Spatiotemporal Mechanisms of Olfactory Processing in the Human Brain

描述（由申请人提供）：越来越清楚的是，嗅觉知觉在各种神经和神经精神疾病中受损。然而，这种对人类嗅觉日益增长的临床欣赏被生理水平上的不良科学理解所抵消。事实上，我们对人类嗅觉系统的大部分基本知识都是从啮齿类动物和昆虫的研究中推断出来的，但在动物身上建立的皮层计算是否与人类相关，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。我们将与西北大学的综合癫痫中心和功能神经外科团队合作，直接记录医学上难治性癫痫患者的大脑气味诱发的脑电图（EEG）活动模式。在标准的手术探查过程中，高密度侵入性电极在内侧颞叶和眶额叶周围的高精度放置，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（梨状）皮层和眶额皮质中气味诱发的振荡活动特征，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对人类嗅觉的更全面的基础研究理解，特别是关于它的时间动态，并将提供与非

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.