Examining the Relationship between Auditory Function and Cognitive Decline in Aging Macaque Monkeys

Abstract

Deficits in auditory function and cognition are hallmarks of normative aging. Recent evidence suggests that hearing-impaired individuals have greater risks of developing cognitive impairment and dementia compared to people with intact auditory function. Little is known regarding the neurobiological bases underlying these associations, partially because they are not well established in animal models of brain aging. The experiments and analyses contained within this thesis were designed to provide insight into the relationship between auditory, visual, and cognitive function. First, two distinct colonies of different macaque species completed a battery of behavioral tests designed to probe frontal and temporal lobe-dependent cognitive functions. Auditory and visual system function was then tested in a subset of the same animals using auditory brainstem response and visual evoked potential electrophysiological recordings. Finally, diffusion magnetic resonance images were acquired from the same subset of animals used in the assessment of auditory and visual system function. Probabilistic tractography methods were used to evaluate the microstructural condition of thalamocortical and corticocortical white matter projection systems associated with sensory function and cognition. Aged monkeys performed more poorly in the cognitive battery, although they were impaired only on certain cognitive functions assessed in the battery, but not others. These same monkeys showed evidence of auditory temporal processing deficits compared with adults, despite auditory thresholds and visual system function not being different between the two age groups. Estimates of auditory temporal processing were correlated with composite cognitive scores, and these associations with behavior were selectively observed with tasks dependent on temporal lobe brain structures. Auditory thresholds and visual system function, on the other hand, were not associated with higher cognitive function. Results from the diffusion tensor imaging experiments showed striking specificity with respect to the relationships between fractional anisotropy in distinct white matter tracts and brain function. Together, the experiments contained within this thesis demonstrate for the first time significant and selective relationships between auditory brainstem responses, thalamocortical and corticocortical connectivity as measured by diffusion MRI, and higher-order cognitive ability. These measures obtained from nonhuman primates should provide deeper mechanistic insights into sensory contributions to cognitive decline in older humans.