1H-magnetic resonance spectroscopy (1H-MRS) is a non-invasive neuroimaging technique that allows for estimation of specific in vivo neurochemical metabolites and neurotransmitters such as GABA (y-amino butyric acid). Numerous post-mortem studies and animal models strongly suggest GABAergic system dysfunction in autism spectrum disorder (ASD). Direct in vivo measurement of GABA has been limited due to technical challenges (e.g. spectral overlap of GABA molecule spectrum with the metabolite Creatine (Cr)). Recently, spectral editing methods such as the MEGA-PRESS technique allow for the separation of GABA from Cr. Presently, a single report has been published using MEGA-PRESS that described GABA downregulation from frontal lobe in children with ASD. This study has yet to be replicated, and it remains unclear whether GABA downregulation observed from one brain area predicts downregulation in other cortical areas.
The objective of the current study was to quantify GABA and Glx measures in a group of (n=17) autistic children (ASD mean age, 11.5 yrs; StDev, 2.65 yrs) and (n=12) typically developing (TD mean age, 12.7 yrs; StDev, 2.64 yrs) children and to attempt to replicate the observation of GABA downregulation from frontal lobe voxels in ASD. GABA and Cr concentrations were assessed from three separate MRS voxel locations (motor, visual and auditory areas). Thus the secondary objective was to determine whether any observed GABA downregulation in ASD is ubiquitous throughout the brain or is regionally specific.
MRI scans were performed with a 3.0 T whole body MR scanner with a thirty-two channel head coil (Siemens Verio). For each participant, a 3D MPRAGE anatomic scan was obtained in an axial orientation (1 mm isotropic voxel resolution; TR/TE=1900/2.87 ms; Inversion time=1100 ms; Flip angle=9°). Single voxel 1H MRS was measured from 3 separate regions of interest (ROIs): Motor ROI (30×30×30 mm): The motor ROI voxel was centered on the “hand-knob” of the left central sulcus. Visual ROI (30×30×30 mm): The visual ROI voxel was positioned medially in the occipital lobe, and positioned to avoid including the sagittal sinus and to remain within the occipital lobe. Auditory ROI(40×30×20 mm): The auditory ROI voxel was aligned to the left mid-temporal lobe and encompassed the superior temporal gyrus. GABA MRS was obtained using the MEGA-PRESS, with TE=68 ms, T=1500ms and 128 pairs of spectra (acquisition time < 7mins per ROI). Semi-automatic post-processing of spectral signals was carried out using the jMRUI software. GABA quantitation was calculated as the within voxel ratio of GABA to Creatine (Cr).
The mean GABA/Cr ratio was not significant for Motor or Visual ROIs. However, the GABA/Cr values from Auditory ROIs were significantly lower in ASD relative to TD controls (p<0.05; two-tailed ttest).
The anticipated GABA decrease from frontal (Motor) ROI was not replicated in our study. However, a significant decrease in auditory GABA/Cr in ASD was observed. This decrease was specific to auditory areas and thus GABA downregulation appears to be regionally specific feature of the ASD brain.
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