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

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.