Age-Related Regional Network of Magnetic Resonance Imaging Gray Matter in the Rhesus Macaque

Abstract

Human structural neuroimaging studies have supported the preferential effects of healthy aging on frontal cortex, but reductions in other brain regions have also been observed. We investigated the regional network pattern of gray matter using magnetic resonance imaging (MRI) in young adult and old rhesus macaques (RMs) to evaluate age effects throughout the brain in a nonhuman primate model of healthy aging in which the full complement of Alzheimer's disease (AD) pathology does not occur. Volumetric T1 MRI scans were spatially normalized and segmented for gray matter using statistical parametric mapping (SPM2) voxel-based morphometry. Multivariate network analysis using the scaled subprofile model identified a linear combination of two gray matter patterns that distinguished the young from old RMs. The combined pattern included reductions in bilateral dorsolateral and ventrolateral prefrontal and orbitofrontal and superior temporal sulcal regions with areas of relative preservation in vicinities of the cerebellum, globus pallidus, visual cortex, and parietal cortex in old compared with young RMs. Higher expression of this age-related gray matter pattern was associated with poorer performance in working memory. In the RM model of healthy aging, the major regionally distributed effects of advanced age on the brain involve reductions in prefrontal regions and in the vicinity of the superior temporal sulcus. The age-related differences in gray matter reflect the effects of healthy aging that cannot be attributed to AD pathology, providing support for the targeted effects of aging on the integrity of frontal lobe regions and selective temporal lobe areas and their associated cognitive functions.

Orbitofrontal Cortex Volume in Area 11/13 Predicts Reward Devaluation, But Not Reversal Learning Performance, in Young and Aged Monkeys

“…Together, these data support a view that aging disrupts the function of the OFC (Schoenbaum et al, 2002;Cook et al, 2007) to support reward-guided behavior (Rudebeck et al, 2013b). This is also consistent with the observed age-dependent reduction in OFC gray matter volume that was observed in this cohort of animals and has been reported for humans (Convit et al, 2001;Resnick et al, 2007;Squarzoni et al, 2012) and other primates (Alexander et al, 2008).…”

“…Moreover, as described in previous studies (Voytko, 1999), the aged monkeys had a significant deficit in object reversal learning that could be attributed to their increased tendency to make perseverative errors (Albert et al, 1990;Moore et al, 2003;Rhodes, 2004). Interestingly, however, area 11/13 volume was associated with reward devaluation but not reversal learning performance.…”

Aging of the cerebral cortex differs between humans and chimpanzees

“…Although functionally significant alterations in cortical morphology during aging are known to occur in nonhuman primates because of microstructural changes in dendritic systems and synaptic densities (8,20,21), our current results indicate that humans are unique in the severity of structural degeneration of neocortical gray matter in elderly individuals, being so extensive and widespread that it is detectable as overt volume loss.…”

“…In contrast to humans, however, such dramatic age-related reduction in the size of these structures has not been observed in macaque monkeys based on manual volume tracing studies (17)(18)(19). More subtle volume loss of prefrontal cortex subregions (i.e., dorsolateral prefrontal cortex and anterior cingulate cortex) in macaques, however, has been reported (20,21). Because macaque monkeys and humans are separated by ∼30 million y of independent evolution, these species differences raise the question of whether the more pronounced effects of neurodegenerative changes in human aging are unique and potentially related to an extended lifespan.…”

Age-related effects in the neocortical organization of chimpanzees: Gray and white matter volume, cortical thickness, and gyrification

“…At the present time there are only two reports of the existence of neurofibrillary tangles in great apes including one in a 41 year old chimpanzee (Rosen et al, 2008), and more recently in a sample of lowland gorillas (Perez et al, 2013). Finally, there is also evidence that apes and monkeys show age-related volumetric decline in the striatum and modest reductions in total brain volume (Alexander et al, 2008; Herndon et al, 1999; Matochik et al, 2000; Rapp and Amaral, 1992). …”