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

更好地了解大脑结构和功能之间的关系是旨在更好地了解人类思维的持续努力的一个组成部分。需要进行基础研究，以加快神经科学和近工程学新技术的发展，以满足与开发治疗、预防和治疗大脑疾病的新方法有关的重要社会需求。在这个更大的背景下，这个合作项目将把统计物理学的方法从对神经元、轴突和树突的微观神经生物学观察延伸到整个灵长类动物大脑的扩散磁共振图像中所看到的大脑组织的介观图像。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结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跨大脑的信息的时间编码和同步的问题。这个团队将联合物理实验室、神经生物学实验室和MRI实验室，研究大脑连接是几何组织的假设，连接通常与弯曲的、但本质上正交的坐标系或3D网格的轴线对齐。所有具有双边对称性的物种的大脑都基于一个正交图的想法并不新鲜。它在胚胎学和进化生物学中已经被认识了近100年，最近在基因表达的研究中得到了详细的验证。初步研究表明，从宏观到细胞水平，这种正交的主题贯穿于大脑的结构，特别是连通性。在这个跨学科的项目中，研究人员将通过观察来自扩散磁共振成像和先进的3D光学显微镜方法的结构数据来量化这种现象，然后应用凝聚态物理的思想和工具来表征大脑的结构和电路，作为有组织的物质。作为第一个例子，在观察到大脑中每个点的3个平滑变化的垂直纤维方向后，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比例，以及从白质到灰质的转变。在功能上，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的简并度非常高，我们将其建模为定向渗流。

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.