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The brain has long been divided into distinct areas based upon its local microstructure, or patterned composition of cells, genes, and proteins. While this taxonomy is incredibly useful and provides an essential roadmap for comparing two brains, there is also immense anatomical variability within areas that must be incorporated into models of brain architecture. In this work we leverage the expressive power of deep neural networks to create a data-driven model of intra- and inter-brain area variability. To this end, we train a convolutional neural network that learns relevant microstructural features directly from brain imagery. We then extract features from the network and fit a simple classifier to them, thus creating a simple, robust, and interpretable model of brain architecture. We further propose and show preliminary results for the use of features from deep neural networks in conjunction with unsupervised learning techniques to find fine-grained structure within brain areas. We apply our methods to micron-scale X-ray microtomography images spanning multiple regions in the mouse brain and demonstrate that our deep feature-based model can reliably discriminate between brain areas, is robust to noise, and can be used to reveal anatomically relevant patterns in neural architecture that the network wasn't trained to find. 

Understanding how neural structure varies across individuals is critical for characterizing the effects of disease, learning, and aging on the brain. However, disentangling the different factors that give rise to individual variability is still an outstanding challenge. In this paper, we introduce a deep generative modeling approach to find different modes of variation across many individuals. Our approach starts with training a variational autoencoder on a collection of auto-fluorescence images from a little over 1,700 mouse brains at 25 μ m resolution. We then tap into the learned factors and validate the model’s expressiveness, via a novel bi-directional technique that makes structured perturbations to both, the high-dimensional inputs of the network, as well as the low-dimensional latent variables in its bottleneck. Our results demonstrate that through coupling generative modeling frameworks with structured perturbations, it is possible to probe the latent space of the generative model to provide insights into the representations of brain structure formed in deep networks. 

Abstract Neural microarchitecture is heterogeneous, varying both across and within brain regions. The consistent identification of regions of interest is one of the most critical aspects in examining neurocircuitry, as these structures serve as the vital landmarks with which to map brain pathways. Access to continuous, three-dimensional volumes that span multiple brain areas not only provides richer context for identifying such landmarks, but also enables a deeper probing of the microstructures within. Here, we describe a three-dimensional X-ray microtomography imaging dataset of a well-known and validated thalamocortical sample, encompassing a range of cortical and subcortical structures from the mouse brain . In doing so, we provide the field with access to a micron-scale anatomical imaging dataset ideal for studying heterogeneity of neural structure. 

In many machine learning applications, it is necessary to meaningfully aggregate, through alignment, different but related datasets. Optimal transport (OT)-based approaches pose alignment as a divergence minimization problem: the aim is to transform a source dataset to match a target dataset using the Wasserstein distance as a divergence measure. We introduce a hierarchical formulation of OT which leverages clustered structure in data to improve alignment in noisy, ambiguous, or multimodal settings. To solve this numerically, we propose a distributed ADMM algorithm that also exploits the Sinkhorn distance, thus it has an efficient computational complexity that scales quadratically with the size of the largest cluster. When the transformation between two datasets is unitary, we provide performance guarantees that describe when and how well aligned cluster correspondences can be recovered with our formulation, as well as provide worst-case dataset geometry for such a strategy. We apply this method to synthetic datasets that model data as mixtures of low-rank Gaussians and study the impact that different geometric properties of the data have on alignment. Next, we applied our approach to a neural decoding application where the goal is to predict movement directions and instantaneous velocities from populations of neurons in the macaque primary motor cortex. Our results demonstrate that when clustered structure exists in datasets, and is consistent across trials or time points, a hierarchical alignment strategy that leverages such structure can provide significant improvements in cross-domain alignment.