Spatiotemporal Coding in the Human Olfactory System

描述（由申请人提供）：越来越清楚的是，嗅觉在各种神经和神经精神疾病中受损。然而，这种对人类嗅觉的日益增长的临床欣赏被对其解剖学和生理学的基本理解所抵消。即使是最基本的假设仍然没有得到探索：人类的嗅觉通路真的是同侧的吗？初级嗅觉皮层到底在哪里？气味信息通过人类嗅觉大脑传递的速度有多快？该探索性研究项目的主要目的是直接从药物难治性癫痫患者的大脑表面研究气味诱发的脑电图（EEG）活动模式，并利用皮层电刺激和皮层-皮层诱发电位绘制嗅觉皮层。在标准手术探查过程中，高密度侵入性电极阵列在颞叶和眶额皮质周围的高度准确放置为嗅觉系统的功能解剖提供了一个独特的窗口，该功能解剖在很大程度上尚未被探索。这里提出的工作将产生一个更全面的基本了解人类嗅觉，帮助诊断和预测癫痫患者的功能结果，并开辟了新的途径，监测疾病的发病和进展，在其他神经系统疾病涉及嗅觉。 公共卫生相关性：嗅觉障碍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，气味辨别的感知缺陷在疾病过程的早期出现，可能是由于大脑的嗅觉边缘区域中神经病理学病变的初始积累。在结合皮质电图技术与嗅觉心理物理学方法治疗难治性癫痫患者中，拟议的研究为人类嗅觉系统的基本组织提供了一个独特的窗口。这项工作的结果可能会直接指导癫痫病灶定位的新工具的开发，以及正在考虑手术干预的癫痫患者的功能结果的预测。本文提出的工作还将为监测其他神经系统疾病的发病和进展提供新的见解，其中嗅觉感知障碍是早期迹象。

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.