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

Abstract

2Age-related episodic memory decline is characterized by striking heterogeneity across 36 individuals. Hippocampal pattern completion is a fundamental process supporting episodic 37 memory. Yet, the degree to which this mechanism is impaired with age, and contributes to 38 variability in episodic memory, remains unclear. We combine univariate and multivariate 39 analyses of fMRI data from a large cohort of cognitively normal older adults (N=100; 60-82 40 yrs) to measure hippocampal activity and cortical reinstatement during retrieval of trial-41 unique associations. Trial-wise analyses revealed that hippocampal activity predicted 42 cortical reinstatement strength, and these two metrics of pattern completion independently 43 predicted retrieval success. However, increased age weakened cortical reinstatement and 44 its relationship to memory behaviour. Critically, individual differences in the strength of 45 hippocampal activity and cortical reinstatement explained unique variance in performance 46 across multiple assays of episodic memory. These results indicate that fMRI indices of 47 hippocampal pattern completion explain within-and across-individual memory variability in 48 older adults. 49 50 51 52 53 54 55 56 57 3 Episodic memory -in particular the ability to form and retrieve associations between multiple 58 event elements that comprise past experiences -declines with age (1-3). Retrieval of an 59 episodic memory relies critically on hippocampal-dependent pattern completion, which 60 entails reactivation of a stored memory trace by the hippocampus in response to a partial 61 cue, leading to replay of cortical activity patterns that were present at the time of memory 62 encoding (4-7). Given observed links between in vivo measures of pattern completion and 63 episodic remembering (8-10), and evidence of altered hippocampal function with age (11-64 12), changes in hippocampal pattern completion may play an important role in explaining 65 age-related impairments in episodic memory. While a leading hypothesis, the degree to 66 which the integrity of pattern completion can explain (a) trial-to-trial differences in episodic 67 remembering within older adults and (b) differences in memory performance between older 68 individuals remain underspecified. 69Functional MRI (fMRI) studies in younger adults suggest that hippocampal pattern 70 completion is associated with at least two key neural markers: (a) an increase in 71 hippocampal univariate activity (13-15) and (b) cortical reinstatement of content-specific 72 activity patterns present during encoding (16-18). Multivariate pattern analyses --machine 73 learning classification (19) and pattern similarity (20) --reveal evidence for cortical 74 reinstatement of categorical event features (10, 21-22) and event-specific details (23-25) 75 during successful recollection. Moreover, hippocampal and cortical metrics of pattern 76 completion covary, such that trial-wise fluctuations in hippocampal univariate retrieval 77 activity predict the strength of cortical r...

Rodent mnemonic similarity task performance requires the prefrontal cortex

“…The ability to discriminate between stimuli that share features declines in advanced age. Specifically, older adults are impaired at distinguishing similar lures from previously seen target stimuli relative to young adults, as assessed by the "mnemonic similarity task" (Camfield, Fontana, Wesnes, Mills, & Croft, 2018;Holden, Toner, Pirogovsky, Kirwan, & Gilbert, 2013;Huffman & Stark, 2017;Reagh et al, 2016;Stark, Kirwan, & Stark, 2019;Stark, Stevenson, Wu, Rutledge, & Stark, 2015;Stark, Yassa, Lacy, & Stark, 2013;Toner, Pirogovsky, Kirwan, & Gilbert, 2009;Trelle et al, 2020;Trelle, Henson, Green, & Simons, 2017). Mnemonic similarity task deficits in advanced age have been reported for older adults who are able to perform on par with young adults in standardized neuropsychological test batteries Reagh et al, 2016;Stark et al, 2013).…”

The Retrieval-related Anterior shift is Moderated by Age and Correlates with Memory Performance

“…The strength and specificity of cortical reinstatement have been reported to be reduced in older age (Bowman et al, 2019; St-Laurent & Buchsbaum, 2019; Folville et al, 2020; Hill et al, 2021, but see Wang et al, 2016; Thakral et al, 2017). The strength of cortical reinstatement has also been reported to predict the likelihood of successful retrieval, leading to the proposal that cortical reinstatement indexes the amount of retrieved episodic content (e.g., Johnson et al, 2009; Trelle et al, 2020; Hill et al, 2021). Thus, age-related reductions in the strength of cortical reinstatement may reflect older adults’ tendency to retrieve less detailed episodic information than their younger counterparts.…”

Rodent mnemonic similarity task performance requires the prefrontal cortex

“…Specifically, older adults are impaired at distinguishing similar lures from previously seen target stimuli relative to young adults, as assessed by the 'mnemonic similarity task' (Toner et al, 2009;Holden et al, 2013;Stark et al, 2013Stark et al, , 2015Stark et al, , 2019Reagh et al, 2016;Huffman and Stark, 2017;Trelle et al, 2017Trelle et al, , 2020Camfield et al, 2018). Mnemonic similarity task deficits in advanced age have been reported for older adults who are able to perform on par with young adults in standardized neuropsychological test batteries (Stark et al, 2013;Reagh et al, , 2016.…”