The human hippocampal-entorhinal network is well-defined in terms of its meso-scale circuitry enabling the mnemonic discrimination of similar memories (pattern separation) and the associative recall of past events (pattern completion). Its connectivity with medial temporal and visual regions shows a parcellation into an anterior-lateral pathway that preferentially processes objects and a posterior-medial pathway that preferentially processes scenes. In healthy older adults, the object pathway, due to its anatomical overlap with the commonly found early stage accumulation of tau pathology, is more likely to be functionally compromised. In this study, we aim to investigate the meso-scale underpinnings of neural resources underlying pattern separation and pattern completion in older adults and SuperAgers with quantified hidden pathology. To that end, we will utilise mobile app-based object- and scene-based mnemonic discrimination (pattern separation) training over 6 months. We will i) determine the upper limits of cognitive improvement and plasticity using behavioural, structural and functional measures, ii) quantify transfer and trade-offs at several levels (across different stimulus types within a modality, across modalities, across processes (pattern separation and completion), and iii) determine how hidden pathology affects plasticity and transfer.

Conceptual framework of the project:

We aim to in­vestigate the meso-scale underpinnings of neural  resources underlying pattern separation and pattern completion in young and older adults and SuperAgers with quantified hidden pathology. We will quantify transfer and transfer distance within defined neu­rocognitive circuits. (DG: dentate gyrus; Subic: Subi­culum; alEC/pmEC: anterior lateral and posterior medial entorhinal cortex; PRC: perirhinal cortex; tERC: transentorhinal cortex; PHC: parahippocampal cortex)