Lifespan trajectories of corpus callosum: Regional differences and cognitive relevance

Abstract

Objectives: The thesis revisit the topic of hemispheric interconnectivity and structural development of the corpus callosum by addressing the issue of proportionality. As the proportionality of callosal growth and decline compared to other brain size measures have been greatly disregarded in the literature, the study aims to give a descriptive account of relative callosal thickness across the lifespan. In addition, the study examines regional differences in lifespan trajectories and possible cognitive consequences of changes in relative callosal thickness. Methods and participants: The study has a mixed longitudinal and cross-sectional design with a sample consisting of 1867 observations from 1014 healthy participants (age range from 4 to 93 years). Data was collected from three studies coordinated by the Lifespan Changes in Brain and Cognition (LCBC) research center. A measure of callosal thickness was determined on the midsagittal surface of T1-weighted magnetic resonance (MR) images. Relative callosal thickness was estimated by relating 60 callosal thickness segments to forebrain volume. Age trajectories were identified by a cluster analysis and then fitted using generalized additive mixed models (GAMM). Cognitive measures were collected from raw scores on Matrix Reasoning and Vocabulary subtests from either WPPSI/WASI. Finally, a mediation analysis was completed with the identified age trajectories, change in age and cognitive measures. Results: The study demonstrates an over-proportional increase of relative callosal thickness in the first three decades of life, mirrored by an over-proportional decline after 60 years of age. Regional specific lifespan trajectories were identified from a five-cluster solution. These trajectories differ substantially on the anterior to posterior division with the most prominent difference being an accentuated growth during development and a ten-year delay of decline in relative callosal thickness for posterior regions (splenium). Significant mediation effects were found for two of the mediation analyses demonstrating that the ventral splenium significantly mediates age-related changes in cognitive performance on both subtests Matrix Reasoning and Vocabulary. Conclusion: The findings does not only confirm an inverted-u-shaped trajectory of callosal size across the lifespan but demonstrate that this growth and decline in callosal size is over-proportional to what could be expected by change in other brain sizes. It also found that increased relative callosal thickness in posterior callosal regions has beneficial consequences for higher-order cognition. Furthermore, the thesis argues that the observed regional specific callosal trajectories could serve as a segmentation procedure for callosal subdivision as it secures adequate relation between callosal structure and function. Additional research on relative callosal measures are necessary to reaffirm the merits of the current analysis, but it does indicate that analyzing the proportionality of callosal size across the lifespan offers valuable insight into the development of hemispheric interconnectivity, as well as its cognitive consequences. To further advance on this knowledge, future work should also prioritize research on clinical populations in order to investigate atypical brain development.