Altered functional connectivity of the language network in ASD: role of classical language areas and cerebellum

Abstract

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

Keywords: Autism spectrum disorders; Cerebellum; Language function; Resting state fMRI.

Fig. 1

This figure shows the statistical group activation maps of language in TD and ASD-LI patients as well as the conjunction map that displays the common activated voxels in TD and ASD-LI patients (p < 0.001, minimal cluster size 10 voxels). The center of the seeds was defined by the peak activations of the conjunction map.

Fig. 2

A and B show the correlation matrices representing functional connectivity links among the eight identified language network regions evaluated in this study in TD (n = 19) (A) and ASD-LI patients (n = 13) (B). C presents the correlation matrices showing differences in functional connectivity between TD and patients among the eight network regions involved in language processing. The color represents the T value of connectivity between the two connected brain regions. Significant correlations (p < 0.001 FDR for within group and p < 0.05 FDR for between group comparison) are indicated with a dot at the center of the matrix square. Below each correlation matrix, significant correlations are schematically represented as lines on an axial slice. Line thickness and color vary according to the scale above. The semi-transparent lines represent the connections to the cerebellum.

Fig. 3

This figure represents the voxel-wise functional connectivity maps using the right cerebellar network region (#) and left Broca region (*) as a seed for whole brain connectivity analyses. The outline of the task-based language activation map of the TD is overlaid to ease the comparison. TD maps present a high degree of spatial specificity, showing correlation almost exclusively with other regions belonging to the language network (p < 0.001, FDR corrected). In the ASD-LI maps an important reduction of connectivity starting from the right cerebellar seed and left IFG (Broca's area) is shown (p < 0.001, FDR corrected). Also, significant differences for a statistical threshold of p < 0.01 FDR-corrected are presented (TD > ASD-LI).