Age-related functional changes in domain-specific medial temporal lobe pathways

Abstract

There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this reduction was equivalent in both domains. However, this was accompanied by significantly reduced domain-specific activity in PrC in older adults compared to what was observed in the young. Furthermore, this reduced domain-specific activity was associated to worse performance in object mnemonic discrimination in older adults. Taken together, we show the fine-grained functional organization of the MTL into domain-specific pathways for objects and scenes and their mnemonic discrimination and further provide evidence that aging might affect these pathways in a differential fashion. Future experiments will elucidate whether the 2 pathways are differentially affected in early stages of Alzheimer's disease in relation to amyloid or tau pathology.

Age differences in retrieval-related reinstatement reflect age-related dedifferentiation at encoding

“…This phenomenon -age-related neural dedifferentiation -has been conjectured to play a role in age-related cognitive decline [20][21][22] . Notably, lower specificity of neural responses to perceptual events has been reported to predict poorer subsequent memory for the events in both young and older adults [23][24][25] . These findings raise the possibility that the distinctiveness or fidelity with which the perceptual features of an event are neurally represented at the time of encoding (that is, its level of neural differentiation) are a determinant of the fidelity with which the features are reinstated at retrieval.…”

Neural differentiation is moderated by age in scene- but not face-selective cortical regions

“…Although subsequent studies have reported convergent findings, the data suggest that age-related dedifferentiation is not ubiquitous. For example, whereas reduced neural selectivity is frequently reported in scene-selective (Carp et al 2011;Voss et al, 2008;Zheng et al, 2018; and face-selective cortical regions Voss et al, 2008;Park et al, 2012), null findings for both of these classes of stimuli have also been reported (for scenes: Berron et al, 2018; for faces : Payer, et al, 2016). The evidence is also divergent for object and word stimuli.…”

Neural substrates of mnemonic discrimination: A whole‐brain fMRI investigation

“…Most studies have used a repetition sensitivity approach (see Kim, 2017 for a review), in which regions sensitive to repetition are first identified by comparing activity to repeated and novel stimuli. Within these repetition-sensitive regions, the neural signature of successful MD is observed as activity to lures that is different from repeated targets and similar to novel stimuli, which has been observed in hippocampus (Berron et al, 2018) and its subfields, specifically the dentate gyrus/cornu ammonis 3 (DG/CA3; Azab, Stark, & Stark, 2014;Bakker, Kirwan, Miller, & Stark, 2008;Kirwan & Stark, 2007;Lacy et al, 2011). In some cases, a lure-similarity approach has been used in conjunction with the repetition sensitivity approach by first identifying regions sensitive to repetition and then testing whether activity to lures that parametrically vary in their degree of similarity to targets is significantly different from repeated targets but not novel stimuli (Lacy et al, 2011).…”