Learning-related representational changes reveal dissociable integration and separation signatures in the hippocampus and prefrontal cortex

Margaret L Schlichting, Jeanette A Mumford, Alison R Preston, Margaret L Schlichting, Jeanette A Mumford, Alison R Preston

Abstract

The episodic memory system enables accurate retrieval while maintaining flexibility by representing both specific episodes and generalizations across events. Although theories suggest that the hippocampus (HPC) is dedicated to represent specific episodes while the medial prefrontal cortex (MPFC) generalizes, other accounts posit that HPC can also integrate related memories. Here we use high-resolution functional magnetic resonance imaging in humans to examine how representations of memory elements change to either differentiate or generalize across related events. We show that while posterior HPC and anterior MPFC maintain distinct memories for individual events, anterior HPC and posterior MPFC integrate across memories. Integration is particularly likely for established memories versus those encoded simultaneously, highlighting the greater impact of prior knowledge on new encoding. We also show dissociable coding signatures in ventrolateral PFC, a region previously implicated in interference resolution. These data highlight how memory elements are represented to simultaneously promote generalization across memories and protect from interference.

Figures

Figure 1. Paradigm overview and behavioural results.
Figure 1. Paradigm overview and behavioural results.
(a) During the study phase (middle), participants intentionally encoded pairs of novel objects. Half of the pairs were presented in a blocked manner (top, pink); half were intermixed (bottom, teal). Identical stimulus exposure phases occurred immediately before (left) and after (right) the study task during hr-fMRI scanning. Pre- and post-study exposure phases were used to obtain estimates of the neural patterns evoked by specific stimuli learned during the study phase. Trial timing and order were matched between pre- and post-study to avoid introducing unequal biases into the neural pattern estimates from the two phases. (b) After scanning, participants completed a two-alternative forced choice test for inference (top, tested first) and directly learned (bottom, tested second) associations. Participants selected which of the two choice stimuli (bottom of screen) was associated with the cue stimulus (top of screen). Correct answers are indicated with dashed circle (not shown to participants). (c) Performance as a function of test trial type and learning condition. Left bar pair, AC inference performance for blocked (pink; 33.3–100%, 92.3±3.1%) and intermixed (teal; 50–100%, 88.5±3.0%) triads. Middle bar pair, AB performance (blocked: 83.3–100%, 96.2±1.4%; intermixed: 66.7–100%, 95.5±1.7%). Right bar pair, BC performance (blocked: 83.3–100%, 96.8±1.3%; intermixed: 83.3–100%, 98.1±1.1%). Bar heights represent group means; error bars denote s.e.m. N=26 participants.
Figure 2. Predictions for RSA.
Figure 2. Predictions for RSA.
Schematic depiction of RSA and predictions for a subset of six triads. Triads 1–3 were studied in a blocked manner (pink); triads 7–9 were intermixed (teal). For all matrices, the colour in each cell represents the predicted change in (Δ) RS between an A item (horizontal) and a C item (vertical) from pre- to post-study. Black cells indicate no change in similarity from pre- to post-study; orange cells indicate learning-related increases in similarity; blue cells indicate learning-related decreases in similarity. White cells represent comparisons across learning condition (for example, intermixed item A7 with blocked item C1), which were excluded from all analyses. Matrices depict predicted item similarities for regions showing integration for both blocked and intermixed learning (top left), separation for both blocked and intermixed learning (top right) and blocked → integration (bottom left), and intermixed → integration (bottom right) interactions with learning condition. Inset bar graphs show predicted average similarities across all within- (darker bars) and across-triad (lighter bars) comparisons. Integration and separation were operationalized as significantly greater (integration) or less (separation) within- than across-triad Δ RS.
Figure 3. HPC representational similarity searchlight results.
Figure 3. HPC representational similarity searchlight results.
(a) HPC regions showing a significant main effect of separation (blue) or a blocked → integration interaction (green) displayed on the 1-mm MNI template brain. Clusters are significant after correction for multiple comparisons within anatomical HPC. Coordinates are in millimetres. (b) Across-participant relationship between anterior HPC volume (x axes) and evidence for integration in the blocked learning condition (y axis, left scatterplot; r=0.43, P=0.03) and separation in the intermixed learning condition (y axis, right scatterplot; r=−0.03, P=0.90) across the whole HPC. Statistics reflect Pearson correlations. N=26 participants. See also Supplementary Fig. 1.
Figure 4. MPFC representational similarity searchlight results.
Figure 4. MPFC representational similarity searchlight results.
MPFC regions showing a significant main effect of integration (orange), a main effect of separation (blue) or a blocked → integration interaction with learning condition (green) displayed on the 1-mm MNI template brain. Clusters are significant after correction for multiple comparisons within anatomical MPFC. Coordinates are in millimetres. N=26 participants. See also Supplementary Fig. 2.
Figure 5. IFG representational similarity searchlight results.
Figure 5. IFG representational similarity searchlight results.
IFG regions showing a significant main effect of separation (blue) or a blocked → integration interaction with learning condition (green) displayed on the 1-mm MNI template brain. Clusters are significant after correction for multiple comparisons within anatomical IFG. Coordinates are in millimetres. N=26 participants. See also Supplementary Fig. 3.

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