Applying microstructural models to understand the role of white matter in cognitive development.

Diffusion MRI (dMRI) holds great promise for illuminating the biological changes that underpin cognitive development. The diffusion of water molecules probes the cellular structure of brain tissue, and biophysical modeling of the diffusion signal can be used to make inferences about specific tissue properties that vary over development or predict cognitive performance. However, applying these models to study development requires that the parameters can be reliably estimated given the constraints of data collection with children. Here we collect repeated scans using a typical multi-shell diffusion MRI protocol in a group of children (ages 7-12) and use two popular modeling techniques to examine individual differences in white matter structure. We first assess scan-rescan reliability of model parameters and show that axon water faction can be reliably estimated from a relatively fast acquisition, without applying spatial smoothing or de-noising. We then investigate developmental changes in the white matter, and individual differences that correlate with reading skill. Specifically, we test the hypothesis that previously reported correlations between reading skill and diffusion anisotropy in the corpus callosum reflect increased axon water fraction in poor readers. Both models support this interpretation, highlighting the utility of these approaches for testing specific hypotheses about cognitive development.