This study used high-resolution functional magnetic resonance imaging (fMRI) to investigate pattern separation in the human hippocampal CA3 and dentate gyrus. Pattern separation is the process of transforming similar representations into highly dissimilar, non-overlapping representations, which is crucial for various cognitive functions attributed to the hippocampus. The researchers designed an incidental encoding task where subjects viewed pictures of everyday objects, including repetitions and slightly different versions of the same object (lures). Activity consistent with pattern separation was observed in the CA3/dentate gyrus, while activity consistent with pattern completion was observed in other regions such as CA1, the subiculum, and the entorhinal and parahippocampal cortices. The results provide strong evidence for the key role of the human CA3/dentate gyrus in pattern separation, supporting computational models that highlight the importance of this region in creating sparse, orthogonalized representations. However, the study's limitations include the inability to distinguish between the dentate gyrus and the CA3 subregion, and the potential for activity changes to reflect novelty rather than pattern separation. Despite these limitations, the findings contribute to a better understanding of the division of labor within the medial temporal lobe (MTL) and its role in cognitive functions.This study used high-resolution functional magnetic resonance imaging (fMRI) to investigate pattern separation in the human hippocampal CA3 and dentate gyrus. Pattern separation is the process of transforming similar representations into highly dissimilar, non-overlapping representations, which is crucial for various cognitive functions attributed to the hippocampus. The researchers designed an incidental encoding task where subjects viewed pictures of everyday objects, including repetitions and slightly different versions of the same object (lures). Activity consistent with pattern separation was observed in the CA3/dentate gyrus, while activity consistent with pattern completion was observed in other regions such as CA1, the subiculum, and the entorhinal and parahippocampal cortices. The results provide strong evidence for the key role of the human CA3/dentate gyrus in pattern separation, supporting computational models that highlight the importance of this region in creating sparse, orthogonalized representations. However, the study's limitations include the inability to distinguish between the dentate gyrus and the CA3 subregion, and the potential for activity changes to reflect novelty rather than pattern separation. Despite these limitations, the findings contribute to a better understanding of the division of labor within the medial temporal lobe (MTL) and its role in cognitive functions.