Neurodevelopment of cognitive control in autism: adolescence to young adulthood

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 DESCRIPTION (provided by applicant): A "tsunami" of adolescents with ASD has begun to transition to adulthood. Despite enormous societal expenditures, many of them continue to experience extremely poor social and role functioning and life satisfaction in early adulthood. There is a great need for more in-depth research to investigate factors contributing to this serious problem and inform the development of interventions. Cognitive control is a critical and component of cognition identified by the RDoC project of the NIMH. Cognitive control impairments related to response inhibition are among the most frequently reported deficits in individuals with ASD, and have been associated with poorer social and adaptive functioning as well as increased repetitive behavior symptoms. While the neural substrates of cognitive control mature substantially during adolescence in typical development (TYP), our Lab has demonstrated that those with ASD experience persistent delays in cognitive control during this period. Relative to TYP, they show reduced use of mature "proactive" control that relies on increased engagement of the lateral prefrontal cortex (LPFC) and fronto-parietal connectivity in preparation for goal- directed behavior. Instead, they become increasingly reliant on late error correction through "reactive" control involving late engagement of the LPFC and the anterior cingulate cortex (ACC). Our findings suggest that persistent over-reliance on immature mechanisms of cognitive control may be associated with poor adult outcomes in ASD. This would imply that the immaturity of cognitive control and its associated neural circuitry constitute potential biomarkers of risk for poor adult functioning, as well as a therapeutic target/endpoint. We test this contention in the proposed behavioral and functional magnetic resonance imaging (fMRI) accelerated longitudinal design (ALD) study of 206 adolescents recruited at ages 12-22 (n = 88 ASD; n = 88 matched TYP). In Specific Aim #1, we compare the developmental trajectory of behavioral measures of cognitive control from adolescence into young adulthood in TYP and ASD. Consistent with our cross-sectional studies, we predict that 2/3 of those with ASD will show a persistent lag in performance on cognitive control tasks through young adulthood, although the remaining 1/3 will show performance comparable to TYP. In Specific Aim #2, we examine the development of the neural mechanisms of cognitive control from adolescence into young adulthood. We hypothesize that, like TYP, the 1/3 showing no lag will exhibit proactive cognitive control, whereas the 2/3 exhibiting a lag will exhibit more persistent development of reactive control. In Specific Aim #3, we investigate relationships between the two modes of cognitive control and adult functioning in young adulthood in ASD. We predict that the use of proactive control will be positively associated with social and role functioning, complex relational information processing, and life satisfaction; whereas reactive control will be associated with internalizing and repetitive behaviors. In addition to being an outcome marker and treatment target, cognitive control holds the potential to serve as a mechanism in experimental therapeutics trials.