Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder

Bradley S. Peterson, Ariana Zargarian, Jarod B. Peterson, Suzanne Goh, Siddhant Sawardekar, Steven C.R. Williams, David J. Lythgoe, Fernando O. Zelaya, Ravi Bansal

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25 Citations (Scopus)
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Background Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with Autism Spectrum Disorder (ASD). Methods We acquired pulsed arterial spin labeling MRI data in 44 generally high functioning ASD simplex participants and 66 typically developing (TD) controls with comparable mean full-scale IQ’s. We compared rCBF values voxel-wise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with NAA (N-acetylaspartate) metabolite levels. Results We detected significantly higher rCBF values throughout frontal white matter and subcortical gray in ASD participants. rCBF correlated positively with socialization deficits in regions where ASD hyperperfusion was greatest. rCBF declined with increasing IQ in the TD group, a correlation that was absent in ASD participants because their rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with NAA metabolite levels throughout frontal white matter, with greater rCBF accompanying lower and increasingly abnormal NAA levels relative to TD controls. Conclusions These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning, and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.
Original languageEnglish
JournalBiological psychiatry
Early online date21 Dec 2018
Publication statusE-pub ahead of print - 21 Dec 2018


  • Autism
  • Magnetic Resonance Imaging
  • Arterial Spin Labeling
  • white matter
  • glia
  • cerebral blood flow


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