The candidate's long-term goal is to develop an independent research program focused on characterizing the development of brain and sensorimotor skills in children with autism. To achieve this goal, the candidate has organized a training program involving coursework, workshops, and consultation with senior experts focused on motor system physiology, the neurobiology of autism, methods for assessing ocular and manual motor control, and brain development. The host institution, the University of Illinois at Chicago (UIC), provides numerous training activities and resources relevant to this award, including regular seminars, lectures and journal clubs on fMRI methods and data analysis, autism research, neuropsychology, neuroanatomy and motor control and movement disorders. The mentor, Dr. John Sweeney, has performed oculomotor and fMRI studies of health and disease for over 25 years, and he has been the primary mentor of 9 K awards. He is co-Director for the UIC Autism Center of Excellence project grant. The candidate is an investigator on the Autism Center of Excellence, which provides him with direct contact with referral sources for the proposed studies and exposure to the broader autism community within Chicago such as the Midwestern Autism Consortium. The candidate will investigate the development of motor control and brain systems in autism. While this is an understudied aspect of autism, considerable evidence suggests motor impairments are present in the majority of affected individuals. Sixty individuals with autism between ages 5-25 years will be compared with 60 age- and IQ- matched healthy controls. Subjects will perform sustained and ballistic motor control tasks for both ocular and manual systems. Preliminary evidence indicates that subjects with autism show reduced: a) visual tracking accuracy, b) manual force stability, c) saccade accuracy, and d) ballistic force accuracy. In addition, the variability-reducing function of the cerebellum is implicated by pilot data showing increased trial- wise variability of saccade and ballistic force accuracy. Parallel fMRI tasks will assess the development of cerebellar ocular and manual motor circuits in the 45 subjects with autism and 45 controls >age 8 years. Pilot data suggest reduced activation in autism within midline cerebellar vermis during eye movement tasks and in lateral cerebellar hemispheres during manual control. Neuropsychological tests of motor skill, as well as clinical neurological examinations of motor function, also will be administered. These studies have promise to clarify the nature and developmental trajectory of motor system dysfunctions in this highly prevalent neurodevelopmental disorder.
Motor impairments and cellular abnormalities in the cerebellum have been documented in the majority of individuals with autism studied to date. The proposed studies will examine motor and cerebellar development in autism. These studies have the potential to elucidate abnormal developmental pathways of motor and cerebellar systems, which in turn could provide clues to pathophysiological mechanisms in autism, assist in more reliable diagnosis, and inform the development of novel treatments targeting cerebellar systems.
|D'Cruz, Anna-Maria; Ragozzino, Michael E; Mosconi, Matthew W et al. (2013) Reduced behavioral flexibility in autism spectrum disorders. Neuropsychology 27:152-60|
|Kawahara, Ei; Maenaka, Shiori; Shimada, Eri et al. (2013) Dynamic regulation of extracellular signal-regulated kinase (ERK) by protein phosphatase 2A regulatory subunit B56ýý1 in nuclei induces cell migration. PLoS One 8:e63729|
|Mosconi, Matthew W; Luna, Beatriz; Kay-Stacey, Margaret et al. (2013) Saccade adaptation abnormalities implicate dysfunction of cerebellar-dependent learning mechanisms in Autism Spectrum Disorders (ASD). PLoS One 8:e63709|