Biological stopwatch found in brain.

Musicians have no trouble monitoring a beat. Short-order cooks intuitively flip the burgers before they burn. In a step toward explaining such timing abilities, investigators have found areas in the human brain dedicated to keeping mental track of intervals ranging from seconds to a few hours.

That finding has led another group of scientists to discover that people with Parkinson's disease have difficulty using this so-called interval clock.

Animals possess a number of biological clocks, the most well known being the circadian clock, which establishes day-long patterns of behavior.

The interval clock is less well understood, but researchers contend that the ability to monitor time intervals accurately is vital to learning and memory.

For example, the salivating response of a dog to a meal bell depends on its brain's understanding that food will come a short time after a bell is rung.

"Time comes into every aspect of an animal's daily life," says Alex Kacelnik of Oxford University in England, who studies interval timing in birds. The interval clock, unlike the circadian clock, is something that people can actively control. "It's much like a stopwatch. You can stop it and start it at will," says John Gibbon of Columbia University. Gibbon and other scientists presented the new findings on the interval clock at a session of the American Association for the Advancement of Science's annual meeting in Baltimore this week.

By giving rats drugs that destroy selected areas of the brain, investigators at Duke University in Durham, N.C., recently discovered several brain regions involved in this clock.

The investigators had trained the rats to recognize specific intervals of time by giving them food only when they pressed a lever after a certain period had passed, explains Warren Meck, who headed the research group. After the researchers damaged the substantia nigra, located in an area of the brain known as the basal ganglia, the rats could no longer judge time intervals.

The substantia nigra contains brain cells that make the neurotransmitter dopamine. The researchers found they could largely restore the brain-damaged rats' ability to judge intervals by giving them l-dopa, a dopamine-stimulating drug used by Parkinson's patients.

With functional magnetic resonance imaging (fMRI), a method that reveals the brain regions employed during a task, Meck and his colleagues have also studied college students as they judged time intervals. "The same circuits we measured in rats are selectively activated," Meck says.

The work in both rats and humans suggests that the substantia nigra acts as a metronome, sending a steady stream of dopamine pulses to another brain region called the striatum. A third part of the brain, the frontal cortex, appears to complete the interval clock's neural circuit.

After the Duke group highlighted the importance of dopamine to the interval clock, Gibbon and his colleagues decided to study people with Parkinson's disease, an illness in which dopamine-generating brain cells mysteriously die.

This neurodegeneration causes obvious problems of motor control. Gibbon's group discovered that it also interferes with the ability of Parkinson's patients to store two time intervals in memory at once.

When Parkinson's patients took l-dopa, they could accurately reproduce intervals of 8 and 21 seconds that they had been trained to measure. When they didn't take the drug, they were unable to judge accurately the second interval on which they had been trained.

Researchers are uncertain whether this timing deficit plays any role in the Parkinson's symptoms that patients experience. Gibbon and his colleagues plan to examine people with other neurodegenerative diseases for similar problems.