Atypical diffusion tensor hemispheric asymmetry in autism

Abstract

Background: Biological measurements that distinguish individuals with autism from typically developing individuals and those with other developmental and neuropsychiatric disorders must demonstrate very high performance to have clinical value as potential imaging biomarkers. We hypothesized that further study of white matter microstructure (WMM) in the superior temporal gyrus (STG) and temporal stem (TS), two brain regions in the temporal lobe containing circuitry central to language, emotion, and social cognition, would identify a useful combination of classification features and further understand autism neuropathology.

Methods: WMM measurements from the STG and TS were examined from 30 high-functioning males satisfying full criteria for idiopathic autism aged 7-28 years and 30 matched controls and a replication sample of 12 males with idiopathic autism and 7 matched controls who participated in a previous case-control diffusion tensor imaging (DTI) study. Language functioning, adaptive functioning, and psychotropic medication usage were also examined.

Results: In the STG, we find reversed hemispheric asymmetry of two separable measures of directional diffusion coherence, tensor skewness, and fractional anisotropy. In autism, tensor skewness is greater on the right and fractional anisotropy is decreased on the left. We also find increased diffusion parallel to white matter fibers bilaterally. In the right not left TS, we find increased omnidirectional, parallel, and perpendicular diffusion. These six multivariate measurements possess very high ability to discriminate individuals with autism from individuals without autism with 94% sensitivity, 90% specificity, and 92% accuracy in our original and replication samples. We also report a near-significant association between the classifier and a quantitative trait index of autism and significant correlations between two classifier components and measures of language, IQ, and adaptive functioning in autism.

Figure 1

Example tensor skewness (TSkew) shapes over the skewness range. All shapes have the same fractional anisotropy level (FA).

Figure 2

Example segmentation of the superior temporal gyrus and temporal stem. A. Raw B. Masked for white matter only

Figure 3

Bivariate plots of the six-dimensional multivariate classifier. Typically developing control values are indicated by open circles, individuals with autism by filled circles. White regions correspond to the combination of tensor coefficients that identifies an individual with autism.