Abstract

Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a ‘posteriorization’ of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI.

Highlights

  • The neurobiology of autism has been studied since the initial description of the disorder [1]

  • We examined whether structural abnormalities in large-scale distributed brain networks could be detected in autism, and hypothesized that autism would demonstrate altered network-level structural architecture consistent with poor development or restricted topology of the salience network (SN), as well as overgrowth of the default mode network (DMN)

  • Marked differences were observed in both SN and DMN in autistic subjects

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Summary

Introduction

The neurobiology of autism has been studied since the initial description of the disorder [1] Both genetic and non-genetic contributing factors have been implicated, but specific etiologic factors remain undefined. Concomitant white matter disruptions have been reported in prefrontal, superior temporal, temporoparietal cortices, and corpus callosum [19], but increases in whole brain white matter volume have been observed [8,16]. How these varied anatomic abnormalities relate to domain-specific cognitive impairment in social and emotional functioning, language and communication deficits, and poor executive function remains unclear

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