The brains of people with autism are marked by several structural abnormalities. One prominent feature is an enlargement of the axon pathways (“white matter”) that connect neurons in different parts of the brain, allowing them to communicate. The pathways in prefrontal cortex, an area involved in executive control, are especially affected in autism: these frontal pathways are disorganized and the volume of white matter is enlarged. These abnormalities disrupt the brain's communication system for thought, emotion, and action. This research project will pinpoint the structural factors that contribute to the enlargement of white matter in the prefrontal cortex in autism. Dr. Barbas' fellow will examine post-mortem tissue from autistic and control individuals for differences in axon density, axon size, myelination, and number of non-neuronal cells that surround axons ("glia"). A second goal of this project is to develop the use of non-invasive imaging of white matter so that future studies will not have to rely on post-mortem tissue. As a first step, the prefrontal pathways in rhesus monkeys will be mapped. These pathways will initially be scanned using non-invasive diffusion tensor imaging (DTI); subsequently, these pathways will be labeled via injections of tracers into the same brains. Information from both DTI and tracer injections will then be compared to help optimize non-invasive scanning and image analysis protocols for future use in humans. What this means for people with autism: Finding the structural factors behind the white matter enlargement may finally reveal the relevant dysfunctional neural processes in autism. These experiments also begin the development of non-invasive imaging methods that will eventually allow more finely-scaled white matter pathway scanning in humans. These techniques will be essential for finding what underlies the neuropathology in autism, which is prerequisite to developing treatments.