Foundations of MRI Corticography for mesoscale organization and neuronal circuitry

中尺度组织和神经元回路的 MRI 皮质成像基础

• 批准号: 9206105
• 负责人: David Alan Feinberg
• 金额: $ 115.19万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9206105
• 关键词: Accounting; Animal Model; Area; Aricept; BRAIN initiative; Blood Vessels; Brain; Brain imaging; Brain region; Cell Density; Cells; Cerebral cortex; Cholinesterase Inhibitors; Computer Simulation; Distant; Electrocorticogram; Electrodes; Electrophysiology (science); FDA approved; Fiber; Fluorescence Microscopy; Foundations; Functional Magnetic Resonance Imaging; Goals; Human; Image; Individual; Link; Magnetic Resonance Imaging; Maps; Measurable; Measures; Microscopic; Microscopy; Modeling; Motor; Mus; Mutant Strains Mice; Neurons; Neurosciences; Ocular dominance columns; Pattern; Pharmacology; Physiologic pulse; Population; Process; Research; Resolution; Rodent; Signal Transduction; Specific qualifier value; Specificity; Specimen; Surface; Technology; Testing; Transcranial magnetic stimulation; Transgenic Mice; United States National Institutes of Health; Variant; Visual Cortex; blood oxygenation level dependent response; brain circuitry; cholinergic; cortex mapping; density; design; donepezil; frontal lobe; functional group; hemodynamics; interest; millimeter; mouse model; neuronal circuitry; neurovascular; next generation; novel strategies; optogenetics; relating to nervous system; response; species difference; temporal measurement

PROJECT SUMMARY Functional MRI (fMRI) is performed at a macroscopic scale of 1 to 3 millimeters spatial resolution. The term `mesoscale' has come to denote the resolution of a finer granularity of neuronal organization, to show functional organization across the depth and along the surface of the cortex. Mesoscale fMRI representation of neural activity, however, is not firmly established. A primary objective of this research is to evaluate fMRI's ability to accurately differentiate neuronal activity in cortical layers and columns. This will allow studies of local circuitry in columnar organization and layers with fiber projections to and from distant brain regions, so that hierarchical and directional connectivity between hundreds of human brain regions may eventually be routinely studied non-invasively in the human brain. This project will leverage state-of-the-art MRI hardware and pulse sequences specifically designed for high- resolution imaging of human cortex in a BRAIN Initiative project for next generation human brain imaging (NIH R24MH106096 ”MRI Corticography” (MRCoG)). It will also use several cutting-edge neuroscience technologies, including CLARITY, optogenetic fMRI (ofMRI), transcranial magnetic stimulation (TMS) and electrocorticography (ECoG), to identify and manipulate neuronal activity underlying the fMRI signal. To determine the spatial specificity and laminar profile of BOLD activity, we will use optogenetic stimulation of neuronal populations in different cortical layers of mouse brain while simultaneously imaging with BOLD fMRI. Secondly, variations of vascular and neuronal density will be disambiguated from variations of co-localized fMRI activity using CLARITY and 3D fluorescence microscopy. In humans, the microscale to mesoscale fMRI mapping will be validated using direct electrophysiological mapping with ultra-high-density ECoG grids and advanced computational modeling. To elucidate whole brain mesoscale circuit interactions in humans, MRCoG will be combined with TMS to test hierarchical organization of frontal cortex and transhemispheric motor connections. In humans, pharmacologically modulated brain circuits will be evaluated using an FDA-approved cholinesterase inhibitor, to determine the laminar profile of mesoscale fMRI when feedforward processing is increased.

项目摘要 功能性MRI（fMRI）以1至3毫米空间分辨率的宏观尺度进行。期限 “中尺度”来表示神经元组织较细的粒度的解决方案，以表明 跨深度和皮质表面的功能组织。中尺度FMRI的表示 然而，神经活动并未确定。这项研究的主要目的是评估fMRI的 能够准确区分皮质层和色谱柱中神经元活性的能力。这将允许对本地进行研究 柱状组织的电路和带有纤维项目的层次往返遥远的大脑区域，以便 有时可能会定期进行层次结构和定向连通性的连通性 在人脑中进行非侵入性研究。 该项目将利用专为高级设计的最新MRI硬件和脉冲序列 在大脑启动项目中，人类皮质的分辨率成像用于下一代人脑成像（NIH） R24MH106096“ MRI皮层学”（MRCOG））。它还将使用几个尖端的神经科学 技术，包括清晰度，光遗传fMRI（OFMRI），经颅磁刺激（TMS）和 电视学（ECOG），以识别和操纵fMRI信号的神经元活性。到 确定大胆活动的空间特异性和层状谱，我们将使用光遗传学刺激 小鼠大脑不同皮层层中的神经元种群，同时用大胆的fMRI进行成像。 其次，血管和神经元密度的变化将与共定位的变化歧视 使用清晰度和3D荧光显微镜的fMRI活性。在人类中，微观尺寸至中尺度fMRI 使用超高密度的ECOG网格和 高级计算建模。为了阐明人类中的整个大脑中尺度电路相互作用，MRCOG 将与TMS结合以测试额叶皮层和透射电动机的层次结构组织 连接。在人类中，将使用FDA批准来评估药物调制的脑电路 胆碱酯酶抑制剂，确定馈送处理时中尺度fMRI的层状谱图 增加。