The Skill, Rule, and Knowledge framework is a highly influential framework in HF/E that led to few empirical validations. In this article, we focused on mental workload predictions suggesting that control modes are supposed to produce gradually higher levels of mental workload. Forty-four participants were given a modified MATB-II task. They had to solve different tasks to illustrate skill-based, rule-based, and knowledge-based control modes. The results showed expected workload levels for skill and rule-based control modes. However, the knowledge-based control mode produced both the lowest mental workload but also the lowest performance of the three modes. We interpreted the results in the light of neurophysiologically plausible studies distinguishing engagement and effort (from overall mental workload). We noticed that participants did not fully engage in the knowledge-based control mode, which then limited their effort and ultimately produced a lower performance compared to the other control modes. We argue that conceptual refinement of mental workload based on neurophysiologically plausible theories illustrates the interest of neurosciences in HF/E.