Duke Researchers Find Brain's Motor Center Keeps Time Too

April 29, 1996

BALTIMORE, Md. -- By measuring activity in the brain as reflected by blood flow, Duke researchers have demonstrated for the first time that the brain's motor control center also keeps track of time. Their experiments show that in both animals and people, the striatum, a portion of the brain once thought only to control movement, keeps track of timing short intervals, from seconds to minutes.

In addition to providing the first map of a neural circuit for an internal clock, the results have implications for Parkinson's disease patients, because the timing mechanism is located within the basal ganglia, which is damaged in people with Parkinson's disease. The findings also may help define the role of timing in learning and memory, said Dr. Warren Meck, associate professor of experimental psychology at Duke University.

Meck reported on the research Monday in a report prepared for the 1996 annual meeting of the American Association for the Advancement of Science.

"We believe timing is the foundation for learning and memory," Meck said in an interview. He suggests that defective timing mechanisms may underlie some learning disabilities and may contribute to dyslexia. Before these experiments, how the brain keeps track of time intervals in the seconds to minutes range was unknown.

"In the animal world, the ability to time short intervals is key to survival," Meck said. "Animals have to be able to determine, for example, if they are getting enough food to eat during a given time interval. They have to have a sense when the yield is no longer worth the effort, and they should move on."

People use this same internal clock to determine if they have enough time to cross a street before an oncoming car reaches them, says Meck.

"The master interval timers are short-order cooks," Meck said. "They have to keep track of multiple items cooking simultaneously, all of which will be done at different time intervals. They have to develop a sense of when the two-minute egg is done, versus the toast, versus the bacon. To do this, they rely on an internal clock and a memory of how long these tasks seemed to take last time."

To measure which parts of the brain are activated when a person needs to keep track of short time intervals, Meck and collaborator Dr. James MacFall, a Duke radiologist, used functional magnetic resonance imaging (fMRI), a new application of clinical MR imaging, which measures the magnetic properties of water inside the body to create images of body organs non-invasively. The MR device measures increases in blood flow, and therefore activity in the brain, and translates that information into images.

Meck and graduate student Sean Hinton asked volunteers to estimate 11-second intervals, without counting, by squeezing a ball just before, or just after, the interval. The researchers measured which parts of the brain were activated while the volunteers were timing the interval. When they subtracted out data on brain activation due to the sensory and motor aspects of the task, they found that some of the most active parts of the brain were the frontal cortex and the striatum, a portion of the brain previously thought to be involved only with motor skills.

The fMRI data support Meck's previous experiments with rats, which he trained to press a lever after a specified time for a food reward. Once they had learned the correct time interval, the rats were given drugs that selectively kill neurons in the part of the basal ganglia called the substantia nigra. This area of the brain normally produces the neurotransmitter dopamine. It is this same area of the brain that is destroyed in Parkinson's disease.

Without functional dopamine-producing neurons in the basal ganglia, the rats could no longer time the duration they had learned previously, although their physical ability to do the task had not been impaired.

But when the rats were given L-dopa, a drug used to treat Parkinson's disease patients, their ability to estimate short time intervals was restored.

"These results suggest that dopamine-producing neurons innervating striatum are crucial to measuring short time intervals," said Meck. "When the striatum is damaged, the ability to learn and remember short time intervals is similarly damaged."

By selectively severing specific nerves in the brains of trained rats, Meck has localized the different parts of the brain that contribute to timing short intervals. The substantia nigra appears to function as a metronome, sending a steady stream of pulses to the striatum. This region, which is also part of the basal ganglia, appears to be a gatekeeper that turns on and off awareness of time intervals and feed that information to the frontal cortex, which stores the information in memory. The complete neural circuit is called a frontal-striatal loop.

"These studies demonstrate for the first time the importance of frontal-striatal loops in people timing short intervals," Meck said. "Now that we are beginning to understand how the brain processes short time intervals, we can explore how timing is integrated with learning and memory. We now have the tools to begin assessing these questions."

Duke University

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