Localized semi-nonnegative matrix factorization (LocaNMF) of widefield calcium imaging data

Widefield calcium imaging enables recording of large-scale neural activity across the mouse dorsal cortex. In order to examine the relationship of these neural signals to the resulting behavior, it is critical to demix the recordings into meaningful spatial and temporal components that can be mapped onto well-defined brain regions. However, no current tools satisfactorily extract the activity of the different brain regions in individual mice in a data-driven manner, while taking into account mouse-specific and preparation-specific differences. Here, we introduce Localized semi-Nonnegative Matrix Factorization (Lo-caNMF), a method that efficiently decomposes widefield video data and allows us to directly compare activity across multiple mice by outputting mouse-specific localized functional regions that are significantly more interpretable than more traditional decomposition techniques. Moreover, it provides a natural subspace to directly compare correlation maps and neural dynamics across different behaviors, mice, and experimental conditions, and enables identification of task- and movement-related brain regions. Author summary While recording from multiple regions of the brain, how does one best incorporate prior information about anatomical regions while accurately representing the data? Here, we introduce Localized semi-NMF (LocaNMF), an algorithm that efficiently decomposes widefield video data into meaningful spatial and temporal components that can be decoded and compared across different behavioral sessions and experimental conditions. Mapping the inferred components onto well-defined brain regions using a widely-used brain atlas provides an interpretable, stable decomposition. LocaNMF allows us to satisfactorily extract the activity of the different brain regions in individual mice in a data-driven manner, while taking into account mouse-specific and preparation-specific differences.