Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tract-based spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.

Automated summary

The rapid early-life white matter maturation is followed by slower and long-lasting development, accompanied by the learning of more complex skills. By the age of 5, differences in behavior and cognition between females and males as well as brain lateralization functions such as language skills start to appear. Diffusion tensor imaging (DTI) can be used to measure the fractional anisotropy (FA) within the white matter, with higher values indicating more advanced brain development. This study examined the normal features of white matter development in early childhood using DTI data from 166 healthy infants (mean age 3.8 weeks) and 144 healthy children (mean age 5.4 years). The results showed sex differences and age-dependent changes in white matter development, as well as the presence of asymmetry in white matter microstructure in infants.