All of us regularly face situations that require the integration of the available information at hand with the established rules that guide behavior in order to generate the most appropriate action. But where individuals differ from one another is most certainly in terms of the different strategies that are adopted during this process. A previous study revealed differential brain activation patterns for the implementation of well established higher-order stimulus-response (S-R) rules depending on inter-individual strategy differences (Wolfensteller and von Cramon, 2010). This raises the question of how these strategies evolve or which neurocognitive mechanisms underlie these inter-individual strategy differences. Using functional magnetic resonance imaging (fMRI), the present study revealed striking strategy-effects across regions of the lateral prefrontal cortex during the implementation of higher-order S-R rules at an early stage of learning. The left rostrolateral prefrontal cortex displayed a quantitative strategy-effect, such that activation during rule integration based on a mismatch was related to the degree to which participants continued to rely on rule integration. A quantitative strategy ceiling effect was observed for the left inferior frontal junction area. Conversely, the right inferior frontal gyrus displayed a qualitative strategy-effect such that participants who at a later point relied on an item-based strategy showed stronger activations in this region compared to those who continued with the rule integration strategy. Together, the present findings suggest that a certain amount of rule integration is mandatory when participants start to learn higher-order rules. The more efficient item-based strategy that evolves later appears to initially require the recruitment of additional cognitive resources in order to shield the currently relevant S-R association from interfering information.