The Theory of Inventive Problem Solving (TRIZ) method and toolkit provides a well-structured approach to support engineering design with pre-defined steps: interpret and define the problem, search for standard engineering parameters, search for inventive principles to adapt, and generate final solutions. The research presented in this paper explores the neuro-cognitive differences of each of these steps. We measured the neuro-cognitive activation in the prefrontal cortex (PFC) of 30 engineering students. Neuro-cognitive activation was recorded while students completed an engineering design task. The results show a varying activation pattern. When interpreting and defining the problem, higher activation is found in the left PFC, generally associated with goal directed planning and making analytical. Neuro-cognitive activation shifts to the right PFC during the search process, a region usually involved in exploring the problem space. During solution generation more activation occurs in the medial PFC, a region generally related to making associations. The findings offer new insights and evidence explaining the dynamic neuro-cognitive activations when using TRIZ in engineering design.