title: GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation.
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.
authors.affiliation: Lurie Family Foundations' MEG Imaging Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: gaetzw@email.chop.edu.
authors.forename: W
authors.initials: W
authors.lastname: Gaetz
authors.affiliation: Lurie Family Foundations' MEG Imaging Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bloy
authors.affiliation: Lurie Family Foundations' MEG Imaging Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Wang
authors.affiliation: Lurie Family Foundations' MEG Imaging Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Port
authors.affiliation: Lurie Family Foundations' MEG Imaging Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Blaskey
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Levy
authors.affiliation: Lurie Family Foundations' MEG Imaging Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: T P L
authors.initials: TP
authors.lastname: Roberts
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid
keywords: ASD; Autism spectrum disorder; GABA; MEGA-PRESS; MRS; Spectroscopy; γ-Aminobutyric acid