Dopamine limits learning in Parkinson’s patients

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Dopamine is the mainstay of treatment for people with Parkinson’s disease, but it comes with a down side. Dopamine-based therapy impairs the brain’s ability to respond quickly to learning challenges, investigators report.

Previous research has shown a puzzling pattern of dopamine effects in Parkinson’s disease, resulting in both enhancements and impairments of mental abilities, Dr. Michael J. Frank, at the University of Colorado Boulder, told AMN Health.

To gain a better understanding of this process, he and his colleagues developed a computer model of the dopamine system in the brain to simulate Parkinson’s disease and the effects of medication.

“Essentially what came out was that it’s not simply the raw level of dopamine that matters, but the dynamic range, the ability of those levels to change quickly as you are learning different things,” Frank said.

Because treatment maintains artificially high dopamine levels, the learning mechanism might be impeded.

To test these computer results, the researchers developed two trial-and-error learning tasks “that were specifically designed to get at people’s implicit biases, to learn about positive versus negative outcomes of their decisions,” he explained.

As described in the online edition of the journal Science, the tests were administered to 30 people with Parkinson’s disease, when they were on medication and when they were off, and to 19 healthy “control” subjects matched for age, education, and verbal IQ.

Negative feedback entailed a computer responding when a subject made a “wrong” choice, and positive feedback involved the computer telling the subject he or she had made a correct choice.

“Patients on medication learned to choose things associated with positive feedback, whereas those off medication learned to avoid things associated with negative feedback,” Frank continued. “Healthy controls learned both to choose things associated with positive feedback and to avoid those associated with negative feedback.”

So it appears that in some cases the brain actually wants dopamine levels to go low just transiently, for example, when learning from negative feedback, he noted.

“The medication might prevent that from happening, because it is stimulating those dopamine cells, not letting the brain take control over its own dopamine system.”

Although these findings have no immediate clinical implications, Frank expects that they will contribute to the development of drugs that target more specific areas of the brain, not only for Parkinson’s disease but also for other neurologic conditions that affect dopamine levels, such as schizophrenia and attention deficit disorder.

SOURCE: Science, November 4th online edition, 2004.

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