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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    • "Additionally , some recent reviews have highlighted a more complex general picture, which also considers hyperconnectivity (depending on the cognitive state, i.e., during a task). These authors propose a scenario where abnormalities should be analyzed from a neurodevelopmental trajectories perspective (Kana et al., 2011; Uddin et al., 2013; Nair et al., 2014). "
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    ABSTRACT: Recent studies have suggested abnormal brain network organization in subjects with Autism Spectrum Disorders (ASD). Here we applied spectral clustering algorithm, diverse centrality measures (betweenness (BC), clustering (CC), eigenvector (EC), and degree (DC)), and also the network entropy (NE) to identify brain sub-systems associated with ASD. We have found that BC increases in the following ASD clusters: in the somatomotor, default-mode, cerebellar, and fronto-parietal. On the other hand, CC, EC, and DC decrease in the somatomotor, default-mode, and cerebellar clusters. Additionally, NE decreases in ASD in the cerebellar cluster. These findings reinforce the hypothesis of under-connectivity in ASD and suggest that the difference in the network organization is more prominent in the cerebellar system. The cerebellar cluster presents reduced NE in ASD, which relates to a more regular organization of the networks. These results might be important to improve current understanding about the etiological processes and the development of potential tools supporting diagnosis and therapeutic interventions.
    IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM 09/2015; DOI:10.1109/TCBB.2015.2476787 · 1.44 Impact Factor
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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: Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.
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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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