Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys

Abstract

The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction (CR), the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter (GM) volume and fractional anisotropy (FA) and mean diffusivity (MD), respectively. We tested the extent to which brain health indexed by GM volume, FA, and MD were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor response times would be correlated with higher volume, higher FA, and lower MD in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower GM volume in frontal and parietal cortices, and lower FA in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased FA in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in CR animals compared to controls, indicating a potential protective effect of the dietary intervention.

Does the brain shrink as the waist expands?

“…CR also considerably reduced stress reactivity (Willette et al, 2012c), where aged monkeys on CR showed less corresponding atrophy per point increase in a z-scored stress factor in many WM tracts, as well as similar amelioration in GM volume or microstructural density for orbital PFC and hippocampus. Finally, CR monkeys had many fewer perseverative errors and achieved task criterion in fewer trials for the most complicated Wisconsin Card Sort Test set-shifting tasks (Sridharan et al, 2012). Fewer errors corresponded to more GM in orbital PFC, an area where CR monkeys have more volume.…”

Methamphetamine-induced increases in putamen gray matter associate with inhibitory control

“…One type of inhibitory control involves the ability to modify behavior adaptively when contingencies change, and lesions to the prefrontal cortex impair this ability in humans and animals (Dias et al, 1996; Fellows and Farah, 2003; Rygula et al, 2010), suggesting that the prefrontal cortex is critical for the maintenance of flexible, goal-directed behaviors (Clarke et al, 2004). Indeed, individual differences in gray-matter volume within the prefrontal cortex are related to performance on tasks of inhibitory control in healthy humans and monkeys (Haldane et al, 2008; Tabibnia et al, 2011; Sridharan et al, 2012). The dorsal striatum also plays a critical role in inhibitory control processes (Bellebaum et al, 2008; Castane et al, 2010; Clarke et al, 2011), suggesting that inhibitory control relies on an integrated network of nuclei within the corticostriatal system.…”

Nutrition, metabolism, and targeting aging in nonhuman primates

“…Brain aging is also delayed by CR. MRI based studies of brain volume reveal preservation of white matter and neuronal volume, and markers of inflammation are significantly lower 13,37,38 . The caudate nucleus and putamen regions are vulnerable to age-associated atrophy and are protected by CR 13,39 .…”