We describe automated technologies to probe the structure of neural tissue at nanometer resolution and use them to generate a saturated reconstruction of a sub-volume of mouse neocortex in which all cellular objects (axons, dendrites, and glia) and many sub-cellular components (synapses, synaptic vesicles, spines, spine apparati, postsynaptic densities, and mitochondria) are rendered and itemized in a database. We explore these data to study physical properties of brain tissue. For example, by tracing the trajectories of all excitatory axons and noting their juxtapositions, both synaptic and non-synaptic, with every dendritic spine we refute the idea that physical proximity is sufficient to predict synaptic connectivity (the so-called Peters' rule). This online minable database provides general access to the intrinsic complexity of the neocortex and enables further data-driven inquiries.

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This manuscript considers the following "graph classification" question: Given a collection of graphs and associated classes, how can one predict the class of a newly observed graph? To address this question, we propose a statistical model for graph/class pairs. This model naturally leads to a set of estimators to identify the class-conditional signal, or "signal-subgraph," defined as the collection of edges that are probabilistically different between the classes. The estimators admit classifiers which are asymptotically optimal and efficient, but which differ by their assumption about the "coherency" of the signal-subgraph (coherency is the extent to which the signal-edges "stick together" around a common subset of vertices). Via simulation, the best estimator is shown to be not just a function of the coherency of the model, but also the number of training samples. These estimators are employed to address a contemporary neuroscience question: Can we classify "connectomes" (brain-graphs) according to sex? The answer is yes, and significantly better than all benchmark algorithms considered. Synthetic data analysis demonstrates that even when the model is correct, given the relatively small number of training samples, the estimated signal-subgraph should be taken with a grain of salt. We conclude by discussing several possible extensions.

Currently, connectomes (e.g., functional or structural brain graphs) can be estimated in humans at $\approx 1~mm^3$ scale using a combination of diffusion weighted magnetic resonance imaging, functional magnetic resonance imaging and structural magnetic resonance imaging scans. This manuscript summarizes a novel, scalable implementation of open-source algorithms to rapidly estimate magnetic resonance connectomes, using both anatomical regions of interest (ROIs) and voxel-size vertices. To assess the reliability of our pipeline, we develop a novel nonparametric non-Euclidean reliability metric. Here we provide an overview of the methods used, demonstrate our implementation, and discuss available user extensions. We conclude with results showing the efficacy and reliability of the pipeline over previous state-of-the-art.Comment: Published as part of 2013 IEEE GlobalSIP conferenc