be overconcerned with future consequences. We predict that ill AN will show an inability to discriminate positive and negative feedback reflecting aberrant anterior ventral striatum (AVS) limbic function. AIM 3: AN tend to be rigid, inflexible and behaviorally inhibited. We will use a stop task3-5 to characterize the neural substrates of inhibitory motor control. We hypothesize that ill AN, relative to CW, will show a demand-specific alteration of a fronto- subthalamic circuit that is necessary for motor inhibition6. Finally, in an Exploratory Aim, we propose to examine how clinical, cognitive, and personality/temperament measures might be correlated to either the BOLD response and/or the integrity of frontostriatal connectivity as determined using diffusion tensor imaging (DTI). Taken together, these aims will enable us to better characterize cognitive and limbic dysfunction in these populations. Understanding biologic vulnerabilities in AN is critical for developing effective treatment interventions for this often chronic and deadly disorder. In addition, there is a lack of understanding of appropriate methodologies necessary to address the unique problems inherent in the study of ill AN. Thus, this R21 application will also characterize confounding factors, such as brain volume, energy metabolism, development stages, and gonadal steroids, with the intent that a future R01 application will incorporate methodology needed to rigorously investigate this population. PUBLIC HEALTH RELEVANCE: There is considerable evidence that alterations in brain function contribute to disturbances of appetite, emotionality, and impulse control in anorexia nervosa. This application will use functional magnetic brain imaging to characterize neuronal circuits and their relationship to behavior. Understanding the pathophysiology of anorexia nervosa is necessary in order to devise new and more effective treatment interventions for this often chronic and deadly disorder.