Harris GJ, Chabris CF, Clark J, Urban T, Aharon I, Steele S et al. Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging. Brain Cogn 61: 54-68

Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Brain and Cognition (Impact Factor: 2.48). 07/2006; 61(1):54-68. DOI: 10.1016/j.bandc.2005.12.015
Source: PubMed


Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in the controls produced robust activation in Broca's area (left inferior frontal gyrus) and in superior medial frontal gyrus and right cerebellum. The ASD group had substantially reduced Broca's activation, but increased left temporal (Wernicke's) activation. Furthermore, the ASD group showed diminished activation differences between concrete and abstract words, consistent with behavioral studies. The current study suggests Broca's area is a region of abnormal neurodevelopment in ASD, which may be linked with semantic and related language deficits frequently observed in ASD.

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    • "Functional underconnectivity between frontal and posterior brain regions was first detected using a sentence comprehension task in children with high-functioning autism [Just et al., 2004]. Reduced interregional collaboration was also shown in other studies using semantic processing tasks [Harris et al., 2006; Kana et al., 2006]. In contrast to this task-dependent functional connectivity, other studies focused on spontaneous low-frequency fluctuations in BOLD signal intensity by low-pass filtering and by removing task-dependent effects from the time series data before calculating functional connectivity links. "
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    ABSTRACT: The development of language, social interaction, and communicative skills are remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the interplay between their brain connectivity and language performance remains largely understudied. Using diffusion tensor imaging tractography and resting-state fMRI, the authors explored the structural and functional connectivity of the language network and its relation to the language profile in a group of healthy control subjects (N = 25) and a group of children with ASD (N = 17). The authors hypothesized that in children with ASD, a neural connectivity deficit of the language network can be related to the observed abnormal language function. They found an absence of the right-hemispheric arcuate fascicle (AF) in 28% (7/25) of the healthy control children and in 59% (10/17) of the children with ASD. In contrast to healthy control children, the absence of the right-hemispheric AF in children with autism was related to a lower language performance as indicated by a lower verbal IQ, lower scores on the Peabody Picture Vocabulary Test, and lower language scores on the Dutch version of the Clinical Evaluation of Language Fundamentals (CELF-4NL). In addition, through iterative fMRI data analyses, the language impairment of children with ASD could be linked to a marked loss of intrahemispheric functional connectivity between inferior frontal and superior temporal regions, known as the cortical language network. Both structural and functional underconnectivity patterns coincide and are related to an abnormal language function in children with ASD. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2014; 35(8). DOI:10.1002/hbm.22424 · 5.97 Impact Factor
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    • "Individuals with ASD underactivate Crus I while processing facial and vocal stimuli (Wang et al., 2007) and during executive functioning paradigms (Solomon et al., 2009). Language tasks elicit abnormal activation in lobule VII in autistic individuals during core aspects of communication such as semantic processing (Harris et al., 2006). Lastly, children with ASD fail to engage the anterior cerebellum (lobule IV/V) during motor tasks when compared to their TD peers (Mostofsky et al., 2009). "
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    ABSTRACT: Neuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8-13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile.
    2014 International Meeting for Autism Research; 05/2014
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    • "Functional and structural neuroimaging are promising methods for investigating the neural correlates underlying the linguistic deficits in autism (Verhoeven et al., 2010; Courchesne et al., 2007). Several functional neuroimaging studies reported aberrant functioning between cortical areas on a range of language tasks (Harris et al., 2006; Just et al., 2004; Kana et al., 2006; Knaus et al., 2010), suggesting that alterations in cortical connectivity and the deficient communication among cortical regions may be part of the language difficulties seen in ASD (Courchesne, 2004; Courchesne et al., 2003). Further evidence for atypical brain connectivity of the language network in ASD has been corroborated by structural imaging studies using diffusion tensor imaging (DTI) (Barnea-Goraly et al., 2004; Fletcher et al., 2010; Keller et al., 2007; Nagae et al., 2012). "
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    ABSTRACT: The development of language, social interaction and communicative skills are remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke’s and Broca’s areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.
    Clinical neuroimaging 01/2014; 4. DOI:10.1016/j.nicl.2014.01.008 · 2.53 Impact Factor
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