Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults

Alexandra N Trelle ,Manasi Jayakumar,Ayesha Nadiadwala,Jiefeng Jiang,Wanjia Guo,Monica K Thieu,Madison P Hunt,Carolyn A Fredericks ,Valerie A Carr ,Geoffrey A Kerchner ,Elizabeth C Mormino ,Natalie Tanner ,Nicole K Corso ,Marc Harrison ,Celia Litovsky ,Anna M Khazenzon ,Scott A Guerin ,Gayle K Deutsch ,Jeffrey D Bernstein ,Sharon J Sha ,Brian K Rutt ,Anthony D Wagner

doi:10.7554/elife.55335

Alexandra N Trelle , Manasi Jayakumar + Show 20 more

Open Access

https://doi.org/10.7554/elife.55335

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Journal: eLife	Publication Date: May 29, 2020
Citations: 40	License type: CC BY 4.0

Affiliation: Stanford University

Abstract

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.

Highlights

Episodic memory – in particular the ability to form and retrieve associations between multiple event elements that comprise past experiences – declines with age (Spencer and Raz, 1995; Ronnlund et al, 2005; Old and Naveh-Benjamin, 2008)
Consistent with predictions, the results revealed that the relationship between hippocampal activity and the probability of an associative hit was partially mediated through category-level cortical reinstatement in ventral temporal cortex (VTC) and angular gyrus (ANG)
Using univariate and multivariate Functional MRI (fMRI), the current investigation characterizes the integrity of hippocampal pattern completion during associative retrieval in a large cohort of putatively healthy older adults

Summary

Introduction

Episodic memory – in particular the ability to form and retrieve associations between multiple event elements that comprise past experiences – declines with age (Spencer and Raz, 1995; Ronnlund et al, 2005; Old and Naveh-Benjamin, 2008). Retrieval of an episodic memory relies critically on hippocampal-dependent pattern completion, which entails reactivation of a stored memory trace by the hippocampus in response to a partial cue, leading to replay of cortical activity patterns that were present at the time of memory encoding (Marr, 1971; McClelland et al, 1995; Tanaka et al, 2014; Staresina et al, 2019). The degree to which the integrity of pattern completion can explain (a) trial-to-trial differences in episodic remembering within older adults and (b) differences in memory performance between older individuals remain underspecified

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