Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder

Abstract

One of the most widely cited features of the neural phenotype of autism is reduced "integrity" of long-range white matter tracts, a claim based primarily on diffusion imaging studies. However, many prior studies have small sample sizes and/or fail to address differences in data quality between those with autism spectrum disorder (ASD) and typical participants, and there is little consensus on which tracts are affected. To overcome these problems, we scanned a large sample of children with autism (n = 52) and typically developing children (n = 73). Data quality was variable, and worse in the ASD group, with some scans unusable because of head motion artifacts. When we follow standard data analysis practices (i.e., without matching head motion between groups), we replicate the finding of lower fractional anisotropy (FA) in multiple white matter tracts. However, when we carefully match data quality between groups, all these effects disappear except in one tract, the right inferior longitudinal fasciculus (ILF). Additional analyses showed the expected developmental increases in the FA of fiber tracts within ASD and typical groups individually, demonstrating that we had sufficient statistical power to detect known group differences. Our data challenge the widely claimed general disruption of white matter tracts in autism, instead implicating only one tract, the right ILF, in the ASD phenotype.diffusion-weighted imaging | connectivity W hat is the key difference in the brains of individuals with autism that accounts for the distinctive cognitive profile of this disorder? One of the most widely claimed brain signatures of autism spectrum disorder (ASD), reported in dozens of papers that used diffusion-weighted imaging (DWI), is reduced integrity of long-range fiber tracts (1). This finding has been taken as evidence that autism is fundamentally a "disconnection" syndrome, in which the core cognitive deficits result from reduced integration of information at the neural and cognitive levels (2-5). For example, it has been argued that the characteristic deficits in social cognition and language arise because these functions require rapid integration of information across spatially distant brain areas (3, 6, 7), which would likely be affected if major white matter tracts are compromised.Evidence for a general reduction in the "integrity"* of white matter in autism has come primarily from diffusion imaging studies that report reduced directionality of the diffusion of water molecules, or fractional anisotropy (FA), and increased speed of diffusion, or mean diffusivity (MD) of many major fiber bundles. However, the literature reveals little actual agreement on the existence and direction of group differences in diffusion parameters (reviewed in ref. 1). White-matter differences have been reported in various brain regions in positive and negative directions. Possible reasons for these inconsistent findings include small sample sizes [mean of ∼20 in each group, with 40% of studies scanning 15 or fewer participants with ASD (1)...

ASD Validity

“…Kirkovski et al (2015) found no differences between high functioning individuals with ASD and typical controls in white matter in major tract bundles determined by any method: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), or axial diffusivity (AD). Koldewyn et al (2014) reported finding no general impaired white matter in ASD. Lefebvre et al (2015) found no differences between 694 individuals diagnosed with ASD and typical controls in the largest white matter tract in the brain-the corpus callosum.…”

Studying Brain Organization via Spontaneous fMRI Signal

“…The literature on techniques to identify and remove motion artifact is currently one of the most rapidly evolving fronts of functional connectivity MRI (e.g., (Bright and Murphy, 2013; Kundu et al, 2013; Power et al, 2014; Yan et al, 2013)), and multiple methods now exist that have evidence for removing much or nearly all motion artifact from resting state datasets. The problems caused by small movements are unfortunately not limited to functional connectivity MRI: previously unrecognized effects of small movements, capable of causing spurious group differences, have recently been reported in the structural connectivity MRI literature (e.g., (Koldewyn et al, 2014; Yendiki et al, 2013)).…”

Motion‐related artifacts in structural brain images revealed with independent estimates of in‐scanner head motion

“…Substantial emphasis has been placed on characterizing how motion‐induced artifacts affect echo‐planar imaging (EPI): both in functional MRI [fMRI; Power et al, 2014; Satterthwaite et al, 2012; Siegel et al, 2014; Van Dijk et al, 2012; Zeng et al, 2014] and diffusion weighted imaging [DWI; Koldewyn et al, 2014; Thomas et al, 2014; Yendiki et al, 2013]. There has been less focus on characterizing how spurious motion‐related biases impact high‐resolution T1‐weighted (T1w) images.…”