Mood problems are very damaging and far-reaching, affecting millions of people worldwide. More attempts should have been made by design researchers to form innovative and feasible design concepts, against current technological background, to produce practical technical artifacts to solve the issue. This monograph focuses on Design Science research and its collaboration with Neuroscience to seek ways to help people with negative moods, depression in particular. Humor, exerting positive influences on both physical and mental health and impacting every aspect concerning social interactions, is worth investigating. Studies on the cognitive processing mechanism of humor appreciation provide knowledge bases, evaluation methods and intervention tools to bridge the gap between Neuroscience research and Design Science research to facilitate the creative design processes, leading to the transfer of positive influences of humor to the technical artifacts by assisting people in regulating their emotions. Rather than emphasizing the technological factor in this emotion design concept, this study was more immersed in the problem itself to recognize the natural states of the potential users via the analysis of Form-of-Life, which prevented us from being constrained by software solutions in isolation. On the basis of Life-Based Design theory, the desired emotion design concept, presented in 5Rs model, was proposed in this monograph. Resorting to mobile phones as the main media connecting potential users and future technical artifacts, this model was integrated with the emerging EEG-based Brain Computer Interfaces to provide a “three in one” system: real-time recording, instant feedback and effective intervention to lay more objective and reliable foundation for the implementation of the future technical artifacts.