Previous studies have reported altered glutamate (Glu) concentrations in the
blood and brain of individuals with autism spectrum disorder (ASD) compared
to neurotypical controls (NC), but the direction (increased or decreased) of
metabolite differences is still unclear. Moreover, the relationship between Glu
and both brain function and clinical manifestations of the disorder require
further investigation. Within this study, we investigated metabolite
concentrations within the dorsal anterior cingulate cortex (dACC), a brain
region functionally associated with inhibitory executive control tasks and also
part of the salience network.
There were 19 participants with ASD and 20 NCs between the ages of 23
and 58 years who participated in this study. A study clinician administered
the Autism Diagnostic Observation Schedule (ADOS) to individuals with ASD
to further confirm their diagnosis. In addition, all participants in this study
completed assessments of general intelligence and attention, which included
an inhibitory executive control task. Researchers also acquired in vivo single-voxel
proton magnetic resonance spectroscopy (1H-MRS) in the dACC to
quantify both Glu and combined Glu and glutamine (Glx) concentrations. We
hypothesised that these metabolite concentrations would be altered
(decreased or increased) in adult participants with ASD compared to NCs
and would correlate with inhibitory performance and ASD severity in
individuals with ASD. Participants also underwent a resting-state functional
magnetic resonance imaging (fMRI) scan to assess the relationship between
functional connectivity and Glu and Glx concentrations. We also
hypothesised that there would be an altered relationship between local Glu
and Glx concentrations and seed-based functional connectivity in adults with
ASD compared to NCs.
There were no significant group differences in Glu or Glx concentrations
between individuals with ASD and NCs. Furthermore, we did not find any
relationship between metabolite concentrations and either inhibitory
performance or clinical symptoms of the disorder. This evidence suggests
that increased or decreased Glu and Glx concentrations were not a core
marker of altered brain function in the dACC in this group of adult individuals
with ASD. When individuals taking psychotropic medications were excluded
from the analysis, there was a significant interaction between age and group
for Glx concentrations. This evidence weakly suggests disease-specific
variations in Glx concentrations over the lifespan of an individual with ASD.
Nevertheless, this result did not survive correction for multiple comparisons
and requires further replication.
In our final experiment, we reported that Glu concentrations were negatively
correlated with right and left dACC seed-based resting-state functional
connectivity to the left medial temporal lobe only in individuals with ASD. We
also reported an interaction between groups in the association between Glx
concentrations and both left and right dACC functional connectivity to other
salience network regions including the insular cortex. This evidence suggests
that local Glu and Glx concentrations were incongruent with long-distance
functional connectivity in individuals with ASD. This analysis was largely
exploratory, but further investigation and replication of these relationships
may further explain the pathophysiology of the disorder as well as provide a
useful marker for therapeutic intervention