Behavioral Flexibility in Autism Spectrum Disorder: The Role of Memory and Its Neural Correlates
Cook, Kevin Michael
Vaidya, Chandan J
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by social and behavioral deficits, including pronounced inflexibility. Behavioral interventions often fail to generalize, possibly due to difficulties in flexibly applying learned skills. One type of knowledge representation that contributes to flexible behavior is termed, schema, and are generalized representations formed by extracting common features across numerous similar experiences. In the brain, encoding of schemas relies on two brain regions – the hippocampus (HPC) for schema-incongruent and the medial prefrontal cortex (mPFC) for schema-congruent associations. Children with ASD exhibit structural enlargement of the HPC and diminished communication between the mPFC and other brain regions. Based on these findings, I hypothesized that inflexibility in ASD is directly related to impairments in schema use and that there is reduced connectivity between the HPC and mPFC in ASD which serves a possible mechanism for schema disruption. Two studies were conducted to answer these questions. First in Study 1, children with and without ASD completed an associative memory task while undergoing a functional magnetic resonance imaging (fMRI) scan. Typically developing (TD) children exhibited sensitivity to schema at encoding in the mPFC and HPC. Children with ASD exhibited no sensitivity in the HPC, while mPFC sensitivity was only observed in those rated as being more flexible, suggesting a reliance on more typical schema use for greater flexibility in ASD. In Study 2, a largescale repository of resting state fMRI was utilized to assess HPC functional connectivity in children with and without ASD. Replicated across two samples and relative to TD children, autistic children exhibited significantly dysregulated connectivity between the HPC and numerous brain networks. Included in the findings was significant underconnectivity between the HPC and mPFC region observed in Study 1. Taken together, these two studies suggest that activation in regions subserving schema use are atypical and are related to flexibility problems and are underconnected in ASD.
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