Quantitative tract-based white matter heritability in 1- and 2-year-old twins

Abstract

White matter (WM) microstructure, as determined by diffusion tensor imaging (DTI), is increasingly recognized as an important determinant of cognitive function and is also altered in neuropsychiatric disorders. Little is known about genetic and environmental influences on WM microstructure, especially in early childhood, an important period for cognitive development and risk for psychiatric disorders. We studied the heritability of DTI parameters, fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) along 34 tracts, including 10 bilateral fiber pathways and the respective subdivision, using quantitative tractography in a longitudinal sample of healthy children at 1 year (N = 215) and 2 years (N = 165) of age. We found that heritabilities for whole brain AD, RD, and FA were 0.48, 0.69, and 0.72 at age 1, and 0.59, 0.77, and 0.76 at age 2 and that mean heritabilities of tract-averaged AD, RD, and FA for individual bundles were moderate (over 0.4). However, the heritability of DTI change between 1 and 2 years of age was not significant for most tracts. We also demonstrated that point-wise heritability tended to be significant in the central portions of the tracts and was generally spatially consistent at ages 1 and 2 years. These results, especially when compared to heritability patterns in neonates, indicate that the heritability of WM microstructure is dynamic in early childhood and likely reflect heterogeneous maturation of WM tracts and differential genetic and environmental influences on maturation patterns.

Keywords: axial diffusivity; diffusion tensor imaging; fractional anisotropy; genetics; quantitative tractography; radial diffusivity.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1

Changes in tract‐averaged DTI values for individual bundles from 1 to 2 years of age. A pair of the same bundles at each age is illustrated side by side with the same color yet the vacant and solid symbols for 1 and 2 years old, respectively. All of the pairs showed significant differences between the two time periods (down square bracket). Abbreviations: Rostrum (rost), genu, body, and splenium (spl) of corpus callosum (CC); left (l) and right (r) prefrontal (pf), premotor (pm), motor (mo), and parietal (pt) projections of the corticothalamic tract (CT); cingulate (c) and hippocampal (h) cinguli (CG); fornices (FX); frontoparietal (fp), frontotemporal (ft), and temporoparietal (tp) parts of arcuate fasciculi (AF); uncinate fasciculi (UF); superior and inferior longitudinal fasciculi (SLF and ILF); inferior fronto‐occipital fasciculi (IFOF); and optic tracts (OT)

Figure 2

Genetic estimates of whole and individual tract‐averaged FA, AD, and RD in 1 and 2 years old. Abbreviations: Rostrum (rost), genu, body, and splenium (spl) of corpus callosum (CC); left (l) and right (r) prefrontal (pf), premotor (pm), motor (mo), and parietal (pt) projections of the corticothalamic tract (CT); cingulate (c) and hippocampal (h) cinguli (CG); fornices (FX); frontoparietal (fp), frontotemporal (ft), and temporoparietal (tp) parts of arcuate fasciculi (AF); uncinate fasciculi (UF); superior and inferior longitudinal fasciculi (SLF and ILF); inferior fronto‐occipital fasciculi (IFOF); and optic tracts (OT)

Figure 3

Relationship between heritability estimates of FA, AD, and RD for 34 bundles. Each point represents heritability estimate of tract‐averaged DTI parameters for individual tracts

Figure 4

Statistically significant heritability estimates of FA along the genu and splenium of the corpus callosum (CC), the inferior longitudinal fasciculus (ILF), the inferior fronto‐occipital fasciculus (IFOF), and the fornix in 1 and 2 years old. The color bar shows heritability estimates of the FA. Heritability estimates with significance are highlighted; nonsignificant portions are white