Event integration and temporal pattern separation: how hierarchical knowledge emerges in hippocampal subfields through learning

Abstract

Everyday life is composed of events organized by changes in contexts, with each event containing an unfolding sequence of occurrences. A major challenge facing our memory systems is how to integrate sequential occurrences within events while also maintaining their details and avoiding over-integration across different contexts. Here we asked if and how distinct hippocampal subfields come to hierarchically, and in parallel, represent both event context and subevent occurrences with learning. Participants viewed sequential events defined as sequences of objects superimposed on shared color frames while undergoing high-resolution fMRI. Importantly, these events were repeated to induce learning. Event segmentation, as indexed by increased reaction times at event boundaries, was observed in all repetitions. Temporal memory decisions were quicker for items from the same event compared to across different events, indicating that events shaped memory behavior. With learning, hippocampal CA3 multivoxel activation patterns clustered to reflect the event context, with more clustering correlated with behavioral facilitation during event transitions. In contrast, in the dentate gyrus temporally proximal items that belonged to the same event became associated with more differentiated neural patterns. A computational model explained these results by dynamic inhibition in the dentate gyrus. Additional similarity measures support the notion that CA3 clustered representations reflect shared voxel populations, while dentate gyrus distinct item representations reflect different voxel populations. These findings suggest an interplay between temporal differentiation in dentate gyrus and attractor dynamics in CA3. They advance our understanding of how knowledge is structured through integration and separation across time and context. SignificanceA major challenge of our memory system is to integrate experiences occurring in the same context to generalize context-appropriate knowledge, while also maintaining distinct representations of these same occurrences to avoid confusion. Here, we uncover a novel mechanism for hierarchical learning in the human hippocampus that might help to resolve this tension. In the CA3 subregion of the hippocampus, the neural representations of items presented sequentially in the same context, but not in different contexts, became more overlapping with learning. In contrast, adjacent items, appearing close in time and in the same context, became increasingly more differentiated in the dentate gyrus. Thus, multiple representations in different hippocampal subregions encoded in parallel might enable simultaneous generalization and specificity in memory.