Decreased left perisylvian GABA concentration in children with autism and unaffected siblings

Abstract

Imbalanced levels of excitation and inhibition (E/I) have been proposed to account for various behavioral and electrophysiological phenotypes in autism. Although proton magnetic resonance spectroscopy (1H-MRS) studies have been published on various metabolite levels in autism, including glutamate, the major excitatory neurotransmitter, few 1H-MRS studies have yet been conducted the major inhibitory neurotransmitter GABA. Seventeen individuals with autism spectrum disorders (ASD) participated in a single-voxel, point resolved spectroscopy (PRESS) study conducted on a 3T magnet. Data were also acquired on 14 unaffected siblings of children with autism, and 17 age- and gender- matched healthy control subjects. GABA concentration was measured along with Creatine (Cr) in a single voxel aligned with the auditory cortex in the perisylvian region of the left hemisphere. The ratio of GABA to Cr was significantly lower in the ASD group than the control subjects. Siblings also exhibited lower GABA/Cr ratios compared to controls. Cr concentration did not differ between groups. The volumes of gray matter, white matter and CSF did not differ between groups in the whole brain or within the spectroscopy voxel. Reduced auditory GABA concentration in ASD is consistent with one previous MRS study of GABA concentration in the frontal lobe in autism, suggesting that multiple neocortical areas may be involved. Lower GABA levels are consistent with theories of ASD as a disorder involving impaired inhibitory neurotransmission and E/I imbalance. The reduction in unaffected siblings suggests that it may be a heritable biomarker, or endophenotype, of autism.

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).…”

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). …”

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

“…Although results appear to be more consistent than when measuring glutamate/Glx. For example, decreased GABA levels in individuals with ASD compared to controls have been reported in motor (Gaetz et al, 2014) and auditory cortex (Gaetz et al, 2014;Rojas, Singel, Steinmetz, Hepburn, & Brown, 2014), and in the ACC (Cochran et al, 2015), although Brix et al (2015) found no differences in GABA levels in the ACC. Other regions, such as the occipital cortex show no differences in GABA levels between participants with and without ASD (Gaetz et al, 2014;Robertson et al, 2015).…”