Brain Reward-Pathway Function and Neurocomputational Modeling in Anorexia Nervosa

描述(由申请者提供)：这个以患者为导向的研究职业发展(K23)奖的总体目标是：1.为申请者提供在进食障碍，特别是限制性神经性厌食症(RAN)方面进行独立功能性磁共振脑成像(FMRI)研究的技能，2.培训申请者使用新的神经计算建模方法，将心理学理论与潜在的神经基础联系起来，以及3.扩展我们对RAN中与食物和非食物(金钱)奖励处理相关的大脑活动的知识。目标1.a.是利用功能磁共振成像和预期和意外传递甜味刺激的范例来研究前腹侧纹状体奖赏通路的功能(O‘Doherty等人，2003年)。我们假设，与对照组女性相比，RAN恢复期和III期的女性前腹侧纹状体的激活程度会降低。在目标1.b中，使用对fMRI数据进行奖赏条件作用的计算模型，我们预计与对照组相比，III组和恢复的前腹侧纹状体RAN的奖赏学习信号减少。目标2.a.是为了研究与CW相比，眼眶前额叶皮质和纹状体激活减少是否存在于III和恢复的RAN中(Tanaka等人，2004年)。相反，我们预计在延迟的货币奖励期间，III和恢复的RAN在背外侧、前额叶和顶叶皮质的激活程度比对照组更大(Tanaka等人，2004年)。在目标2.b中，利用所获得的脑数据的计算模型，我们预计在III和恢复的RAN中，与对照组相比，前腹侧纹状体即刻减少，但背侧纹状体延迟奖赏加工增加。这项研究使用了新的技术和范式。它将极大地推动饮食失调研究领域的发展，也将是为申请者提供功能磁共振成像和神经计算建模培训的绝佳机会。申请者将由饮食失调、功能磁共振脑成像和神经计算建模领域的知名专家指导，并将参加科罗拉多大学认知科学和心理学项目的课程。神经性厌食症是所有精神疾病中死亡率最高的。这一应用将有助于识别奖励系统在限制A型中的干扰途径，将为疾病机制提供新的见解，并将为我们开发先进的治疗方法提供新的信息。

DESCRIPTION (provided by applicant): The overall goal of this Mentored Patient-Oriented Research Career Development (K23) Award is to 1. Provide the applicant with the skills to perform independent functional magnetic resonance brain imaging (fMRI) research in Eating Disorders, specifically Restricting Type Anorexia Nervosa (RAN), 2. Train the applicant in novel Neurocomputational Modeling approaches that link psychological theory with underlying neural substrates, and 3. Extend our knowledge on brain activity in RAN in relation to food and non-food (monetary) reward processing. Aim 1 .a. is to investigate the functionality of anteroventral striatum reward pathways using fMRI and a paradigm of expected and unexpected delivery of sweet taste stimuli (O'Doherty et al 2003). We hypothesize that women Recovered from and III with RAN will have reduced anteroventral striatum activation compared to control women. In Aim 1.b., using computational models for reward conditioning on the fMRI data, we expect reduced reward learning signals in III and Recovered RAN in the anteroventral striatum compared to controls. Aim 2.a. is to investigate if reduced orbitofrontal cortex and striatum activation compared to CW exists in III and Recovered RAN in response to monetary immediate reward (Tanaka et al 2004). In contrast we expect III and recovered RAN to have greater activation than controls in the dorsolateral prefrontal and parietal cortex during delayed monetary reward (Tanaka et al 2004). In Aim 2.b., using computational models on the acquired brain data, we expect in III and Recovered RAN reduced anteroventral striatum immediate, but increased dorsal striatum delayed reward processing compared to controls. This study uses novel technologies and paradigms. It will both advance the field of Eating Disorders research greatly as well as will be an excellent opportunity to provide the applicant with training in fMRI and Neurocomputational Modeling. The applicant will be mentored by renowned experts in the field of Eating Disorders, fMRI Brain Imaging and Neurocomputational Modeling, and he will attend courses in the Cognitive Science and Psychology Program at the University of Colorado. Anorexia Nervosa has the highest mortality among all psychiatric disorders. This application will help identify pathways of disturbance of the reward system in Restricting type AN, will provide new insight into the disease mechanism, and will provide us with new information for the development of advanced treatments.