Spatiotemporal Mechanisms of Olfactory Processing in the Human Brain

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生理水平上的科学理解所抵消。事实上，我们对人类嗅觉系统的许多基本知识都是从啮齿动物和昆虫的研究中推断出来的，但在动物中建立的皮层计算是否与人类有关在很大程度上是未知的。本研究的主要目的是阐明人类嗅觉系统中气味处理的时空机制。与西北大学的综合癫痫中心和功能性神经外科团队合作，我们将直接从患有医学难治性癫痫发作的患者的人脑中记录气味诱发的脑电图（EEG）活动模式。在标准手术探查过程中，高密度侵入性电极在内侧颞叶和眶额叶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，具有无与伦比的时间和空间分辨率。研究旨在比较嗅球，嗅觉（梨状）皮质和眶额皮质中的气味诱发振荡活动曲线，并了解这些不同的大脑区域如何相互作用以支持嗅觉分类感知和编码。这里提出的工作将产生一个更全面的基础研究人类嗅觉的理解，特别是关于其时间动态，并将提供一个直接的联系， 人类动物研究。从临床转化的角度来看，该项目可能有助于诊断和预测癫痫患者的功能结局，并为监测其他涉及嗅觉的神经系统疾病的发病和进展开辟了新的途径。

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 scientific understanding at the physiological level. Indeed, much of our basic knowledge about the human olfactory system is inferred from studies in rodents and insects, but whether the cortical computations established in animals are relevant for humans is largely unknown. The major aim of this research project is to elucidate the spatiotemporal mechanisms of odor processing in the human olfactory system. In collaboration with the Comprehensive Epilepsy Center and Functional Neurosurgery teams at Northwestern, we will record odor-evoked patterns of electroencephalographic (EEG) activity directly from the human brain in patients with medically intractable seizures. The highly accurate placement of high-density invasive electrodes around the medial temporal and orbital frontal lobes during standard surgical exploration offers a unique window into the functional anatomy of the olfactory system with unparalleled temporal and spatial resolution. Studies are designed to compare odor-evoked oscillatory activity profiles in the olfactory bulb, olfactory (piriform) cortex, and orbitofrontal cortex, and to understand how these different brain regions interact to support olfactory categorical perception and coding. Work proposed here will yield a more comprehensive basic research understanding of human olfaction, particularly with regard to its temporal dynamics, and will provide a direct link to non human animal studies. From a clinical translational perspective, this project may 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.