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

Neuroscience Training Program, University of Wisconsin-Madison Madison, WI, USA
Frontiers in Aging Neuroscience (Impact Factor: 4). 11/2012; 4:31. DOI: 10.3389/fnagi.2012.00031
Source: PubMed


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.

Download full-text


Available from: Joseph W Kemnitz
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RATIONALE: Problematic drug use is associated with difficulty in exerting self-control over behaviors, and this difficulty may be a consequence of atypical morphometric characteristics that are exhibited by drug-experienced individuals. The extent to which these structural abnormalities result from drug use or reflect neurobiological risk factors that predate drug use, however, is unknown. OBJECTIVES: The purpose of this study is to determine how methamphetamine affects corticostriatal structure and how drug-induced changes relate to alterations in inhibitory control. METHODS: Structural magnetic resonance images and positron emission tomography (PET) scans, assessing dopamine D2-like receptor and transporter availability, were acquired in monkeys trained to acquire, retain, and reverse three-choice visual discrimination problems before and after exposure to an escalating dose regimen of methamphetamine (or saline, as a control). Voxel-based morphometry was used to compare changes in corticostriatal gray matter between methamphetamine- and saline-exposed monkeys. The change in gray matter before and after the dosing regimen was compared to the change in the behavioral performance and in dopaminergic markers measured with PET. RESULTS: Methamphetamine exposure, compared to saline, increased gray matter within the right putamen. These changes were positively correlated with changes in performance of methamphetamine-exposed monkeys in the reversal phase, and were negatively correlated with alterations in D2-like receptor and DAT availability. CONCLUSIONS: The results provide the first evidence that exposure to a methamphetamine dosing regimen that resembles human use alters the structural integrity of the striatum and that gray-matter abnormalities detected in human methamphetamine users are due, at least in part, to the pharmacological effects of drug experience.
    Full-text · Article · Jun 2013 · Psychopharmacology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the splenium of corpus callosum in the white matter, followed by genu of the corpus callosum and the posterior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.
    No preview · Article · Nov 2013 · Neural Regeneration Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Classical studies in animal preparations suggest a strong role for spinal control of posture. In humans it is now established that the cerebral cortex contributes to postural control of unperturbed and perturbed standing. The age-related degeneration and accompanying functional changes in the brain, reported so far mainly in conjunction with simple manual motor tasks, may also affect the mechanisms that control complex motor tasks involving posture. This review outlines the age-related structural and functional changes at spinal and cortical levels and provides a mechanistic analysis of how such changes may be linked to the behaviorally manifest postural deficits in old adults. The emerging picture is that the age-related reorganization in motor control during voluntary tasks, characterized by differential modulation of spinal reflexes, greater cortical activation and cortical disinhibition, is also present during postural tasks. We discuss the possibility that this reorganization underlies the increased coactivation and dual task interference reported in elderly. Finally, we propose a model for future studies to unravel the structure-function-behavior relations in postural control and aging.
    Full-text · Article · Mar 2014 · Frontiers in Aging Neuroscience
Show more