Brain and Adipose Contributors to Food Seeking in Youth with Adrenal Hyperplasia

 描述（由申请人提供）：拟议的指导研究的目标是调查儿童寻求食物行为的神经生物学，并为Mimi Kim博士提供深入的培训和指导，使其成为儿童肥胖和代谢的独立研究者。该提案针对先天性肾上腺皮质增生（CAH）儿童作为研究大脑和脂肪肥胖贡献者的自然人类模型。她的长期目标是成为儿童肥胖症临床研究的领导者，重点是预防和治疗。金博士于2009年加入南加州大学凯克医学院儿科和洛杉矶儿童医院内分泌科，师从包括CAH在内的儿童内分泌紊乱专家米切尔·格夫纳博士。CAH患儿存在神经内分泌功能和与自我控制和奖赏相关的脑结构异常，比非CAH患儿更容易肥胖。具体来说，金博士将测量食物寻求行为，身体脂肪，代谢激素和大脑活动的区域参与奖励（例如，杏仁核和杏仁核）和抑制控制（前额叶皮层）在CAH儿童和未受影响的对照组（非CAH）。先前的研究表明，患有CAH的儿童杏仁核体积和功能异常，在动机行为中抑制控制能力下降。CAH儿童的食物寻求行为尚未被研究;然而，有大量关于杏仁核功能受损和食物寻求行为的动物研究。Kim博士假设：1）在CAH中观察到的小杏仁核与肥胖有关，2）CAH儿童对高度可口的食物线索表现出更少的抑制控制和更大的大脑奖励反应。具体目标是：1）确定杏仁核大小是否与CAH青年与非CAH青年的肥胖和身体组成呈负相关; 2）确定CAH青年中抑制性控制区域的激活是否减少，奖励区域的激活是否增加以响应食物线索;以及3）根据目标1评估CAH和非CAH组中关于食物选择的决策。通过指导培训和教学式学习，Kim博士将在以下方面发展特定的专业知识：1）大脑和腹部的结构磁共振成像（MRI），2）大脑的功能性MRI和在扫描仪中执行基于食物线索的任务，3）涉及食物决策的神经行为任务，以及4）用于进行人类研究的统计方法。在来自多个学科的高度专家和协作导师的指导下，Kim博士将获得技术技能，并了解如何有效地进行和领导团队科学。她的项目将建立一个人类模型，用于使用复杂的MRI测量来研究儿童的杏仁核、食欲、觅食行为和肥胖。了解儿童食物寻求行为的神经生物学可以为患有和不患有CAH的肥胖儿童提供急需的干预措施。

 DESCRIPTION (provided by applicant): The goal of the proposed mentored research is to investigate the neurobiology of food-seeking behaviors in children, and to provide Dr. Mimi Kim the in-depth training and mentorship to become an independent investigator in childhood obesity and metabolism. This proposal targets children with congenital adrenal hyperplasia (CAH) as a natural human model for the study of brain and adipose contributors to obesity. Her long-term goal is to become a clinical research leader in childhood obesity with an emphasis on prevention and treatment. Dr. Kim joined the Department of Pediatrics at the Keck School of Medicine of USC and the Division of Endocrinology at Children's Hospital Los Angeles in 2009 under the mentorship of Dr. Mitchell Geffner, an expert in childhood endocrine disorders, including CAH. Children with CAH have abnormalities in neuroendocrine function and brain structures related to self-control and reward, and are more likely to be obese than children without CAH. Specifically, Dr. Kim will measure food-seeking behavior, body fat, metabolic hormones, and brain activity in regions involved in reward (e.g., amygdala and nucleus accumbens) and inhibitory control (pre-frontal cortex) in children with CAH and in an unaffected comparison group (Non-CAH). Prior research has shown that children with CAH have abnormal amygdala volumes and function, and decreased inhibitory control during motivated behavior. Food-seeking behaviors have not been studied in children with CAH; however, there is a wealth of animal research on impaired amygdala function and food- seeking behavior. Dr. Kim hypothesizes that 1) a small amygdala, as observed in CAH, is associated with obesity, and that 2) children with CAH exhibit less inhibitory control and greater brain reward response to highly palatable food cues. The specific aims are to: 1) determine whether amygdala size is inversely associated with adiposity and body composition in CAH youth vs. Non-CAH youth; 2) determine whether activation of inhibitory control regions is decreased and activation of reward regions is increased in response to food cues in CAH youth; and 3) evaluate decision-making with regard to food choices in CAH and Non-CAH groups from Aim 1. Through mentored training and didactic learning, Dr. Kim will develop specific expertise in: 1) structural magnetic resonance imaging (MRI) of the brain and abdomen, 2) functional MRI of the brain and administering a food cues-based task in the scanner, 3) a neurobehavioral task involving food decision- making, and 4) statistical methods useful for conducting human research. Guided by highly expert and collaborative mentors from multiple disciplines, Dr. Kim will acquire technical skills and an understanding of how to effectively conduct and lead team science. Her project will establish a human model for the study of the amygdala, appetite, food-seeking behaviors, and obesity in children using sophisticated MRI measures. Understanding the neurobiology of food-seeking behaviors in children could inform much-needed development of interventions for obese children with and without CAH.