Frontal networks in adults with autism spectrum disorder

Abstract

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

Keywords: arcuate fasciculus; autism spectrum disorder; diffusion tractography; frontal networks; language.

Autism spectrum disorder (ASD) is proposed to reflect atypical connectivity between higher-order association areas. Using diffusion imaging, Catani et al. reveal associations between ASD and white matter abnormalities of the frontal lobe, and suggest that the condition is linked to aberrant developmental trajectories of frontal networks that persist in adulthood.

Figure 1

TBSS analysis of differences in fractional anisotropy between ASD subjects and neurotypical controls. Red regions indicate reduced fractional anisotropy values in ASD. Arc = arcuate fasciculus; CC = corpus callosum; Cing = cingulum; Unc = uncinate fasciculus.

Figure 2

The anatomy of the arcuate fasciculus in relation to childhood ASD symptoms. (A) Tractography dissections of the three segments of the arcuate fasciculus. (B) Negative correlation between the number of streamlines of the left anterior segment and the B3 score (stereotyped, repetitive and idiosyncratic speech) of the ADI-R (r = −0.340; P = 0.005) in the ASD group. (C) In the ASD group, participants with a significant history of stereotyped utterance and delayed echolalia in childhood had a significantly lower number of streamlines in the anterior segment of the arcuate fasciculus. (D) Similarly, ASD subjects with severely impaired reciprocal conversation in childhood had a significantly lower number of streamlines in the anterior segment of the arcuate fasciculus compared to ASD subjects with moderate symptoms.

Figure 3

The anatomy of the limbic tracts in relation to childhood ASD symptoms. (A) Tractography reconstructions of the limbic pathways. (B) Negative correlation between the number of streamlines of the left uncinate fasciculus and the total A4 score for impaired socioemotional reciprocity in the ADI-R (Pearson’s correlation = −0.295; P = 0.01) in the ASD group. ASD participants with a (C) significant history of impaired use of facial expression in childhood and (D and E) late use of first single words had a significantly lower fractional anisotropy (FA) and higher radial diffusivity in the left uncinate fasciculus.

Figure 4

Tractography reconstruction of the segments of the corpus callosum according to Witelson’s division (1989).