Aging studies consistently show a relationship between decreased gray matter volume and decreased performance on working memory tasks. Few aging studies have investigated white matter changes in relation to functional brain changes during working memory tasks. Twenty-five younger and 25 older adults underwent anatomical magnetic resonance imaging (MRI) scans to measure gray matter volume, diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) as a measure of white matter integrity, and functional magnetic resonance imaging (fMRI) while performing a working memory task. Significant increases in activation (fMRI) were seen in the left dorsal and ventral lateral prefrontal cortex with increased working memory load and with increased age (older showing greater bilateral activation). Partial correlational analyses revealed that even after controlling for age, frontal FA correlated significantly with fMRI activation during performance on the working memory task. These findings highlight the importance of white matter integrity in working memory performance associated with normal aging. 1. Introduction Although there is some debate about the magnitude of age-related effects on gray matter (GM) and white matter (WM), it is generally accepted that both GM and WM volumes decline with advanced age [1–3]. Furthermore, declines in certain cognitive skills are also anticipated with advanced age [4]. Examinations of cortical volume and behavior suggest a relationship between volume loss and declines in cognitive skills. In particular, fluid-intelligence skills such as working memory, believed largely mediated by frontal-subcortical structures [4–8], appear particularly susceptible to age-related changes [9–12]. Multiple neuroimaging techniques have been utilized in isolation to examine the diffuse neural networks supporting complex behaviors, but only recently have multimodal imaging techniques such as standard structural imaging, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) been utilized concurrently to elucidate the relationship between volume loss, white matter integrity, and declines in cognitive functions associated with healthy aging. Standard magnetic resonance imaging (MRI) structural studies have historically examined structure-function relationships in aging with an emphasis on volumetric alterations. While debate exists regarding the relationship between volume and function, these prior studies have reported correlations between frontal gray matter (GM) density and behavioral measures of executive function
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