Drs. Charles Blaha and Guy Mittleman

Some autistic patients can talk for hours on a subject and recite facts to the point that it’s socially inappropriate. They can give minuscule details on a model train set, for instance, telling their audience about a steam or diesel locomotive, freight cars, passenger cars, couplers and steel rail joiners. But they can’t track what’s going on in their social context and be able to say, “That’s enough information. Let me move on to something else.” They have lost theory of mind. They have a deficit in the conscious awareness of their ability to assess social situations.

Drs. Guy Mittleman and Charles Blaha, professors in behavioral neuroscience in the College of Arts and Sciences’ Department of Psychology, have a theory that some of the cognitive deficits associated with autism result from a disconnection between the cerebellum, located in the back of the brain, and the frontal cortex. This disconnection is thought to occur as a result of a loss of important neurons in the cerebellum called Purkinje cells.

Mittleman and Blaha are co-principal investigators on a $2 million grant that will allow them to investigate this disconnection theory as well as a key element being regulated in the frontal cortex, dopamine, a chemical transmitter that modulates the activity of cortical neurons.

Their five-year study will use an animal (mouse) model of autism and has a four-pronged approach: Mittleman will study the behavior of the animals in a cognitive task; Blaha’s neurochemistry lab will look at the ability of the cerebellum to release dopamine in the mouse frontal cortex; Dr. Heck Detlef at the University of Tennessee Health Science Center will look at the electrophysiological events that occur along the nerve pathways from the cerebellum to the cortex; and Dr. Dan Goldowitz, a neuroanatomist at the University of British Columbia-Vancouver, will map the actual physical anatomy of the cerebellum-cortex connection.

The grant is the first one to propose that there is a distinct association between the loss of Purkinje cells in the cerebellum and frontal cortex function. Mittleman says that the team has been researching autism for at least five years. “I think our conceptualization of the problem is pretty far advanced, and it’s different than a lot of other people’s. Other scientists are searching for what sort of brain damage underlies autism. We have a relatively refined hypothesis.”

Blaha says the study is a novel exploration. “Our research presents a unique opportunity to investigate the link between the cerebellum and cortex. It is our hope that this will lead to new lines of investigation and methods of treating autism.”

— by Ann Brock