Sequence memories in the hippocampal-entorhinal region scale to temporal reference frames


Time is the fundamental dimension along which we organize our experience. For example, sequences of events shape our episodic memory. The hippocampus and, more recently, the anterior-lateral entorhinal cortex have been implicated in memory for event sequences. Specifically, multi-voxel pattern similarity in these regions scales with learned temporal relationships of events encountered in a sequence. However, the precise nature of these representations remains to be understood: Do we merely store the sequential order of events or do we learn temporal relations along a continuous dimension? Is time represented as a passive “absolute”, akin to the readout of a stopwatch, or can temporal relationships be adjusted flexibly depending on the task at hand? Here, we combined a novel learning task with fMRI to investigate the level of complexity at which temporal relations are represented in the hippocampal-entorhinal memory system. Participants encountered four event sequences, which we refer to as virtual days, and were to infer when individual events occurred during the virtual days based on infrequent unmaskings of an otherwise hidden clock. Importantly, we manipulated the speed of this clock between virtual days to (partially) dissociate event times from their sequential order and the time objectively elapsing between them. Participants successfully learned event times and their mnemonic responses reflected information beyond sequence order and objectively elapsed time, indicating that knowledge of temporal relations was referenced to the hidden clock. We further investigated how learning changed multi-voxel pattern representations in the anterior hippocampus and the anterior-lateral entorhinal cortex. Representational change relative to a pre-learning baseline scan reflected the temporal relationships of events in both the hippocampus and entorhinal cortex. Interestingly, our findings suggest a dissociation between representations of temporal relations of events from the same or a different virtual day. Together, we show that participants’ memory scaled with the temporal structure of the virtual days with respect to the hidden clock and thereby demonstrate that event representations in the hippocampus and entorhinal cortex are shaped by learned temporal relationships within and across sequences. Thereby, our findings provide novel insights into how multiple event sequences are organized in the hippocampal-entorhinal memory system.

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