The candidate is a biomedical engineer, committed to developing neuroimaging and behavioral strategies to elucidate developmental mechanisms leading to motor and social deficits in children with Autism Spectrum Disorder (ASD). School-age children with ASD exhibit particular difficulty with tasks that rely on hand-eye coordination and show what appears to be an ASD-specific discounting of visual feedback when learning novel movements. In addition, non-specific perturbations to motor development are observable within the first year of life in infants who later develop ASD and may be among the earliest signs of ASD. Early imitation behavior, which depends critically on visual-motor integration, has been linked with subsequent language and play development in children with ASD and is a common target for intervention. Thus, closer examination of the emergence of motor, and specifically visual-motor, deficits is of critical importance to ASD. We propose to investigate trajectories of visual-motor integration in infants at risk for ASD using both behavioral and brain imaging approaches. To carry out this research, we have begun to develop a novel behavioral measure of visual-motor coordination in infants during a ball-catching task. We will also use resting state functional connectivity MRI (fcMRI) data collected during natural sleep to extract neural measures of visual-motor integration from the same infants.
Aims 1 and 2 are focused on extracting these behavioral and neural measures of visual-motor function from AOSI videos and fcMRI data compiled by the Infant Brain Imaging Study (IBIS). We will investigate whether baseline abnormalities and developmental trajectories for these behavioral and neural measures of visual-motor integration differentially predict functional outcomes in affected high-risk infants versus unaffected high-risk infants and controls. Exploratory Aim 3 will then test whether behavioral and neural measures of visual-motor integration can predict individual responses to a parent- mediated intervention using visual-manual activities to target socially engaged imitation. If successful, identifying the neurodevelopmental basis of visual-motor abnormalities in ASD could help stratify ASD into more tractable conditions, which could help identify children in need of early intervention and help determine how to most effectively intervene to help these children fulfill their potential. The candidate has fully engaged a superb advisory team composed of mentors and consultants with complementary skill sets that reflect the interdisciplinary nature of her work. Primary mentor Dr. Stewart Mostofsky, co-mentor Dr. John Pruett and consultants Dr. Rebecca Landa, Joseph Piven, Kelly Botteron and Brian Caffo, are internationally-recognized scientists with a diverse range of expertise in ASD research, clinical care, infant development, developmental imaging science and statistics. Kennedy Krieger Institute has committed to supporting the candidate by providing the necessary laboratory space and financial resources needed to carry out the proposed research. This Mentored Research Scientist Development Award will provide the candidate with a critical training period to acquire knowledge and skills necessary to successfully implement the proposed research project and to develop an independent research career pursuing the interplay of early motor, visual and social skill development in ASD.
This study will investigate developmental patterns of behavior and brain function hypothesized to contribute to impaired acquisition of skills necessary for normal motor and social-communicative development in autism. This work is expected to contribute to a more nuanced understanding of the neurodevelopmental pathways that lead to a diagnosis of autism. This knowledge will help to stratify autism into more tractable conditions, which will not only help identify children in need of early intervention, but will also improve the range of interventions available to them.
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| Stoodley, Catherine J; D'Mello, Anila M; Ellegood, Jacob et al. (2017) Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. Nat Neurosci 20:1744-1751 |
| Calhoun, Vince D; Wager, Tor D; Krishnan, Anjali et al. (2017) The impact of T1 versus EPI spatial normalization templates for fMRI data analyses. Hum Brain Mapp 38:5331-5342 |
| Choe, Ann S; Nebel, Mary Beth; Barber, Anita D et al. (2017) Comparing test-retest reliability of dynamic functional connectivity methods. Neuroimage 158:155-175 |
