The Involvement of the Cerebellum in Sensory Over-Responsivity in Autism - Project Summary/Abstract The vast majority of children with autism spectrum disorder (ASD) have sensory processing atypicalities, with sensory over-responsivity (SOR) in particular being a common challenge to their quality of life. SOR has been associated with poor social adaptive, emotional and daily-life skills. Despite its impairing effect on the daily functioning of ASD children, there are currently few evidence-based treatments for SOR. The proposed dissertation research will examine the role of cerebellar function in youth with ASD and SOR. The cerebellum plays a key role in sensorimotor coordination and has been repeatedly reported to be structurally and functionally abnormal in ASD individuals. Abnormalities in the ASD cerebellum have also been linked to multiple ASD symptoms, including general sensory processing atypicalities. However, to our knowledge, no studies to date have investigated the link between cerebellar function and SOR in ASD. The proposed study will characterize functional alterations in the ASD cerebellum during sensory exposure, as well as at rest, and examine how these atypicalities relate to SOR. Participants will consist of 60 ASD and 40 typically developing (TD) participants, ages 8-17, matched for age and sex. The aims of the study include using functional magnetic resonance imaging (fMRI) to investigate 1) atypicalities in cerebellar activation in response to mildly aversive sensory stimulation in ASD compared to TD, 2) the association between cerebellar activation in ASD and both behavioral and neural markers of SOR, and 3) how task-based (during sensory stimulation) and resting- state cerebellar functional connectivity differs in ASD compared to TD youth and whether these differences relate to within-ASD SOR severity. Characterizing the neural basis of SOR is an important step towards formulating effective interventions to improve the everyday lives of children with ASD who experience SOR and ensuring that treatment is personalized based on individual differences in ASD-related symptomatology. These aims are consistent with the NIMH strategic plan goal of delineating functional development of brain regions and circuitry to characterize developmental trajectories of mental illness. This R36 Fellowship will provide Melis Cakar, a Neuroscience graduate student at the University of California, Los Angeles, with financial support and resources to carry out the proposed dissertation research and advance the field’s knowledge on the cerebellum’s role in ASD. The applicant will be supported by mentorship provided by co-advisors, Drs. Shulamite Green and Mirella Dapretto, and the dissertation committee members, including Dr. Susan Bookheimer (referee), experts in neurodevelopmental, autism and SOR functional neuroimaging research as well as by ample resources and infrastructure for research and training available to the candidate at UCLA. The proposed project will prepare the candidate to pursue her career goal of becoming an independent academic researcher who will be able to conduct cutting-edge research on typical and atypical neurodevelopment using state-of-the-art neuroimaging methods.
