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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    • "Many neuroimaging studies, using both functional MRI (fMRI) and diffusion tensor imaging (DTI) done during both task-specific (Koshino et al., 2005; Koshino et al., 2008; Just et al., 2007; Kana et al., 2006) and resting-state (idle) conditions (Cherkassky et al., 2006; Weng et al., 2010), have shown that individuals with ASD have reduced longrange (distant) brain connectivity when compared to people with neurotypical development. A separate set of studies have shown reduced short-range (local) connectivity (Kana et al., 2011; Koshino et al., 2005; Koshino et al., 2008; Just et al., 2007). Yet results from other studies have demonstrated increases in connectivity, both longrange (Cheng et al., 2010; Ben Bashat et al., 2007; Supekar et al., 2013) and short-range (Weng et al., 2010; Anderson et al., 2011; Khan et al., 2013; Lewis et al., 2013; Keown et al., 2013). "
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    ABSTRACT: Background: While there is increasing evidence of altered brain connectivity in autism, the degree and direction of these alterations in connectivity and their uniqueness to autism has not been established. The aim of the present study was to compare connectivity in children with autism to that of typically developing controls and children with developmental delay without autism. Methods: We assessed EEG spectral power, coherence, phase lag, Pearson and partial correlations, and epileptiform activity during the awake, slow wave sleep, and REM sleep states in 137 children aged 2 to 6. years with autism (n = 87), developmental delay without autism (n = 21), or typical development (n = 29). Findings: We found that brain connectivity, as measured by coherence, phase lag, and Pearson and partial correlations distinguished children with autism from both neurotypical and developmentally delayed children. In general, children with autism had increased coherence which was most prominent during slow wave sleep. Interpretation: Functional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity.
    Full-text · Article · Nov 2015 · EBioMedicine
    • "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.
    No preview · Article · Sep 2015 · IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM
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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.
    Full-text · Article · Jul 2015
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