Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders

Department of Psychology, University of Alabama at Birmingham, CIRC 235G, 1719 6th Avenue South, Birmingham, AL 35294, United States.
Physics of Life Reviews (Impact Factor: 7.48). 12/2011; 8(4):410-37. DOI: 10.1016/j.plrev.2011.10.001
Source: PubMed


Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to 'disrupted cortical connectivity' to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills such as Theory-of-Mind, cognitive flexibility, and information processing; and 2) how connection abnormalities relate to, and may determine, behavioral symptoms hallmarked by the triad of Impairments in ASD. Furthermore, we will relate the disrupted cortical connectivity model to existing cognitive and neural models of ASD.

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    • "ASCs are now increasingly understood to present with system-wide differences in neural information processing (Minshew and Goldstein, 1998; Belmonte et al., 2004a, 2004b; Welchew et al., 2005; Geschwind and Levitt, 2007; Kana et al., 2011; Vissers et al., 2012; Uddin et al., 2013; Di Martino et al., 2014), and are conceptualised as " nonfocal, systemic… distributed neural systems disorder[s] " (Minshew and Goldstein, 1998), rather than disorders of focal brain regions. The search for autism endophenotypes in brain connectivity is a fledgling field. "
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    ABSTRACT: This is the accepted manuscript of a paper that will be published in Neuroimage: Clinical. It is currently under an indefinite embargo.
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    • "Although spoken language impairments in ASD are widespread and pervasive, a commonly accepted model of this dysfunction is a disruption of the left fronto-temporal cortical pathway. Various lines of investigation, including structural and functional neuroimaging studies, have implicated the fronto-temporal circuitry including regions such as the left inferior frontal gyrus (IFG) and the left superior and middle temporal regions (STG, MTG) in the development of normal speech and language function , with a role in both perceptual and linguistic aspects of speech processing [Eyler, Pierce, & Courchesne, 2012; Kana, Libero, & Moore, 2011; Lai et al., 2012; Wan et al., 2012]. While extensive research has implicated this pathway in the spoken language deficit in ASD, music and song processing, which share significant perceptual as well as neural resources with speech in typical populations [Koelsch, 2011; Schön et al., 2010], remain largely unexplored in autism. "
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    ABSTRACT: Co-occurrence of preserved musical function with language and socio-communicative impairments is a common but understudied feature of Autism Spectrum Disorders (ASD). Given the significant overlap in neural organization of these processes, investigating brain mechanisms underlying speech and music may not only help dissociate the nature of these auditory processes in ASD but also provide a neurobiological basis for development of interventions. Using a passive-listening functional magnetic resonance imaging paradigm with spoken words, sung words and piano tones, we found that 22 children with ASD, with varying levels of functioning, activated bilateral temporal brain networks during sung-word perception, similarly to an age and gender-matched control group. In contrast, spoken-word perception was right-lateralized in ASD and elicited reduced inferior frontal gyrus (IFG) activity which varied as a function of language ability. Diffusion tensor imaging analysis reflected reduced integrity of the left hemisphere fronto-temporal tract in the ASD group and further showed that the hypoactivation in IFG was predicted by integrity of this tract. Subsequent psychophysiological interactions revealed that functional fronto-temporal connectivity, disrupted during spoken-word perception, was preserved during sung-word listening in ASD, suggesting alternate mechanisms of speech and music processing in ASD. Our results thus demonstrate the ability of song to overcome the structural deficit for speech across the autism spectrum and provide a mechanistic basis for efficacy of song-based interventions in ASD. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 12/2014; 8(2). DOI:10.1002/aur.1437 · 4.33 Impact Factor
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    • "In sum, the current evidence from neuroimaging research indicates partly overlapping neural mechanisms of ToM impairment in SZ and ASD, particularly with reduced activation in the left meFG, middle temporal gyrus (MTG), precuneus, right IFG, IPL and precentral gyrus and increased activation in the left IFG and right meFG. This could imply similar pathological mechanisms, such as changes in neural connectivity , grey-matter volumes and neurotransmitter abnormalities, which have been associated with both disorders (Cheung et al. 2010; Neuhaus et al. 2010; Kana et al. 2011; Coghlan et al. 2012; Coyle et al. 2012; Fitzsimmons et al. 2013; Greimel et al. 2013). "
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    ABSTRACT: Social neuroscience is a flourishing, interdisciplinary field that investigates the underlying biological processes of social cognition and behaviour. The recent application of social neuroscience to psychiatric research advances our understanding of various psychiatric illnesses that are characterized by impairments in social cognition and social functioning. In addition, the upcoming line of social neuroscience research provides new techniques to design and evaluate treatment interventions that are aimed at improving patients' social lives. This review provides a contemporary overview of social neuroscience in psychiatry. We draw together the major findings about the neural mechanisms of social cognitive processes directed at understanding others and social interactions in psychiatric illnesses and discuss their implications for future research and clinical practice.
    Psychological Medicine 10/2014; 45(06):1-21. DOI:10.1017/S0033291714002487 · 5.94 Impact Factor
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