The medial temporal lobe (MTL) supports the formation and retrieval of long-term declarative memories, or memories for facts and every-day events. One limitation on this type of memory is the highly overlapping nature of common episodes. Within cognitive psychology, it is widely accepted that interference between information learned at different times is a major limitation on memory. In spite of several decades of intense research in the fields of interference theory and the neurobiological underpinnings of declarative memory, there is little direct evidence bearing on how the MTL resolves this interference to form accurate memories of every-day facts and events. Computational models of MTL function have proposed a mechanism whereby the MTL, specifically the hippocampus, performs pattern separation, whereby overlapping representations are made less similar. Later stages of the hippocampus are thought to support pattern completion, the process through which noisy or degraded cues are able to reactivate a previously stored representation. These processes are thought to be complementary and may occur within the same brain structure. This research uses converging methods to investigate pattern separation and pattern completion processes in the MTL. First, we used high-resolution fMRI scanning and advanced cross-participant alignment techniques to resolve activity at the level of hippocampal subregions. Using these techniques we conducted a series of experiments that varied pattern separation demands in a modified continuous recognition task with both faces and objects. Consistent with computational models' predictions, there was increased activity in several MTL regions for both stimulus types on trials with increased pattern separation demands. Finally, we conducted a parallel experiment with amnesic patients with damage thought to be limited to the hippocampus. Behavioral performance by the amnesic patients indicate that pattern separation processes are impaired relative to controls for object stimuli, though this effect is reduced when considering the face stimuli. Taken together, these results generally support the predictions of the computational models that pattern separation processes are dependent upon the MTL and the hippocampus in particular.
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