Neural organization of odor coding in human piriform cortex

描述(由申请人提供)：这是一份申请NIDCD K08指导临床科学家发展奖的申请，授予Jay A.Gottfred，医学博士，博士，由M.-Marsel Mesulam博士，医学博士，西北大学神经学教授，以及Lawrence Marks博士，博士，耶鲁大学心理学教授共同指导。阐明气味的物理属性和感知属性之间的生物学联系是嗅神经科学中的一个关键问题。为什么一种挥发性有机化合物闻起来像巧克力，另一种闻起来像奶酪？几乎没有系统的研究来解决这些问题。这项拟议项目的长期目标是了解人类大脑中气味编码的性质。功能神经成像技术将与交叉适应、知觉学习和经典条件反射的嗅觉范例相结合，以表征初级嗅觉(梨状)皮质的神经反应特性。这些研究将得到嗅觉心理物理学方法的补充，以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，戈特弗里德博士将学习人类嗅觉心理物理学的新技能(马克斯博士)，获得神经成像方面的额外培训(阿普卡里安、吉特尔曼、帕里什博士)，并接受行为神经科学(梅苏拉姆博士)和临床神经心理学(温特劳布博士)的指导，所有这些都将得到感官信息理论、统计学、实验设计和核磁共振物理学的教学指导。在这个项目中获得的知识应该会让戈特弗里德博士发展成为一名独立的人类嗅觉临床医生兼研究员，专门研究跨越基础嗅觉神经科学和临床行为神经学之间的功能成像应用程序。嗅觉异常在包括阿尔茨海默氏症、帕金森氏病和亨廷顿病在内的许多神经疾病中占有突出地位。因此，系统地了解健康受试者的嗅觉功能可能会对这些神经退行性疾病的病理生理学、诊断甚至治疗有新的见解。通过帮助阐明气味是如何在完整的人脑中表现出来的，拟议中的研究可能会对启发我们对阿尔茨海默氏症和其他神经疾病的理解有重要的实用价值。

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.