Underconnected, but How? A Survey of Functional Connectivity MRI Studies in Autism Spectrum Disorders

Abstract

Growing consensus suggests that autism spectrum disorders (ASD) are associated with atypical brain networks, thus shifting the focus to the study of connectivity. Many functional connectivity studies have reported underconnectivity in ASD, but results in others have been divergent. We conducted a survey of 32 functional connectivity magnetic resonance imaging studies of ASD for numerous methodological variables to distinguish studies supporting general underconnectivity (GU) from those not consistent with this hypothesis (NGU). Distinguishing patterns were apparent for several data analysis choices. The study types differed significantly with respect to low-pass filtering, task regression, and whole-brain field of view. GU studies were more likely to examine task-driven time series in regions of interest, without the use of low-pass filtering. Conversely, NGU studies mostly applied task regression (for removal of activation effects) and low-pass filtering, testing for correlations across the whole brain. Results thus suggest that underconnectivity findings may be contingent on specific methodological choices. Whereas underconnectivity reflects reduced efficiency of within-network communication in ASD, diffusely increased functional connectivity can be attributed to impaired experience-driven mechanisms (e.g., synaptic pruning). Both GU and NGU findings reflect important aspects of network dysfunction associated with sociocommunicative, cognitive, and sensorimotor impairments in ASD.

Epilepsy and Autism

“…Similar to the rodent studies, there is increasing evidence from both imaging and neurophysiologic studies pointing to altered brain connectivity as a key feature of the pathophysiology of ASD (Casanova and Trippe 2009;Dinstein et al 2011;Kana et al 2011;Muller et al 2011). Additionally, there is some evidence that the changes in neuronal organization in ASD are differentially expressed with age, marked by early life brain overgrowth including increased neuron number, followed by decreases in both structural volumes and neuron number as the brain ages.…”

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

“…While defining subtypes of ASD based on FC may help to resolve some discrepancies in the literature regarding the nature of FC in ASD, it has been proposed that differences in analysis approaches between studies are the most likely causes of inconsistent results between studies of FC in ASD (Hull et al, 2016). For instance, Muller et al (2011) found that studies supporting the "general underconnectivity" hypothesis of ASD were more likely to not use lowpass filtering and to utilize ROIs as opposed to whole-brain analyses. It has also been reported that removal of the global signal alters group differences in FC observed between participants with ASD and TD participants (Gotts et al, 2013).…”

Default mode network in young male adults with autism spectrum disorder: Relationship with autism spectrum traits

“…Rs-FCs of DMN are significantly affected by the head motion of participants during fMRI scanning; that is, long-distance correlations are decreased by participant motion, whereas many short-distance correlations are increased [43][44][45][46][47]. To investigate the effect of head motion and motion artifacts in rs-FCs, the root mean square (RMS) of six movement parameters obtained in the realignment process (x-, y-, z translations and x-, y-, z rotations), mean frame-to-frame RMS motion [43] and frame-wise displacement (FD) [45] were calculated for each participant.…”