The Disrupted Connectivity Hypothesis of Autism Spectrum Disorders: Time for the Next Phase in Research

During the past decade, the disrupted connectivity theory has generated considerable interest as a pathophysiologic model for autism spectrum disorder (ASD). This theory postulates that deficiencies in the way the brain coordinates and synchronizes activity among different regions may account for the clinical symptoms of ASD. This review critically examines the current structural and functional connectivity data in ASD and evaluates unresolved assumptions and gaps in knowledge that limit the interpretation of these data. Collectively, studies often show group alterations in what are thought of as measures of cerebral connectivity, although the patterns of findings vary considerably. There are three principal needs in this research agenda. First, further basic research is needed to understand the links between measures commonly used (e.g., diffusion tensor imaging, functional magnetic resonance imaging, electroencephalography) and other (e.g., histologic, computational) levels of analysis. Second, speculated causes of inconsistencies in the literature (e.g., age, clinical heterogeneity) demand studies that directly evaluate these interpretations. Third, the field needs well-specified mechanistic models of altered cerebral communication in ASD whose predictions can be tested on multiple levels of analysis.