Abstract
Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD.
Highlights
There is extensive evidence to suggest that autism is a disorder characterized by disrupted functional and structural neural connectivity
OVERVIEW OF RESULTS Section 3.1 Results relate to Question 1 outlined in Methods section Overview of Methods—are there white matter (WM) tracts between all pairs of regions of interest (ROIs) that are functionally connected? This section includes a summary of the between-group differences in www.frontiersin.org functional connectivity, which are reported in McGrath et al (2012)
IF THERE WERE WHITE MATTER TRACTS THAT DIRECTLY LINKED PAIRS OF BRAIN REGIONS SHOWING ABNORMAL FUNCTIONAL CONNECTIVITY, WERE THERE STRUCTURAL ABNORMALITIES OF THIS WHITE MATTER IN THE Autism Spectrum Disorder (ASD) GROUP? Changes in white matter between left BA19 and left caudate head There were WM tracts directly connecting the regions in left BA19 and left caudate head in 9 controls and 11 participants
Summary
There is extensive evidence to suggest that autism is a disorder characterized by disrupted functional and structural neural connectivity. Abnormal inter- and intra-regional functional connectivity has been described whilst participants have performed various neuropsychological paradigms and whilst in the resting state. In parallel with functional connectivity research, a number of diffusion imaging studies in autism have demonstrated aberrant “structural connectivity”—a term referring to the integrity of white matter (WM) micro- and macrostructure. Abnormal functional connectivity between brain regions in autism may arise from disrupted organization of WM, but its pathophysiology is unknown. In relation to structural connectivity, several studies have explored the correlation between WM organization and autism symptom severity. Increased severity of restricted and repetitive behaviors was correlated with increased FA in left precentral gyrus and posterior brain regions (Cheung et al, 2009), with reduced FA in the right anterior
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