Alexandra N Trelle , 1 , Valerie A Carr 1 , Scott A Guerin 1 , Monica K Thieu 1 , Manasi Jayakumar 1 , Wanjia Guo 1 , Ayesha Nadiadwala 1 , Nicole K Corso 1 , Madison P Hunt 1 , Celia P Litovsky 1 , Natalie J Tanner 1 , Gayle K Deutsch 2 , Jeffrey D Bernstein 1 , Marc B Harrison 1 , Anna M Khazenzon 1 , Jiefeng Jiang 1 , Sharon J Sha 2 , Carolyn A Fredericks 2 , Brian K Rutt 3 , Elizabeth C Mormino 2 , Geoffrey A Kerchner 2 , Anthony D Wagner , 1
29 May 2020
Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.