Recognition Memory is Associated with Distinct Patterns of Regional Gray Matter Volumes in Young and Aged Monkeys

Abstract

Cognitive aging varies tremendously across individuals and is often accompanied by regionally specific reductions in gray matter (GM) volume, even in the absence of disease. Rhesus monkeys provide a primate model unconfounded by advanced neurodegenerative disease, and the current study used a recognition memory test (delayed non-matching to sample; DNMS) in conjunction with structural imaging and voxel-based morphometry (VBM) to characterize age-related differences in GM volume and brain-behavior relationships. Consistent with expectations from a long history of neuropsychological research, DNMS performance in young animals prominently correlated with the volume of multiple structures in the medial temporal lobe memory system. Less anticipated correlations were also observed in the cingulate and cerebellum. In aged monkeys, significant volumetric correlations with DNMS performance were largely restricted to the prefrontal cortex and striatum. Importantly, interaction effects in an omnibus analysis directly confirmed that the associations between volume and task performance in the MTL and prefrontal cortex are age-dependent. These results demonstrate that the regional distribution of GM volumes coupled with DNMS performance changes across the lifespan, consistent with the perspective that the aged primate brain retains a substantial capacity for structural reorganization.

Keywords: cerebellum; memory; neurocognitive aging; rhesus monkey; voxel-based morphometry.

Figure 1

Performance in the delayed nonmatching to sample (DNMS) task. (A) Task schematic (see Methods for details; ITI, intertrial interval). (+, baited; −, unbaited). (B) Mean number of trials to reach criterion (90% correct) with a 10 sec delay interval. (C) Average percent correct (±S.E.) in young (red) and aged (blue) monkeys at the 15, 30, 60, 120, and 600 sec delays. (D) Average percent correct averaged across delays (composite score).

Figure 2

Distribution of gray matter volumes significantly correlated with (A) DNMS trials-to-criterion and (B) DNMS composite score in the young group. Positively correlated clusters are plotted in red, negatively correlating clusters in blue.

Figure 3

Distribution of gray matter volumes correlated with (A) DNMS trials-to-criterion and (B) DNMS composite score in aged monkeys. Positively correlated clusters are in red and negatively correlated clusters in blue.

Figure 4

GM volumes demonstrating an interaction between age and (A) DNMS acquisition (trials to criterion) and (B) DNMS composite score (i.e., accuracy across delays). The interaction threshold was P < 0.05, with an extent threshold of k = 100 voxels (voxel size = 0.3 mm³).