Dorsolateral Prefrontal Cortex Metabolic Profiles in Autism Spectrum Disorder Correlate Atypically with Nonverbal IQ and Typically with Attention Switching

Abstract

BackgroundThe neurometabolic profile of associated with autism spectrum disorder (ASD) has been reported to be abnormal by some studies showing region specific metabolite levels in ASD, while others report no group differences. The neurometabolic profile of the left dorsolateral prefrontal cortex (DLPFC) is of particular interest due to the DLPFC relevance to cognitive and executive function, and to ASD.MethodWe used 1H-MRS to investigate neurometabolic profiles in the DLPFC of ASD and sex/IQ-matched typically developing (TD) children (ages 9-13). We focused on levels of Glutamate and Glutamine (Glx) due to many reported Glx abnormalities ASD, and of Choline (Cho) because of its relationship to intelligence quotient (IQ) and to attentional re-orienting difficulties.ResultsWhile no significant group differences were observed in absolute concentrations, metabolite levels were correlated with the behavioral phenotype of ASD children. In the ASD group but not the TD group, nonverbal IQ (NVIQ) was negatively associated with Cho (r=-0.59, p=0.026) and positively associated with Glx/Cr (r=0.66, p=0.011). Furthermore, attentional-switching scores in the ASD group correlated negatively with Cho (r=-0.69, p=0.009), and positively with Glx/Cr for both the ASD (r=0.73, p=0.004) and TD (r=0.54, p=0.040) groups.ConclusionsCho and Glx/Cr have different neurometabolic roles in modulating NVIQ in ASD compared to TD children, while their role in attentional switching seems preserved in ASD. Elucidating the apparently divergent role of neurometabolites in ASD in the absence of significant group differences in absolute levels is an important step towards understanding and mapping the neural correlates of ASD. These results are also relevant in the context of the significant cognitive function heterogeneity associated with the ASD phenotype, as they suggest possible underlying neural mechanisms that do not overlap which those expected from typical development.