Changes in Functional Brain Network and White Matter Connectivity Underlying Language Comprehension in Children with Autism after a Reading Intervention

Background: With the rising prevalence in autism spectrum disorders (ASD), there is a growing need for improved understanding of the neurobiology of this disorder in order to develop targeted interventions. Behavioral studies have reported that high-functioning children with ASD struggle with different aspects of oral and reading comprehension, including pragmatics, semantics, and phonological processes (Williams et al., 2008), while their decoding and word identification skills remain intact (Nation et al., 2006; Norbury & Nation, 2011). Neuroimaging research has demonstrated alterations in synchronization of brain areas underlying language comprehension, including semantics and integration of social information, (Groen et al., 2010), lexical over thematic processing (Just et al., 2004), and pragmatics and syntax (Groen et al., 2008).

Objectives:  This functional magnetic resonance imaging (fMRI) study investigates the changes in the integrity of the reading network in the brain in children with ASD as a result of a 10-week (200 hours) visualizing language intervention. This is investigated at three levels: 1) a language comprehension task; 2) task-free resting state; and 3) white matter connectivity.

Methods: We used fMRI and diffusion tensor imaging (DTI) fiber tractography to investigate our questions. A word-similarities task (e.g., orange, apple, mango, table. Is the fourth word similar to the other three?) and resting state scan were presented while children underwent fMRI. 32 children with ASD (ages 8-13 years) were scanned twice, with 17 children receiving the intervention between scans (ASD-EXP), and 15 wait-list control children (ASD-WLC). In addition, 27 typically-developing (TD) children were scanned once. Data were acquired from a Siemens 3.0T Allegra head-only scanner.

Results: The main results of this study involve changes in function and structure of the reading network in ASD-EXP participants. These results are: (1) in word-similarities task, the ASD-EXP group of children showed increased activation in the right middle occipital gyrus and lingual gyrus pre- to post-imaging session; In addition, when compared to ASD-WLC participants, the ASD-EXP group showed greater activation in both language regions (e.g., Wernicke’s area) and frontal regions (e.g., MPFC) post-intervention (p<0.001, cluster corrected); (2) Resting state functional connectivity results showed increased connectivity post-intervention in the ASD-EXP group between Broca’s area and supramarginal gyrus and between Wernicke’s area and left-lateralized language regions. Additionally, correlation of functional connectivity and improvement in reading comprehension in the ASD-EXP group revealed greater connectivity in both Broca’s and Wernicke’s area; Lastly, (3) DTI data showed that after intervention, the ASD-EXP group demonstrated increased fractional anisotropy (FA) in the right arcuate fasciculus and thalamic radiation.

Conclusions: We found that strengthening of functional connectivity of frontal and posterior language regions, as well as increased white matter integrity, was positively correlated with behavioral improvement in reading comprehension. Overall, this study provides multiple sources of evidence (task-based fMRI, resting state fMRI, and DTI) showing improvement in the brain circuitry underlying language processing in children with ASD after reading intervention. The findings of this study emphasize the importance of targeted interventions for children with ASD, and are encouraging for future studies to continue to assess intervention-related changes in brain circuitry.