Differential effects of aging and epilepsy in discriminating and reactivating memories

Abstract

How are memories stored and subsequently retrieved? Pattern separation and pattern completion are distinct neurocognitive hippocampal processes that are thought to facilitate encoding and retrieval of memories. However, the way in which these operations affect the quality of memory remains unclear and there is currently no single behavioural task in humans to measure both mechanisms simultaneously. Here, we describe a novel paradigm which provides a distinct measure of each process and apply it to people with focal epilepsy, a condition associated with hippocampal dysfunction, comparing them with healthy young and older participants. Pattern separation and pattern completion were observed in healthy younger individuals. A specific deficit in pattern completion was identified in people with focal epilepsy, while the healthy older cohort showed degraded ability to perform pattern separation. To understand the underlying mechanisms, we simulated human performance using an auto-associative neural network. Modelling indicated that disruption in different populations of neurons could explain the observed memory profiles. These findings show that pattern separation and pattern completion are distinct processes that can be measured from a single behavioural task and are differentially affected by focal epilepsy and aging.