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              <p>Background. Voltage-sensitive dye optical imaging is a promising technique for studying in vivo neural assemblies dynamics where functional clustering can be visualized in the imaging plane. Its practical potential is however limited by many artifacts. New Method. We present a novel method, that we call "SMCS" (Spatially Structured Sparse Morphological Component Separation), to separate the relevant biological signal from noise and artifacts. It extends Generalized Linear Models (GLM) by using a set of convex non-smooth regularization priors adapted to the morphology of the sources and artifacts to capture. Results. We make use of first order proximal splitting algorithms to solve the corresponding large scale optimization problem. We also propose an automatic parameters selection procedure based on statistical risk estimation methods. Comparison with Existing Methods. We compare this method with blank subtraction and GLM methods on both synthetic and real data. It shows encouraging perspectives for the observation of complex cortical dynamics. Conclusions. This work shows how recent advances in source separation can be integrated into a biophysical model of VSDOI. Going beyond GLM methods is important to capture transient cortical events such as propagating waves.</p>
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