Impaired sensory processing is a common but poorly understood aspect of the behavioral traits of Autism Spectrum Disorder (ASD). Recent work suggests that a deficit in cortical inhibitory transmission may underlie some impairments in sensory processing. To date, no studies have shown that changes in neurochemical measures of cortical inhibition (e.g. GABA concentration) are related to behavior targeting the inhibitory system. In this study we combine tactile psychophysics and non-invasive measurements of the inhibitory neurotransmitter GABA (using Magnetic Resonance Spectroscopy; MRS) to investigate atypical touch sensitivity in ASD.
Objectives:
We tested two related hypotheses: (1) TDC and ASD pediatric populations differ in their response to tactile stimuli, which can be characterized by an absence of adaptation mechanisms (through GABA-B-ergic processes) in children with ASD. (2) This difference in tactile processing can be partly attributed to decreased levels of GABA within the sensorimotor cortex.
Methods:
Behaviour: 17 typically developing children (TDC) and 6 children diagnosed with ASD (ages 8-12) participated (2 female, all right-handed). Subject and parental consent was obtained under the approval of the IRB at Johns Hopkins University and the Kennedy Krieger Institute. Behavioural: All participants received a battery of vibrotactile tasks. Children performed (1) a static and a dynamic threshold task (stimulus frequency: 25 Hz). (2) Three 2-alternative forced choice (2AFC) amplitude discrimination tasks (no adaptation, single site adaptation & dual site adaptation; 500 ms, 25 Hz, starting amplitudes 100 & 200µ) (3) Sequential and simultaneous frequency discrimination tasks (starting frequency 30 & 40 Hz). Neuroimaging: Edited MRS measurements of GABA were made in a ‘sensorimotor’ volume centred on the right motor hand-area for 5 participants in each group. All scanning was carried out on a Philips 3T MRI-scanner. GABA concentration in was quantified from the ratio of the integral of the edited GABA signal to the integral of the unsuppressed water signal from the same volume.
Results:
Static detection threshold was significantly lower than dynamic detection threshold in TDCs (p < 0.02), but not the ASD group (p>0.2). Amplitude discrimination increased after single-site adaptation compared to no-adaptation in the TDC group (p<0.01), but not in the ASD group (p > 0.5). There were no significant differences in frequency discrimination performance between the two tasks or groups. There was a significant reduction in GABA concentration for the ASD group compared to TDCs (p < 0.05). In addition, preliminary analysis shows a correlation between GABA concentration and frequency discrimination in the TDC group (R = -0.67, p <0.05; also see Puts et al., 2011), but this correlation is absent in the ASD group (R =0.26, p > 0.5).
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. Analysis of the behavioural data suggests that mechanisms underlying adaptation are impaired in ASD, and these are potentially GABA-B-ergic related and the absence of a correlation between GABA and frequency discrimination in ASD suggests this as well.