A theoretical rut: revisiting and critically evaluating the generalized under/over-connectivity hypothesis of autism.

In 2004, two papers proposed that pervasive functional under-connectivity (Just et al., ) or a trade-off between excessive local connectivity at the cost of distal under-connectivity (Belmonte et al., ) characterizes atypical brain organization in autism. Here, we take stock of the most recent and rigorous functional and structural connectivity findings with a careful eye toward evaluating the extent to which they support these original hypotheses. Indeed, the empirical data do not support them. From rsfMRI studies in adolescents and adults, there is an emerging consensus regarding long-range functional connections indicating cortico-cortical under-connectivity, specifically involving the temporal lobes, combined with subcortical-cortical over-connectivity. In contrast, there is little to no consensus regarding local functional connectivity or findings from task-based functional connectivity studies. The structural connectivity data suggest that white matter tracts are pervasively weak, particularly in the temporal lobe. Together, these findings are revealing how deeply complex the story is regarding atypical neural network organization in autism. In other words, distance and strength of connectivity as individual factors or as interacting factors do not consistently explain the patterns of atypical neural connectivity in autism. Therefore, we make several methodological recommendations and highlight developmental considerations that will help researchers in the field cultivate new hypotheses about the nature and mechanisms of potentially aberrant functional and structural connectivity in autism.