Linking GABA to Tactile Function in ASD: A Pilot Magnetic Resonance Spectroscopy (MRS) Study

Background: Sensory processing difficulties are a prevalent but poorly understood aspect of the behavioural presentation of Autism Spectrum Disorder (ASD). Recent work from post-mortem and animal studies suggests that a deficit in cortical inhibitory transmission may underlie and explain some aspects of these symptoms. To date, however, no research has yet substantiated this proposal by demonstrating that neurobiological measures of cortical inhibitory deficits are connected to sensory symptoms observed behaviourally. In this study we combine tactile psychophysics and non-invasive measurements of the inhibitory neurotransmitter GABA (using Magnetic Resonance Spectroscopy; MRS) to measure and quantify aspects of atypical touch sensitivity in ASD.

Objectives: This pilot study investigates two hypotheses: (1) The performance of participants with ASD on a tactile discrimination task will not be affected by the presence of a prior adapting stimulus – a task thought to be crucially reliant on localized cortical-cortical interactions mediated by GABAergic transmission (Tannan et al., 2008) (2) ASD participants will have decreased levels of GABA metabolites in sensorimotor cortex as measured using MRS.

Methods: 8 individuals with a diagnosis of ASD and 8 neurotypicals (NT) participated in a combined neuroimaging and tactile perceptual assessment paradigm (all participants were male and right-handed). The study was approved by the Cardiff University School of Psychology ethics committee, and informed consent was obtained for all participants. Behavioral: A two alternative forced-choice (2AFC) tracking protocol was used to evaluate the amplitude discriminative capacity of each participant. Suprathreshold vibrotactile stimuli (480ms; 25Hz) were simultaneously delivered to fingertips of LD2/3, and amplitude thresholds were compared between groups during both adapting and non-adapting conditions. Neuroimaging: Edited MRS measurements of GABA were made in a (3x3x3) cm³ ‘sensorimotor’ volume centred on the right motor hand knob. All scanning was carried out on a GE Signa HDx 3T MRI scanner, using an 8-element head coil for receive and the body coil for transmit. GABA concentration in ‘institutional units’ was quantified from the ratio of the integral of the edited GABA signal (determined by fitting to a Gaussian model) to the integral of the unsuppressed water signal from the same volume.

Results: We observed a significant increase (p<0.05) in vibrotactile amplitude threshold in NTs with adaptation. No change in thresholds with adaption was found in our ASD group, similar to previous reports. Our neuroimaging data showed a difference in GABA concentration in sensorimotor cortex between groups which approached significance, with GABA concentration in our ASD group being lower, (p=0.07).

Conclusions: Our preliminary behavioural results replicate previous findings, and when taken with our MRS findings we interpret our data to be consistent with the presence of reduced GABAergic-mediated inhibition in this population.