<p>Despite the notion that cognitive conflict and new mental sets are linked to conceptual change, what happens inside the human brain remains a mystery. We therefore investigated the brain mechanisms underlying cognitive conflict and mental sets that contribute to radical and weak conceptual change using electroencephalography (EEG) technology. This study involved 58 science majors (17 females and 41 males) who completed 40 computer-based weak and radical conceptual change tasks designed to provoke cognitive conflict and introduce mental sets, while their brain activity was simultaneously recorded via EEG. The results demonstrated that weak tasks produced better conceptual change performance, as reflected in higher explanation scores, greater confidence, fewer experienced conflicts, and shorter prediction and thinking times compared to radical tasks. During the process of successful conceptual change, frontal midline theta activity was significantly higher for radical tasks than weak tasks at the stages of question, prediction, experiment video, and thinking. Furthermore, central parietal alpha activity did not differ significantly between radical and weak tasks across the six stages. Generalized estimating equation analysis indicated that frontal midline theta activity at the experiment video-watching stage was the predominant factor for predicting the success of conceptual change, followed by central parietal alpha activity at the experiment video-watching stage. Activation of the frontal midline and parietal brain regions appears to be associated with cognitive processes that induce cognitive conflict and introduce mental sets, thereby contributing to conceptual change. It provides insight into the future application of brain-computer interfaces (BCI) to monitor scientific conceptual change in real time.</p>