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

描述（由申请人提供）：食物香味是食物风味和享乐品质所固有的强有力的食欲线索，并且这样的线索可以促进暴饮暴食。饮酒同样会“刺激”食欲，并在酒精的急性作用下导致暴饮暴食。虽然化学感觉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和肥胖受试者中的差异处理只是最近才开始的。此外，也没有研究酒精暴露如何改变大脑对食物气味的反应，或者它的抑制特性如何促进暴饮暴食。了解对此类食欲刺激做出反应的大脑部位，以及它们如何被体脂肪和酒精暴露所改变，将提供有关导致饮食失控的神经系统的重要见解。我们的初步数据表明，当闻到食物气味时，肥胖的受试者比瘦的受试者在海马体和海马体中表现出更大的血氧水平依赖（BOLD）反应。因此，该提议的主要假设是：A）瘦的和肥胖的受试者对增强进食动机的嗅觉线索具有不同的边缘系统反应，以及B）急性酒精中毒i）增强大脑对食物气味的奖励系统反应，以及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，我们修改了功能性磁共振成像（fMRI）的范例成功地用于研究酒精饮料的气味在酒精中毒的风险和正在进行的工作，抑制控制下的酒精暴露的主题。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、海马和杏仁核）区域的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“开胃酒”对食物气味反应的影响。这项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成像研究不同，我们将奖励系统对食物线索的反应与真实的世界条件联系起来，包括：1）受试者在不破坏或干扰昼夜节律的实际进餐间隔的进食行为，2）卡路里的有意义的减少对大脑对食物线索的反应的影响（如在节食条件下所经历的），和3）餐前饮酒对大脑对食物线索的反应，抑制，饮食行为。为了实现这些目标，我们还将使用食物香味，这是一种特别突出的刺激，比食物图像更直接地传达奖励的存在。 公共卫生相关性： 肥胖是一个重要的公共卫生问题，与心血管疾病、糖尿病和癌症的发展有关。这项应用的研究将使用大脑成像技术：1）阐明食物香味如何激活大脑中的奖励系统以促进食物摄入，以及瘦女性和肥胖女性之间这些反应的差异，2）确定酒精中毒促进暴饮暴食的大脑通路和行为机制。

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.