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

描述(由申请人提供)：食物的香味是一种强烈的食欲暗示，是食物的味道和享乐品质的内在特征，这种暗示可能会促进暴饮暴食。饮酒同样会刺激食欲，在酒精的剧烈作用下会导致暴饮暴食。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，但测试这种感觉线索在瘦身和肥胖受试者中是如何被区别处理的，直到最近才开始。此外，还没有关于酒精暴露如何改变大脑对食物气味的反应的研究，或者酒精抑制气味如何促进暴饮暴食的研究。了解大脑对这种食欲刺激做出反应的位置，以及它们是如何被体脂和酒精暴露改变的，这将为人们提供关于导致食欲失控的神经系统的关键见解。我们的初步数据表明，当闻到食物气味时，肥胖的受试者在脑岛和海马体中表现出比瘦受试者更大的血氧水平依赖(BOLD)反应。因此，这一建议的主要假设是：A)瘦的和肥胖的受试者对增强进食动力的嗅觉线索有不同的边缘反应，B)急性酒精中毒I)加强大脑对食物气味的奖励系统的反应，II)影响参与行为抑制和进食限制的大脑系统。为了验证这些假设，我们改进了功能磁共振成像(FMRI)范式，成功地用于研究酒精中毒高危人群的酒精饮料香气，以及正在进行的酒精暴露下的抑制控制工作。我们的具体目标是：1)确定肥胖对特定边缘-额叶(眼眶-额叶皮质、额叶内侧皮质、杏仁核、海马体和脑岛)区域香气诱导反应的影响，2)检查卡路里摄入量与食品香气反应之间的关系，以及3)研究“apiritif”对食物气味反应的影响。这项建议中的研究特别新颖，因为与以前对肥胖或食物线索反应的神经成像研究不同，我们将把奖励系统对食物线索的反应与现实世界的条件联系起来，包括：1)受试者在不破坏或干扰昼夜节律的现实进餐间隔内的进食行为；2)有意义的减少卡路里对大脑对食物线索的反应的影响(就像节食条件下所经历的那样)；3)饭前饮酒对大脑对食物线索的反应、抑制和饮食行为的影响。为了实现这些目标，我们还将使用食物气味，这是一种特别显著的刺激，比食物图像传达出更直接的奖励。 与公共健康相关：肥胖是一个重大的公共健康问题，与心血管疾病、糖尿病和癌症的发展有关。这项应用中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，以及瘦身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途径和行为机制。

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.