Complementary Roles of Human Hippocampal Subfields in Differentiation and Integration of Spatial Context

Abstract

The unique circuitry of the hippocampus is thought to support the encoding and retrieval of context-rich episodic memories. Given the neuroanatomical differences between the hippocampal subfields, determining their functional roles during representation of contextual features in humans is an important yet unaddressed research goal. Prior studies suggest that during the acquisition of information from the environment, the dentate gyrus (DG) and CA3 subfields rapidly differentiate competing contextual representations, whereas CA1, situated downstream from CA3/DG, is believed to process input from both CA3 and neocortical areas via the temporoammonic pathway. To further explore the functionality of these roles, we used high-resolution fMRI to investigate multivariate response patterns within CA3/DG and CA1 during the processing of spatial context. While undergoing functional imaging, participants viewed videos of virtual environments and were asked to discriminate between similar, yet geometrically distinct cities. We manipulated a single contextual feature by systematically morphing the city configurations from one common geometric shape to another, resulting in four cities—two distinctively shaped cities and two intermediate “morphed” cities. Pattern similarity within CA3/DG scaled with geometric changes to the environment. In contrast, CA1 pattern similarity, as well as interregional pattern similarity between CA1 and parahippocampal cortex, increased for the regularly shaped configurations compared to the morphs. These results highlight different roles for subfields CA3/DG and CA1 in memory and advance our understanding of how subcomponents of the human hippocampal circuit represent contextual features of memories.

Hippocampal Attractor Dynamics Predict Memory-Based Decision Making

“…Although it is infeasible to register place cell activity in humans using fMRI, given that the distribution of place cells in rodent hippocampus is nontopographic with respect to the spatial distribution of their firing fields [37], the aforementioned rodent place cell pattern shows striking similarities with our data. Our data are consistent with the absence of sigmoidal neural response patterns in the human hippocampus when participants view highly similar visual scenes [38,39] and a linear scaling of hippocampal responses with changes in the configuration of landmarks in four virtual environments [40]. The attractor-like behavior of place cells also accords with observations in rodents that repeated exposure to less-distinct environments is accompanied by a slower, gradual development of distinct place cell representations [41].…”

Temporal and spatial context in the mind and brain

“…This unified account of spatial context, temporal context and spatiotemporal context aligns well with recent fMRI studies virtual reality suggesting not only that similar regions participate in recovery of spatial and temporal context [66, 67, 64] (see also Fig. 2B).…”

Integrating new findings and examining clinical applications of pattern separation

“…Overall, convergent data have suggested that CA3 is capable of exhibiting pattern completion or pattern separation, depending on the magnitude of the change in sensory input. The CA1 subfield generally appears to respond linearly to incremental changes in sensory input; however, under some conditions it may respond with an abrupt nonlinear change, perhaps reflecting a switch in its dominant input from the entorhinal cortex to CA3 18–20 (but see Stokes et al 21 ). This could be a result of explicit task influences or the requirement for a mnemonic judgment instead of free exploration 19,22 .…”