Functional connectivity and spatiotemporal dynamics in unanesthetized rodents

未麻醉啮齿动物的功能连接和时空动力学

• 批准号: 8190859
• 负责人: Shella D Keilholz
• 金额: $ 20.5万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8190859
• 关键词: Address; Affect; Algorithms; Alzheimer' s Disease; Anesthesia procedures; Anesthetics; Animals; Area; Autistic Disorder; Blood; Blood Vessels; Brain; Calculi; Clinical; Complex; Data; Development; Electrodes; Electroencephalography; Electrophysiology (science); Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Human; Image; Isoflurane; Length; Lesion; Magnetic Resonance Imaging; Maps; Measurement; Medetomidine; Mental disorders; Microelectrodes; Modality; Modeling; Motion; Neurophysiology - biologic function; Noise; Outcome; Pathway interactions; Patients; Pattern; Physiological; Play; Process; Property; Rattus; Reporting; Resolution; Rodent; Rodent Model; Role; Scanning; Schizophrenia; Series; Signal Transduction; Site; Source; Stimulus; Stress; Surface; Techniques; Time; Variant; Work; awake; base; blood oxygen level dependent; clinically relevant; hemodynamics; insight; multimodality; nervous system disorder; relating to nervous system; research study; spatiotemporal; tool

DESCRIPTION (provided by applicant): Functional connectivity MRI (fcMRI) is a powerful tool for deciphering spontaneous network activity within the brain. Changes in functional connectivity have been observed in patients with Alzheimer's disease, schizophrenia, and autism, suggesting that fcMRI is sensitive to clinically relevant alterations in the brain. Despite the growing popularity of this technique, our understanding of the spontaneous neural and hemodynamic fluctuations underlying the variations in the blood oxygenation dependent (BOLD) MRI signal used to map functional connectivity is far from complete. Our lab has pioneered the development of simultaneous fcMRI and multisite microelectrode recording in the rodent in order to determine the neural basis for functional connectivity and the spatiotemporal patterns observed in the BOLD signal. Our preliminary results indicate that the relationship between neural activity and BOLD fluctuations is strongly dependent upon the type and depth of anesthesia used. In addition to their primary action on neural activity, most anesthetics also directly impact hemodynamics, and it can be difficult to uncouple the effects. In this study, we will compare functional connectivity and BOLD spatiotemporal dynamics to microelectrode recordings in both anesthetized and unanesthetized rats. This work will either validate the anesthetized rodent as a model for future multimodality studies to elucidate the neurovascular processes underpinnings fcMRI, or serve as a stepping stone for further experiments in unanesthetized rodents. The specific aims of this study are: 1. Implement fcMRI for unanesthetized rats and determine how functional connectivity and spatiotemporal dynamics compare to measurements in anesthetized animals. Using a specialized holder for unanesthetized rats now commercially available, rats will be acclimatized to the scanner over several days to minimize stress. fcMRI data will be acquired in the awake rat, under isoflurane, and under medetomidine. Differences between connectivity in four functional networks will be examined. The spatiotemporal dynamics of the BOLD fluctuations will also be mapped using a template-creation algorithm developed by our lab, and the relationship between the templates within rats will be used to characterize the spatiotemporal dynamics for each condition. 2. Determine the neural sources of functional connectivity differences in awake compared to anesthetized rats using electrophysiology. To separate the vascular effects of the anesthetics from neural effects, simultaneous microelectrode recording/fcMRI studies will be first obtained from awake animals, and then they will be transitioned to anesthesia. We will compare band-limited local field potential (LFP) signal coherence to BOLD signal correlation to determine which neural properties are the basis of fcMRI in each state. We will also calculate the transfer function for comparing LFPs and fMRI directly under each condition to identify changes. PUBLIC HEALTH RELEVANCE: The goal of this project is to determine how commonly-used anesthetics affect functional connectivity and the spatiotemporal dynamics of the blood oxygenation level dependent (BOLD) MRI signal. These experiments will either validate the anesthetized rat as a platform for future multimodality studies of the relationship between the BOLD signal, neural activity, and hemodynamics, or will serve as the first steps toward future multimodal experiments in unanesthetized rodents.

描述（由申请人提供）：功能连接MRI（fcMRI）是一种用于破译大脑内自发网络活动的强大工具。在阿尔茨海默病、精神分裂症和自闭症患者中观察到功能连接的变化，表明fcMRI对大脑中临床相关的改变敏感。尽管这项技术越来越受欢迎，我们的理解自发神经和血液动力学波动的变化，血氧依赖（BOLD）的MRI信号用于映射功能连接还远远没有完成。我们的实验室率先在啮齿动物中开发了同步fcMRI和多位点微电极记录，以确定功能连接的神经基础和在BOLD信号中观察到的时空模式。我们的初步结果表明，神经活动和BOLD波动之间的关系是强烈依赖于所使用的麻醉的类型和深度。除了它们对神经活动的主要作用之外，大多数麻醉剂还直接影响血液动力学，并且可能难以分离这些影响。在这项研究中，我们将比较功能连接和BOLD时空动态微电极记录在麻醉和未麻醉大鼠。这项工作将验证麻醉啮齿动物作为未来多模态研究的模型，以阐明fcMRI基础的神经血管过程，或作为在未麻醉啮齿动物中进行进一步实验的垫脚石。本研究的具体目的是：1。对未麻醉的大鼠实施fcMRI，并确定功能连接和时空动力学如何与麻醉动物的测量结果进行比较。使用目前市售的未麻醉大鼠专用保持器，使大鼠在几天内适应扫描仪，以尽量减少压力。将在清醒大鼠、异氟烷和美托咪定下采集fcMRI数据。四个功能网络的连接之间的差异将被检查。BOLD波动的时空动态也将使用我们实验室开发的模板创建算法进行映射，并且大鼠内模板之间的关系将用于表征每种条件的时空动态。2.使用电生理学确定清醒与麻醉大鼠功能连接差异的神经来源。为了将麻醉剂的血管效应与神经效应分开，将首先从清醒动物中获得同步微电极记录/fcMRI研究，然后将其转换为麻醉。我们将比较带限局部场电位（LFP）信号相干性与BOLD信号相关性，以确定哪些神经特性是每个状态下fcMRI的基础。我们还将计算传递函数，用于在每种条件下直接比较LFPs和fMRI，以识别变化。 公共卫生相关性：该项目的目标是确定常用麻醉剂如何影响功能连接和血氧水平依赖（BOLD）MRI信号的时空动态。这些实验要么将验证麻醉大鼠作为未来BOLD信号、神经活动和血流动力学之间关系的多模式研究的平台，要么将作为未来在未麻醉啮齿动物中进行多模式实验的第一步。