Collaborative Research: Unraveling Cerebral Connectivity with Diffusion MRI, Microscopy and Statistical Physics

合作研究：利用扩散 MRI、显微镜和统计物理学揭示大脑连通性

• 批准号: 1505000
• 负责人: Andrei Ruckenstein
• 金额: $ 106.77万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1505000&HistoricalAwards=false
• 关键词: Collaborative; Research; Unraveling; Cerebral; Connectivity

A better understanding of the relationship between brain structure and function is an integral component of the on-going efforts aimed at developing a better understanding of the human mind. Fundamental research is required to accelerate the development of new technologies for neuroscience and near engineering in order to address important societal needs with respect to the development of new ways to treat, prevent, and cure brain disorders. In this larger context, this collaborative project will extend methods of statistical physics to bridge from microscopic neurobiological observations of neurons, axons and dendrites to the mesoscopic images of brain organization seen in diffusion MRI images of the entire primate brain. A particular focus will be to address the question of how the processes of the brain might exploit this special architecture for the representation and processing of information, and in particular, how this regular structure might support time-coding and synchronization of information across the brain.Joining a physics laboratory, a neurobiology laboratory, and an MRI laboratory, this team will investigates the hypothesis that brain connectivity is geometrically organized, with connectivity generally aligned with the axes of a curved, but essentially orthogonal coordinate system or 3D grid. The idea that the brain of all species with bilateral symmetry is based on an orthogonal plan is not new. It has been recognized in embryology and evolutionary biology for nearly 100 years and more recently has been validated in detail in studies of gene expression. Preliminary studies have suggested that this orthogonal motif pervades the structure of the brain, and particularly connectivity, from macroscopic down to a cellular level. In this interdisciplinary project, the investigators will quantify this phenomenon by looking at structural data from both diffusion MRI and advanced methods of 3D light microscopy and then apply the ideas and tools of condensed matter physics to characterize the structure and circuits of the brain as organized matter. As a first example, having observed 3 orthogonal fiber directions at each point in the brain that vary smoothly, it is natural to model this as a liquid crystal with a deformation energy and temperature. Then, one can investigate its scaling in the brain, and transitions such as those from white matter to gray matter. Functionally, we hypothesize that this rectilinear grid, may provide a new mechanism for neural activity to be temporally correlated, owing to its extremely high degeneracy of path lengths and transmission delays, which we will model as a directed percolation.

更好地理解大脑结构和功能之间的关系是旨在更好地理解人类思维的持续努力的一个组成部分。需要基础研究来加速神经科学和近工程新技术的开发，以满足在开发治疗、预防和治愈脑部疾病的新方法方面的重要社会需求。在这个更大的背景下，这个合作项目将扩展统计物理学的方法，从神经元、轴突和树突的微观神经生物学观察到整个灵长类动物大脑的扩散 MRI 图像中看到的大脑组织的细观图像。一个特别的重点将是解决大脑的过程如何利用这种特殊的架构来表示和处理信息的问题，特别是这种规则的结构如何支持整个大脑的时间编码和信息同步。该团队将联合物理实验室、神经生物学实验室和 MRI 实验室，研究这样的假设：大脑连接是几何组织的，连接通常与大脑的轴对齐。 弯曲的，但本质上是正交坐标系或 3D 网格。所有具有双边对称性的物种的大脑都基于正交平面的想法并不新鲜。近 100 年来，它在胚胎学和进化生物学中得到了认可，最近在基因表达研究中得到了详细验证。初步研究表明，这种正交图案遍及大脑的结构，特别是从宏观到细胞水平的连接性。在这个跨学科项目中，研究人员将通过查看扩散 MRI 和 3D 光学显微镜先进方法的结构数据来量化这种现象，然后应用凝聚态物理学的思想和工具来表征作为有组织物质的大脑的结构和回路。作为第一个例子，在大脑中每个点观察到 3 个正交纤维方向平滑变化后，很自然地将其建模为具有变形能量和温度的液晶。然后，人们可以研究它在大脑中的缩放，以及从白质到灰质的转变。从功能上讲，我们假设这种直线网格可能为神经活动提供一种新的时间相关机制，因为它的路径长度和传输延迟具有极高的简并性，我们将其建模为定向渗透。