Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders

Individuals on the autism spectrum are often reported as being hyper- and/or hypo-reactive to sensory input. These sensory disturbances were one of the key observations that led to the development of the altered excitation-inhibition (E-I) model of autism, which posits that an increase ratio of excitatory to inhibitory signaling may explain certain phenotypical expressions of autism spectrum disorders (ASD). While there has been strong support for the altered E-I model of autism, much of the evidence has come from animal models. With regard to in-vivo human studies, evidence for altered E-I balance in ASD come from studies adopting magnetic resonance spectroscopy (MRS). Spectral-edited MRS can be used to provide measures of the levels of GABA+ (GABA + macromolecules) and Glx (glutamate + glutamine) in specific brain regions as proxy markers of excitation and inhibition respectively. In the current study, we found region-specific elevations of Glx elevated in the sensorimotor cortex but not thalamus) but not GABA+ in ASD. Higher levels of Glx were associated with more parent reported difficulties of hyper- and hypo-reactivity to sensory input, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Together, these results provide strong empirical support for increased excitation by way of elevated Glx in ASD. Critically, our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.