2007 Augmentation Grants

2007 Augmentation Grants
2007 Innovative Technology for Autism (ITA) Grants
2007 Mentor Based Fellowships
2007 Opportunity and Bridge Grants
2007 Physician/Investigator Beginning Autism Research (PIBAR)
2007 Special Co-Funding with Dana Foundation

Stewart Mostofsky, M.D.
Kennedy Krieger Institute
$50,000 for 1 year

Augmentation of motor skill learning in autism: Anatomic MRI

People with autism experience difficulties with movement. Some have difficulty skipping or pedaling a tricycle, and social and communicative gestures such as waving or blowing a kiss can also be difficult to execute. These impairments may be due to problems with motor learning, which would make it difficult to acquire complex patterns of movements. These motor deficits may stem from abnormalities within a number of brain areas that control motor learning and function.

This project seeks to understand the neural basis of these motor deficits by finding relationships between brain anatomy and motor function. The focus on motor function is an advantage because, unlike many behavioral measures of autism, measures of motor function are highly quantifiable and reproducible. These measures will be compared to detailed brain images obtained with anatomic magnetic resonance imaging (aMRI). This proposal plans to continue detailed mapping of cortical and subcortical brain structures, including cerebral cortex, basal ganglia, thalamus, and cerebellum. Different measures of structure such as volume and thickness will be made from these high-resolution images, and compared to motor function to pinpoint brain areas affected by autism.

What this means for people with autism: Investigations of motor skill learning and the associated brain areas can help pinpoint the dysfunctional neural circuits in autism. Comparisons of motor function and high-resolution images of brain structure will help reveal the neural basis of these difficulties, and will advance our understanding of the brain regions involved in social and communicative gestures.

Valerie Hu, Ph.D.
George Washington University
$200,000 for 1 year

Developing a systems approach to autism

Autism may result from a complex interaction between genetic, metabolic, and environmental factors. In examining the genetic factors in autism, which genes are actually converted into protein (“expressed”) can matter as much as which genes have mutations. The importance of gene expression in autism was demonstrated recently by Dr. Hu's group in a study of the rare cases of identical twins in which only one twin has autism. Although genetically identical, many genes involved in neural development and function were expressed differently between the twins. Additional evidence suggests that metabolic pathways that produce steroid hormones and neuropeptides are altered in autism, and these products may also influence gene expression and neural development.

This project will explore the mechanisms that regulate gene expression in cell lines derived from people with autism, and it will screen for steroid hormones and neuropeptides in these cell lines. Finally, experiments will study the interaction of genetic, metabolic (steroid hormones), and environmental (oxidative stress) factors in a neuronal cell model. Specifically, the effect of turning off certain genes alone, and in combination with exposure to steroid hormones or oxidative stress will be examined.

What this means for people with autism: Understanding the complex interplay of genetic, metabolic, and environmental factors in a single cell will be a major step toward understanding how these factors may interact to cause autism.