GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation

Neuroimage. 2014 Feb 1;86:1-9. doi: 10.1016/j.neuroimage.2013.05.068. Epub 2013 May 24.

Abstract

(1)H magnetic resonance spectroscopy ((1)H MRS) and spectral editing methods, such as MEGA-PRESS, allow researchers to investigate metabolite and neurotransmitter concentrations in-vivo. Here we address the utilization of (1)H MRS for the investigation of GABA concentrations in the ASD brain, in three locations; motor, visual and auditory areas. An initial repeatability study (5 subjects, 5 repeated measures separated by ~5days on average) indicated no significant effect of reference metabolite choice on GABA quantitation (p>0.6). Coefficients of variation for GABA+/NAA, GABA+/Cr and GABA+/Glx were all of the order of 9-11%. Based on these findings, we investigated creatine-normalized GABA+ ratios (GABA+/Cr) in a group of (N=17) children with autism spectrum disorder (ASD) and (N=17) typically developing children (TD) for Motor, Auditory and Visual regions of interest (ROIs). Linear regression analysis of gray matter (GM) volume changes (known to occur with development) revealed a significant decrease of GM volume with Age for Motor (F(1,30)=17.92; p<0.001) and Visual F(1,16)=14.41; p<0.005 but not the Auditory ROI (p=0.55). Inspection of GABA+/Cr changes with Age revealed a marginally significant change for the Motor ROI only (F(1,30)=4.11; p=0.054). Subsequent analyses were thus conducted for each ROI separately using Age and GM volume as covariates. No group differences in GABA+/Cr were observed for the Visual ROI between TD vs. ASD children. However, the Motor and Auditory ROI showed significantly reduced GABA+/Cr in ASD (Motor p<0.05; Auditory p<0.01). The mean deficiency in GABA+/Cr from the Motor ROI was approximately 11% and Auditory ROI was approximately 22%. Our novel findings support the model of regional differences in GABA+/Cr in the ASD brain, primarily in Auditory and to a lesser extent Motor but not Visual areas.

Keywords: ASD; Autism spectrum disorder; GABA; MEGA-PRESS; MRS; Spectroscopy; γ-Aminobutyric acid.

Publication types

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

MeSH terms

  • Adult
  • Cerebral Cortex / metabolism*
  • Child
  • Child Development Disorders, Pervasive / metabolism*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Neurotransmitter Agents / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Neurotransmitter Agents
  • gamma-Aminobutyric Acid