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

Abstract

1H-magnetic resonance spectroscopy (1H-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 1H-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 grey 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 was 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.

Oblique Orientation Discrimination Thresholds Are Superior in Those with a High Level of Autistic Traits

“…This suggestion is consistent, in part, with the suggestion from Bertone et al (2005) that increased lateral inhibition, which is a corollary of increased GABA, underpins GABA levels in frontal (Harada et al, 2011), auditory (Gaetz et al, 2013;Rojas et al, 2013), and motor cortex (Gaetz et al, 2013). However, no differences in GABA levels were found in lenticular nuclei (Harada et al, 2011) or occipital cortex (Gaetz et al, 2013). In addition, blood-plasma levels of GABA have been shown to be increased in children with autism (Dhossche et al, 2002), suggesting that it is premature to rule out the possibility that GABA levels are increased in autism.…”

Superior orientation discrimination and increased peak gamma frequency in autism spectrum conditions.

“…Existing literature provides conflicting evidence with regards to other sensory modalities. As discussed above, at least some individuals with ASC show enhanced auditory discrimination, indicating increased inhibition in auditory cortex; however MRS studies have found lower GABA levels in auditory cortex in ASC (Gaetz et al 2014;Rojas et al, 2014). …”

Subcortical Glutamate Mediates the Reduction of Short-Range Functional Connectivity with Age in a Developmental Cohort

“…fMRI task. We investigated functional connectivity related to spontaneous background activity (Fox et al, 2006;Norman-Haignere et al, 2012) during a spatial working memory task. The task consisted of a display of 11 circles positioned on a circular grid.…”