Gyrification patterns in monozygotic twin pairs varying in discordance for autism

Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York 13210, USA.
Autism Research (Impact Factor: 4.33). 10/2009; 2(5):267-78. DOI: 10.1002/aur.98
Source: PubMed


In order to disentangle genetic and environmental contributions to cortical anomalies in children with autism, we investigated cortical folding patterns in a cohort of 14 monozygotic (MZ) twin pairs who displayed a range of phenotypic discordance for autism, and 14 typically developing community controls. Cortical folding was assessed with the gyrification index, which was calculated on high resolution anatomic MR images. We found that the cortical folding patterns across most lobar regions of the cerebral cortex was highly discordant within MZ twin pairs. In addition, children with autism and their co-twins exhibited increased cortical folding in the right parietal lobe, relative to age- and gender-matched typical developing children. Increased folding in the right parietal lobe was associated with more symptoms of autism for co-twins. Finally, the robust association between cortical folding and IQ observed in typical children was not observed in either children with autism or their co-twins. These findings, which contribute to our understanding of the limits of genetic liability in autism, suggest that anomalies in the structural integrity of the cortex in this PDD may disrupt the association between cortical folding and intelligence that has been reported in typical individuals, and may account, in part, for the deficits in visual spatial attention and in social cognition that have been reported in children with autism.

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    • "Overall, there are converging lines of evidence consistent with differential expansion being a mechanism for gyrification; the idea of connectivity as the primary function of gyrification has generally not been supported (Sun and Hevner, 2014; Ronan et al., 2014; for studies modeling increased cortical thickness without gyrification, see Murre and Sturdy, 1995 and Ruppin et al., 1993). Of the small number of gyrification studies published to date, the phenotype has been studied largely in relation to neuropsychiatric disorders such as Alzheimer's disease, autism, velocardial facial syndrome, and schizophrenia (Liu et al., 2012; Wallace et al., 2013; Schaer et al., 2006, 2013; Kates et al., 2009; Palaniyappan and Liddle, 2012; Nanda et al., 2013). Wallace et al. (2013) reported that while autism-spectrum cases did not differ from controls in SA, they exhibited significant posterior gyrification increases bilaterally. "
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    ABSTRACT: The phenotypic and genetic relationship between global cortical size and general cognitive ability (GCA) appears to be driven by surface area (SA) and not cortical thickness (CT). Gyrification (cortical folding) is an important property of the cortex that helps to increase SA within a finite space, and may also improve connectivity by reducing distance between regions. Hence, gyrification may be what underlies the SA-GCA relationship. In previous phenotypic studies, a 3-dimensional gyrification index (3DGI) has been positively associated with cognitive ability and negatively associated with mild cognitive impairment, Alzheimer's disease, and psychiatric disorders affecting cognition. However, the differential genetic associations of 3DGI and SA with GCA are still unclear. We examined the heritability of 3DGI, and the phenotypic, genetic, and environmental associations of 3DGI with SA and GCA in a large sample of adult male twins (N =512). Nearly 85% of the variance in 3DGI was due to genes, and 3DGI had a strong phenotypic and genetic association with SA. Both 3DGI and total SA had positive phenotypic correlations with GCA. However, the SA-GCA correlation remained significant after controlling for 3DGI, but not the other way around. There was also significant genetic covariance between SA and GCA, but not between 3DGI and GCA. Thus, despite the phenotypic and genetic associations between 3DGI and SA, our results do not support the hypothesis that gyrification underlies the association between SA and GCA. Copyright © 2014 Elsevier Inc. All rights reserved.
    NeuroImage 11/2014; 106. DOI:10.1016/j.neuroimage.2014.11.040 · 6.36 Impact Factor
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    • "ASD on one 2D coronal slice. Using more advanced computation of gyrification on the cortical surface extracted from 3D images, (Kates et al., 2009) and (Wallace et al., 2013) also revealed "
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    ABSTRACT: Autism Spectrum Disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from a general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology.
    Clinical neuroimaging 03/2014; 4. DOI:10.1016/j.nicl.2014.03.008 · 2.53 Impact Factor
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    • "Measuring gyrification abnormalities at any age may signal early adverse events and contribute to our understanding of both the timing and the nature of brain alterations in neurodevelopmental disorders. Previous studies have noted alterations to cortical shape in autism (Levitt et al., 2003; Nordahl et al., 2007; Shokouhi et al., 2012), and some have used the Gyrification Index (GI; Hardan et al., 2004; Casanova et al., 2009; Kates et al., 2009; Jou et al., 2010; Meguid et al., 2010). Given that the cortex grows primarily through radial expansion (Rakic, 1988), the GI was specifically designed to identify early defects in cortical development. "
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    ABSTRACT: The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anistropy and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism.
    Frontiers in Human Neuroscience 11/2013; 7:750. DOI:10.3389/fnhum.2013.00750 · 3.63 Impact Factor
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