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.

Cerebellar Contributions to Language in Typical and Atypical Development: A Review

“…Specifically, in ASD patients there was a significant reduction in the connections between the right posterior lateral cerebellar hemisphere (lobules VI, Crus I, and Crus II) with the left dorsolateral prefrontal cortex, left premotor cortex, and left inferior frontal gyrus. This reduction of functional connectivity in the language network is proposed to be related to abnormal language function in children with autism spectrum disorder, although notably in this study the cortico-cerebellar connectivity was not significantly related to a verb generation task (Verly et al, 2014). The results from the small number of studies are promising, although more research is needed to establish a firm link between cerebellar function and language development in this population.…”

“…The deficits in language function seen in both children and adults who sustained cerebellar injury and reduced functional connectivity also support the notion of the cerebellum’s role in language function and development (Baillieux et al, 2010; Riva 1998; Scott et al, 2001; Verly et al, 2014). Finally, there are some intriguing findings suggesting the importance of the cerebellum to language function in children with disordered language function, although these studies should be considered preliminary.…”

Risk Factors Associated With Language in Autism Spectrum Disorder: Clues to Underlying Mechanisms

“…In other studies, associations between atypical connectivity and cortical organization in specific neural systems have been found in relation to behavioral impairments associated with ASD (Ameis & Catani, 2015). For example, several studies have found relationships among atypical structure, lateralization, and functional connectivity in language regions (e.g., Knaus et al, 2010;Verly et al, 2014;Williams et al, 2013); however, there is still no consistent pattern of findings, largely because of heterogeneity among participants and differences in methodology across studies.…”

Autism, Development and Neural Plasticity

“…In the later-developing cortical regions, severe disruptions resulted in a diminished functional connectivity among the regions of autistic brains (Verly et al 2014a, b;Wass 2011;Ziats and Rennert 2013b). Long-distance underconnectivity is reported in many studies showing an abnormal brain connectivity associated to an upregulated GABA neurotransmission (Di et al 2011;Kana et al 2009;Wass 2011;Minshew and Keller 2010;Just et al 2007), whereas others show a lower functional connectivity between the higher-order working memory/executive areas and the visuospatial regions at frontal and parietal-occipital level demonstrated by a combination of behavioral, functional magnetic resonance imaging (fMRI), functional connectivity, and corpus callosum morphometry , Pate et al 2010.…”