Abstract
BackgroundThe corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined.MethodsWe employed diffusional kurtosis imaging (DKI) metrics to characterize white matter properties within five discrete segments of the corpus callosum in 17 typically developing (TD) adults and 16 age-matched participants with ASD without co-occurring intellectual disability (ID). The DKI metrics included axonal water fraction (faxon) and intra-axonal diffusivity (Daxon), which reflect axonal density and caliber, and extra-axonal radial (RDextra) and axial (ADextra) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined.ResultsASD group had significantly decreased callosal faxon and Daxon (p = .01 and p = .045), particularly in the midbody, isthmus, and splenium. Regression analysis showed that variation in DKI metrics, primarily in the mid and posterior callosal regions explained up to 70.7% of the variance in processing speed scores for TD (p = .001) but not for ASD (p > .05).ConclusionDecreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants.
Highlights
The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD)
We investigated the relationship between callosal white matter properties and cognitive measurements indexing information processing based on two observations: (1) the corpus callosum is known to support processing speed [10, 44], and (2) impaired processing speed has been consistently reported in ASD [21, 54]
In one of the four indices in the intelligence test, Processing Speed Index (PSI), ASD participants (93.44 ± 18.37) scored substantially lower than typically developing (TD) controls (108.71 ± 14.28) (p = .012), with significant group differences found in both subtest scores— Digit Symbol-Coding (DigitSC) (p = .028) and Symbol Search (SS) (p = .008) (Table 1)
Summary
The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). Prior morphometric and diffusion imaging studies have revealed that, compared to neuro-typical participants, autistic subjects have smaller volumes of both the entire callosum [2, 23] and callosal sub-regions [22, 56], decreased white matter density [12, 53, 59], and increased diffusivity [7, 38, 47] These findings support the aberrant neural connectivity hypothesis of ASD [5, 8, 34], which posits that the social and cognitive symptoms by which ASD is defined are related to a decrease in neural connectivity resulting from pervasive abnormalities in long-range white matter pathways. Abnormal myelin development in the corpus callosum has been proposed [20] evidence supporting this hypothesis remains incipient
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