Spatiotemporal Coding in the Human Olfactory System

描述(由申请人提供)：越来越清楚的是，嗅觉在各种各样的神经和神经精神障碍中受到损害。然而，临床上对人类嗅觉的日益增长的欣赏被对其解剖学和生理学的基本了解所抵消。即使是最基本的假设也没有得到探索：人类的嗅觉通路真的是同侧的吗？初级嗅觉皮质到底在哪里？气味信息通过人类嗅觉大脑传输的速度有多快？这一探索性研究项目的主要目的是研究药物难治性癫痫患者直接从人脑表面的气味诱发脑电(EEG)活动的模式，并用皮质电刺激和皮质诱发电位定位嗅皮层。在标准的手术探查中，高密度侵入性电极阵列在颞叶和眶前皮质周围的高精度放置为了解嗅觉系统的功能解剖提供了一个独特的窗口，而嗅觉系统的功能解剖在很大程度上尚未被探索。本文提出的工作将对人类嗅觉有一个更全面的基础了解，有助于癫痫患者的诊断和功能结局的预测，并为监测其他涉及嗅觉的神经疾病的发病和进展开辟新的途径。 公共卫生相关性：嗅觉异常与多种神经和神经精神障碍具有特别的临床相关性，包括复杂的部分性癫痫、阿尔茨海默病、帕金森病和精神分裂症。在许多情况下，气味辨别的知觉缺陷在病程早期出现，可能是由于大脑嗅觉边缘区域最初积累的神经病理损害。在将皮质脑电技术与嗅觉心理物理方法结合起来治疗难治性癫痫患者时，拟议的研究为了解人类嗅觉系统的基本组织提供了一个独特的窗口。这项工作的发现可能会直接指导癫痫病变定位和预测癫痫患者功能结局的新工具的开发，这些患者正在考虑进行手术治疗。这里提出的工作还将为监测其他神经疾病的发病和进展提供新的见解，在这些疾病中，嗅觉障碍是早期迹象。

DESCRIPTION (provided by applicant): It is increasingly clear that olfactory perception is impaired in a wide variety of neurological and neuropsychiatric disorders. However, this growing clinical appreciation for the human sense of smell is offset by a poor basic understanding of its anatomy and physiology. Even the most fundamental assumptions remain unexplored: Is the human olfactory pathway really ipsilateral? Where exactly is primary olfactory cortex? How fast is odor information transmitted through the human olfactory brain? The major aim of this exploratory research project is to investigate odor-evoked patterns of electroencephalographic (EEG) activity directly from the surface of the human brain in patients with medically intractable epilepsy and to map the olfactory cortex with electrical cortical stimulation and cortico-cortical evoked potentials. The highly accurate placement of a high-density invasive electrode array around the temporal and orbitofrontal cortices during standard surgical exploration offers a unique window into the functional anatomy of the olfactory system which has been largely unexplored. Work proposed here will yield a more comprehensive basic understanding of human olfaction, help in diagnosis and prediction of functional outcome in epilepsy patients, and open up new avenues for monitoring disease onset and progression in other neurological disorders involving the sense of smell. PUBLIC HEALTH RELEVANCE: Abnormalities in the sense of smell have particular clinical relevance for a wide variety of neurological and neuropsychiatric disorders, including complex partial epilepsy, Alzheimer's disease, Parkinson's disease, and schizophrenia. In many instances, perceptual deficits of odor discrimination arise early in the course of illness, likely due to the initial accumulation of neuropathological lesions in olfactory limbic regions of the brain. In combining electrocorticography techniques with olfactory psychophysical approaches in patients with medically refractory epilepsy, the proposed research offers a unique window into the fundamental organization of the human olfactory system. Findings from this work may directly guide the development of new tools for lesion localization in epilepsy and for the prediction of functional outcome in epilepsy patients who are being considered for surgical intervention. The work proposed here will additionally provide new insights into monitoring onset and progression of other neurological diseases in which olfactory perceptual impairments are an early sign.