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

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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.