This study investigates the role of the human hippocampal CA3/dentate gyrus (CA3/DG) in pattern separation, a process that transforms similar memories into distinct, non-overlapping representations. Using high-resolution fMRI (1.5 mm³), researchers measured brain activity during incidental memory encoding in 18 subjects. The task involved viewing pictures of everyday objects, with trials including new objects, repetitions, and slightly different versions (lures) of previously shown objects. Activity consistent with pattern separation was observed in the CA3/DG, while activity consistent with pattern completion was seen in other regions like CA1 and the subiculum. The CA3/DG showed activity similar to first presentations of stimuli, indicating a bias towards pattern separation. In contrast, other regions showed activity more similar to repetitions, suggesting a bias towards pattern completion. The study found that the CA3/DG exhibited a strong bias towards pattern separation, with lure trials showing activity similar to first presentations. This is consistent with computational models that suggest the dentate gyrus creates sparse, orthogonalized representations, which are then projected to CA3. These findings support the idea that the CA3/DG plays a key role in pattern separation, a critical function of the hippocampus in memory processing. The study also highlights the limitations of fMRI in distinguishing between the dentate gyrus and CA3, and notes that while the CA3/DG shows activity consistent with pattern separation, other regions may also contribute to this process. The results provide compelling evidence for the role of the human CA3/DG in pattern separation and support computational models of hippocampal function.This study investigates the role of the human hippocampal CA3/dentate gyrus (CA3/DG) in pattern separation, a process that transforms similar memories into distinct, non-overlapping representations. Using high-resolution fMRI (1.5 mm³), researchers measured brain activity during incidental memory encoding in 18 subjects. The task involved viewing pictures of everyday objects, with trials including new objects, repetitions, and slightly different versions (lures) of previously shown objects. Activity consistent with pattern separation was observed in the CA3/DG, while activity consistent with pattern completion was seen in other regions like CA1 and the subiculum. The CA3/DG showed activity similar to first presentations of stimuli, indicating a bias towards pattern separation. In contrast, other regions showed activity more similar to repetitions, suggesting a bias towards pattern completion. The study found that the CA3/DG exhibited a strong bias towards pattern separation, with lure trials showing activity similar to first presentations. This is consistent with computational models that suggest the dentate gyrus creates sparse, orthogonalized representations, which are then projected to CA3. These findings support the idea that the CA3/DG plays a key role in pattern separation, a critical function of the hippocampus in memory processing. The study also highlights the limitations of fMRI in distinguishing between the dentate gyrus and CA3, and notes that while the CA3/DG shows activity consistent with pattern separation, other regions may also contribute to this process. The results provide compelling evidence for the role of the human CA3/DG in pattern separation and support computational models of hippocampal function.