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

H-1 magnetic resonance spectroscopy (H-1 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 H-1 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 -5 days 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. (C) 2013 Elsevier Inc. All rights reserved.