In this talk, I demonstrate a Brain Informatics based systematic approach to an integrated understanding of macroscopic and microscopic level working principles of the brain by means of experimental, computational, and cognitive neuroscience studies, as well as utilizing advanced Web intelligence centric information technologies. I discuss research issues and challenges with respect to brain big data computing from three aspects of Brain Informatics studies that deserve closer attention: systematic investigations for complex brain science problems, new information technologies for supporting systematic brain science studies, and Brain Informatics studies based on Web intelligence research needs. These three aspects offer different ways to study traditional cognitive science, neuroscience, mental health and artificial intelligence.