Episodic memory is known to rely on the hippocampus, but how the hippocampus organizes different episodes to permit their subsequent retrieval remains controversial. One major area of debate hinges on a discrepancy between two hypothesized roles of the hippocampus: differentiating between similar events to reduce interference and assigning similar representations to events that share overlapping items and contextual information. Here, we used multivariate analyses of activity patterns measured with fMRI to characterize how the hippocampus distinguishes between memories based on similarity at the level of items and/or context. Hippocampal activity patterns discriminated between events that shared either item or context information but generalized across events that shared similar item–context associations. The current findings provide evidence that, whereas the hippocampus can reduce mnemonic interference by separating events that generalize along a single attribute dimension, overlapping hippocampal codes may support memory for events with overlapping item–context relations. This lends new insights into the way the hippocampus may balance multiple mnemonic operations in adaptively guiding behavior.

Highlights d Learning of associations based on different task substructures d Memories of task structures guide future decisions d Greater representational similarity based on the same structure in hippocampus and OFC d Representation of task structure is highly correlated between hippocampus and OFC

The method of loci is a highly effective mnemonic that recruits existing salient memory for spatial locations and uses the information as a scaffold for remembering a list of items (Yates, 1966). One possible account for the effectiveness of the spatial method of loci comes from the perspective that it utilizes evolutionarily preserved mechanisms for spatial navigation within the hippocampus (Maguire et al. in Proceedings of the National Academy of Sciences, 97(8), 4398-4403, 2000; O'Keefe & Nadel, 1978; Rodriguez et al. in Brain Research Bulletin, 57(3), 499-503, 2002). Recently, though, neurons representing temporal information have also been described within the hippocampus (Eichenbaum in Nature Reviews Neuroscience, 15(11), 732-744, 2014; Itskov, Curto, Pastalkova, & Buzsáki in The Journal of Neuroscience, 31(8), 2828-2834, 2011; MacDonald, Lepage, Eden, & Eichenbaum in Neuron, 71(4), 737-749, 2011; Mankin et al. in Proceedings of the National Academy of Sciences, 109(47), 19462-19467, 2012; Meck, Church, & Matell in Behavioral Neuroscience, 127(5), 642, 2013), challenging the primacy of spatial-based functions to hippocampal processing. Given the presence of both spatial and temporal coding mechanisms within the hippocampus, we predicted that primarily temporal encoding strategies might also enhance memory. In two different experiments, we asked participants to learn lists of unrelated nouns using the (spatial) method of loci (i.e., the layout of their home as the organizing feature) or using two novel temporal methods (i.e., autobiographical memories or using the steps to making a sandwich). Participants' final free recall performance showed comparable boosts to the method of loci for both temporal encoding strategies, with all three scaffolding approaches demonstrating performance well above uninstructed free recall. Our findings suggest that primarily temporal representations can be used effectively to boost memory performance, comparable to spatial methods, with some caveats related to the relative ease with which participants appear to master the spatial versus temporal methods.

During navigation, information at multiple scales needs to be integrated. Single-unit recordings in rodents suggest that gradients of temporal dynamics in the hippocampus and entorhinal cortex support this integration. In humans, gradients of representation are observed, such that granularity of information represented increases along the long axis of the hippocampus. The neural underpinnings of this gradient in humans, however, are still unknown. Current research is limited by coarse fMRI analysis techniques that obscure the activity of individual voxels, preventing investigation of how moment-to-moment changes in brain signal are organized and how they are related to behavior. Here, we measured the signal stability of single voxels over time to uncover previously unappreciated gradients of temporal dynamics in the hippocampus and entorhinal cortex. Using our novel, single voxel autocorrelation technique, we show a medial-lateral hippocampal gradient, as well as a continuous autocorrelation gradient along the anterolateral-posteromedial entorhinal extent. Importantly, we show that autocorrelation in the anterior-medial hippocampus was modulated by navigational difficulty, providing the first evidence that changes in signal stability in single voxels are relevant for behavior. This work opens the door for future research on how temporal gradients within these structures support the integration of information for goal-directed behavior.