Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder

Abstract

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.brain structure | gyrification | morphometry A utism spectrum disorders (ASDs) are a group of neurodevelopmental conditions characterized by impaired social communication, social reciprocity, and repetitive/stereotypic behavior (1). There is consensus that ASD is accompanied by developmental differences in brain anatomy and connectivity (2). However, the specific neurobiological substrate of ASD remains elusive.Neuroimaging evidence suggests that ASD is accompanied by anatomical differences in several large-scale neurocognitive networks (3), which typically include the cerebellum (4), the amygdalahippocampal complex (5), fronto-temporal regions (6), and the caudate nuclei (7). These gross-anatomical abnormalities are likely to reflect differences in the cytoarchitectonic make-up of individual brain regions in ASD, as can be observed in postmortem studies. For instance, individuals with ASD may have a reduced size, but increased number, of minicolumns (8), which could underpin differences in cortical surface area (9, 10). Also, individuals with ASD may have an excess number of neurons in some brain regions (11), which in turn may affect measures of cortical thickness (9, 12). Therefore, different morphometric features of the cortical surface provide proxy measures of various aspects of local gray-matter arc...

Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan

“…Panel I reproduced from Wallace and colleagues, by permission of Oxford University Press. 23 Panel J reproduced from Ecker and colleagues, 10 by permission of the National Academy of Sciences of the USA.…”

No Association between Cortical Gyrification or Intrinsic Curvature and Attention-deficit/Hyperactivity Disorder in Adolescents and Young Adults

“…Furthermore, the related measure of wiring cost was found altered in a group of adults with autism spectrum disorder (ASD; Ecker et al, 2013). ASD has also been associated with gyrification and long range connectivity abnormalities (Anagnostou and Taylor, 2011; Schaer et al, 2013).…”

Cortical Surface-Based Construction of Individual Structural Network with Application to Early Brain Development Study

“…Leveraging spherical cortical surface patches, our method generates biologically-meaningful individual networks, of which the node areas are comparable across ages and subjects. Note that, connections in the individual network may reflect the direct or indirect fiber connectivity in white matter or similar genetic influence between two regions [1] or intrinsic micro-structural connectivity in gray matter [16]. This method can also be used to construct individual networks using other cortical attributes, such as sulcal depth and cortex folding degree.…”