Multimodal Diffusion-MRI and MEG Assessment of Auditory and Language System Development in Autism Spectrum Disorder

Abstract

Background: Auditory processing and language impairments are prominent in children with autism spectrum disorder (ASD). The present study integrated diffusion MR measures of white-matter microstructure and magnetoencephalography (MEG) measures of cortical dynamics to investigate associations between brain structure and function within auditory and language systems in ASD. Based on previous findings, abnormal structure-function relationships in auditory and language systems in ASD were hypothesized.

Methods: Evaluable neuroimaging data was obtained from 44 typically developing (TD) children (mean age 10.4 ± 2.4 years) and 95 children with ASD (mean age 10.2 ± 2.6 years). Diffusion MR tractography was used to delineate and quantitatively assess the auditory radiation and arcuate fasciculus segments of the auditory and language systems. MEG was used to measure (1) superior temporal gyrus auditory evoked M100 latency in response to pure-tone stimuli as an indicator of auditory system conduction velocity, and (2) auditory vowel-contrast mismatch field (MMF) latency as a passive probe of early linguistic processes.

Results: Atypical development of white matter and cortical function, along with atypical lateralization, were present in ASD. In both auditory and language systems, white matter integrity and cortical electrophysiology were found to be coupled in typically developing children, with white matter microstructural features contributing significantly to electrophysiological response latencies. However, in ASD, we observed uncoupled structure-function relationships in both auditory and language systems. Regression analyses in ASD indicated that factors other than white-matter microstructure additionally contribute to the latency of neural evoked responses and ultimately behavior. RESULTS also indicated that whereas delayed M100 is a marker for ASD severity, MMF delay is more associated with language impairment.

Conclusion: Present findings suggest atypical development of primary auditory as well as auditory language systems in ASD. Findings demonstrate the need for additional multimodal studies to better characterize the different structural features (white matter, gray matter, neurochemical concentration) that contribute to brain activity, both in typical development and in ASD. Finally, the neural latency measures were found to be of clinical significance, with M100 associated with overall ASD severity, and with MMF latency associated with language performance.

Keywords: auditory pathways; autism spectrum disorders (ASD); diffusion MRI; language; magnetoencephalography (MEG); multimodal imaging.

Figure 1

White matter measurement regions of interest, as defined with diffusion MR tractography, are shown. An axial slice through the auditory radiation tracts shows connectivity from the auditory cortex to thalamus (yellow, left). A 3D rendering of left-hemisphere arcuate fasciculus is shown (right).

Figure 2

Developmental trajectory of left and right auditory radiation microstructure are shown with 95% confidence intervals (shading). Left-hemisphere FA increased at a faster rate in the TD vs. ASD group (p < 0.01). No right-hemisphere group difference in maturation was observed.

Figure 3

Developmental trajectory of left and right auditory M100 latency. M100 latency shortened with age across the population (p < 0.0001). Although no group difference in rate of maturation was observed, the TD group trended toward faster maturation.

Figure 4

Developmental trajectory (slope) of auditory radiation FA (left) and auditory cortex M100 latency (right). Left-hemisphere FA development was significantly slower in ASD vs. TD (p < 0.01). Although not reaching significance, the left-hemisphere M100 latency showed a similar pattern of more rapid development in TD vs. ASD. For both MEG and DTI measures, a lack of hemispheric asymmetry or specialization is evident in the ASD group.

Figure 5

The correlation between M100 and SRS is observed in the partial regression leverage plot. The ordinate (y-axis) of the leverage plot shows the residuals of the response variable (SRS) when regressed on all model parameters except M100. The abscissa (x-axis) of the leverage plot shows the residuals from regressing M100 against the other independent variables. M100 is a significant predictor of SRS (p = 0.02).

Figure 6

Relationship between CELF-4 score and MMF latency is shown for ASD (red) and TD (blue). The correlation is significant for ASD (p < 0.005). Although not significant in TD, the slope suggests a negative correlation between MMF and language ability.

Figure 7

Leverage plot of arcuate fasciculus FA vs. MMF latency in TD showing a significant correlation (p < 0.01). Left and right hemisphere measures are combined in the scatter plot.