Pattern Separation beyond the Hippocampus: A High-Resolution Whole-Brain Investigation of Mnemonic Discrimination in Healthy Adults

Abstract
Episodic memory depends on the computational process of pattern separation in order to establish distinct memory representations of similar episodes. Studies of pattern separation in humans rely on mnemonic discrimination tasks, which have been shown to tax hippocampal‐dependent pattern separation. Although previous neuroimaging research has focused on hippocampal processing, little is known about how other brain regions, known to be involved in recognition memory performance, are involved in mnemonic discrimination tasks. Conversely, neuroimaging studies of pattern separation with whole‐brain coverage lack spatial resolution to localize activation to hippocampal subfields. In this study, 48 healthy young adult participants underwent whole‐brain high‐resolution functional MRI (fMRI) scanning while completing a mnemonic discrimination task. A priori region‐of‐interest analyses revealed activation patterns consistent with pattern separation in distinct hippocampal subregions, particularly in the subiculum. Connectivity analyses revealed a network of cortical regions consistent with the memory retrieval network where fMRI activation was correlated with hippocampal activation. An exploratory whole‐brain analysis revealed widespread activation differentially associated with performance of the mnemonic discrimination task. Taken together, these results suggest that a network of brain regions contribute to mnemonic discrimination performance, with the hippocampus and parahippocampal cortex as a hub in the network displaying clear signals consistent with pattern separation and regions such as the dorsal medial prefrontal cortex particularly important for successful lure discrimination.