Reduced GABA and altered somatosensory function in children with autism spectrum disorder

Abstract

Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children.

Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured.

Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism.

Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Keywords: GABA; MRS; autism; magnetic resonance spectroscopy; somatosensory; tactile; touch.

Figure 1

A. Sensorimotor (SM1) MRS voxel location. The voxel was placed on the hand area of the right primary motor cortex and rotated to align with the edge of the brain. B. Good quality spectra from all participants retained (6 ASD and 3 TDC excluded). C. Occipital voxel location. The voxel was placed on the midline and the bottom edge aligned with the cerebellar tentorium. D. Good quality spectra were acquired in 16 children with ASD and 16 TDC.

Figure 2

Psychophysical Tasks. A. Static and dynamic detection threshold. Participants were asked to detect a weak stimulus that was either Static, or Dynamic (increasing in amplitude) and determine stimulus location. B. Amplitude discrimination with- and without single site adaptation. In each trial, participants were asked to judge which of two simultaneously applied test stimuli was most intense, trials were preceded by 1s adapting stimulus in the adaptation condition. C. Sequential frequency discrimination. Participants were asked to judge which of two sequentially applied stimuli had the highest frequency.

Figure 3

Correlative analysis. A. GABA concentration is correlated with dynamic detection threshold in cohorts combined as well as in ASD separately. B. GABA concentration is positively correlated with the difference between a static and dynamic detection threshold in cohorts combined and ASD separately, with higher GABA levels leading to a stronger effect. C. GABA concentration correlates with single-site adaptation amplitude discrimination performance in TDC but not in ASD. D. GABA concentration correlates with frequency discrimination performance in TDC but not in ASD.