Lateralization of sensorimotor behavior and cortical-cerebellar networks in autism

项目总结

PROJECT SUMMARY Autism spectrum disorder (ASD) is a neurodevelopmental disorder for which brain mechanisms are not yet well understood. Resting state functional magnetic resonance imaging (fMRI) studies of ASD have implicated reduced functional specialization of select brain networks, but functional specialization of sensorimotor networks in ASD is not well understood. Addressing this knowledge gap is important because sensorimotor behaviors are consistently impacted in ASD, are supported by discrete, well mapped, cortical-cerebellar networks implicated in ASD, and support the development of higher-order cognitive and adaptive skills that are compromised in ASD. Advancing knowledge of the functional specialization of sensorimotor networks in ASD may provide important information on underlying brain processes while also guiding therapeutic strategies. The proposed research will test the central hypothesis that individuals with ASD show reduced lateralization of sensorimotor behavior and the function and structure of associated cortical-cerebellar networks. Under Aim 1, participants with ASD and typically developing (TD) controls will be compared on precision measures of dominant and non-dominant hand sensorimotor control. Individuals with ASD are predicted to show reduced lateralized advantage during dominant- compared to non-dominant performance. Under Aim 2, participants will complete similar precision sensorimotor tests during task-based fMRI. During dominant hand behavior, individuals with ASD are expected to show (1) increased activation and functional connectivity of ipsilateral primary motor cortex (M1) and contralateral cerebellum, and (2) reduced activation and functional connectivity of contralateral M1 and ipsilateral cerebellum. Across both hands, individuals with ASD are expected to show reduced activation and connectivity of right posterior parietal cortex (PPC). Under Aim 3, participants will complete a structural MRI which will provide information on cortical-cerebellar volume. Morphometric analyses of bilateral M1, premotor cortex, PPC, and cerebellum will be conducted. Individuals with ASD are expected to show reduced cortical and cerebellar volumetric asymmetry. The proposed studies are integrated with a training plan designed to provide the fellow with specialized training in sensorimotor behavior and physiology, developmental cognitive neuroscience methods (including measures of functional connectivity and structural morphometry), and statistical methods for characterizing longitudinal development. This training will be supported by the Sponsor whose expertise is in sensorimotor physiology in ASD, and a team of Contributors with complementary expertise in sensorimotor development, functional brain mechanisms of ASD, structural brain development in ASD, and advanced statistical analysis methods for characterizing development. The candidate's Training Plan will support the candidate's advancement towards his long-term goal of developing a research program examining brain mechanisms of sensory and motor issues in neurodevelopmental disorders.