Atypical Development of White Matter Microstructure in Adolescents with Autism Spectrum Disorders

Diffusion tensor imaging (DTI) studies in adolescents with autism spectrum disorders (ASD) indicate aberrant neurodevelopment of frontal white matter (WM), potentially underlying abnormal social cognition and communication in ASD. Here, we further use tract-based spatial statistics (TBSS) to examine the developmental change of WM skeleton (i.e., the most compact whole-brain WM) during adolescence in ASD. This whole-brain DTI used TBSS measures fractional anisotropy (FA) and longitudinal and radial diffusivities in fifty adolescents, 25 ASD and 25 controls. Results show that adolescents with ASD versus controls had significantly reduced FA in the right posterior limb of internal capsule (increased radial diffusivity distally and reduced longitudinal diffusivity centrally). Adolescents with ASD versus controls (covarying for age and IQ) had significantly greater FA in the frontal lobe (reduced radial diffusivity), right cingulate gyrus (reduced radial diffusivity), bilateral insula (reduced radial diffusivity and increased longitudinal diffusivity), right superior temporal gyrus (reduced radial diffusivity), and bilateral middle cerebellar peduncle (reduced radial diffusivity). Notably, a significant interaction with age by group was found in the right paracentral lobule and bilateral superior frontal gyrus as indicated by an age-related FA gain in the controls whilst an age-related FA loss in the ASD. To our knowledge, this is the first study to use TBSS to examine WM in individuals with ASD. Our findings indicate that the frontal lobe exhibits abnormal WM microstructure as well as an aberrant neurodevelopment during adolescence in ASD, which support the frontal disconnectivity theory of autism.