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The corpus callosum, the principal white matter structure enabling interhemispheric information transfer, is heterogeneous in its microstructural composition, heterotopic in its anteroposterior cortical connectivity, and differentially susceptible to aging. In vivo characterization of callosal features is possible with diffusion tensor imaging (DTI), a magnetic resonance imaging method sensitive to the detection of white matter's linear structure. We implemented a quantitative fiber tracking approach to examine age-related variation in regional microstructural characteristics [fractional anisotropy (FA) and apparent diffusion coefficient (ADC)] of callosal fibers in 10 younger (29 +/- 5 years) and 10 older (72 +/- 5 years) healthy adults. Fiber tracking was performed on 2.5 mm isotropic voxels collected at 3 T. Fiber targets comprised the midsagittal corpus callosum, divided into six regions based on known callosal anatomical projections. FA and ADC for each voxel of each fiber identified were determined; lower FA and higher ADC reflect degraded microstructural tissue integrity. Older subjects had lower FA (P < 0.002), higher ADC (P < 0.006), and fewer (P < 0.005) fibers than younger subjects. Group x region interactions indicated disproportionately lower FA (P = 0.0001) and higher ADC (P < 0.006) in the older than younger group in frontal fiber bundles relative to posterior bundles. As a test of the functional significance of the fiber bundle metrics, the older subjects were administered the Stroop Task, which showed significant correlations between regional fiber bundle integrity and performance. These results validate this quantitative fiber tracking approach and confirm the selective vulnerability of frontal white matter systems to normal aging, likely substrates of age-related declines in cognitive processes dependent on prefrontal circuitry integrity.

Normal aging and chronic alcoholism result in disruption of brain white matter microstructure that does not typically cause complete lesions but may underlie degradation of functions requiring interhemispheric information transfer. We examined whether the microstructural integrity of the corpus callosum assessed with diffusion tensor imaging (DTI) would relate to interhemispheric processing speed. DTI yields estimates of fractional anisotropy (FA), a measure of orientation and intravoxel coherence of water diffusion usually in white matter fibers, and diffusivity ( ), a measure of the amount of intracellular and extracellular fluid diffusion. We tested the hypothesis that FA and would be correlated with (i) the crossed--uncrossed difference (CUD), testing visuomotor interhemispheric transfer; and (ii) the redundant targets effect (RTE), testing parallel processing of visual information presented to each cerebral hemisphere. FA was lower and higher in alcoholics than in controls. In controls but not alcoholics, large CUDs correlated with low FA and high in total corpus callosum and regionally in the genu and splenium. In alcoholics but not controls, small RTEs, elicited with equiluminant stimuli, correlated with low FA in genu and splenium and high in the callosal body. The results provide in vivo evidence for disruption of corpus callosum microstructure in normal aging and alcoholism that has functional ramifications for efficiency in interhemispheric processing.

Brain structure changes in size with normal aging, but the rate at which different structures change is controversial. We used magnetic resonance imaging (MRI) performed twice, 4 years apart, to compare rates of age-related size change of the corpus callosum, which has been inconsistently observed to thin with age, with change in the lateral ventricles, which are well established to enlarge. Subjects were 215 community dwelling, elderly men (70-82 years old at initial MRI), who were participants in a longitudinal study of cardiovascular risk factors. Percent change in size was significant for both the callosal and ventricular measures, but annual rate of ventricular expansion (2.9%) was significantly greater than annual rate of callosal thinning (-0.9%). Callosal regions showed statistically equivalent rates of shrinkage; ventricular dilatation was symmetrical. Neither callosal and ventricular rates of change correlated with each other (r = 0.01), nor did genu and splenium rates of change correlate with each other (r = 0.05). Tests of speeded processing were administered contemporaneously with both MRIs to examine functional ramifications of observed brain changes. Decline in the Mini-Mental State Examination was related to thinning of the splenium, and decline in Stroop test word reading was selectively related to thinning of the callosal body. These longitudinal data support the contentions that differential rates of change occur in different brain regions in normal aging, age-related callosal thinning contributes to functional declines, and rate of change in one region can be independent of rate of change in another region, even within a brain structure.