Integrated fMRI Methods to Study Neurophysiology and Circuit Dynamics at Laminar and Columnar Level

项目描述 基于血氧水平依赖（BOLD）对比的功能磁共振成像（fMRI）已成为一种新的成像技术。 强大的神经成像模式，并已获得了突出的地位，在神经科学成像大脑 工作状态下的激活和休息时的功能连接。然而，大多数fMRI研究都集中在 在宏观尺度上系统水平上的脑活动的功能映射。近日，高分辨率 fMRI显示了绘制基本功能活动的可行性， 从视觉优势到方向列的计算单位。这种前所未有的神经成像 这种能力为研究大脑功能、连接和电路提供了令人兴奋的机会， 介观尺度。然而，神经计算过程分布在六个皮质 从软膜表面到白色物质的薄层，并进行前馈，反馈和 根据皮层深度分离的局部连接。能够映射此类层流和 跨大型网络的列相关功能和连接极具挑战性， 迄今尚未实现。此外，BOLD信号仅反映神经元的次级效应。 活动，BOLD测量和潜在神经活动之间的转换变为 复杂的在不同的空间尺度，和神经BOLD的相关性在层/柱水平没有 由于各种技术障碍而被研究。功能磁共振成像中另一个高度相关的未回答的问题是 神经元抑制如何改变神经动力学和网络，以及fMRI BOLD信号。由于 正常大脑活动的高度复杂性必然涉及兴奋和抑制 过程，选择性地研究BOLD与抑制性的神经相关性是一个艰巨的挑战 神经调节为了解决这些问题和挑战，该提案旨在推动技术 通过开发创新的多模态功能磁共振成像方法， 具有功能映射特异性的同时神经刺激、记录和fMRI采集， 分辨率下降到介观尺度。尖端技术和先进的工具将使我们能够 在细胞柱状和层状水平上研究脑功能和连接-两个最基本 神经计算单元，用于大脑功能所必需的微电路，并且仍然覆盖大型网络 通过猫脑中的丘脑-皮质和皮质-皮质连接。这项研究将首次 提供有关空间和时间的神经动力学的新知识，以及fMRI BOLD的神经相关性 在层/柱状水平响应于兴奋性或抑制性神经调节的信号。这种知识 不可能从人类大脑研究中获得，但应该会导致变革性的突破， 理解定义的计算单元、动态功能和 人类大脑的网络;并提供新的见解电生理学基础和映射特异性 功能性磁共振成像在层状和柱状水平。

Project Description Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD) contrast has become a powerful neuroimaging modality and has gained a prominent position in neuroscience for imaging brain activation at working state and functional connectivity at rest. However, most of fMRI research focus on functional mapping of brain activity at the system level with macroscopic scale. Recently, high-resolution fMRI at ultrahigh field has shown the feasibility of mapping the functional activity of elementary computational units from ocular dominance to orientation column. Such unprecedented neuroimaging ability opens up exciting opportunities for studying brain function, connectivity and circuitry at the mesoscopic scale. Nevertheless, the neural computational processes are distributed across six cortical laminae spanning from the pial surface to the white matter, and engage feed-forward, feed-backward and local connections that are segregated according to the cortical depth. Ability to map such laminar and columnar dependent functionality and connectivity across large networks is extremely challenging and has not been achieved to date. Moreover, the BOLD signal only reflects the secondary effect of neuronal activity, the transformation between the BOLD measure and the underlying neural activity becomes complicated at varied spatial scale, and the neuro-BOLD correlation at the laminar/columnar level has not been studied due to a variety of technical hurdles. Another highly relevant unanswered question in fMRI is how does neuronal inhibition change the neural dynamics and networks, and the fMRI BOLD signal. Owing to the high complexity of normal brain activities unavoidably involving both excitatory and inhibition processes, it is a daunting challenge to selectively study the neural correlate of BOLD to inhibitory neuromodulation. To address these questions and challenges, this proposal aims to push the technology envelope beyond the current level by developing innovative multimodal fMRI approaches capable of simultaneous neural stimulation, recording and fMRI acquisition with functional mapping specificity and resolution down to the mesoscopic scale. The cutting-edge technology and developed tools will allow us to investigate brain function and connectivity at cellular columnar and laminar levels—two most fundamental neural computational units for micro-circuits essential for brain function, and still cover large networks through thalamo-cortical and cortico-cortical connections in the cat brain. For the first time, the research will provide new knowledge about the neural dynamics in space and time, and neural correlates of fMRI BOLD signal in response to excitatory or inhibitory neuromodulation at laminar/columnar levels. Such knowledge is impossible to gain from the human brain research, but should lead to transformative breakthroughs in understanding the structure-function relationship of defined computational units, dynamic functions and networks of the human brain; and provide new insights into electrophysiology basis and mapping specificity of fMRI at the laminar and columnar levels.