Perceptual Coding and Modulation of Odor Objects in the Human Brain

描述（由申请人提供）：这是向 NIH/NIDCD 请求为西北大学 Feinberg 医学院神经病学助理教授 Jay A. Gottfried 博士提供一项新研究者发起的研究项目拨款 (R01) 奖。了解大脑如何产生对外部世界的内部感知长期以来一直是神经科学研究的重点。目前，人们对“气味物体”的神经处理知之甚少，即有气味的物体产生的气味（例如薄荷味、花香）的质量或特征。该项目的长期科学目标是表征人脑中气味质量编码的功能架构，并了解学习、背景和经验在这些感知代码的形成和调节中的作用。使用人类受试者可以直接口头报告他们的感知体验，为解决这些问题提供了明显的优势。在这里提出的研究中，嗅觉功能神经成像技术将与感觉心理物理方法和计算模型相结合，以描述有关气味物体的神经信息如何（而不是简单地在哪里）在大脑中编码。具体来说，多元统计算法将与高分辨率成像技术相结合，以检验气味质量和类别采用人类嗅觉大脑中空间分布活动模式的形式的假设。拟议的研究还将这些技术与气味感觉剥夺、嗅觉知觉错觉和预期效应的新范式结合起来，以研究实验诱导的整体大脑活动的变化是否与气味质量感知的平行变化相一致。通过强调动态条件下大脑活动与气味物体感知之间的密切联系，这些研究将证明人类嗅觉皮层中气味诱发的整体模式满足真正的气味质量嗅觉代码的标准。公共健康相关性：嗅觉异常与阿尔茨海默病 (AD) 患者具有特殊的临床相关性，这些患者在病程早期就会出现嗅觉识别和辨别能力的缺陷，并且通常在出现明显的认知症状（例如记忆丧失）之前出现。鉴于阿尔茨海默病病理学在大脑嗅觉边缘区域的早期积累，人类嗅觉成像技术应该是评估这种神经退行性疾病边缘功能障碍的高度敏感的方法，从而开辟了开发非侵入性成像生物标志物来预测哪些个体有患 AD 风险的可能性。最终，随着新的 AD 治疗和预防策略的出现，对可靠诊断工具的需求，特别是症状前阶段的诊断工具，将变得越来越重要，而拟议的健康受试者影像学研究应为此提供重要信息。

Description (provided by applicant): This is a request to the NIH/NIDCD for a New Investigator-initiated Research Project Grant (R01) Award for Jay A. Gottfried, MD, PhD, Assistant Professor of Neurology at Northwestern University Feinberg School of Medicine. Understanding how the brain creates internal perceptions of the external world has long been a key focus of neuroscientific research. Currently little is known about the neural processing of "odor objects," that is, the quality or character of a smell (e.g., minty, floral) arising from an odorous object. The long-term scientific goal of this project is to characterize the functional architecture of odor quality coding in the human brain, and to understand the roles of learning, context, and experience in the formation and modulation of these perceptual codes. The use of human subjects, who can provide direct verbal reports of their perceptual experience, offers distinct advantages for addressing these questions. In the research proposed here, olfactory functional neuroimaging techniques will be combined with sensory psychophysical approaches and computational models to characterize how (rather than simply where) neural information about odor objects is encoded in the brain. Specifically, multivariate statistical algorithms will be integrated with high-resolution imaging technologies to test the hypothesis that odor qualities and categories take the form of spatially distributed activity patterns in the human olfactory brain. The proposed studies will also pair these techniques with novel paradigms of odor sensory deprivation, olfactory perceptual illusions, and expectancy effects, to investigate whether experimentally induced changes in ensemble brain activity will coincide with parallel changes in odor quality perception. By highlighting the close affiliation between brain activity and odor object perception under dynamic conditions, these studies will demonstrate that odor-evoked ensemble patterns in human olfactory cortex satisfy criteria for a genuine olfactory code of odor quality. PUBLIC HEALTH RELEVANCE: Abnormalities in the sense of smell have particular clinical relevance for patients with Alzheimer's disease (AD), in whom deficits of smell identification and discrimination arise early in the course of illness, and often before the emergence of overt cognitive symptoms such as memory loss. Given the early accumulation of Alzheimer's pathology in olfactory limbic regions of the brain, human olfactory imaging techniques should be a highly sensitive method for assessing limbic dysfunction in this neurodegenerative disorder, opening up the possibility of developing a non-invasive imaging biomarker to predict which individuals are at risk for developing AD. Ultimately, with the emergence of novel therapeutic and preventative strategies for AD on the horizon, the need for reliable diagnostic tools, particularly for pre-symptomatic stages, will become increasingly critical, and the proposed imaging research in healthy subjects should provide important information toward this end.