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Abstract Following significant advances in image acquisition, synapse detection, and neuronal segmentation in connectomics, researchers have extracted an increasingly diverse set of wiring diagrams from brain tissue. Neuroscientists frequently represent these wiring diagrams as graphs with nodes corresponding to a single neuron and edges indicating synaptic connectivity. The edges can contain “colors” or “labels”, indicating excitatory versus inhibitory connections, among other things. By representing the wiring diagram as a graph, we can begin to identify motifs, the frequently occurring subgraphs that correspond to specific biological functions. Most analyses on these wiring diagrams have focused on hypothesized motifs—those we expect to find. However, one of the goals of connectomics is to identify biologically-significant motifs that we did not previously hypothesize. To identify these structures, we need large-scale subgraph enumeration to find the frequencies of all unique motifs. Exact subgraph enumeration is a computationally expensive task, particularly in the edge-dense wiring diagrams. Furthermore, most existing methods do not differentiate between types of edges which can significantly affect the function of a motif. We propose a parallel, general-purpose subgraph enumeration strategy to count motifs in the connectome. Next, we introduce a divide-and-conquer community-based subgraph enumeration strategy that allows for enumeration per brain region. Lastly, we allow for differentiation of edges by types to better reflect the underlying biological properties of the graph. We demonstrate our results on eleven connectomes and publish for future analyses extensive overviews for the 26 trillion subgraphs enumerated that required approximately 9.25 years of computation time. 

Reconstructed terabyte and petabyte electron microscopy image volumes contain fully-segmented neurons at resolutions fine enough to identify every synaptic connection. After manual or automatic reconstruction, neuroscientists want to extract wiring diagrams and connectivity information to analyze the data at a higher level. Despite significant advances in image acquisition, neuron segmentation, and synapse detection techniques, the extracted wiring diagrams are still quite coarse, and often do not take into account the wealth of information in the densely reconstructed volumes. We propose a synapse-aware skeleton generation strategy to transform the reconstructed volumes into an information-rich yet abstract format on which neuroscientists can perform biological analysis and run simulations. Our method extends existing topological thinning strategies and guarantees a one-to-one correspondence between skeleton endpoints and synapses while simultaneously generating vital geometric statistics on the neuronal processes. We demonstrate our results on three large-scale connectomic datasets and compare against current state-of-the-art skeletonization algorithms. 

Most current state-of-the-art connectome reconstruction pipelines have two major steps: initial pixel-based segmentation with affinity prediction and watershed transform, and refined segmentation by merging over-segmented regions. These methods rely only on local context and are typically agnostic to the underlying biology. Since a few merge errors can lead to several incorrectly merged neuronal processes, these algorithms are currently tuned towards over-segmentation producing an overburden of costly proofreading. We propose a third step for connectomics reconstruction pipelines to refine an over-segmentation using both local and global context with an emphasis on adhering to the underlying biology. We first extract a graph from an input segmentation where nodes correspond to segment labels and edges indicate potential split errors in the over-segmentation. In order to increase throughput and allow for large-scale reconstruction, we employ biologically inspired geometric constraints based on neuron morphology to reduce the number of nodes and edges. Next, two neural networks learn these neuronal shapes to further aid the graph construction process. Lastly, we reformulate the region merging problem as a graph partitioning one to leverage global context. We demonstrate the performance of our approach on four real-world connectomics datasets with an average variation of information improvement of 21.3%.