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Research Explains Possible Origin Of Parkinson't Tremors

COLUMBUS, Ohio - A mathematician at Ohio State University and his colleagues may have found the origin of tremors suffered by people with Parkinson's disease.

David Terman

This work could potentially aid the development of new treatments for Parkinson's and other neurological conditions, said David Terman, professor of mathematics at Ohio State.

When researchers constructed a computer model of electrochemical activity in a Parkinson's-affected brain, they noticed unusual patterns in the way brain cells fired signals back and forth.

"In a normal brain, every cell is doing its own thing, and the signals create a random pattern," Terman said. "But in our model, we saw cells firing together in lockstep, creating a synchronized pattern that matched the timing of Parkinson's tremors."

"Our computer model shows that the pattern of the signals is important, too -- not just the frequency."

The finding, reported in a recent issue of the Journal of Neuroscience, could help solve a long-standing mystery in the medical community. Loss of the neurotransmitter dopamine is generally believed to be the cause of Parkinson's, but exactly how that loss leads to tremors is unknown.

In the past, researchers have thought that a dramatic increase in frequency of neural signals was to blame; during Parkinson's episodes, the neurons in a key part of the brain fire almost twice as fast as normal. While this increase in frequency could be used to explain other Parkinson's symptoms, such as stiffness or slowness of movement, it cannot easily explain tremor, Terman explained.

"Our computer model shows that the pattern of the signals is important, too -- not just the frequency," Terman said.

The computer model is a software simulation of brain cells and the electrical signals that travel between them. The researchers were able to reproduce the normal, random firing of brain cells.

When they simulated the loss of dopamine, a different firing pattern emerged. The cells behaved as if they belonged to two separate groups. Cells in group A would fire all at once, while signals in group B were suppressed; then the cells in group B would fire at once, while signals in group A were suppressed.

Terman's collaborators on this project include Alice Yew, assistant professor of mathematics at Ohio State; Jonathan Rubin, assistant professor of mathematics at the University of Pittsburgh; and Charles Wilson, professor of life sciences at the University of Texas at San Antonio.

The three mathematicians modeled the basal ganglia, a mass of brain cells believed to be responsible for voluntary movement and situated just above the brain stem. Researchers believe that the loss of dopamine characteristic of Parkinson's is the result of certain cells in one part of the basal ganglia dying off.

To create the model, the mathematicians drew upon data from studies on actual brain cells that other researchers had done in the past. One of those researchers is study coauthor Wilson, and the other is Mark Bevan, assistant professor of anatomy and neurobiology at the University of Tennessee in Memphis.

Then the researchers compared the computer model to Wilson's experimental results with rat brain cells in the laboratory.

By comparing the model to real-life neurons, the researchers were able to come up with a possible scenario that would create the Parkinsonian firing pattern.

The scenario goes like this: a shortage of dopamine causes one part of the basal ganglia, called the striatum, to send a too-strong neural signal to another part, called the globus pallidus. This signal alters the interaction between the globus pallidus and yet another part of the basal ganglia -- the subthalamic nucleus.

It is in this last interaction that the on-again, off-again, rhythmic neural signals of Parkinson's emerge, the researchers believe.

Eventually, Terman and his colleagues hope to expand their computer model to include other brain regions that interact with the basal ganglia. But this first portion of the work could provide researchers with new directions for Parkinson's therapies.

Terman cited work currently underway at the Cleveland Clinic, where researchers are implanting electrodes in the subthalamic nucleus of Parkinson's patients as an experimental therapy.

"Perhaps our work could help guide those experiments," Terman said.

The National Science Foundation and the National Institute of Neurological Disorders and Stroke supported this work.


Contact: David Terman, (614) 292-5285; Terman.1@osu.edu [Note: Terman's office phone does not have voice mail; to leave a message, send email or call the Department of Mathematics main office at (614) 292-4975.]

Written by Pam Frost Gorder, (614) 292-9475; Gorder.1@osu.edu