Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking
Open accessAbstract
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.
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Early tractography studies found consistent aging-related changes in specific fiber bundles, including decreased FA, increased MD, and decreased tract volume.
“Early tractography studies usually estimated the aging effect on specific fiber bundles such as the corpus callosum (Sullivan et al., 2006), uncinate fasciculus (Hasan et al., 2009a), and fornix (Stadlbauer et al., 2008b), which show consistent changes including decreased FA, increased MD and decreased tract volume.”
From Quantitative mapping of the brain’s structural connectivity using diffusion MRI tractography: A review (2022) · cites this paper as Sullivan et al., 2006
The Results report lower FA and higher ADC in older adults’ callosal fiber bundles; higher ADC supports the cited increase in mean diffusivity. They also report fewer identified fibers, but do not report decreased tract volume. The Discussion (p. 1035) says overall corpus callosum size did not differ by age. (LLM, conf=0.88)
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- Authors
- Sullivan, E. V., Adalsteinsson, E., & Pfefferbaum, A.
- Affiliations
- Stanford Medicine (US)
- SRI International (US)
- Corresponding author
- Sullivan, Edith V.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-10-05
- Volume
- 16
- Issue
- 7
- Pages
- 1030-1039
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2135956445
- Cited by
- 280
- References
- 8
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 9 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 10 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 15 · 2013: 19 · 2012: 6
- FWCI
- 23.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Cerebral Cortex (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA-05965, R01AA012388, AA12388, AA10723)
- National Institute on Aging (R01AG017919, AG17919)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- corpus callosum, aging, white matter microstructure, fractional anisotropy, apparent diffusion coefficient, tractography, diffusion tensor imaging, interhemispheric connectivity, Stroop task, cognitive aging
- MeSH terms
- Adult, Age Factors, Aged, Aging, Corpus Callosum, Female, Humans, Male, Nerve Fibers, Neural Pathways, Diffusion Magnetic Resonance Imaging
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