Funded Grants

Uncovering the neural basis of developmental disability

Childhood developmental disorders are an emerging and important focus of current research in neuroscience. Some such disorders are clearly selective for one neurological system, such as vision, while others (e.g., autism) are complex and probably involve many systems. Research into childhood developmental disability is at a crossroads, as evidenced by a wealth of recent literature reviews and journal focus issues (e.g., Nature Neuroscience, October, 2006). Moving this field forward requires new ideas, tools, and approaches, from the molecular genetic to the behavioral and cognitive. I propose to contribute to this effort using a unique combination of behavioral and neural analysis of normal and abnormal development in an animal model. The model is the non-human primate, which has been shown to be an excellent one for studying cognitive and sensory development and disability. The initial focus of the work will be on amblyopia, a developmental disability of visual perception, but the broader goal is to provide the tools with which to address important questions of cognitive and perceptual development that relate directly to many childhood neurological disorders.

I would like to develop the knowledge and technology with which to directly study the emergence of developmental neurological disabilities. Current advances in the tools available for neuroscience research, for example, magnetoencephalography and functional imaging, have allowed us to ask general questions about localization of function in the adult human brain. However, they do not by themselves uncover the neural mechanisms underlying perceptual and cognitive performance. Moreover, these tools are difficult to use in infants and young children, although the age at which reliable functional imaging can be accomplished is dropping steadily. Two key issues must be addressed to overcome these problems. First, the relationship between activation patterns in functional imaging and underlying neuronal maturation needs to be defined. Secondly, the relationship between neuronal maturation and the development of sensory and cognitive ability needs to be understood. These issues can only be understood by direct investigation using an animal model. I plan to use a combination of assays to pursue these goals in the developing macaque monkey: quantitative psychophysics, functional imaging, and neurophysiology in awake animals. I have previously established methodology for psychophysical testing and functional imaging in infant monkeys, although these techniques have not previously been used in combination. The proposed work would allow me to use these techniques in parallel to relate changes in activation patterns directly to changes in performance. The technology for neurophysiology in awake infant monkeys does not currently exist; that will be developed as part of this project.

The development of this methodology and the new knowledge it will provide will allow us to directly investigate important questions regarding the neural basis of childhood developmental disability. The long-term hope is that this knowledge will be applied to early detection and intervention strategies for affected children.