Reward System Responses to Food Aromas: Effects of Obesity and Alcohol Intake

描述（由申请人提供）：食物的香味是强大的食欲线索，是食物的味道和享乐品质的内在特征，这种线索可以促进暴饮暴食。同样，饮酒也会“启动”食欲，并在酒精的急性作用下导致暴饮暴食。虽然化学感觉大脑网络的神经成像是一个主要的研究领域，但测试这些感觉线索在瘦人和肥胖者之间是如何被不同地处理的，直到最近才开始。此外，没有研究表明酒精会如何改变大脑对食物气味的反应，也没有研究表明酒精的去抑制特性会如何促进暴饮暴食。了解对这种食欲刺激做出反应的大脑位点，以及它们是如何被身体脂肪和酒精所改变的，将为了解导致食欲失控的神经系统提供重要的见解。我们的初步数据表明，当闻到食物气味时，肥胖受试者在脑岛和海马体中表现出比苗条受试者更大的血氧水平依赖（BOLD）反应。因此，该建议的主要假设是：A)瘦和肥胖受试者对增强进食动机的嗅觉线索有不同的边缘反应，B)急性酒精中毒i)增强大脑对食物气味的奖励系统反应，ii)影响涉及行为抑制和进食限制的大脑系统。为了验证这些假设，我们修改了功能磁共振成像（fMRI）范式，成功地用于研究酒精中毒风险受试者的酒精饮料香气，并在酒精暴露下进行抑制控制的工作。我们的具体目标是：1)确定肥胖对特定边缘-额叶（眶额皮质、内侧额叶皮质、杏仁核、海马和岛叶）区域食物香味诱导反应的影响；2)检查热量摄入与食物香味诱导反应之间的关系；3)研究“apiritif”对食物气味反应的影响。本提案中的研究特别新颖，因为与先前关于肥胖或食物线索反应的神经影像学研究不同，我们将奖励系统对食物线索的反应与现实世界的情况联系起来，包括：1)受试者在不破坏或干扰昼夜节律的实际用餐间隔内的饮食行为，2)有意义的卡路里减少对大脑对食物线索反应的影响（如在节食条件下所经历的），以及3)饭前饮用酒精对大脑对食物线索、抑制和饮食行为的反应的影响。为了实现这些目标，我们还将使用食物香气，这是一种特别显著的刺激，比食物图像更能传达奖励的存在。

DESCRIPTION (provided by applicant): Food aromas are powerful appetitive cues that are intrinsic to foods' flavor and hedonic qualities, and such cues can facilitate overeating. Alcohol consumption similarly "primes" appetite, and contributes to overeating while under alcohol's acute effects. While neuroimaging of chemosensory brain networks is a major field of inquiry, testing how such sensory cues are differentially processed in lean and obese subjects has only recently begun. Further, there are no studies of how alcohol exposure alters the brain response to food odors, or how its disinhibiting qualities could facilitate overeating. Knowing the brain loci that respond to such appetitive stimuli, and how they are modified by body fat and alcohol exposure, will provide critical insights about the neural systems that underlie loss of control of eating. Our preliminary data suggest that when smelling food odors, obese subjects show a greater blood oxygen level-dependent (BOLD) response than lean subjects in the insula and hippocampus. Therefore, the main hypotheses of this proposal are that: A) Lean and obese subjects have different limbic responses to the olfactory cues that enhance motivation to eat, and B) Acute alcohol intoxication i) potentiates the brain's reward system response to food odors, and ii) affects brain systems involved in behavioral inhibition and eating restraint. To test these hypotheses, we have modified functional magnetic resonance imaging (fMRI) paradigms successfully used to study alcoholic drink aromas in subjects at risk for alcoholism and in ongoing work of inhibitory control under alcohol exposure. Our specific aims are to: 1) Determine the effect of adiposity on food aroma-induced responses of specific limbic-frontal (orbitofrontal cortex, medial frontal cortex, amygdala, hippocampus, and insula) areas, 2) Examine the relationships between caloric intake and food aroma-induced responses, and 3) Study the "apiritif" effect on the response to food odors. The studies in this proposal are particularly novel because, unlike prior neuroimaging research of obesity or food-cue responsiveness, we will relate the reward system response to food cues to real world conditions, including: 1) Subjects' eating behavior at realistic meal intervals that do not disrupt or interfere with circadian rhythms, 2) The effect of a meaningful reduction in calories on brain responses to food cues (as would be experienced under dieting conditions), and 3) The effect of alcohol as consumed before meals on the brain response to food cues, inhibition, and eating behavior. To accomplish these aims we will also use food aromas, which are particularly salient stimuli that convey a more immediate presence of reward than do food images. PUBLIC HEALTH RELEVANCE: Obesity is a significant public health problem associated with development of cardiovascular disease, diabetes and cancer. Studies in this application will use brain imaging techniques to: 1) clarify how food aromas activate reward systems in the brain to promote food intake, and differences in these responses between lean and obese women, 2) determine the brain pathways and behavioral mechanisms through which alcohol intoxication facilitates overeating.