CA1 subfield contributions to memory integration and inference

Abstract

The ability to combine information acquired at different times to make novel inferences is a powerful function of episodic memory. One perspective suggests that by retrieving related knowledge during new experiences, existing memories can be linked to the new, overlapping information as it is encoded. The resulting memory traces would thus incorporate content across event boundaries, representing important relationships among items encountered during separate experiences. While prior work suggests that the hippocampus is involved in linking memories experienced at different times, the involvement of specific subfields in this process remains unknown. Using both univariate and multivariate analyses of high-resolution functional magnetic resonance imaging (fMRI) data, we localized this specialized encoding mechanism to human CA1 . Specifically, right CA1 responses during encoding of events that overlapped with prior experience predicted subsequent success on a test requiring inferences about the relationships among events. Furthermore, we employed neural pattern similarity analysis to show that patterns of activation evoked during overlapping event encoding were later reinstated in CA1 during successful inference. The reinstatement of CA1 patterns during inference was specific to those trials that were performed quickly and accurately, consistent with the notion that linking memories during learning facilitates novel judgments. These analyses provide converging evidence that CA1 plays a unique role in encoding overlapping events and highlight the dynamic interactions between hippocampal-mediated encoding and retrieval processes. More broadly, our data reflect the adaptive nature of episodic memories, in which representations are derived across events in anticipation of future judgments.

Keywords: associative inference; episodic memory; high-resolution fMRI; integrative encoding; pattern similarity.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1

Associative inference task. (a) Participants learned overlapping pairs of objects during the study phases. AB (e.g., clipboard-truck) pairs were presented first. BC (e.g., truck-binoculars) pairs were learned later and included familiar items from the AB pairs (i.e., the truck in this example). (b) During test phases, participants were presented with three objects. The top item served as the cue; the bottom items were the two choices. A direct test trial is shown on the left, in which the participant is required to select truck when cued with clipboard. In the inference example (right), the participant should choose the binoculars, as both the clipboard and binoculars were paired with the truck during learning. For both direct and inference test trials, familiar items that were members of a different triad from the same study scan served as foils. Correct choices are circled for illustrative purposes only (not shown to participants).

Figure 2

Schematic depiction and rationale of neural pattern similarity analysis (NPSA). (a) Average patterns of activation associated with specific trial types were extracted for each anatomical ROI. Here we depict the cross-participant analysis (see Neural pattern similarity analysis section of Materials and Methods), which was estimated irrespective of memory performance. Trials were modeled according to event type (AB, BC for study phase; AC for test phase) using a GLM. Parameter estimates associated with conditions of interest were then extracted for each voxel within the ROI (example ROI shown in yellow). The intensity in each cell in the grayscale matrix schematic represents the parameter estimate for a single voxel in the brain. The similarity of two patterns was then determined by computing a Pearson correlation between the two matrices. (b) Predictions for NPSA when existing memories are retrieved and linked to current experience during overlapping event encoding. Example AB study, BC study, and inference test screens are shown; simplified hypothetical mean patterns of activation associated with each trial type are depicted next to the corresponding condition. As BC study trials provide a unique opportunity to link prior memories with current experience, we predicted greater reinstatement of BC than AB study patterns during AC inference judgments. Reinstatement of study patterns evoked during overlapping event encoding would be reflected by a higher correlation between BC-AC study-test (thick blue arrow) than between AB-AC study-test (thin green arrow).

Figure 3

Results from univariate analysis demonstrating relationship between CA1 processes during overlapping event encoding and subsequent inference success. Right CA1 was the only hippocampal region to demonstrate a signature consistent with study-phase retrieval of prior memories in service of later inference. This region showed greater subsequent inference effects for BC relative to AB study trials as a function of AC performance. Inset, sagittal view showing location of cluster along anterior-posterior extent of hippocampus. Significant activation was restricted to the hippocampal body. Activation map has been transformed to the space of a single participant’s T2 coronal image for visualization purposes. Cluster is significant after correction for multiple comparisons (voxel threshold: p < 0.025, uncorrected; cluster size threshold: p < 0.05).

Figure 4

Results from multivariate neural pattern similarity analysis demonstrating an encoding signature specific to overlapping events in bilateral CA1. (a) Performance-based analysis. Study-test pattern similarity limited to triads for which both direct memory judgments (AB, BC) were correct. Trials were split based on whether the corresponding inference (AC) judgment was later correct (dark bars) or incorrect (light bars). AB-AC study-test pattern similarity is shown in green; BC-AC study-test pattern similarity is shown in blue. (b) RT-based analysis. Study-test pattern similarity for direct correct and AC inference correct triads. Trials were further split based on median reaction time into fast (dark gray bars) and slow (light gray bars) inference judgments. Bars depicting AB-AC study-test pattern similarity are outlined in green; bars for BC-AC pattern similarity are outlined in blue. For both (a) and (b), asterisks (*) denote significant follow-up paired t-tests (p < 0.05); tensor product symbol (⊗) denotes significant interaction (p < 0.01). Error bars denote across-participant SEM. (c) Cross-participant analysis. Scatterplots depict continuous relationship between study-test pattern similarity (AB-AC study-test, green; BC-AC study-test, blue) and inference performance. Best-fit lines and statistics on plots were calculated using Pearson correlation. Significant correlation at p < 0.005 denoted with bold type.

Figure 5

Neural pattern similarity results in anterior hippocampus (a), DG/CA2,3 (b), subiculum (c), and posterior hippocampus (d). None of these regions showed evidence of a specialized BC encoding mechanism. Data are presented as in Figure 4a and c. Top charts, performance based analysis. Significant main effects of inference performance were observed in anterior hippocampus, subiculum, and posterior hippocampus (all p < 0.01; not marked on charts). Bottom scatterplots, cross-participant analysis depicting continuous relationship between study-test pattern similarity and inference performance. All correlations were non-significant at the critical p threshold of 0.005.