Recent technological advances, significant algorithmic progress in artificial intelligence, and immersion of deep transdisciplinary team collaborations led to an explosion of the volume of biomedical data and proliferation of data-modeling and computational-inference techniques throughout the biomedical sciences. These breakthroughs are paired with enormous challenges and unique opportunities to experiment, innovate, validate, and translate new discoveries into healthcare enhancements, systemic cost efficiencies, and improvements of all human experiences. The central nervous system represents a prime example of a complex driving motivational system with a wealth of foundational knowledge, a large number of explicit barriers, and a substantial phenotypic heterogeneity. This special issue of the journal Neuroinformatics will focus on modern data science techniques and cutting-edge artificial intelligence approaches, and their direct applications in brain mapping, neuroscience, medical informatics, cognitive science, computational inference, normal aging, and pathological brain development.