Left‐Hemispheric Microstructural Abnormalities in Children With High‐Functioning Autism Spectrum Disorder

Abstract

Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD.

Reduced Hemispheric Asymmetry of White Matter Microstructure in Autism Spectrum Disorder

“…On the other hand, Joseph et al, 54 in an examination limited to the AF, found no significant MD asymmetry in TD or ASD groups, possibly related to smaller sample size or younger age of participants. Furthermore, our findings did not coincide with those in Peterson et al, 57 who reported rightward asymmetry of MD in TD participants (not tested statistically) and increased MD in the left hemisphere in 8–12-year-old children with ASD compared to TD children. However, a direct test of the asymmetry index produced no significant group difference.…”

Atypical longitudinal development of speech‐evoked auditory brainstem response in preschool children with autism spectrum disorders

“…These results suggest that auditory processing at the brainstem level is impaired and inefficient in preschool children with ASD. This dysfunction in subcortical auditory processing may be associated with impaired progress of myelination in the auditory system [Perkins et al, 2014;Peterson, Mahajan, Crocetti, Mejia, & Mostofsky, 2015;Roberts et al, 2013] and/or an aberrant development of the white matter in preschool children with ASD [Bashat et al, 2007;Weinstein et al, 2015]. Language development relies heavily on accurate coding of acoustic features of speech.…”

Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies

“…Poustka et al (2012) revealed decreased FA values in the uncinate fasciculus and right superior longitudinal fasciculus as well as a negative correlation between the FA values of the affected fiber tracts and the severity of ASD symptoms [100]. A more recent study by Peterson et al (2015) found widespread increases in MD in many regions of the left hemisphere in children with ASD as compared to typically-developing children [101], supporting the left hemispheric abnormality or atypical hemispheric dominance that has been hypothesized in ASD for the past three decades [102–104]. Peterson et al (2015) used an atlas-based ROI analysis in HFA children and found significantly increased MD of the outer-zone cortical WM, suggesting hypomyelination and increased short-range cortico-cortical connections which might be due to the early WM overgrowth [101].…”