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; 6:56. 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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Available from: Don Rojas, Oct 01, 2015
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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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    ABSTRACT: In light of the new DSM-5 autism spectrum disorders diagnosis in which the autism spectrum reflects a group of neurodevelopmental disorders existing on a continuum from mild to severe expression of autistic traits, and recent empirical findings showing a continuous distribution of autistic traits in the general population, our voxel based morphometry study compares normal individuals with high autistic traits to normal individuals with low autistic traits. We hypothesize that normal individuals with high autistic traits in terms of empathizing and systemizing [high systemizing (HS)/low empathizing (LE)] share brain irregularities with individuals that fall within the clinical autism spectrum disorder. We find differences in several social brain network areas between our groups. Specifically, we find increased gray matter (GM) volume in the orbitofrontal cortex, the cuneus, the hippocampus and parahippocampus and reduced GM volume in the inferior temporal cortex, the insula, and the amygdala in our HS/LE individuals relative to our HE/LS (low autistic traits in terms of empathizing and systemizing) individuals.
    Frontiers in Human Neuroscience 05/2015; 9. DOI:10.3389/fnhum.2015.00264 · 2.99 Impact Factor
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    • "Segmentations from the DESPOT1 acquisitions also have elevated values of within-centre variance in sub-cortical structures, although the ratio relative to the neocortex is greater. This effect was particularly pronounced in data from Centre 3. Two example regions in which grey matter differences associated with ASC have previously been reported [Rojas et al., 2006] were identified by anatomical atlas [Tzourio- Mazoyer et al., 2002] as representative of regions where there is a large (bilateral putamen) and small (bilateral fusiform gyrus) difference in within-centre variance between centres operating machines from different manufacturers. "
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    ABSTRACT: There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2014; 35(8). DOI:10.1002/hbm.22465 · 5.97 Impact Factor
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    • "The social deficits, restricted interests and repetitive behaviors observed in many DBDs have been linked to a range of neural structures including limbic, cortical-striatal circuitry, and cortical gray matter volume. In ASD, common findings include: enlarged cerebellum relative to controls (Hardan et al. 2001; Minshew and Williams 2007); enlarged amygdalae (Abell et al. 1999; Groen et al. 2010; Howard et al. 2000; Juranek et al. 2006; Munson et al. 2006; Murphy et al. 2012; Schumann et al. 2004; Sparks et al. 2002), enlarged caudate (Hollander et al. 2005; Langen et al. 2007; Sears et al. 1999) and enlarged hippocampal volume (Groen et al. 2010; Rojas et al. 2004, 2006; Schumann et al. 2004; Sparks et al. 2002; see also Amaral et al. 2008 for a review; c.f. Saitoh et al. 2001 reporting reduced dentata volume in ASD). "
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    ABSTRACT: The social-cognitive deficits associated with several neurodevelopmental and neuropsychiatric disorders have been linked to structural and functional brain anomalies. Given the recent appreciation for quantitative approaches to behavior, in this study we examined the brain-behavior links in social cognition in healthy young adults from a quantitative approach. Twenty-two participants were administered quantitative measures of social cognition, including the social responsiveness scale (SRS), the empathizing questionnaire (EQ) and the systemizing questionnaire (SQ). Participants underwent a structural, 3-T magnetic resonance imaging (MRI) procedure that yielded both volumetric (voxel count) and asymmetry indices. Model fitting with backward elimination revealed that a combination of cortical, limbic and striatal regions accounted for significant variance in social behavior and cognitive styles that are typically associated with neurodevelopmental and neuropsychiatric disorders. Specifically, as caudate and amygdala volumes deviate from the typical R > L asymmetry, and cortical gray matter becomes more R > L asymmetrical, overall SRS and Emotion Recognition scores increase. Social Avoidance was explained by a combination of cortical gray matter, pallidum (rightward asymmetry) and caudate (deviation from rightward asymmetry). Rightward asymmetry of the pallidum was the sole predictor of Interpersonal Relationships and Repetitive Mannerisms. Increased D-scores on the EQ-SQ, an indication of greater systemizing relative to empathizing, was also explained by deviation from the typical R > L asymmetry of the caudate.These findings extend the brain-behavior links observed in neurodevelopmental disorders to the normal distribution of traits in a healthy sample.
    Brain Imaging and Behavior 05/2014; 9(2). DOI:10.1007/s11682-014-9304-1 · 4.60 Impact Factor
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