An Association between Sensory Responsiveness and Cortical GABA Concentration in Autism-Spectrum Disorder

Background: Individuals with autism spectrum disorders (ASD) often show sensory abnormalities (Marco et al., 2011). Studies have argued that an altered γ-aminobutyric acid (GABA)-mediated signaling within particular brain circuits may explain this symptom in ASD (Cellot and Cherubini, 2014). We previously found increased sensory hyper-responsiveness in ASD associates with greater temporal resolution to discriminate two successive sensory stimuli that were temporally spaced by varying intervals (Ide et al., 2017). Functional magnetic resonance imaging (fMRI) experiment revealed that neural activity in few brain regions associate with high temporal resolution of stimuli. The ventral premotor cortex (vPMC) was especially associated with the severity of sensory hyper-responsiveness (Ide et al., 2018, submitted). However, whether GABA concentration in vPMC mediates excitatory / inhibitory roles contributing to the overall severity of sensory hyper- / hypo- responsivity still remains unclear.

Objectives: We sought to determine whether sensory hyper- / hypo- responsiveness are associated with cortical GABA concentration and hypothesized that altered GABAergic signaling within the brain circuit involving vPMC induces aberrant sensory processing.

Methods: We recruited 12 typically developing participants (TD; 5 males) and 3 male ASDs. We took their responses on Adolescent / Adult Sensory Profile (AASP; Brown et al., 2001) for characterization of altered sensation. The questionnaire has four sub-scales: Low Registration and Sensation Seeking (passive and active hypo-responsiveness), Sensory Sensitivity and Sensation Avoiding (passive and active hyper-responsiveness).

We performed in vivo measurement of GABA concentration with proton magnetic resonance spectroscopy (H¹-MRS). We initially performed 3D-MPRAGE imaging for anatomical images to locate regions of interest (ROIs) in participants and then ran MEGA-PRESS sequence twice to quantify GABA: one for vPMC and another for primary visual cortex (V1) as a control region. We calculated the ratio of GABA to N-acetyl aspartate (NAA) and N-acetylaspartylglutamate (NAAG) for each ROI and used them as within subject indices for metabolite concentration.

Results: A correlation between the ratio of vPMC to V1 of GABA concentration and AASP scores showed a positive association between subjective Sensation Seeking scores and GABA concentration across all participants (r = 0.66, p < 0.01; Figure 1). The same analysis excluding the three ASDs revealed that the GABA level positively correlated with Low Registration (r = 0.58, p = 0.05) and Sensation Seeking (r = 0.60, p = 0.04), respectively. There was no association of other scores with GABA concentration.

Conclusions: Our preliminary results comprising of TDs and ASDs suggest that a higher GABA concentration may show reduced sensitivity and behavioral reactivity to stimuli. Taken together with our earlier finding of an association between vPMC and sensory hypersensitivity, there is a possibility that atypical facilitatory / inhibitory roles played by relative GABA concentration in vPMC may result in dysfunctions of sensory processing as regards hyper- / hypo- responsiveness.

Our current, small sample size limits us from concluding unequivocally about the relationship, between GABA concentration of vPMC and sensory processing in ASD. We are measuring more number of patients to elucidate whether GABAergic neural signalling in ASD could be involved with different aspects of sensory responsiveness.