The Cingulum Bundle in Developing Children and Adolescents with Autism Spectrum Disorders: A Diffusion Tensor Tractography Study

Background: In the autism spectrum disorders (ASD), brain overgrowth in early life may drive white matter dysconnectivity. Impaired white matter connectivity within limbic circuitry may contribute to the socio-emotional dysfunction that characterizes ASD. Structural examination of white matter connections can now be achieved using diffusion tensor imaging (DTI), a novel technique that can infer properties of white matter tissue in the living human brain. Preliminary DTI evidence has pointed to structural disturbance within the cingulum bundle, a key limbic white matter tract, in adults with ASD. Objectives: This study aims to examine structural connectivity of the cingulum bundle in developing children and adolescents with ASD, compared to controls, using diffusion tensor tractography. Methods: Diffusion tensor images were acquired for 18 children and adolescents with ASD (age range 7-18 years; mean 12.2 ± 3.1) and 17 age and sex matched healthy controls (age range 8-17; mean 12.6 ± 3.3) on a 3T Siemens Allegra head-dedicated MRI system. Deterministic tractography was performed using a single region of interest approach to reconstruct the cingulum bundle. Average fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity values, were quantified for the right and left cingulum bundle. Independent samples t-tests were performed to determine between-group differences in DTI indices: (1) in the overall sample of participants, (2) in a sub-group of developing children within the overall sample, and (3) in a sub-group of developing adolescents within the overall sample. We define children as those participants that were under the age of 12 at the time of scanning, and adolescents as participants 12 years of age and older, at the time of DTI scanning. Results: The results of our study show that mean diffusivity is significantly increased in ASD in the left cingulum bundle (p = .044), when considering the overall sample of participants. No other differences in the overall sample were found. However, when developing children with ASD were compared to matched controls, mean diffusivity was significantly increased in the ASD group for the left (p = .004) and right (p = .042) cingulum bundle. Radial diffusivity was also significantly increased for the left (p = .035) and right (p = .049) cingulum bundles, in developing children with ASD. No other differences were found among the sub-group of developing children. Interestingly, when developing adolescents with ASD were compared to matched controls, no differences in DTI measures were found between groups. Conclusions: Our results suggest potential disruption of the cingulum bundle, in ASD. Exceptionally striking, were findings of altered mean diffusivity and radial diffusivity in the cingulum bundle in developing children with ASD but not in developing adolescents, possibly indicating immaturity of the cingulum bundle that is specific to children with ASD. In particular, significant increases in radial diffusivity in developing children with ASD, potentially indicates impaired myelination of the cingulum bundle during the childhood phase of brain development.