Toddlers later diagnosed with autism exhibit multiple structural abnormalities in temporal corpus callosum fibers

Abstract

Interhemispheric functional connectivity abnormalities are often reported in autism and it is thus not surprising that structural defects of the corpus callosum (CC) are consistently found using both traditional MRI and DTI techniques. Past DTI studies however, have subdivided the CC into 2 or 3 segments without regard for where fibers may project to within the cortex, thus placing limitations on our ability to understand the nature, timing and neurobehavioral impact of early CC abnormalities in autism. Leveraging a unique cohort of 97 toddlers (68 autism; 29 typical) we utilized a novel technique that identified seven CC tracts according to their cortical projections. Results revealed that younger (<2.5 years old), but not older toddlers with autism exhibited abnormally low mean, radial, and axial diffusivity values in the CC tracts connecting the occipital lobes and the temporal lobes. Fractional anisotropy and the cross sectional area of the temporal CC tract were significantly larger in young toddlers with autism. These findings indicate that water diffusion is more restricted and unidirectional in the temporal CC tract of young toddlers who develop autism. Such results may be explained by a potential overabundance of small caliber axons generated by excessive prenatal neural proliferation as proposed by previous genetic, animal model, and postmortem studies of autism. Furthermore, early diffusion measures in the temporal CC tract of the young toddlers were correlated with outcome measures of autism severity at later ages. These findings regarding the potential nature, timing, and location of early CC abnormalities in autism add to accumulating evidence, which suggests that altered inter-hemispheric connectivity, particularly across the temporal lobes, is a hallmark of the disorder.

Autism spectrum disorder: advances in diagnosis and evaluation

“…These findings are complemented by a smaller study of community identified 1 year to 4 year old children with ASD who had atypical development of white matter ultrastructure relative to typically developing controls, particularly in the frontal tracts86 and within the corpus callosum in those younger than 30 months 87…”

Structural connectivity of the amygdala in young adults with autism spectrum disorder

“…Despite evidence from lesion studies and volumetric analyses that highlight the importance of the amygdala in ASD, to the best of our knowledge, no study has investigated amygdala connectivity directly in ASD. A number of previous studies of ASD have investigated microstructural differences in WM pathways that connect to temporal lobe structures: in young children with ASD, elevated FA has been identified in temporal lobe projections (Fingher et al, ) and the uncinate fasciculus, which links the temporal and frontal lobes (Solso et al, ), and reduced diffusivity reported in corpus callosum projections that link the temporal lobe with the occipital lobe (Fingher et al, ). Conversely in older children with ASD, significantly reduced FA has been reported in WM surrounding the amygdala (Noriuchi et al, ) and in the inferior longitudinal fasciculus (ILF) and the inferior fronto‐occipital fasciculus (IFOF) (both of which connect temporal lobe structures, including the amygdala) (Jou et al, ).…”

Loss ofCntnap2Causes Axonal Excitability Deficits, Developmental Delay in Cortical Myelination, and Abnormal Stereotyped Motor Behavior

“…Based on these observations, it remains to be established whether Cntnap2 disruption may cause neurodevelopmental deficits through disruption of axonal action potential dynamics or aberrant brain myelination. Their study is of importance to gain understanding of reduced white matter integrity and conductivity implicated in neurodevelopmental disorders (Vissers et al 2012;Rane et al 2015;Wolff et al 2015;Fingher et al 2017).…”