Atypical diffusion tensor hemispheric asymmetry in autism

Authors

  • Nicholas Lange,

    Corresponding author
    1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    2. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
    3. Neurostatistics Laboratory, McLean Hospital, Belmont, Massachusetts
    • McLean Hospital, 115 Mill Street, Belmont, MA 02478
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  • Molly B. DuBray,

    1. Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, Utah
    2. Interdepartmental Neuroscience Program, University of Utah, Salt Lake City, Utah
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  • Jee Eun Lee,

    1. Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, Utah
    2. Interdepartmental Neuroscience Program, University of Utah, Salt Lake City, Utah
    3. School of Medicine, University of Utah, Salt Lake City, Utah
    4. The Brain Institute at the University of Utah, Salt Lake City, Utah
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  • Michael P. Froimowitz,

    1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    2. Neurostatistics Laboratory, McLean Hospital, Belmont, Massachusetts
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  • Alyson Froehlich,

    1. Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, Utah
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  • Nagesh Adluru,

    1. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, Wisconsin
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  • Brad Wright,

    1. School of Medicine, University of Utah, Salt Lake City, Utah
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  • Caitlin Ravichandran,

    1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    2. Laboratory for Psychiatric Biostatistics, McLean Hospital, Belmont, Massachusetts
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  • P. Thomas Fletcher,

    1. School of Computing, University of Utah, Salt Lake City, Utah
    2. Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah
    3. The Brain Institute at the University of Utah, Salt Lake City, Utah
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  • Erin D. Bigler,

    1. Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, Utah
    2. The Brain Institute at the University of Utah, Salt Lake City, Utah
    3. Department of Psychology, Brigham Young University, Provo, Utah
    4. Neuroscience Center, Brigham Young University, Provo, Utah
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  • Andrew L. Alexander,

    1. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, Wisconsin
    2. Department of Medical Physics, University of Wisconsin, Madison, Wisconsin
    3. Department of Psychiatry, University of Wisconsin, Madison, Wisconsin
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  • Janet E. Lainhart

    1. Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, Utah
    2. Interdepartmental Neuroscience Program, University of Utah, Salt Lake City, Utah
    3. School of Medicine, University of Utah, Salt Lake City, Utah
    4. The Brain Institute at the University of Utah, Salt Lake City, Utah
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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.

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