Abstract
BackgroundOne of the most reported neural features of autism spectrum disorder (ASD) is the alteration of multiple long-range white matter fiber tracts, as assessed by diffusion-weighted imaging and indexed by reduced fractional anisotropy (FA). Recent methodological advances, however, have shown that this same pattern of reduced FA may be an artifact resulting from excessive head motion and poorer data quality and that aberrant structural connectivity in children with ASD is confined to the right inferior longitudinal fasciculus (ILF). This study aimed at replicating the observation of reduced FA along the right ILF in ASD, while controlling for group differences in head motion and data quality. In addition, we explored associations between reduced FA in the right ILF and quantitative ASD characteristics, and the involvement of the right ILF in visual processing, which is known to be altered in ASD.MethodGlobal probabilistic tractography was performed on diffusion-weighted imaging data of 17 adolescent boys with ASD and 17 typically developing boys, matched for age, performance IQ, handedness, and data quality. Four tasks were administered to measure various aspects of visual information processing, together with questionnaires assessing ASD characteristics. Group differences were examined and the neural data were integrated with previously published findings using Bayesian statistics to quantify evidence for replication and to pool data and thus increase statistical power. (Partial) correlations were calculated to investigate associations between measures.ResultsThe ASD group showed consistently reduced FA only in the right ILF and slower performance on the visual search task. Bayesian statistics pooling data across studies confirmed that group differences in FA were confined to the right ILF only, with the evidence for altered FA in the left ILF being indecisive. Lower FA in the right ILF tended to covary with slower visual search and a more fragmented part-oriented processing style. Individual differences in FA of the right ILF were not reliably associated with the severity of ASD traits after controlling for clinical status.ConclusionOur findings support the growing evidence for reduced FA along a specific fiber tract in ASD, the right ILF.
Highlights
One of the most reported neural features of autism spectrum disorder (ASD) is the alteration of multiple long-range white matter fiber tracts, as assessed by diffusion-weighted imaging and indexed by reduced fractional anisotropy (FA)
Statistics for the diffusion-weighted imaging (DWI) data quality measures average volume-by-volume translation, average volume-byvolume rotation, percentage of slices with signal dropout, and average signal drop-out severity are displayed in Table 2 and indicate that groups were well matched in terms of DWI data quality
Given our aim to replicate the findings of Koldewyn and colleagues [16], we primarily focused on the FA values of the white matter tracts, especially of the right inferior longitudinal fasciculus (ILF)
Summary
One of the most reported neural features of autism spectrum disorder (ASD) is the alteration of multiple long-range white matter fiber tracts, as assessed by diffusion-weighted imaging and indexed by reduced fractional anisotropy (FA). Reduced diffusivity along the principal axis (i.e., axial diffusivity or AD) and increased diffusivity perpendicular to it (i.e., radial diffusivity or RD), resulting in a reduced directionality of diffusion (i.e., lower fractional anisotropy or FA), are considered indicative of reduced white matter integrity and reduced structural connectivity [11] This interpretation might be misleading as the exact microstructural and macrostructural substrates of reduced FA are only partly understood (e.g., axonal density, axonal diameter, degree of myelination, homogeneity of axon orientation) [12, 13]. In the present report, we will refer to the observed diffusion properties per se, without making inferences about white matter integrity
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