Hippocampal Mismatch Signals Are Modulated by the Strength of Neural Predictions and Their Similarity to Outcomes

Abstract

The hippocampus is thought to compare predicted events with current perceptual input, generating a mismatch signal when predictions are violated. However, most prior studies have only inferred when predictions occur without measuring them directly. Moreover, an important but unresolved question is whether hippocampal mismatch signals are modulated by the degree to which predictions differ from outcomes. Here, we conducted a human fMRI study in which subjects repeatedly studied various word-picture pairs, learning to predict particular pictures (outcomes) from the words (cues). After initial learning, a subset of cues was paired with a novel, unexpected outcome, whereas other cues continued to predict the same outcome. Critically, when outcomes changed, the new outcome was either "near" to the predicted outcome (same visual category as the predicted picture) or "far" from the predicted outcome (different visual category). Using multivoxel pattern analysis, we indexed cue-evoked reactivation (prediction) within neocortical areas and related these trial-by-trial measures of prediction strength to univariate hippocampal responses to the outcomes. We found that prediction strength positively modulated hippocampal responses to unexpected outcomes, particularly when unexpected outcomes were close, but not identical, to the prediction. Hippocampal responses to unexpected outcomes were also associated with a tradeoff in performance during a subsequent memory test: relatively faster retrieval of new (updated) associations, but relatively slower retrieval of the original (older) associations. Together, these results indicate that hippocampal mismatch signals reflect a comparison between active predictions and current outcomes and that these signals are most robust when predictions are similar, but not identical, to outcomes.

Consolidation Promotes the Emergence of Representational Overlap in the Hippocampus and Medial Prefrontal Cortex

“…We chose posterior medial cortex (PMC), a critical region in the recollection network that has been shown to reinstate encoding patterns during retrieval (Bird et al, 2015; Kuhl et al, 2011; Long et al, 2016; Chen et al, 2017) to serve as a control region. Critically, we defined this region from the same contrast as the mPFC ROI.…”

Hippocampal contributions to serial‐order memory

“…Such a mechanism, potentially based on the pattern completion processes of the hippocampus (Marr, 1971;Horner, Bisby, Bush, Lin, & Burgess, 2015), appears distinct from the pattern separating mechanisms of the hippocampus (Marr, 1971;McNaughton & Morris, 1987;O'Reilly & McClelland, 1994;Leutgeb, Leutgeb, Moser, & Moser, 2007;Yassa & Stark, 2011). Research on this process has shown that the hippocampus responds to highly similar or overlapping stimuli Bakker, Kirwan, Miller, & Stark, 2008;Duncan, Curtis, & Davachi, 2009;Long, Lee, & Kuhl, 2016) and creates distinct representations of such stimuli, potentially in an effort to minimize interference (Hulbert & Norman, 2015;Favila, Chanales, & Kuhl, 2016;Chanales, Oza, Favila, & Kuhl, 2017).…”

Memory integration constructs maps of space, time, and concepts

“…For instance, what are the boundary conditions that determine when representations of overlapping memories are integrated rather than separated, and how might we manipulate the formation of integrated codes of experience? While initial findings suggest that the strength of existing knowledge [18], the degree of memory reactivation during encoding [17], the magnitude of memory-based prediction errors [15], and task demands [84] all impact the likelihood of integration, more work is needed to understand the full complement of conditions that influence how we represent related episodes in memory. As noted above, different memory circuits (e.g., anterior and posterior hippocampus) may integrate information at different scales.…”

“…Medial PFC, which is thought to represent mental models that guide behavior [13, 14], may further bias hippocampal pattern completion to the most relevant prior knowledge [9]. Hippocampus then signals deviations between current events and reactivated memories, triggering memory updating [1, 15, 16]. Finally, new content is integrated with existing mental models via hippocampus—mPFC interactions [17–19].…”