Spatiotemporal Mechanisms of Olfactory Processing in the Human Brain

摘要 我们实验室的研究重点是了解人类大脑如何编码和解释信息 关于气味刺激。通常被认为是微不足道的“第五”感觉，人类的嗅觉实际上是显着的 健壮。人的鼻子可以辨别分子结构上细微差别的气味， 成千上万种独特的气味，并将我们带回过去，重新激活遥远的记忆和情感状态。 此外，嗅觉系统（在人类和非人类动物中）是一个越来越有吸引力和强大的 用于研究正常和病理条件下的脑功能的模型。 研究人类嗅觉系统传统上依赖于两种类型的方法：功能 磁共振成像（fMRI）和头皮脑电图。虽然这些非侵入性方法已经产生了 关于气味处理的重要见解，可测试问题的范围是有限的，由于时间（MRI）和 空间（EEG）约束。特别是，在理解生理学方面存在严重的知识差距。 是人类嗅觉的基础在过去的几年里，我们有机会获得颅内 来自具有耐药性癫痫发作的癫痫患者的EEG（iEEG）记录。作为标准手术的一部分 在临床前评估中，患者接受手术，在手术期间，将侵入性深度电极植入患者的 脑定位致痫灶。这种方法提供了一个宝贵的机会， 高时空分辨率的嗅觉皮层处理。我们最近的研究表明， 刺激在人梨状皮质（PC）中引起3-7 Hz（“θ”频率）节律振荡， 气味在嗅闻开始后100毫秒就引起明显的θ活动。我们还证明了θ PC和海马体之间的相位耦合在气味而不是空气的存在下增加。 这些新的发现为这里概述的实验提供了一个平台。通过利用我们在嗅觉方面的专业知识 认知神经科学与最先进的iEEG信号分析工具，我们将建立一个生理 在群体动力学和网络相互作用水平上的人类嗅觉处理基础。我们 根据动物模型的数据，拟议的研究旨在测试基于前瞻性的假设驱动 关于气味感知机制的问题。目标1将讨论如何改变 气味刺激的基本特征改变PC神经动力学，如通过θ振荡的变化所评估的 功能.目的2探讨PC-海马耦联在气味辨别中的作用。目标3将审查是否 PC theta在气味感知中起着因果作用，并将确定theta可以 形状气味处理。这里开发的概念方法应有助于指导未来的基础和临床 评估人脑中嗅觉振荡的生物相关性的研究策略。

ABSTRACT Research in our laboratory focuses on understanding how the human brain encodes and interprets information about odor stimuli. Often regarded as the trivial “fifth” sense, the human sense of smell is in fact remarkably robust. The human nose can discriminate odors with subtle differences in molecular structure, distinguish thousands of unique smells, and transport us back in time to reactivate distant memories and emotional states. Additionally, the olfactory system (in human and non-human animals) is an increasingly attractive and powerful model for studying brain function under normal and pathological conditions. Studies investigating the human olfactory system have traditionally relied on two types of methods: functional magnetic resonance imaging (fMRI) and scalp-based EEG. While these non-invasive approaches have yielded important insights about odor processing, the scope of testable questions is limited due to temporal (MRI) and spatial (EEG) constraints. In particular, there is a critical knowledge gap in understanding the physiological basis of the human sense of smell. Over the last few years, we have had the opportunity to obtain intracranial EEG (iEEG) recordings from epilepsy patients with medically resistant seizures. As part of a standard surgical pre-clinical evaluation, patients undergo surgery during which invasive depth electrodes are implanted into the brain to localize epileptogenic foci. This approach provides an invaluable opportunity to characterize human olfactory cortical processing with high spatiotemporal resolution. Our recent studies have established that odor stimuli evoke rhythmic oscillations of 3-7 Hz (“theta” frequency) in human piriform cortex (PC), and that distinct odors evoke distinct theta activity as soon as 100 ms after the onset of a sniff. We have also shown that theta phase coupling between PC and hippocampus increases in the presence of odor but not air. These novel findings provide a platform for experiments outlined here. By leveraging our expertise in olfactory cognitive neuroscience with state-of-the-art iEEG signal analysis tools, we will establish a physiological foundation of human olfactory processing at the level of population dynamics and network interactions. Our proposed studies, informed by data from animal models, are designed to test forward-based, hypothesis-driven questions about the mechanistic underpinnings of odor perception. Aim 1 will address how changes in fundamental features of odor stimuli alter PC neural dynamics as assessed by changes in theta oscillatory features. Aim 2 will test the role of PC-hippocampal coupling in odor discrimination. Aim 3 will examine whether PC theta plays a causal role in odor perception, and will identify potential mechanisms by which theta can shape odor processing. The conceptual approaches developed here should help guide future basic and clinical research strategies for assessing the biological relevance of olfactory oscillations in the human brain.