Determining the Functional Brain Networks that Underlie Children’s Overeating and Adiposity Gain

项目摘要 儿童肥胖是一种全球流行病，与负面的身体和心理社会健康结果有关4， 而预防儿童肥胖的行为干预产生的效果很小，而且变化很大。增加进食量 缺乏饥饿(EAH)已被确定为儿童肥胖的进食表型，但 在肥胖症发展之前导致EAH增加的机制尚不清楚。更好的 了解导致儿童EAH增加和体重增加的机制对于 制定更有效的肥胖预防计划。暴饮暴食被认为是由于不平衡造成的 在参与食物提示反应和奖赏处理的大脑区域(即，反应系统)中， 参与抑制和认知控制(即，调节系统)7-12。 这些增加暴饮暴食和肥胖风险的神经系统之间的联系尚不清楚。建房 关于我的赞助人的R01研究，该研究旨在检查神经和认知预测肥胖增加的因素 7-8岁儿童肥胖的家庭风险不同，这项建议旨在确定功能性 反应性和调节性大脑系统之间的连接模式(即，神经网络特性) EAH和肥胖的增加是基础。假设反应性和反应性之间较弱的连接性 监管系统和反应系统内更强的连接性将与更大的EAH和 儿童肥胖症的增加。为了验证这些假说，在接触辐射期间收集的神经成像(FMRI)数据 食物线索将与EAH实验室评估的食物摄入量数据一起使用，在此期间，儿童 在吃饱一顿标准餐后，提供各种美味的零食。拟人化 肥胖的评估将在基线时收集，并使用双x射线吸收测量仪进行一年的随访 (DXA)。将使用创新的网络分析和先进的统计方法来识别和表征 儿童特有的神经网络来自先验的“反应性”和“调节性”大脑感兴趣区域。创新 这一建议提供了(1)使用复杂的定量技术来检查儿童的神经 接触食物线索期间的网络和(2)网络分析与客观评估的结合 享乐主义饮食和肥胖的纵向测量，这将为神经提供新的见解 在脆弱的青春期前，促进暴饮暴食和体重增加风险的因素。在……里面 此外，在本提案中组建的跨学科导师团队将在以下方面提供严格的培训 用于进食行为研究、神经网络分析和科学交流的实验设计 这将有助于推进我作为一名独立研究员的职业生涯。拟议的研究将加强我们的 了解支持暴饮暴食和肥胖增加的神经机制，这将使 制定干预措施，以减轻过量能量摄入和肥胖的发展。

Project Summary Childhood obesity is a global pandemic associated with negative physical and psychosocial health outcomes4, and behavioral interventions to prevent childhood obesity produce small and variable effects5. Increased eating in the absence of hunger (EAH) has been identified as an obesogenic eating phenotype in children6, but the mechanisms that contribute to increased EAH prior to the development of obesity are unclear. A better understanding of the mechanisms that engender increased EAH and weight gain in children is critical to the development of more effective obesity prevention programs. Overeating is posited to result from an imbalance in brain regions involved in food cue reactivity and reward processing (i.e., a reactive system) with those involved in inhibition and cognitive control (i.e., a regulatory system)7–12. However, the patterns of functional connectivity between these neural systems which increase overeating and risk for obesity are unclear. Building on my sponsor’s R01 study, which is designed to examine neural and cognitive predictors of adiposity gain in children 7-8 years old who vary by familial risk for obesity, this proposal aims to identify the functional connectivity patterns (i.e., neural network properties) between reactive and regulatory brain systems that underlie EAH and adiposity gain. It is hypothesized that weaker connectivity between the reactive and regulatory system, and stronger connectivity within the reactive system, will be related to greater EAH and adiposity gain in children. To test these hypotheses, neuroimaging (fMRI) data collected during exposure to food cues will be used alongside food intake data from a laboratory assessment of EAH, during which children are offered a variety of palatable snack foods after eating a standard meal to fullness. Anthropomorphic assessments of adiposity will be collected at baseline and 1-year follow-up using dual x-ray absorptiometry (DXA). Innovative network analyses and advanced statistical methods will be used to identify and characterize child-specific neural networks from a priori “reactive” and “regulatory” brain regions of interest. Innovations offered by this proposal are (1) the use of sophisticated quantitative techniques to examine children’s neural networks during exposure to food cues and (2) the integration of network analyses with objectively-assessed hedonic eating and longitudinal measures of adiposity, which together will provide novel insight into the neural factors that promote overeating and risk for weight gain during the vulnerable pre-adolescent period. In addition, the inter-disciplinary mentorship team assembled in this proposal will provide rigorous training in experimental design for ingestive behavior research, neural network analyses, and scientific communication that will help advance my career as an independent researcher. The proposed study will enhance our understanding of the neural mechanisms supporting overeating and adiposity gain, which will inform the development of interventions to mitigate excess energy intake and the development of obesity.