Frontal networks in adults with autism spectrum disorder.

Marco Catani,Bhismadev Chakrabarti,Michel Thiebaut De Schotten,Seán Froudist-Walsh,John Suckling,Henrietta Howells,Mrc Aims Consortium,Alexander Leemans,Stefano Sandrone,Michael C Craig,Lucio D’Anna,Flavio Dell’Acqua,Amber N V Ruigrok,Abigail Thompson,Edward T Bullmore,Christine Ecker,Meng‐Chuan Lai ,Sally Wheelwright ,Simon Baron‐Cohen ,Michael Lombardo ,Sanja Budisavljević ,Declan Murphy

doi:10.1093/brain/awv351

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.

Highlights

1% of the population have an autistic spectrum disorder (ASD), with a male:female ratio of 2.5:1 (Lai et al, 2014)
We subsequently explored whether anatomical differences in the left long and anterior segments of the arcuate fasciculus were associated with language and communication impairment
In this multicentre study we investigated the anatomy of white matter networks in adults with ASD

Summary

Introduction

1% of the population have an autistic spectrum disorder (ASD), with a male:female ratio of 2.5:1 (Lai et al, 2014). Functional neuroimaging studies have reported altered activation of these regions during tasks involving social, emotion and language processing (Baron-Cohen et al, 1999; Pierce et al, 2001; Just et al, 2004; Ashwin et al, 2007; Philip et al, 2012). Some of these findings have not been consistently replicated (Stigler et al, 2011). These factors are necessary for optimum performance of higher-order tasks that rely on integrated information processing (Fields, 2008)

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