The Hippocampus and Neocortical Inhibitory Engrams Protect against Memory Interference.

Koolschijn RS
Emir UE
Pantelides AC
Nili H
Behrens TE
Barron HC

Our experiences of everyday life often overlap, yet we are able to selectively recall individual memories to guide our behaviour. Here, we investigated how overlapping memories are protected from interfering with each other. Using non-invasive brain imaging and stimulation in healthy human volunteers, we show that two brain areas, the hippocampus and cortex, play an important role in guarding memories.

Scientific Abstract

Our 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.

In this study we investigated the neural mechanisms that protect overlapping memories from interference. Using ultra-high field 7T Magnetic Resonance Imaging (MRI) in healthy human volunteers, we show that neocortical inhibition plays an important role. To modulate neocortical inhibition we applied non-invasive brain stimulation to lateral occipital cortex (left hand panel). Underneath the stimulating electrode, we observed a transient reduction in the concentration of cortical GABA, measured using ultra-high field 7T Magnetic Resonance Spectroscopy (MRS). In addition, this reduction in GABA predicted an increase in memory interference measured using representational functional MRI (fMRI) (right hand panel). These finding suggest that inhibition in the neocortex plays a key role in protecting overlapping memories from interference.
2019. Neuron 101:528-541
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