Neural organization of odor coding in human piriform cortex

描述（由申请人提供）：这是Jay a . Gottfried，医学博士，NIDCD K08指导临床科学家发展奖的申请，在西北大学神经学教授M.-Marsel Mesulam博士的指导下，以及耶鲁大学心理学教授Lawrence Marks博士的共同指导下。澄清气味的物理属性和感知属性之间的生物学联系是嗅觉神经科学的一个关键问题。为什么一种挥发性有机化合物“闻起来”像巧克力，而另一种像奶酪？很少有系统的研究来解决这些问题。该项目的长期目标是了解人类大脑中气味编码的本质。功能神经成像技术将与嗅觉交叉适应、知觉学习和经典条件反射的范式相结合，以表征初级嗅觉（梨状）皮层的神经反应特性。这些研究将辅以嗅觉心理物理学方法来评估感觉经验和联想学习对气味质量感知和辨别的行为影响。-作为职业发展计划的一部分，Gottfried博士将学习人类嗅觉心理物理学（Marks博士）的新技能，并接受神经影像学（Marks博士）的额外培训。Apkarian, Gitelman, Parrish)，并接受行为神经科学（Mesulam博士）和临床神经心理学（Weintraub博士）的指导，并辅以感觉信息理论，统计学，实验设计和MRI物理方面的教学指导。在这个项目中获得的知识将使Gottfried博士发展成为一名独立的临床医生和人类嗅觉研究者，专门研究跨越基本嗅觉神经科学和临床行为神经学之间接口的功能成像应用。嗅觉异常在许多神经系统疾病中都很突出，包括阿尔茨海默病、帕金森病和亨廷顿病。因此，对健康受试者嗅觉功能的系统了解可能会对这些神经退行性疾病的病理生理学、诊断甚至治疗产生新的见解。通过帮助阐明气味在完整的人类大脑中是如何表现的，这项拟议的研究可能对启发我们对阿尔茨海默病和其他神经系统疾病的理解具有重要的实用价值。

DESCRIPTION (provided by applicant): This is a request for an NIDCD K08 Mentored Clinical Scientist Development Award for Jay A. Gottfried, MD, PhD, under the mentorship of Dr. M.-Marsel Mesulam, MD, Professor of Neurology, Northwestern University, and the co-mentorship of Dr. Lawrence Marks, PhD, Professor of Psychology, Yale University. Clarifying the biological links between physical and perceptual attributes of odor is a critical issue in olfactory neuroscience. Why does one volatile organic compound "smell" like chocolate, and another like cheese? There has been little systematic research to address these questions. The long-term objective of the proposed project is to understand the nature of odor coding in the human brain. Functional neuroimaging techniques will be combined with olfactory paradigms of cross-adaptation, perceptual learning, and classical conditioning to characterize the neural response properties of primary olfactory (piriform) cortex. These studies will be complemented by olfactory psychophysics approaches to assess the behavioral influence of sensory experience and associative learning on odor quality perception and discrimination. - As part of the career development plan, Dr. Gottfried will learn new skills in human olfactory psychophysics (Dr. Marks), gain additional training in neuroimaging (Drs. Apkarian, Gitelman, Parrish), and receive supervision in behavioral neuroscience (Dr. Mesulam) and clinical neuropsychology (Dr. Weintraub), all complemented by didactic instruction in sensory information theory, statistics, experimental design, and MRI physics. The knowledge acquired during this project should allow Dr. Gottfried to develop into an independent clinician-investigator in human olfaction specializing in functional imaging applications that span the interface between basic olfactory neuroscience and clinical behavioral neurology. Abnormalities in the sense of smell figure prominently in a number of neurological disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Therefore, a systematic understanding of olfactory function in healthy subjects may lead to new insights concerning the pathophysiology, diagnosis, and perhaps even treatment of these neurodegenerative conditions. By helping to clarify how smells are represented in the intact human brain, the proposed research may have important utility in enlightening our understanding of Alzheimer's disease and other neurological disorders.