Brain anatomy and its relationship to behavior in adults with autism spectrum disorder: a multicenter magnetic resonance imaging study.

CONTEXT: There is consensus that autism spectrum disorder (ASD) is accompanied by differences in neuroanatomy. However, the neural substrates of ASD during adulthood, as well as how these relate to behavioral variation, remain poorly understood. OBJECTIVE: To identify brain regions and systems associated with ASD in a large, well-characterized sample of adults. DESIGN: Multicenter case-control design using quantitative magnetic resonance imaging. SETTING: Medical Research Council UK Autism Imaging Multicentre Study (MRC AIMS), with sites comprising the Institute of Psychiatry, Kings College London; the Autism Research Centre, University of Cambridge; and the Autism Research Group, University of Oxford. PARTICIPANTS: Eighty-nine men with ASD and 89 male control participants who did not differ significantly in mean age (26 and 28 years, respectively) and full-scale IQ (110 and 113, respectively). MAIN OUTCOME MEASURES: (1) Between-group differences in regional neuroanatomy assessed by voxel-based morphometry and (2) distributed neural systems maximally correlated with ASD, as identified by partial least-squares analysis. RESULTS: Adults with ASD did not differ significantly from the controls in overall brain volume, confirming the results of smaller studies of individuals in this age group without intellectual disability. However, voxelwise comparison between groups revealed that individuals with ASD had significantly increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and significant reductions in the occipital and medial parietal regions compared with controls. These regional differences in neuroanatomy were significantly correlated with the severity of specific autistic symptoms. The large-scale neuroanatomic networks maximally correlated with ASD identified by partial least-squares analysis included the regions identified by voxel-based analysis, as well as the cerebellum, basal ganglia, amygdala, inferior parietal lobe, cingulate cortex, and various medial, orbital, and lateral prefrontal regions. We also observed spatially distributed reductions in white matter volume in participants with ASD. CONCLUSIONS: Adults with ASD have distributed differences in brain anatomy and connectivity that are associated with specific autistic features and traits. These results are compatible with the concept of autism as a syndrome characterized by atypical neural "connectivity."