Summary: Activation of GABA targets makes visual processing in autistic adults more similar to that of non-autistic adults.
Source: King’s College London
Researchers at King’s College London report measurable differences in how the brain chemical GABA regulates visual processing, and show these differences can be modified pharmacologically.
The study found that when autistic adults received a drug that activates GABAB receptors, their visual responses became more like those observed in non-autistic adults.
Published in Science Translational Medicine, the work outlines a new approach to identifying candidate interventions for sensory symptoms in autism and provides a way to measure who responds to treatment.
The study received partial funding from the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre.
Autistic people often experience sensory differences, including altered visual processing, which for some causes significant distress. Until now, the brain mechanisms underlying these visual processing differences in autism were not well understood in living humans.
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that controls neural activity across the central nervous system. Previous genetic and post-mortem studies suggested alterations in elements of the GABA system in autism, but direct evidence of functional differences in the living brain has been lacking.
This study combined electroencephalography (EEG) recordings over occipital cortex—the brain region that processes vision—with measurements of GABA concentration using proton magnetic resonance spectroscopy (1H‑MRS). The team examined steady-state visual evoked potentials (SSVEPs) elicited by a passive visual paradigm that varied foreground contrast and background interference, testing responses with and without the GABAB agonist arbaclofen (STX209).
Forty-four adults took part in the experiment, including 19 autistic participants. After double-blind, randomized oral administration of placebo or 15–30 mg of arbaclofen, the researchers compared EEG responses across stimulus conditions and related them to baseline occipital GABA+ (GABA plus co-edited macromolecules) levels.
Under placebo, neurotypical participants showed SSVEP responses that varied with foreground contrast and were modulated by background suppression: higher contrast stimuli and the presence of interfering background altered response amplitude. In contrast, autistic participants showed similar response amplitudes across the different stimulus conditions, and the influence of background suppression on the foreground response was reduced.
Baseline GABA+ levels did not differ between groups, but in neurotypical adults GABA+ correlated with the neural response to maximum foreground contrast when background interference was strongest; this correlation was absent in the autistic group. These findings suggest that GABAergic regulation of visual sensitivity operates differently in autism.
When given 30 mg of arbaclofen, neurotypical participants experienced a disruption in sensitivity to visual stimuli, whereas autistic participants showed a shift toward the neurotypical pattern: arbaclofen reduced the differences in visual processing between groups, effectively normalizing the autistic participants’ SSVEP responses under the tested conditions.
The authors conclude that GABAergic function, specifically GABAB receptor activity, plays a fundamental role in visual sensory processing and that modulating this system can change how visual information is processed in autistic adults.
The study’s approach offers a practical way to screen potential pharmacological interventions and to identify individuals who are likely to respond, which could improve the design and efficiency of future clinical trials. By selecting participants with measurable brain responses to an intervention, researchers may better target treatments and reduce the likelihood of negative results from large, heterogeneous trials.
Joint first authors Andreia Pereira, who recently completed her PhD, and Qiyun Huang, Research Associate at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), emphasise that this is the first direct evidence linking a specific visual brain response to GABA regulation in humans and that it differs between neurotypical and neurodiverse individuals. Senior author Professor Grainne McAlonan highlighted that the method could help prioritize and de-risk candidate interventions and focus subsequent studies on sensory symptoms that matter most to autistic people.
Joint senior author Professor Declan Murphy noted that better understanding individual differences in brain chemistry may enable more personalized and effective evaluation of new therapeutic options for autism, addressing the variability that has hindered previous late‑stage trials.
Overall, these results indicate that GABAB receptor modulation can alter visual sensory processing and that measuring neural responses to such modulation provides a promising biomarker for assessing and stratifying treatments aimed at sensory symptoms in autism.
About this visual neuroscience and ASD research news
Author: Press Office
Source: King’s College London
Contact: Press Office – King’s College London
Image: The image is in the public domain
Original Research: Open access.
“GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder” by Andreia Pereira et al. Science Translational Medicine
Abstract
GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder
Sensory atypicalities in autism spectrum disorder (ASD) are thought to arise, at least in part, from differences in γ-aminobutyric acid (GABA) receptor function. Evidence to date has been largely indirect, coming from correlational studies and preclinical models.
In this study, the researchers directly evaluated GABAergic function in 44 adults (n = 19 with ASD). Occipital GABA+ concentration was measured with 1H‑MRS. Steady-state visual evoked potentials (SSVEPs) elicited by a passive surround suppression paradigm were recorded after double-blind randomized oral administration of placebo or 15–30 mg of arbaclofen (STX209), a GABAB receptor agonist.
Under placebo, neurotypical participants’ SSVEP responses varied with foreground contrast and were modulated by background suppression. In ASD participants, all stimulus conditions produced similar response salience and background suppression of the foreground response was weaker. While GABA+ levels did not differ between groups, GABA+ correlated with the neural response to maximum foreground contrast during maximal background interference in neurotypicals but not in ASD.
Administration of 30 mg arbaclofen disrupted sensitivity to visual stimuli in neurotypical adults but made the visual processing of autistic adults more “typical,” eliminating the group differences observed under placebo. These results indicate that GABAergic function is central to visual sensory neurobiology in autism and can be modulated by GABAB activity.