Abstract
BackgroundThere is a lack of agreement about functional connectivity differences in individuals with autism spectrum disorder (ASD). Studies using absolute strength have found reduced connectivity, while those using relative strength––a measure of system topology––reveal mostly enhanced connectivity. We hypothesized that mixed findings may be driven by the metric of functional connectivity.MethodsResting-state echo planar 3 T functional magnetic resonance imaging scans were acquired on a Siemens Verio Scanner from 6 to 17-year-old youth with ASD (n = 81) and a matched typically developing control group (n = 82). All functional time series data were preprocessed using a confound regression procedure that has been previously validated in large-scale developmental datasets. It has also been shown to be highly effective at reducing the influence of motion artifact on connectivity data. We extracted time series data from a 333-node parcellation scheme, which was previously mapped to 13 functional systems. A Pearson’s correlation was calculated and transformed to Fisher’s z between every pair of nodes to create a weighted 333 × 333 adjacency matrix. Mean absolute functional connectivity strength was the mean Fisher’s z of the matrix. Relative functional connectivity was corrected for individual differences in mean absolute functional connectivity (i.e., each connection in the matrix was divided by their mean z), and functional connectivity was evaluated within and across each of the functional networks in the parcellation scheme.ResultsAbsolute functional connectivity strength was lower in ASD, and lower functional connectivity was correlated with greater ASD symptom severity. Relative functional connectivity was higher for the ASD group in the ventral attention and retrosplenial-temporal systems, with lower cross-system functional connectivity between the ventral attention and somatomotor-mouth systems. Functional connectivity within the ventral attention and retro-splenial systems correlated significantly with ASD symptom severity.ConclusionsWithin a context of globally weaker functional connectivity, youth with ASD have an atypical topology of brain systems that support social perception and communication. This study clarifies the mixed results reported previously and demonstrates that the functional connectivity metric influences the observed direction of functional connectivity differences for individuals with ASD.
Highlights
There is a lack of agreement about functional connectivity differences in individuals with autism spectrum disorder (ASD)
When looking for global functional connectivity properties, we evaluate the absolute strength of functional connections in the brain—do individuals with ASD have stronger or weaker connections among brain regions compared to those without ASD? When looking at the topology of functional connectivity patterns, we evaluate the relative strength of these connections—do individuals with ASD show a different pattern of functional connectivity within and across cognitive systems compared to those without ASD? While topology is often measured with graph-theory metrics in neuroscience [28], in the mathematics literature, the pattern of edge weights can be described as composing the network’s topology
Diminished absolute mean connectivity strength in youth with ASD The absolute mean connectivity strength was lower in youth with ASD (Fisher’s z M = 0.05, SD = 0.03) than Typically developing control (TDC) (Fisher’s z M = 0.07, SD = 0.05) after controlling for age, sex, IQ, in-scanner motion, and scan sequence, F(1, 156) = 6.50, p = 0.01, η2p = 0.04, 95% confidence interval (CI) = [−0.007, −0.032])
Summary
There is a lack of agreement about functional connectivity differences in individuals with autism spectrum disorder (ASD). Autism spectrum disorder (ASD) occurs in ~1.5% [1] of the population, a prevailing hypothesis is that perturbations of the functional connections among brain regions are associated with several functional impairments [2,3,4,5]. Initial resting-state functional connectivity studies in ASD targeted regions comprising a single system (e.g., regions supporting vision) or a handful of systems [4,5,6, 9,10,11,12, 16, 17, 19,20,21,22,23] These studies led to an early hypothesis of reduced functional connectivity in ASD [24]. A limitation to this early research is that conclusions were being drawn from data that excluded multiple cognitive systems
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