scMRI Reveals Large-Scale Brain Network Abnormalities in Autism

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.

Structural covariance of neostriatal and limbic regions in patients with obsessive–compulsive disorder

“…2 Normal structural covariance patterns have been shown to be altered in patients with different brain disorders. Among those with psychiatric conditions, such alterations have been described mostly in patients with schizophrenia, 15,16 although there have also been reports in those with autism 17,18 and obsessive-compulsive disorder (OCD). In patients with OCD, Pujol and colleagues 19 described positive volume correlations between cortical areas (dorsomedial prefrontal, medial orbito frontal and insular cortices) shown to be reduced in volume in comparison with healthy controls, suggesting that volume al terations in patients with OCD were coordinated in patterns of structural covariance.…”

Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity

“…Indeed, given this link to connectivity, structural covariance networks are particularly appealing to examine neuropsychiatric disorders in which aberrations in structural and functional networks have been implicated. Alterations in net-20 works of structural covariance have been demonstrated in autism (Zielinski et al, 2012;Bernhardt et al, 2014;Valk et al, 2015;Bethlehem et al, 2017), schizophrenia (Shi et al, 2012;Wheeler et al, 2014;Alexander-Bloch et al, 2014), epilepsy (Bernhardt et al, 2011;Yasuda et al, 2015;Bernhardt et al, 2016), and grapheme-color synesthesia (Hänggi et al, 2011), to name a few such disorders.…”

Decreased centrality of cortical volume covariance networks in autism spectrum disorders

“…However, there are only a few studies to date exploring differences in putative measures of gray-matter connectivity in ASD (Zielinski et al 2012).…”