Hippocampal subfield bold signal and mnemonic discrimination task performance in cognitive aging

Abstract

Background Cognitive aging is associated with impaired episodic memory formation (Small et al., 1999), which requires the neurocomputational process of pattern separation to disambiguate similar stimulus input. Pattern separation relies on the dentate gyrus (DG) (Yassa & Stark, 2011), a hippocampal subfield that is susceptible to age‐related change (Small et al., 2011). Cognitive aging is also associated with impaired performance on putative measures of behavioral pattern separation (Yassa et al., 2010), called mnemonic discrimination tasks in humans. Prior work using high‐resolution fMRI suggests that age‐related impairments in mnemonic discrimination are linked to aberrant activation patterns in the DG/CA3 (Yassa et al., 2010). Whereas aging is associated with impaired DG integrity and mnemonic discrimination ability, cardiorespiratory fitness is associated with enhanced DG integrity and improved mnemonic discrimination ability. Given that cardiorespiratory fitness has been positively linked to DG/CA3 integrity in young adults (Nauer et al., 2019), it is conceivable that in older adults, cardiorespiratory fitness will modulate age‐related changes in DG/CA3 activation, which in turn, will dampen age‐related impairments in mnemonic discrimination. Methods 18 older adults (55‐85 years) and 18 young adults (18‐35 years) underwent a submaximal treadmill test to estimate cardiorespiratory fitness and high‐resolution fMRI to examine hippocampal subfield BOLD signal during encoding and retrieval of a mnemonic discrimination task (MDT). Results In older adults, we found increased right DG/CA3 BOLD signal in incorrect mnemonic discrimination trials contrasted with correct mnemonic discrimination trials, specifically during stimulus retrieval. Additionally, in both young and older adults, we found that right DG/CA3 BOLD signal in the mnemonic discrimination fMRI contrast during stimulus encoding marginally significantly predicted MDT corrected accuracy. Finally, in both young and older adults, fitness significantly negatively predicted left DG/CA3 BOLD signal in the mnemonic discrimination fMRI contrast during stimulus retrieval. Conclusions These results suggest that DG/CA3 BOLD signal relates to performance on a MDT designed to tax pattern separation, and that cardiorespiratory fitness modulates BOLD signal in these subregions. Altogether, these results suggest a link between fitness, DG/CA3 functional integrity, and mnemonic discrimination that may be critical to understanding how to dampen age‐related impairments in episodic memory.