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

ABSTRACT: 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.

SUBMITTER: He JL

PROVIDER: S-EPMC8322079 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

He Jason L JL Oeltzschner Georg G Mikkelsen Mark M Deronda Alyssa A Harris Ashley D AD Crocetti Deana D Wodka Ericka L EL Mostofsky Stewart H SH Edden Richard A E RAE Puts Nicolaas A J NAJ

Translational psychiatry 20210729 1

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 ...[more]

PMID: 34326312

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Project description:ImportanceMore than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention.ObjectiveTo determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects.Design, setting, and participantsFunctional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age- and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents' ratings of children's SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014.Main outcomes and measuresRelative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex.ResultsThe mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05).Conclusions and relevanceResults demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.

Dataset Information

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

Publications

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

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