The function of respiratory-linked local field potential oscillations in human olfactory and limbic brain regions

人类嗅觉和边缘脑区域与呼吸相关的局部场电位振荡的功能

基本信息

批准号：
9913507
负责人：
Christina Maria Zelano
金额：
$ 41.65万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9913507
关键词：
Air Movements Amygdaloid structure Anatomy Anxiety Anxiety Disorders Area Attention Behavior Brain Brain Stem Brain imaging Brain region Breathing Cause of Death Chemicals Code Communication Data Detection Diagnosis Diffusion Disease Electric Stimulation Electroencephalography Emotions Environment Epilepsy Fostering Foundations Frequencies Functional Magnetic Resonance Imaging Functional disorder Generalized Anxiety Disorder Goals Human Imaging Techniques Inhalation Knowledge Learning Limbic System Link Magnetic Resonance Imaging Measures Medial Mediating Memory Modality Modification Monitor Nature Nose Odors Olfactory Pathways Oral Parkinson Disease Patients Periodicity Phase Psychophysics Research Respiration Respiration Disorders Respiratory Signs and Symptoms Respiratory physiology Rodent Role Sampling Smell Perception Stimulus Structure Structure of terminal stria nuclei of preoptic region Techniques Testing anxious clinical anxiety clinical application experimental study insight nervous system disorder neural network neuroimaging neuromechanism novel olfactory bulb piriform cortex relating to nervous system respiratory response spectrograph sudden unexpected death in epilepsy tractography

项目摘要

Since it is not possible to encounter a smell in our external environment without first inhaling through the nose, stimulus sampling in the olfactory system is inextricably linked to breathing. Respiratory-driven local field potential (LFP) oscillations are important for odor coding mechanisms in the rodent olfactory bulb, but their role in higher olfactory structures such as piriform cortex is not well understood, with even less known about respiratory oscillations in the human brain. While breathing drives oscillations in the brain, the reverse must also be true; stimulus sampling in the olfactory system requires overriding of autonomic respiratory rhythms in order to achieve intentional sniffing and fast adaptive sniff modifications in response to chemical stimuli. The overarching goal of this proposal is to understand the function of respiratory oscillations in the human brain, including their role in the formation of odor-evoked responses in olfactory brain regions and fostering communication across limbic networks involved in odor sampling and fast adaptive sniffing modifications. We also aim to elucidate limbic networks involved in olfactory sampling behaviors. To measure LFPs from medial olfactory structures in the human brain, we will use intracranial electroencephalography (iEEG) with a high sampling rate (up to 10,000Hz), allowing analysis of limbic LFP oscillations across a range of frequencies. We will use a combination of iEEG, direct electrical stimulation, psychophysics and functional neuroimaging and tractography techniques to accomplish the goals of three Specific Aims. First, we will test the hypothesis that slow respiratory-linked LFP oscillations organize the spectral and temporal structure of odor-evoked responses in human piriform cortex. To isolate the impact of slow respiratory-driven oscillations on odor codes, we will deliver odors in the presence and absence of sniffs, accomplished by velopharyngeal closure paired with artificial air flow through the nose. Second, we will test the hypothesis that slow respiratory oscillations across a limbic network of regions important for respiratory control mediate odor sampling, or sniffing behaviors. Here we will use iEEG techniques, electrical stimulation and MRI techniques to study limbic networks involved in the control of nasal breathing with a particular emphasis on the amygdala. Third, we will use iEEG, electrical stimulation and psychophysics to test the hypothesis that adaptive fast sniffing reductions in response to potentially threatening odors are mediated by the amygdala, and can generalize to non-olfactory stimuli in anxious states. The proposed studies have several direct clinical applications. Research on Sudden Unexpected Death in Epilepsy (SUDEP), the most common cause of death in patients with Epilepsy, implicates respiratory dysfunction as a potential cause, with converging evidence for an amygdalar role in the disease (13,14). In so far as our proposal aims to deepen understanding of the neural mechanisms of the amygdala's role in respiratory control, these studies will be important in gaining a better understanding of SUDEP. Our research will also elucidate dysfunctional olfactory-limbic networks underlying clinical anxiety.

由于我们不可能在不先通过鼻子吸入的情况下遇到外部环境中的气味，嗅觉系统中的刺激采样与呼吸有着千丝万缕的联系。呼吸驱动的局部场电位（LFP）振荡对于啮齿动物嗅球的气味编码机制很重要，但它们的作用在梨状皮层等高级嗅觉结构中，人们对它的了解还不是很清楚，甚至更少了解人脑的呼吸振荡。当呼吸驱动大脑振荡时，相反的情况也必须发生也为真；嗅觉系统中的刺激采样需要超越自主呼吸节律为了实现有意识的嗅探和快速适应性嗅探修改以响应化学刺激。这该提案的首要目标是了解人脑中呼吸振荡的功能，包括它们在嗅觉大脑区域气味诱发反应的形成中的作用，并促进跨边缘网络的通信涉及气味采样和快速自适应嗅觉修改。我们还旨在阐明参与嗅觉采样行为的边缘网络。从内侧测量 LFP 为了研究人脑的嗅觉结构，我们将使用具有高灵敏度的颅内脑电图（iEEG）采样率（高达 10,000Hz），允许分析一系列频率范围内的边缘 LFP 振荡。我们将结合使用 iEEG、直接电刺激、心理物理学和功能神经影像学纤维束成像技术来实现三个具体目标。首先，我们将检验以下假设：与呼吸相关的慢速 LFP 振荡组织气味诱发反应的光谱和时间结构在人类梨状皮质中。为了隔离缓慢呼吸驱动的振荡对气味代码的影响，我们将在有或没有嗅的情况下传递气味，通过腭咽闭合配合完成人工气流通过鼻子。其次，我们将检验减缓呼吸振荡的假设对于呼吸控制很重要的区域边缘网络介导气味采样或嗅探行为。这里我们将使用 iEEG 技术、电刺激和 MRI 技术来研究参与控制鼻呼吸，特别强调杏仁核。第三，我们将使用iEEG、电学刺激和心理物理学来测试以下假设：适应性快速嗅觉减少响应潜在的威胁气味是由杏仁核介导的，并且可以推广到非嗅觉刺激焦虑的状态。拟议的研究有几个直接的临床应用。突发事件研究癫痫意外死亡 (SUDEP) 是癫痫患者最常见的死亡原因，涉及呼吸功能障碍是一个潜在原因，有证据表明杏仁核在该疾病中发挥作用 (13,14)。就我们的建议而言，旨在加深对杏仁核神经机制的理解由于 SUDEP 在呼吸控制中的作用，这些研究对于更好地了解 SUDEP 非常重要。我们的研究还将阐明导致临床焦虑的功能失调的嗅觉边缘网络。