Many modern neuroimaging studies acquire large spatial images of the brain observed sequentially over time. Such data are often stored in the forms of matrices. To model these matrix-variate data we introduce a class of separable processes using explicit latent process modeling. To account for the size and two-way structure of the data, we extend principal component analysis to achieve dimensionality reduction at the individual level. We introduce necessary identifiability conditions for each model and develop scalable estimation procedures. The method is motivated by and applied to a functional magnetic resonance imaging study designed to analyze the relationship between pain and brain activity.