Investigating Superficial White Matter Connections Using Diffusion Tensor Tractography

Background: Neurological function is sub-served by large-scale neural networks, comprised of short and long-range white matter fibres that link neighbouring and geographically distant grey matter regions. In Autism Spectrum Disorders (ASD), underconnectivity of long-range white matter connections, and over-connectivity of short-range white matter connections has been postulated to contribute to illness symptoms. Diffusion tensor imaging (DTI) tractography, enabling virtual reconstruction and microstructural characterization of white matter tracts, has been used extensively to map typical development of long-range white matter connectivity, facilitating examination for long-range underconnectivity in ASD. As yet, the typical development of short-range white matter connections remains unknown, hampering comparisons with ASD, and investigation for structural signs of short-range overconnectivity in this disorder.  

Objectives: Here, we undertook DTI tractography of short and long-range white matter connections in typically developing children and adolescents for the first time to test the feasibility of short-range white matter examination in vivo using DTI.

Methods: DTI scans were acquired for 19 typically developing children and adolescents (11 males; 9 females; age range 6-15 years; mean = 10 ± 2.5 years) using a 1.5 T MRI scanner. For short-range white matter tract reconstruction, a standardized lobar mask was used to create frontal, parietal, temporal and occipital lobe regions of interest. Probabilistic tractography was undertaken to reconstruct white matter remaining within discrete lobar regions, representing intra-lobar, short-range, white matter connections. For long-range white matter tract examination, seed masks from a standardized tractography template were used to reconstruct the cingulum bundle, inferior longitudinal, inferior fronto-occipital, arcuate, and uncinate fasciculi. Fractional anisotropy (FA), mean diffusivity (MD), axial (AxD) and radial diffusivity (RxD) values were calculated for white matter reconstructions. Bivariate correlation matrices for short and long-range white matter diffusion measures and age were examined.

Results: Correlations for age and white matter tract diffusion measures were significant for short-range white matter connections within the left temporal lobe for FA (r = 0.64, p = 0.003), and RxD (r = 0.57; 0.009), and left parietal lobe (FA: r = 0.57, p = 0.009). A significant correlation was also found between age and left arcuate fasiculus RxD (r = 0.58, p = 0.01). 

Conclusions: Our work indicates that short and long-range white matter connections are undergoing microstructural changes between childhood and adolescence that may reflect increased coherence and continued myelination of underlying white matter pathways. Results indicating the presence of developmental change in left temporal and left parietal short-range white matter, as well as the left arcuate fasciculus, may point to changes in local and distributed connectivity across the left hemisphere language processing network between childhood and adolescence. Our results support the feasibility of undertaking DTI examination of short-range white matter connections in developing children, paving the way for interrogation of the short-range overconnectivity theory in ASD.