Individuals on the autism spectrum are often reported as being hyper- and/or hyporeactive to sensory input. These sensory symptoms 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 inhibition and excitation respectively. In the current study, we found region-specific elevations of Glx in the primary sensorimotor cortex (SM1) in ASD. There were no group differences of GABA+ in either the SM1 or thalamus. Higher levels of Glx were associated with more parent reported difficulties of sensory hyper- and hyporeactivity, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Critically, the finding of elevated Glx provides strong empirical support for increased excitation in ASD. Our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.

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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.

Sensory differences and anxiety disorders are highly prevalent in autism. Studies have shown that sensory differences and anxiety are associated and demonstrate an important role for intolerance of uncertainty (IU) within this relationship. However, those studies predominantly assessed sensory reactivity using questionnaires (i.e., observational reports), which can be subjective, and do not differentiate between perceptual, affective, and behavioural levels of sensory processing. Psychophysical approaches can offer useful additional insight, by providing objective measures of sensory differences at the perceptual level. In the current study, we used a validated battery of psychophysical vibrotactile tasks to assess how alterations in sensory perception contribute to observationally assessed sensory reactivity, IU, and anxiety. Data from 38 autistic children (aged 8 12 years; 27 with co-occurring Attention Deficit/Hyperactivity Disorder) were included in the analyses. Consistent with previous findings, observational parent-report measures of sensory reactivity, anxiety, and child-reported IU, were positively intercorrelated. Mediation analyses showed that IU fully mediated an association between sensory reactivity and anxiety, and that anxiety partially mediated an association between sensory reactivity and IU. Of the measured vibrotactile thresholds, only simultaneous frequency discrimination (SFD) thresholds significantly correlated with parent-reported sensory reactivity. Interestingly, we found that sensory reactivity fully mediated an association between SFD threshold and anxiety, and between SFD threshold and IU. Taken together, these findings suggest a mechanistic pathway whereby low-level perceptual alterations contribute to sensory differences at the affective level, leading in turn to increased IU and anxiety. This stepwise association can inform therapeutic interventions for IU and anxiety in autism.