The sense of touch plays a central role in healthy human development. In addition to serving as a primary means through which infants learn about their physical environments, touch from caregivers provides children with social-emotional messages, serving as a foundation for the development of more sophisticated social and communication skills. A high proportion of children with autism spectrum disorder (ASD) exhibit abnormal reactions to touch, although the neural mechanisms underlying these abnormalities are poorly understood. The purpose of this Mentored Research Scientist Development Award (K01) is to support the candidate in establishing an independent line of research focused on elucidating the neural mechanisms of tactile abnormalities in children with ASD. Better understanding in this area is needed to inform the development of new interventions and identify biological markers that could be used for early detection and more targeted treatment of sensory features in autism. Training will focus on the acquisition of new skills and knowledge in magnetoencephalography (MEG) source localization, magnetic resonance spectroscopy (MRS), ASD clinical assessment, and sensory features in ASD. Training in these areas will be accomplished in part through completion of the proposed research, which aims to identify neural correlates of atypical tactile processing in children with ASD using multimodal neuroimaging. In the first of two studies, neural responses to mechanical and affective forms of tactile stimulation will be obtained from 6- to 10-year-old children with ASD and typically developing (TD) controls using magnetoencephalography (MEG). In-vivo estimates of cortical metabolites in sensorimotor cortex will be acquired from these same participants using edited MRS. The MRS analysis will focus on concentrations of gamma-Aminobutyric acid (GABA), which plays a key role in regulating neural responses to sensory stimuli and has been implicated in the pathology of ASD. Parent report and observational assessments of sensory processing will be administered for all children in order to decipher associations between the acquired brain measures and individual differences in tactile reactivity and tactile perception. In a second study, the same MEG and MRS measures will be acquired from TD infants between 3 ? 24 months of age to provide a scientific and methodological foundation for future studies to extend the current research on the neurobiological mechanisms of tactile abnormalities in ASD to infants at increased risk for the disorder. Longitudinal prospective studies with this population are promising for identifying biomarkers for early, pre- symptomatic detection and stratification into appropriate treatment groups. In addition to completing the proposed research, the principal investigator will complete a structured career-development plan that includes mentorship, courses, workshops, and scientific meetings. By the completion of this K01, the principal investigator will have the expertise and preliminary needed to apply for R01 funding and address important open questions regarding somatosensory processes in development and ASD as an independent investigator.
The proposed research will advance the limited understanding of the mechanisms underlying abnormal tactile processing in children with autism spectrum disorder (ASD) with the aim to inform the development of new interventions and biomarkers for sensory dysfunction in ASD. The proposed work will also provide a scientific and methodological foundation for future research to examine the origin of these abnormalities in infants at increased risk for the disorder.
