Linear model decomposition for voltage-sensitive dye imaging signals: Application in awake behaving monkey

► A linear model (LM) for denoising spatio-temporal VSDI signal at single-trial level. ► The LM is essential to achieve VSDI single-trial analysis on behaving monkey. ► The LM can accommodate for a large range of VSDI response dynamics. ► The LM improved significantly spatial maps and response dynamics in VSDI. ► The LM reduces trial-to-trial variability and improves response detectability in VSDI.