Foundations of MRI Corticography for mesoscale organization and neuronal circuitry

项目总结 功能磁共振成像(FMRI)是在1到3毫米空间分辨率的宏观尺度上进行的。这一术语 “中尺度”已经开始表示更细粒度的神经元组织的分辨率，以显示 大脑皮层深层和表层的功能性组织。中尺度的fMRI表现 然而，神经活动并没有得到牢固的确立。这项研究的一个主要目标是评估fMRI 能够准确区分皮质层和皮质柱中的神经元活动。这将允许研究当地的 柱状组织中的电路和具有往返于远端大脑区域的纤维投射的层，因此 数百个人脑区域之间的分层和定向连接最终可能会成为例行公事 在人脑中进行非侵入性研究。 该项目将利用最先进的磁共振硬件和脉冲序列，专门为高 下一代人脑成像(NIH)脑计划中的人脑皮质分辨率成像 R24MH106096“磁共振皮质成像”(MRCOG))。它还将使用几项尖端神经科学 技术，包括Clarity、光遗传功能磁共振成像(OfMRI)、经颅磁刺激(TMS)和 皮层脑电(ECoG)，以识别和操纵潜在的fMRI信号的神经元活动。至 确定BOLD活动的空间特异性和层状轮廓，我们将使用光遗传刺激 小鼠大脑不同皮质层中的神经元群体，同时使用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 应用清晰度和3D荧光显微镜进行fMRI活性检测。在人类中，从微尺度到中尺度的fMRI 将使用超高密度ECoG网格和直接电生理标测来验证标测 高级计算建模。为了阐明人类全脑中尺度回路的相互作用，MRCOG 将与TMS结合测试额叶皮质和跨大脑运动的分级组织 关系。在人类身上，药物调节的大脑回路将使用FDA批准的 胆碱酯酶抑制剂，以确定前馈处理时中尺度功能磁共振成像的层状轮廓 增加了。

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.