Tactile hypersensitivity and GABA concentration in the sensorimotor cortex of adults with autism

Abstract

Sensory hypersensitivity is frequently encountered in autism spectrum disorder (ASD). Gamma‐aminobutyric acid (GABA) has been hypothesized to play a role in tactile hypersensitivity. The aim of the present study was twofold. First, as a study showed that children with ASD have decreased GABA concentrations in the sensorimotor cortex, we aimed at determining whether the GABA reduction remained in adults with ASD. For this purpose, we used magnetic resonance spectroscopy to measure GABA concentration in the sensorimotor cortex of neurotypical adults (n = 19) and ASD adults (n = 18). Second, we aimed at characterizing correlations between GABA concentration and tactile hypersensitivity in ASD. GABA concentration in the sensorimotor cortex of adults with ASD was lower than in neurotypical adults (decrease by 17%). Interestingly, GABA concentrations were positively correlated with self‐reported tactile hypersensitivity in adults with ASD (r = 0.50, P = 0.01), but not in neurotypical adults. In addition, GABA concentrations were negatively correlated with the intra‐individual variation during threshold measurement, both in neurotypical adults (r = −0.47, P = 0.04) and in adults with ASD (r = −0.59, P = 0.01). In other words, in both groups, the higher the GABA level, the more precise the tactile sensation. These results highlight the key role of GABA in tactile sensitivity, and suggest that atypical GABA modulation contributes to tactile hypersensitivity in ASD. We discuss the hypothesis that hypersensitivity in ASD could be due to suboptimal predictions about sensations. Autism Research 2019, 12: 562–575. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary People with autism spectrum disorder (ASD) often experience tactile hypersensitivity. Here, our goal was to highlight a link between tactile hypersensitivity and the concentration of gamma‐aminobutyric acid (GABA) (an inhibitory neurotransmitter) in the brain of adults with ASD. Indeed, self‐reported hypersensitivity correlated with reduced GABA levels in brain areas processing touch. Our study suggests that this neurotransmitter may play a key role in tactile hypersensitivity in autism.

Weaker neural suppression in autism

“…Consistent with recent pharmacological work in nonhuman primates 22 , our recent study using lorazepam (a GABAA receptor modulator) in NT humans 1 showed that strengthening inhibition yields weaker, rather than stronger spatial suppression during motion discrimination. Our current MRS results are in line with previous observations of normal GABA+ levels within visual cortex in people with autism 13,15,17 (but see 14 for a more nuanced report). Thus, although there is evidence for weaker inhibition in mouse models of ASD 7,[9][10][11] , our results do not support the notion that weaker inhibition drives weaker neural suppression in humans with ASD.…”

“…However, evidence for a widespread reduction in inhibition is either indirect or inconclusive. For example, there is evidence for decreased inhibition from genetic models of ASD in mice 7,[9][10][11] , but results in humans remain equivocal 8,[12][13][14][15][16][17] . An alternative is that modulatory processes that suppress neural responses, but do not rely directly on neural inhibition, are either disrupted or differentially engaged in ASD.…”

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

“…Other studies have investigated differences in GABA and showed no differences in the VIS [Gaetz et al, ; Robertson et al, ], striatum [Harada et al, ; Horder et al, ], and medial prefrontal cortex [Horder et al, ]. However, other studies have reported lower GABA levels in other areas, such as the sensorimotor cortex [Puts et al, ; Sapey‐Triomphe et al, ], frontal lobe [Harada et al, ; Kubas et al, ], and auditory cortex [Gaetz et al, ; Port et al, ; Rojas et al, ].…”

“…Other studies have investigated differences in GABA and showed no differences in the VIS [Gaetz et al, 2014;Robertson et al, 2016], striatum [Harada et al, 2011;Horder et al, 2018], and medial prefrontal cortex [Horder et al, 2018]. However, other studies have reported lower GABA levels in other areas, such as the sensorimotor cortex [Puts et al, 2017;Sapey-Triomphe et al, 2019], frontal lobe [Harada et al, 2011;Kubas et al, 2012], and auditory cortex [Gaetz et al, 2014;Port et al, 2017;Rojas et al, 2014]. Although these mixed results may result from regionspecific group differences, methodological variability across studies may also contribute to these inconsistent findings.…”

“…Magnetic resonance spectroscopy (MRS) has been used successfully to measure neurochemicals in vivo , including N ‐acetyl aspartate (NAA), total creatine (tCr), total choline (tCho), myo‐inositol (mI), with a particular focus on glutamate and glutamine (Glx) and GABA, where reliable GABA measurements requires edited MRS techniques. To date, these studies have provided evidence of equivalent GABA levels compared to TD individuals in the VIS [Gaetz et al, ; Robertson, Ratai, & Kanwisher, ], striatum [Harada et al, ; Horder et al, ], and medial prefrontal cortex [Horder et al, ], as well as lower GABA concentrations in the sensorimotor cortex [Puts et al, ; Sapey‐Triomphe, Lamberton, Sonié, Mattout, & Schmitz, ], frontal lobe [Harada et al, ; Kubas et al, ], and auditory cortex [Gaetz et al, ; Port et al, ; Rojas, Singel, Steinmetz, Hepburn, & Brown, ]. While there are several methodological differences between these studies, they suggest that discrete, region‐specific differences in GABA may be present in individuals with ASD.…”