Cognitive and Neural Flexibility in Autism

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 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a complex neurodevelopment disorder of largely unknown etiology affecting 1 in 68 children. While much progress has been made towards understanding the neurobiology of social and communication deficits associated with the disorder, very little is known regarding the neurobiological basis of restricted and repetitive behaviors central to the ASD diagnosis. The goal of the current project is to understand the relationship between cognitive flexibility and brain function during evoked (task) and intrinsic (resting) states in youth with and without ASD. Cognitive flexibility, the capacity to switch between mental processes, is often impaired in children with ASD in ways that can severely impact transitions during day-to- day activities of life. Cognitive inflexibilitymay underlie the emergence of restricted and repetitive behaviors in ASD. Understanding the neural mechanisms underlying cognitive inflexibility in ASD is critical for tailoring therapies to treat tis under-studied yet pervasive symptom. The PI has recently published preliminary evidence of reduced dynamic range of connectivity patterns, or neural inflexibility, in children with ASD. The proposed research will go beyond these preliminary findings and explicitly test whether one aspect of restricted and repetitive behaviors --cognitive inflexibility-- is linked with a corresponding neural inflexibility in ASD. A novel approach to assessing brain function and dysfunction is the quantification of dynamic functional connectivity, or time-varying patterns of functional coupling between brain regions. The goals of the study are to address three aims: 1) to understand the neural bases of cognitive flexibility in children with ASD and TD children during evoked brain states, 2) to understand the neural bases of cognitive flexibility in children with ASD and TD children during intrinsic brain states, and 3) to investigate relationships between activation patterns during evoked brain states, dynamic functional connectivity patterns during intrinsic brain states, and behavioral measures of flexibility in ASD. To address these aims, the project will implement traditional task- based functional MRI, dynamic functional connectivity analyses of resting-state fMRI, and integration of task and resting state fMRI with behavioral measures of cognitive flexibility. This program of research responds to the Interagency Autism Coordinating Committee's strategic plan to understand the neural circuitry that is affected in ASD. As behavioral inflexibility is an important cause of difficulties in carin for autistic individuals, these findings will potentially have a major impact on quality of life for children with ASD and their caregivers.