Neural Bases of Self-regulatory Control in Bulimia Nervosa

 描述(由申请人提供)：最近的证据表明，自我调节控制的障碍可能有助于神经性暴食症(BN)的发展和持续。BN患者对进食和代偿行为的“失控”可能部分是由于抑制控制的缺陷和相关的皮质纹状体回路的大脑功能障碍造成的。此外，最近的BN病理模型表明，情绪自我调节方面的障碍可能与特定于障碍的行为有关。自我调节控制能力的缺陷可能 还允许反复暴饮暴食和大小便成为一种根深蒂固的行为模式。识别和表征BN的脑部异常，可以提供针对这些异常的新的干预措施，这是当务之急。国家精神卫生研究所战略计划的一个主要目标包括促进发现导致精神疾病的大脑行为过程。与这一战略目标和为BN开发新的有针对性的治疗方法的需要相一致，Ruth L.Kirschstein国家研究服务奖(NRSA)是一个为期三年的研究和培训计划，重点是调节成年BN多种自我调节能力的重叠的皮质纹状体神经回路。以前对BN中控制相关缺陷的研究受到了使用单一任务来研究单一神经认知过程的限制。这项拟议的研究在患有BN的女性(n=30)和对照组(n=30)中评估了三种形式的自我调节(运动抑制、情绪调节和目标定向动作控制)的行为和神经决定因素，并检查了这些能力和BN症状之间的关系。该项目结合了功能磁共振成像(FMRI)、进食障碍症状评估和经过充分验证的神经认知任务。该项目旨在检验以下假设：1)患有BN的女性在运动抑制控制和情绪调节任务中表现出皮质纹状体活性下降和表现受损，2)BN女性将表现出目标导向控制能力不足，3)BN参与者的症状越严重，皮质纹状体激活的损害越大，包括这三个领域的自我调节能力的模型将最好地预测BN的严重程度。据我们所知，这个项目是第一个检查大脑在消极和积极情绪调节过程中的激活 他还是第一个研究BN在目标导向控制和基于习惯的反应方面潜在的相对失衡的人。这项NRSA将通过为申请者提供收集、分析和解释功能磁共振成像和行为数据所需的高级技能和研究经验，以及神经发育的入门培训，为未来饮食失调的神经基础研究奠定基础。该项目在同一样本中对运动、情感和目标定向行为控制的多个非症状特异性探针进行了新颖的集成，从而可以区分这些自我调节控制能力对BN病理的相对贡献。

 DESCRIPTION (provided by applicant): Recent evidence suggests that impairments in self-regulatory control may contribute to the development and persistence of bulimia nervosa (BN). "Loss of control" over eating and compensatory behaviors in BN may result, in part, from deficits in inhibitory control and associated brain-based dysfunction in corticostriatal circuits. In additin, recent models of BN pathology suggest that impairments in self-regulation of emotion may relate to disorder-specific behaviors. Deficits in the ability to exert self-regulatory control may also allow repeated binge eating and purging to become an entrenched behavioral pattern. Identification and characterization of brain-based abnormalities in BN, which could inform novel interventions that target these abnormalities, is imperative. A main objective of the National Institute of Mental Health Strategic Plan includes promoting discovery of brain-behavior processes that contribute to mental illness. Consistent with this strategic objective and the need to develop new and targeted treatments for BN, the proposed Ruth L. Kirschstein National Research Service Award (NRSA) is a three-year program of research and training focused on the overlapping corticostriatal neural circuits mediating multiple self-regulatory capacities in adult BN. Prior studies of control-related deficits in BN have been limited by their use of a singl task to study a single neurocognitive process. The proposed study assesses, among women with BN (n = 30) and group-matched controls (n = 30), the behavioral and neural determinants of three forms of self-regulation (motor inhibition, emotion regulation, and goal-directed action control) and examines relations among these capacities and BN symptoms. The project combines functional magnetic resonance imaging (fMRI), eating disorder symptom assessment, and well-validated neurocognitive tasks. The project aims to test the hypotheses that: 1) women with BN will demonstrate decreased corticostriatal activation and impaired performance during motor inhibitory control and emotion regulation tasks, 2) women with BN will demonstrate deficient goal-directed control abilities, and 3) BN participants with more severe symptoms will demonstrate the greatest impairments in corticostriatal activation, and a model including self-regulatory abilities in all three domains will best predict BN severity. To our knowledge, this project is the first to examine brain activation during negative and positive emotion regulation in BN and the first to investigate a potential relative imbalance in goal-directed control and habit-based responding in BN. This NRSA will lay groundwork for future investigations of the neural substrates of eating disorders by providing the applicant with the advanced skills and research experience needed to collect, analyze, and interpret fMRI and behavioral data, along with introductory training in neurodevelopment. The project's novel integration of multiple, non-symptom-specific probes of motor, affective, and goal-directed behavioral control within the same sample permits distinction of the relative contributions of these self- regulatory control capacities to BN pathology.