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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    • "The majority of post-mortem studies of ASD report decreased Purkinje cell counts in the cerebellar cortex (Fatemi et al., 2002; Bauman and Kemper, 2005), and ASD-like symptoms can be induced by specifically targeting cerebellar Purkinje cells in animal models (Tsai et al., 2012). Cerebellar structural differences are associated with social and communication impairments as well as restricted interests and repetitive behaviors, the hallmarks of the ASD diagnosis, in both human studies (Pierce and Courchesne, 2001; Rojas et al., 2006; Riva et al., 2013; D'Mello et al., 2015) and animal models of ASD (Ingram et al., 2000; Brielmaier et al., 2012; Tsai et al., 2012). The cerebellar cortex was consistently abnormal in an analysis of over 26 mouse models of ASD (Ellegood et al., 2015), and cerebellar atrophy is characteristic of one of the most widely used animal models of ASD, the valproic acid model (Ingram et al., 2000). "
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    ABSTRACT: The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.
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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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