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

• 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
• 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

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.

由于不可能在我们的外部环境中遇到气味而不首先通过鼻子吸入， 嗅觉系统中的刺激采样与呼吸有着不可分割的联系。呼吸驱动局部场 潜在的（LFP）振荡对于啮齿动物嗅球中的气味编码机制很重要，但它们的作用 在更高级的嗅觉结构如梨状皮质中的作用还没有很好的了解， 人类大脑中的呼吸振荡。当呼吸驱动大脑的振荡时，反过来也必须 也是真的;刺激采样在嗅觉系统中需要凌驾自主呼吸节律， 以实现有意的嗅闻和响应于化学刺激的快速自适应嗅闻修改。的 该提议的首要目标是理解人脑中呼吸振荡的功能， 包括它们在嗅觉脑区形成气味诱发反应中的作用， 跨边缘网络的通信涉及气味采样和快速自适应嗅探修改。我们 也旨在阐明边缘网络参与嗅觉采样行为。从内侧测量LFP 在人类大脑的嗅觉结构，我们将使用颅内脑电图（iEEG）与高 采样率（高达10，000 Hz），允许在一系列频率范围内分析边缘LFP振荡。我们 将使用iEEG、直接电刺激、心理物理学和功能性神经成像的组合， 纤维束成像技术，以实现三个具体目标的目标。首先，我们将测试假设， 缓慢的振荡联系LFP振荡组织气味诱发反应的频谱和时间结构 在人类梨状皮质。为了隔离缓慢的振荡驱动的气味代码的影响，我们将 在存在和不存在嗅闻的情况下传递气味，通过与 人工气流通过鼻子。第二，我们将测试的假设，缓慢的呼吸振荡跨越 对呼吸控制重要的区域的边缘网络介导气味采样或嗅闻行为。这里 我们将使用iEEG技术，电刺激和MRI技术来研究参与大脑边缘系统的网络。 控制鼻呼吸，特别强调杏仁核。第三，我们将使用iEEG，电 刺激和心理物理学来测试适应性快速嗅探减少的假设， 潜在的威胁性气味是由杏仁核介导的，并且可以概括为非嗅觉刺激， 焦虑的国家所提出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， 呼吸功能障碍是一个潜在的原因，有证据表明杏仁核在疾病中起作用 (13，14）。我们的建议旨在加深对杏仁核神经机制的理解， 这些研究对于更好地了解SUDEP具有重要意义。我们 研究还将阐明临床焦虑症背后的嗅觉边缘网络功能障碍。