White matter development in early puberty: a longitudinal volumetric and diffusion tensor imaging twin study

Abstract

White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals) and again at age 12 (126 individuals). Over the three-year interval, white matter volume (+6.0%) and surface area (+1.7%) increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium), and fractional anisotropy increased (+3.0%). Genes influenced white matter volume (heritability ~85%), surface area (~85%), and fractional anisotropy (locally 7% to 50%) at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r = -0.62) and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization.

Figure 1. Significant tissue expansion: Significant Jacobian values > 1 overlaid on the model brain.

Values range from 1.02 (purple) to 1.30 (bright red). Expansion was observed in regions covering the arcuate fasciculus (E), cerebellar penduncle (A), cinguli (C) , corpus callosum (B,C), cortical spinal tract (B,F), uncinate fasciculus (D) and on the gray matter / cerebral spinal fluid boundary (A-F), the latter likely representing brain growth. For visualization purposes, values were resampled to model brain resolution.

Figure 2. Increases of relative fractional anisotropy between the ages of 9 and 12, projected onto the group average fiber bundle.

Left, top and right view. For visualization purposes, values were smoothed along the bundle using LOESS .

Figure 3. The relationship between changes in pure white matter fractional anisotropy and changes in white matter volume in the three-year interval.

Figure 4. Relative white matter surface area expansion of AAL regions in the left and right hemisphere.

Please note that expansion is based (and projected on) AAL regions rather than representing continuous expansion. *Areas in which girls had larger expansion than boys.

Figure 5. Histograms of fractional anisotropy in pure white matter at age 9 and age 12.

In the 14 children with relatively large volumetric white matter growth mean fractional anisotropy was 0.43 at both ages. In 13 children with relatively small volumetric white matter growth, mean fractional anisotropy increased from 0.41 to 0.44.