Perceptual Coding and Modulation of Odor Objects in the Human Brain

描述(由申请人提供)：这是向NIH/NIDCD申请由新研究员发起的研究项目补助金(R01)奖，授予西北大学范伯格医学院神经学助理教授Jay A.Gottred医学博士。长期以来，了解大脑如何产生对外部世界的内部感知一直是神经科学研究的关键重点。目前对“气味物体”的神经处理知之甚少，即气味物体产生的气味(如薄荷、花香)的性质或特征。该项目的长期科学目标是描述人脑中气味质量编码的功能结构，并了解学习、背景和经验在这些知觉编码的形成和调节中的作用。使用人类受试者，他们可以提供他们感知经验的直接口头报告，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，以表征关于气味对象的神经信息是如何(而不仅仅是在哪里)在大脑中编码的。具体地说，多元统计算法将与高分辨率成像技术相结合，以测试气味质量和类别在人类嗅觉大脑中以空间分布活动模式的形式存在的假设。这项拟议的研究还将把这些技术与气味感觉剥夺、嗅觉错觉和预期效应的新范例配对，以调查实验诱导的整体大脑活动的变化是否会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和气味对象感知之间的密切联系，这些研究将证明人类嗅觉皮质中气味诱发的整体模式满足气味质量的真正嗅觉代码的标准。公共卫生相关性：嗅觉异常对阿尔茨海默病(AD)患者具有特殊的临床相关性，在阿尔茨海默病(AD)患者中，嗅觉识别和辨别能力缺陷在病程早期出现，通常在出现明显的认知症状(如记忆力丧失)之前。鉴于阿尔茨海默病的病理早期积累在大脑的嗅觉边缘区域，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，从而为开发一种非侵入性成像生物标记物来预测哪些人有患阿尔茨海默病的风险开辟了可能性。最终，随着AD新的治疗和预防策略的出现，对可靠的诊断工具的需求将变得越来越重要，特别是对于症状前阶段，拟议的健康受试者成像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.