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

Biol Psychiatry. 2019 Apr 1;85(7):584-595. doi: 10.1016/j.biopsych.2018.11.026. Epub 2018 Dec 21.

Abstract

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 magnetic resonance imaging data in 44 generally high-functioning participants with ASD simplex and 66 typically developing control subjects with comparable mean full-scale IQs. We compared rCBF values voxelwise 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 N-acetylaspartate metabolite levels.

Results: We detected significantly higher rCBF values throughout frontal white matter and subcortical gray matter in participants with ASD. rCBF correlated positively with socialization deficits in participants with ASD in regions where hyperperfusion was greatest. rCBF declined with increasing IQ in the typically developing group, a correlation that was absent in participants with ASD, whose rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with N-acetylaspartate metabolite levels throughout the frontal white matter, with greater rCBF accompanying lower and increasingly abnormal N-acetylaspartate levels relative to those of typically developing control subjects.

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.

Keywords: Arterial spin labeling; Autism; Cerebral blood flow; Glia; Magnetic resonance imaging; White matter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Autism Spectrum Disorder* / diagnostic imaging
  • Autism Spectrum Disorder* / metabolism
  • Autism Spectrum Disorder* / physiopathology
  • Cerebrovascular Circulation / physiology*
  • Child
  • Female
  • Frontal Lobe* / diagnostic imaging
  • Frontal Lobe* / metabolism
  • Frontal Lobe* / physiopathology
  • Gray Matter* / diagnostic imaging
  • Gray Matter* / metabolism
  • Gray Matter* / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuroimaging
  • Spin Labels
  • White Matter* / diagnostic imaging
  • White Matter* / metabolism
  • White Matter* / physiopathology
  • Young Adult

Substances

  • Spin Labels
  • Aspartic Acid
  • N-acetylaspartate