Hippocampal subfield and medial temporal cortical persistent activity during working memory reflects ongoing encoding

Abstract

Previous neuroimaging studies support a role for the medial temporal lobes in maintaining novel stimuli over brief working memory (WM) delays, and suggest delay period activity predicts subsequent memory. Additionally, slice recording studies have demonstrated neuronal persistent spiking in entorhinal cortex, perirhinal cortex (PrC), and hippocampus (CA1, CA3, subiculum). These data have led to computational models that suggest persistent spiking in parahippocampal regions could sustain neuronal representations of sensory information over many seconds. This mechanism may support both WM maintenance and encoding of information into long term episodic memory. The goal of the current study was to use high-resolution fMRI to elucidate the contributions of the MTL cortices and hippocampal subfields to WM maintenance as it relates to later episodic recognition memory. We scanned participants while they performed a delayed match to sample task with novel scene stimuli, and assessed their memory for these scenes post-scan. We hypothesized stimulus-driven activation that persists into the delay period-a putative correlate of persistent spiking-would predict later recognition memory. Our results suggest sample and delay period activation in the parahippocampal cortex (PHC), PrC, and subiculum (extending into DG/CA3 and CA1) was linearly related to increases in subsequent memory strength. These data extend previous neuroimaging studies that have constrained their analysis to either the sample or delay period by modeling these together as one continuous ongoing encoding process, and support computational frameworks that predict persistent activity underlies both WM and episodic encoding.

Keywords: delayed matching-to-sample; high-resolution fMRI; hippocampus; medial temporal lobes; working memory.

FIGURE 1

Tasks and behavioral results. Recognition memory task adapted from Schon et al. (2004). (A) Participants were first shown a series of 144 randomized, trial unique but content similar outdoor scenes in the context of a delayed match to sample (DMS) working memory (WM) task during fMRI scanning. Approximately 15 min after completion of the fMRI scanning session, participants were administered a surprise subsequent memory test (SMT) where they were shown all 144 DMS images, plus 144 lure images, and asked to rate their recognition confidence. Participants were blind to the ratio of old to new images on the SMT. (B) Overall DMS task accuracy, separated by match and non-match trials. Ticks, thick lines, and thin lines show medians, 50% intervals, and 95% intervals, respectively. (C) SMT response distributions for old and lure stimuli, separated by confidence rating. Error bars show SD.

FIGURE 2

fMRI results for ongoing encoding (sample + delay model without signal decay). Preliminary analysis of a putative encoding epoch (sample + delay periods from DMS task; see Figure 1) shows regions where increased activity during DMS task performance was linearly related to stronger episodic memory at later test. Results are shown in red within 3D renderings of our regions of interest (ROIs) from both dorsal (A) and ventral (B) perspectives. Part (C) shows example ROI tracings from anterior and posterior slices, and the region of BOLD signal coverage averaged across participants. Note the apparent lack of major signal dropout in EC. Figures were made using functionality from the R rgl and misc3d packages (Feng and Tierney, 2008; Adler et al., 2014).

FIGURE 3

Observed data and model fit of three encoding models. The top row shows the raw data from a 5 mm sphere around the peak voxel in L. PHC, averaged over all participants and all trials. Whole time series are z-scored within participant prior to averaging to transform the data to a common scale; the horizontal gray line represents the mean of the raw time series. Dotted lines correspond to the onsets of sample and delay periods, respectively. Note that due to the sluggishness of the hemodynamic response, signal from a given time point is shifted later by ∼6 s. The bottom three rows test the fits (gray lines) of three separate models against the observed data (black lines). Dark gray lines are averages from 20 random posterior predictive simulations, depicting what we would expect the data to look like if the underlying model were true. Regions where the observed data do not overlap with the simulations represent discrepancy between observed data and model fit.

FIGURE 4

fMRI results for ongoing encoding with slow decay. Main results from slow decay model analysis showing regions where BOLD response is initiated at the onset of the sample stimulus (see Figure 1) and persists into the delay period, slowly decaying with time (see Figure 3). The magnitude of this activity was linearly related to subsequent strength of episodic memory. Results are shown in red within 3D renderings of our ROIs from both dorsal (A) and ventral (B) perspectives. Individual slices (C) follow Table 1 in showing the locations of peak voxels within main clusters. Figures were made using functionality from the R rgl and misc3d packages (Feng and Tierney, 2008; Adler et al., 2014).