Abstract
SummaryOur experiences often overlap with each other, yet we are able to selectively recall individual memories to guide decisions and future actions. The neural mechanisms that support such precise memory recall remain unclear. Here, using ultra-high field 7T MRI we reveal two distinct mechanisms that protect memories from interference. The first mechanism involves the hippocampus, where the blood-oxygen-level-dependent (BOLD) signal predicts behavioral measures of memory interference, and representations of context-dependent memories are pattern separated according to their relational overlap. The second mechanism involves neocortical inhibition. When we reduce the concentration of neocortical GABA using trans-cranial direct current stimulation (tDCS), neocortical memory interference increases in proportion to the reduction in GABA, which in turn predicts behavioral performance. These findings suggest that memory interference is mediated by both the hippocampus and neocortex, where the hippocampus separates overlapping but context-dependent memories using relational information, and neocortical inhibition prevents unwanted co-activation between overlapping memories.
Highlights
Our decisions and actions are often guided by past experiences that overlap with each other in content or sensory information
The drop in neocortical GABA induced by brain stimulation predicted an increase in neocortical memory interference, which in turn predicted deficits in behavioral performance. Together these results suggest that memory interference is mediated by two distinct mechanisms: a hippocampal mechanism in which contextual representations are organized according to behaviorally relevant relationships, and a neocortical mechanism in which inhibition protects overlapping memories from unwanted co-activation
Participants who showed greater cross-stimulus suppression during periods of EI imbalance made more errors. These results suggest that a reduction in neocortical GABAergic tone leads to an increase in neural memory interference, which manifests in behavior as an increase in memory errors
Summary
Our decisions and actions are often guided by past experiences that overlap with each other in content or sensory information. At the neural level, anticorrelated firing patterns for opposing contexts can be observed in the hippocampal output regions (Butterly et al, 2012; McKenzie et al, 2014) These contextual representations likely reflect the natural consequence of pattern separation, a competitive mechanism supported by the architecture of the hippocampus that orthogonalizes representations of overlapping memories (Yassa and Stark, 2011). It remains unclear how information within contextual representations is organized. Elements that have different relational positions across two overlapping but context-dependent memories are maximally separated
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