Date: Friday, April 6, 2018
Time: 12:00pm – 1:00pm
Speaker: Caroline Robertson, Ph.D.
Affiliation: Postdoctoral Fellow, MIT McGovern Institute, Incoming Assistant Professor, Dartmouth College

Talk Title: “Advancing a Marker of Reduced GABAergic Action in the Autistic Brain: Pharmacological Investigations”

 Abstract: We have recently developed a robust and replicated behavioral marker of autism in visual perception -- reduced perceptual suppression during binocular rivalry (Robertson et al., 2013, JNeuro) -- which links to the reduced action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the autistic brain (Robertson et al., 2016, Current Biology).

Our current work aims to develop this marker as tool to facilitate animal and genetic research and pharmacological interventions in the condition. Towards this end, here we tested a causal link between the strength of perceptual suppression during rivalry and the inhibitory neurotransmitter, GABA, using pharmacological manipulations.

22 healthy adults participated in each of three separate studies, investigating the effects of a GABAA modulator (Clobazam; study 1), a GABAB modulator (Arbaclofen; study 2), and a Cl- channel modulator (Bumex; study 3) on binocular rivalry dynamics.  Each study took place over 3 days, in a counter-balanced double-blind design. On each of the experimental days, a participant was given either a drug or a placebo, and participated in a short binocular rivalry experiment after the drug had come into effect. Each GABAergic modulator exerted a strong effect and specific effect on perceptual suppression during rivalry. Importantly, binocular rivalry dynamics were highly test-retest reliable across testing days (all Rho > 0.65, all p < 0.001), and measures of drowsiness did not influence key results.

These findings provide a causal, mechanistic link between the GABA pathway and perceptual suppression, as suggested by our previous Magnetic Resonance Spectroscopy research and computational models of rivalry. These results also identify specific aspects of the GABAergic pathway which are involved in supporting binocular rivalry. All in all, our results flag perceptual suppression as a marker of GABAergic drug response.