Foundations of MRI Corticography for mesoscale organization and neuronal circuitry

项目摘要 功能性MRI（fMRI）是在1至3毫米空间分辨率的宏观尺度下进行的。术语 “中尺度”已经开始表示神经元组织的更细粒度的分辨率，以显示 在皮层的深度和沿着表面的功能组织。中尺度fMRI表现 然而，神经活动并没有牢固地建立起来。这项研究的主要目的是评估功能磁共振成像的 准确区分皮质层和皮质柱中神经元活动的能力。这将使当地的研究 在柱状组织和层与纤维投射到和从遥远的大脑区域，使电路， 数百个人类大脑区域之间的层次和方向连接最终可能会被常规地 在人脑中进行非侵入性研究。 该项目将利用最先进的MRI硬件和脉冲序列，专门为高分辨率成像设计。 在用于下一代人脑成像（NIH）的BRAIN Initiative项目中， R24MH106096“MRI皮质描记术”（MRCoG））。它还将使用几个尖端的神经科学 技术，包括磁共振成像，光遗传fMRI（ofMRI），经颅磁刺激（TMS）和 皮质电图（ECoG），以识别和操纵fMRI信号下的神经元活动。到 为了确定BOLD活性的空间特异性和层状分布，我们将使用光遗传学刺激， 在小鼠大脑的不同皮层的神经元群体，同时与BOLD功能磁共振成像。 其次，血管和神经元密度的变化将从共定位的变化中消除歧义。 fMRI活动，使用三维荧光显微镜。在人类中，微尺度到中尺度的功能磁共振成像 将使用超高密度ECoG网格的直接电生理标测对标测进行验证， 先进的计算模型。为了阐明人类全脑中尺度回路的相互作用，MRCoG 将与TMS相结合，以测试额叶皮层和跨半球运动的分层组织 连接.在人类中，将使用FDA批准的 胆碱酯酶抑制剂，以确定前馈处理时中尺度fMRI的层状轮廓， 增加

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.