The Role of Sustained Attention in the Association Between Dual Pathways and Language Function in Youths with High-Functioning Autism

Background:  Language-communication deficit is one of the three core symptoms of autism. Our prior investigation found altered structure-function relations in autism suggest involvement of the dorsal (including arcuate fasciculus and superior longitudinal fasciculus Ⅲ) and ventral pathways (including inferior frontal-occipital fasciculus and inferior longitudinal fasciculus) in compensating for the deficient semantic processing found in autism. In addition, literature documents the relationship between attention performance and language function. We hypothesized that the dual pathways in autism may work as a different mechanism compared to neurotypicals.

Objectives:  The current study further investigates the role of attention performance in the association between dual pathways and language function. 

Methods:  Forty right-handed male youths with HFA and 40 matched neurotypical participants, aged 8 to 21, were assessed by the psychiatric interview (ADI-R and K-SADS-E) with their parents, intelligence test, the Conner’s Continuous Performance Test (CCPT) and diffusion spectrum imaging (DSI). Images were acquired on a 3T MRI system with a 32-channel head coil (Tim Trio, Siemens, Erlangen, Germany). DSI tractography was reconstructed using a streamline-based algorithm adapted for DSI data and the targeted tracts were selected by expert-monitored multiple regions of interest (ROIs). ROIs for reconstructing the dual pathways followed the description by Saur et al. (Saur et al., 2008). To select ROIs of each targeted tract objectively, we used MARINA software to define cortical regions as ROIs on the MNI template. For the dorsal pathway, two ROIs were identified, specifically, one at the left opercular part of inferior frontal gyrus (BA 44/46) and the other at the left superior temperal gyrus (BA 22). For the ventral pathway, the left orbital part of IFG (BA 47), left middle temporal gyrus (BA 21) and left fusiform gyrus (BA 37) were identified. Generalized fractional anisotropy values were computed along individual targeted fiber tracts to investigate alterations in microstructure integrity.

Results:  We found that youths with HFA significantly scored lower in verbal IQ (106 vs 113) and verbal comprehension index (VCI, 107 vs 113) than neurotypicals without difference in performance IQ (106 vs. 109). Youths with HFA had significantly lower GFA of the left ventral pathway than neurotypicals. However, left-greater-than-right asymmetry of dual pathways was absent in HFA youths. Lateralization index of the dorsal pathway was positively correlated with Verbal IQ in neurotypicals (r=0.321, p=0.046). There were significant correlations between sustained attention and vigilance domains of the CCPT measures and GFA of right dorsal pathways as well as GFA of left ventral pathways (vigilance only) in HFA youths. Moreover, negative correlations between sustained attention and Verbal IQ/VCI in HFA youths (r=-0.420, p=0.008; r=-0.341, p=0.033, respectively).

Conclusions:  Our results suggest the altered white matter alterations and less leftward lateralization of dual pathways in HFA and dual pathways involved not only language but also attention in HFA. Moreover, attention performance (particularly sustained attention) may mediate the prediction of microstructured integrity of dual pathway to language function. Taken together, the roles of the dual pathways may differ between HFA youths and neurotypicals.