Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23), OO (n = 16), or typical development (TD; n = 20) completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri) and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened "compensatory" activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus) and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development.
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