A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Summer, 2021 | Number 3, Volume 35

Imbalance of inhibitory, excitatory brain signaling linked to sensory issues

The majority of individuals with autism spectrum disorders (ASD) exhibit hyper- or hyporeactivity to stimuli, and a new study adds to evidence that this altered reactivity may result from an imbalance of excitatory and inhibitory signaling in the brain. 

Jason He and colleagues used a technique called spectral-edited magnetic resonance spectroscopy to analyze GABA and glutamate levels in two brain regions specifically involved in tactile processing: the primary sensorimotor cortex (SMI) and the thalamus. GABA is an inhibitory neurotransmitter, while glutamate is excitatory. Because there are challenges involved in measuring GABA and glutamate, the researchers actually measured GABA+ (GABA plus macromolecules) and Glx (glutamate plus glutamine). 

Studying 73 children with ASD and 92 controls, the researchers report that they found region-specific elevations of Glx in the SMI of the children with ASD. Higher levels of Glx were associated with more parent-reported issues involving sensory hyper- or hypoactivity. In addition, during tactile perception, higher levels of Glx in the thalamus in individuals with ASD were associated with reductions in “feed-forward” inhibition—a mechanism critical for preventing over-excitation and reducing taskirrelevant noise during signal processing. The researchers detected no differences between individuals with ASD and controls in GABA+ in either the SMI or the thalamus. 

“Collectively,” the researchers say, “our findings provide strong evidence in support of the altered excitation-inhibition balance theory of ASD.”


“Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders,” Jason L. He, Georg Oeltzschner, Mark Mikkelsen, Alyssa Deronda, Ashley D. Harris, Deana Crocetti, Ericka L. Wodka, Stewart H. Mostofsky, Richard A. E. Edden, and Nicolaas A. J. Puts, Translational Psychiatry, July 2021 (free online). Address: [email protected].