Wednesday, December 23, 2015

Reduced GABAergic action in the autistic brain

Robertson, Caroline E. et al. Current Biology. Reduced GABAergic Action in the Autistic Brain.  Published Online: December 17, 2015


  • Behavioral marker of inhibitory/excitatory neurotransmission is perturbed in autism
  • Marker predicts higher-order autistic symptom severity
  • Inhibitory and excitatory neurotransmitters measured in the brain predict behavior
  • Action of the inhibitory neurotransmitter, GABA, is reduced the autistic brain


An imbalance between excitatory/inhibitory neurotransmission has been posited as a central characteristic of the neurobiology of autism, inspired in part by the striking prevalence of seizures among individuals with the disorder. Evidence supporting this hypothesis has specifically implicated the signaling pathway of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in this putative imbalance: GABA receptor genes have been associated with autism in linkage and copy number variation studies, fewer GABA receptor subunits have been observed in the post-mortem tissue of autistic individuals and GABAergic signaling is disrupted across heterogeneous mouse models of autism. Yet, empirical evidence supporting this hypothesis in humans is lacking, leaving a gulf between animal and human studies of the condition. Here, we present a direct link between GABA signaling and autistic perceptual symptomatology. We first demonstrate a robust, replicated autistic deficit in binocular rivalry, a basic visual function that is thought to rely on the balance of excitation/inhibition in visual cortex. Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism. These results suggest a disruption in inhibitory signaling in the autistic brain and forge a translational path between animal and human models of the condition.

"These findings mark the first empirical link between a specific neurotransmitter measured in the brains of individuals with autism and an autistic behavioral symptom," says Caroline Robertson of Harvard University and MIT's McGovern Institute for Brain Research....

In binocular rivalry, two conflicting images are presented simultaneously, one to each eye. To make out one image or the other, the brain must inhibit neural signals to push one out of visual awareness. Typically, developing individuals suppress a visual image from awareness for many seconds at a time. People with autism, on the other hand, struggle to suppress the visual images.

Robertson, senior author Nancy Kanwisher of MIT, and their colleagues wanted to find out whether this difficulty could be traced to differences in GABA levels in the autistic brain. They asked 21 people with autism and 20 typical control individuals to complete a binocular rivalry task. As expected, adults with autism were slower to suppress the visual images.

The researchers then used magnetic resonance spectroscopy to measure GABA concentrations in the brain while individuals completed the task. Those measurements showed a strong link in typical control participants between binocular rivalry dynamics and levels of GABA. That connection between perception and GABA brain chemistry was completely absent in the brains of people with autism.

"Individuals with autism are known to have detail-oriented visual perception--exhibiting remarkable attention to small details in the sensory environment and difficulty filtering out or suppressing irrelevant sensory information," Robertson says. "It's long been thought this might have something to do with inhibition in the brain, and our findings lend support to this notion."

They note, however, that the GABA dysfunction that they've uncovered may vary substantially among people on the autism spectrum. There are also many other neurotransmitters that may play important roles in the behavioral manifestations of autism.

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