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

Abstract

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.

Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling

“…However, this apparent inconsistency could be reconciled by characterising these findings as evidence of a local dysregulation of optimal processing that may present as either increased or decreased gamma band power depending on context and task and/or on the symptom profile of the ASD cohort. This would mirror the heterogeneity evident in ASD, a factor which is noted in other reviews of ASD research and interpretation (Dickinson et al, 2016;Picci et al, 2016;Simon & Wallace, 2016).…”

“…The study of neuronal circuit dysfunction specifically in ASD has formed a major part in connectivity research and has, similarly, been the subject of a number of reviews (Belmonte et al, 2004;Geschwind & Levitt, 2007;Hahamy et al, 2015;Müller et al, 2011;Rippon et al, 2007;Vissers, Cohen, & Geurts, 2012;Wass, 2011;Picci, Gotts, & Scherf, 2016). The consensus from early findings of task-related activity was of accumulating evidence of longdistance structural and functional underconnectivity between specialised cortical regions underpinning a wide-range of perceptual and cognitive processes (Hughes, 2007;Just, Cherkassky, Keller, Kana, & Minshew, 2007;Just, Cherkassky, Keller, & Minshew, 2004;Koshino et al, 2008).…”

“…A recent review by Picci et al, 2016 pointed out that several studies have reported connectivity patterns varying with symptom severity, thus suggesting that the 'heterogeneity' issue is also evident in the cortical as well as the symptom profiling of ASD and should be taken into account in exploring the possibility that measures of cortical connectivity might serve as a useful endophenotype in ASD (Moseley et al, 2015;Simon & Wallace, 2016).…”

Is functional brain connectivity atypical in autism? A systematic review of EEG and MEG studies

“…A popular hypothesis considers autism to be characterized by long-range underconnectivity potentially combined with local overconnectivity [6,25–27]. This hypothesis is predominantly supported by structural and functional MRI and post-mortem immunocytochemistry investigations.…”

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

“…However, complex patterns of both increased and decreased FC have been found in neuroimaging studies of ASD, and results are inconsistent across studies (see Hull et al, 2016;Picci et al, 2016;and Uddin et al, 2013b for reviews). Further, there has yet to be a framework describing atypical FC in ASD that is supported consistently across studies.…”