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

因为在我们的外部环境中，如果不首先通过鼻子吸入气味是不可能的， 嗅觉系统的刺激采样与呼吸有着千丝万缕的联系。呼吸驱动局域场 电位(LFP)振荡对啮齿动物嗅球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中，如梨状皮质，人们对此还不太了解，对 人类大脑中的呼吸振荡。虽然呼吸驱动大脑的振荡，但相反的必须 这也是真的；嗅觉系统中的刺激采样需要覆盖自主呼吸节律 以实现对化学刺激的故意嗅探和快速自适应嗅觉修改。这个 这项提议的首要目标是了解人脑中呼吸振荡的功能， 包括它们在嗅觉脑区气味诱发反应的形成和培养中的作用 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 旨在阐明边缘网络与嗅觉采样行为的关系。从内侧测量LFP 在人类大脑的嗅觉结构中，我们将使用高强度的颅内脑电(IEEG) 采样率(高达10,000赫兹)，允许分析一系列频率范围内的边缘LFP振荡。我们 将使用iEEG、直接电刺激、心理物理学和功能神经成像的组合， 为实现三个特定目标而采用的制版技术。首先，我们将检验假设 慢呼吸相关的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。为了分离缓慢的呼吸驱动的振荡对气味代码的影响，我们将 在有嗅觉和没有嗅觉的情况下传递气味，通过闭合腭咽和 人工空气流过鼻子。第二，我们将检验这样一种假设，即 对于呼吸控制很重要的区域的边缘网络是气味采样或嗅探行为的中介。这里 我们将使用iEEG技术、电刺激和MRI技术来研究边缘网络参与 控制鼻腔呼吸，特别强调杏仁核。第三，我们将使用iEEG，电子 刺激和心理物理学来测试适应性快速嗅觉减少对 潜在的威胁气味是由杏仁核传递的，并可以概括为非嗅觉刺激。 焦虑的状态。建议的研究有几个直接的临床应用。关于突发事件的研究 癫痫患者最常见的死亡原因是癫痫的意外死亡(SUDEP)，这与 呼吸功能障碍是一种潜在的原因，有大量证据表明杏仁核在该病中的作用 (13，14)。鉴于我们的建议旨在加深对杏仁核神经机制的理解 鉴于这些研究在呼吸控制中的作用，这些研究将对更好地了解SUDEP具有重要意义。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。

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.