Alterations in Frontal Lobe Tracts and Corpus Callosum in Young Children with Autism Spectrum Disorder

Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA.
Cerebral Cortex (Impact Factor: 8.67). 12/2009; 20(9):2103-13. DOI: 10.1093/cercor/bhp278
Source: PubMed


Major frontal lobe tracts and corpus callosum (CC) were investigated in 32 children with autism spectrum disorder (ASD, mean age: 5 years), 12 nonautistic developmentally impaired children (DI, mean age: 4.6 years), and 16 typically developing children (TD, mean age: 5.5 years) using diffusion tensor imaging tractography and tract-based spatial statistics. Various diffusion and geometric properties were calculated for uncinate fasciculus (UF), inferior fronto-occipital fasciculus (IFO), arcuate fasciculus (AF), cingulum (Cg), CC, and corticospinal tract. Fractional anisotropy was lower in the right UF, right Cg and CC in ASD and DI children; in right AF in ASD children; and in bilateral IFO in DI children, compared with TD children. Apparent diffusion coefficient was increased in right AF in both ASD and DI children. The ASD group showed shorter length of left UF and increased length, volume, and density of right UF; increased length and density of CC; and higher density of left Cg, compared with the TD group. Compared with DI group, ASD group had increased length, volume, and density of right UF; higher volume of left UF; and increased length of right AF and CC. Volume of bilateral UF and right AF and fiber density of left UF were positively associated with autistic features.

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Available from: Malek Makki, Apr 28, 2015
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    • "For example,Chen et al. (2011)reported a negative correlation between white matter indices and social deficits in ASD, where increased Social Responsiveness Scale scores correlated with reduced fractional anisotropy in right uncinate fasciculus. SimilarlyKumar et al. (2010)used tractography to show that macrostructural alterations within the uncinate fasciculus in ASD were correlated with the severity of symptoms, including socio-emotional deficits, on the Gilliam Autism Rating Scale. One interesting study that used DTI after a communication intervention in 22 low functioning young males with ASD found a positive correlation of uncinate fasciculus fractional anisotropy with both therapy duration and symptom improvement measured using the Child Autism Rating Scale (Pardini et al., 2012). "
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    ABSTRACT: It has been postulated that autism spectrum disorder is underpinned by an ‘atypical connectivity’ involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a ‘whole brain’ non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate—predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.
    Full-text · Article · Jan 2016 · Brain
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    • "The uncinate fasciculus has been linked to different aspects of social development (Elison et al., 2013), recognition of complex emotions (Fujie et al., 2008), semantic cognition (Catani et al., 2013a,b; Catani and Mesulam, 2008; Catani and Bambini, 2014), and social behavior (D'Anna et al., in press). Damage to this network is related to deficits in socio-emotional processing in disorders such as autism (Pugliese et al., 2009; Kumar et al., 2010; Thomas et al., 2011;, in press), psychopathy (), borderline personality disorder (Lischke et al., 2015), apathy (Hollocks et al., 2015), mood disorders (McIntosh et al., 2008; Carballedo et al., 2012; Zhang et al., 2012), obsessive-compulsive disorder (Peng et al., 2014), anorexia nervosa (Lipsman et al., 2015), and alcoholism (Schulte et al., 2012). Overall, individual differences in socio-emotional behaviour and vulnerability to specific neuropsychiatric disorders have been associated with the variability in the structure of the three limbic networks listed above. "
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    ABSTRACT: Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum (medial default-mode network), the ventral cingulum and the fornix (hippocampal-diencephalic-retrosplenial network) and the uncinate fasciculus (temporo-amygdala-orbitofrontal network). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, i.e. fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.
    Full-text · Article · Dec 2015 · Social Cognitive and Affective Neuroscience
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    • "years [Weinstein et al., 2011], and 0.5–2 years [Wolff et al., 2012]. In contrast, reduced WM integrity with lower FA and higher MD has also been found in various WM regions in slightly older children with ASD of 4.79 6 2.43 years [Sundaram et al., 2008], 2.5–8.9 years [Kumar et al., 2010], and 2–8 years [Walker et al., 2012]. Thus, WM microstructural changes of ASD are both regionand age-dependent, especially in early development. "
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    ABSTRACT: Atypical age-dependent changes of white matter (WM) microstructure play a central role in abnormal brain maturation of the children with autism spectrum disorder (ASD), but their early manifestations have not been systematically characterized. The entire brain core WM voxels were surveyed to detect differences in WM microstructural development between 31 children with ASD of 2-7 years and 19 age-matched children with typical development (TD), using measurements of fractional anisotropy (FA) and radial diffusivity (RD) from diffusion tensor imaging (DTI). The anatomical locations, distribution, and extent of the core WM voxels with atypical age-dependent changes in a specific tract or tract group were delineated and evaluated by integrating the skeletonized WM with a digital atlas. Exclusively, unidirectional FA increases and RD decreases in widespread WM tracts were revealed in children with ASD before 4 years, with bi-directional changes found for children with ASD of 2-7 years. Compared to progressive development that raised FA and lowered RD during 2-7 years in the TD group, flattened curves of WM maturation were found in multiple major WM tracts of all five tract groups, particularly associational and limbic tracts, in the ASD group with trend lines of ASD and TD crossed around 4 years. We found atypical age-dependent changes of FA and RD widely and heterogeneously distributed in WM tracts of children with ASD. The early higher WM microstructural integrity before 4 years reflects abnormal neural patterning, connectivity, and pruning that may contribute to aberrant behavioral and cognitive development in ASD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Dec 2015 · Human Brain Mapping
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