Atypical measures of diffusion at the gray-white matter boundary in autism spectrum disorder in adulthood

Anke Bletsch, Tim Schafer, Caroline Mann, Derek Sayre Andrews, Eileen M Daly, Maria Gudbrandsen, Amber N. V. Ruigrok, Robert Dallyn, Rafael Romero-Garcia, Meng-Chuan Lai, Michael V. Lombardo, Michael C. Craig, John Suckling, Edward T. Bullmore, Simon Baron-Cohen, Declan G. M. Murphy, Flavio Dell'Acqua, Christine Ecker

Research output: Contribution to journalArticlepeer-review


Autism spectrum disorder (ASD) is a highly complex neurodevelopmental condition that is accompanied by neuroanatomical differences on the macroscopic and microscopic level. Findings from histological, genetic, and more recently in vivo neuroimaging studies converge in suggesting that neuroanatomical abnormalities, specifically around the gray-white matter (GWM) boundary, represent a crucial feature of ASD. However, no research has yet characterized the GWM boundary in ASD based on measures of diffusion. Here, we registered diffusion tensor imaging data to the structural T1-weighted images of 92 adults with ASD and 92 matched neurotypical controls in order to examine between-group differences and group-by-sex interactions in fractional anisotropy and mean diffusivity sampled at the GWM boundary, and at different sampling depths within the superficial white and into the gray matter. As hypothesized, we observed atypical diffusion at and around the GWM boundary in ASD, with between-group differences and group-by-sex interactions depending on tissue class and sampling depth. Furthermore, we identified that altered diffusion at the GWM boundary partially (i.e., ~50%) overlapped with atypical gray-white matter tissue contrast in ASD. Our study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.

Original languageEnglish
Pages (from-to)467-484
Number of pages18
Issue number2
Publication statusPublished - 1 Feb 2021


  • diffusion tensor imaging
  • multimodal imaging
  • myelinated and unmyelinated gray matter
  • superficial white matter

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