Regional gray matter changes in autism associated with social and repetitive behavior symptoms

Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, 80220, USA.
BMC Psychiatry (Impact Factor: 2.21). 02/2006; 6(1):56. DOI: 10.1186/1471-244X-6-56
Source: PubMed


Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures.
We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM).
Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes.
Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism.

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    • "We used the calibrated severity score rather than raw ADOS scores, which is a superior metric of symptom severity because of its independence from chronological age and verbal IQ (Gotham et al., 2009). Our DMN midline functional connectivity findings converge with prior evidence of altered midline functional connectivity in ASD youth and adults (Cherkassky et al., 2006; Doyle-Thomas et al., 2015; Eilam- Stock et al., 2014; Jung et al., 2014; Monk et al., 2009; Weng et al., 2010), as well as atypical structural findings (Ameis et al., 2013; Cauda et al., 2011; Duerden et al., 2012; Ikuta et al., 2014; Jiao et al., 2010; Oblak et al., 2010, 2011; Rojas et al., 2006; Shukla et al., 2011; Uddin et al., 2011; Waiter et al., 2004) and task-evoked functional connectivity findings (Bolling et al., 2011; Kleinhans et al., 2008; Mason et al., 2008). "
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    ABSTRACT: Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.
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    • "Hence, there is a need to study the differences in gray matter composition obtained via structural MRI for effective classification of ASD patients and healthy controls. Previous studies using structural MRI of ASD patients have observed regional differences in gray matter composition in the areas around the frontal cortex like middle frontal gyrus, inferior frontal gyrus and medial orbito frontal cortex (Bonilha et al., 2008; Hadjikhani, Joseph, Snyder, & Tager-Flusberg, 2006; Hardan et al., 2006; Hardan, Libove, Keshavan, Melhem, & Minshew, 2009; Hyde, Samson, Evans, & Mottron, 2010; McAlonan, et al., 2005; Waiter et al., 2004) and volumetric differences in gray matter around the superior temporal sulcus, inferior parietal lobule, cingulate and fusiform gyrus (Boddaert et al., 2004; Bonilha et al., 2008; Hadjikhani et al., 2006; McAlonan et al., 2005; Rojas et al., 2006; Waiter et al., 2004). These studies explored gray matter differences in specific regions of the brain, however, in the case of MRIs from children whose brain is still developing fast, the specific regions may not be fully grown to facilitate a clear demarcation of their boundaries. "
    Expert Systems with Applications 07/2015; DOI:10.1016/j.eswa.2015.07.031 · 2.24 Impact Factor
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    • "Our study finds increased left hippocampal GM volume in the HS/LE group relative to the HE/LS group. Rojas et al. (2006) report increased GM in the medial temporal lobe area in the left hippocampus, left middle temporal, and right fusiform gyrus in individuals with ASD compared to normal controls. Schumann et al. (2004) report bilaterally enlarged hippocampal volume in children and adolescents with ASD compared to normal controls. "
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