Hippocampal spatial and sequential representations of event structure scaffold precise episodic temporal order memory

Abstract The hippocampus plays an important role in representing spatial locations and sequences and for transforming representations via pattern separation and completion. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci (MOL), a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to fMRI activation patterns revealed that hippocampal subfields contained representations of both temporal context and multiple features of sequence structure, including location identity, distance, and sequence boundaries. Critically, the hippocampal CA1 and CA23DG exhibited spatial and sequential pattern separation, respectively, enabling the encoding of multiple items in the same location and reducing swap errors across adjacent locations. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.