Aging, implicit sequence learning, and white matter integrity

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Thesis (Ph.D.)--Georgetown University, 2009.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Cognitive neuroscience of aging research investigates neural mechanisms associated with cognitive stability and decline in older versus younger adults. This field has been dominated by neuroimaging techniques that emphasize brain function over structure, gray over white matter, and isolated brain regions over neural networks. Furthermore, the scope of the field has been limited by a focus on explicit cognitive processes (e.g., working memory, executive functions). To broaden our current understanding, this dissertation examined relationships among healthy aging, implicit sequence learning, and white matter integrity. In the first study, diffusion tensor imaging (DTI), which measures diffusion of molecular water, was used to characterize age-related differences in multiple measures of white matter integrity. Results revealed age-related declines in fractional anisotropy (FA), a measure of diffusion coherence, with the magnitude of these differences being largest in frontal white matter. Additional measures of diffusion parallel (axial diffusivity, AD) and perpendicular (radial diffusivity, RD) to the primary diffusion direction revealed region-specific patterns of age group differences that may reflect differential aging of microstructural (e.g., degree of myelination) and macrostructural (e.g., coherence of fiber orientation) properties of white matter. In the second study, white matter integrity correlates of implicit sequence learning were examined in younger and healthy older adults. Implicit sequence learning was assessed with the alternating serial reaction time task (ASRT). Significant learning was seen in both age groups (i.e., faster and more accurate responses to frequent, pattern-related events compared to intervening, random events), with an age-related decline in the late learning stage. In line with functional imaging studies that identified subcortical (e.g., caudate, hippocampus) and cortical (e.g., dorsolateral prefrontal cortex, DLPFC) correlates of implicit sequence learning, integrity of caudate-DLPFC and hippocampus-DLPFC tracts was related to sequence learning in the ASRT, and these relationships did not differ with age group. Additionally, age-related differences in caudate-DLPFC tract integrity mediated age-related differences in sequence learning. Taken together, results of these studies support the theory of white matter disconnection, which proposes that age-related declines in white matter integrity may explain age-related cognitive declines, as communication between distributed cortical regions involved in the task is disrupted.
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