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New clues to why Parkinson's patients are so impulsive

Friday, October 26, 2007

WASHINGTON -- Your brain is supposed to fire a "hold your horses" signal when faced with a tough choice. But a brain implant that stops the tremors of Parkinson's disease may block that signal -- a new explanation for why some Parkinson's patients become hugely impulsive.

Scientists have long known that anti-Parkinson medications occasionally spark compulsions like pathological gambling.

Research published Thursday found another treatment, a pacemaker-like brain implant, can trigger a completely different kind of impulsiveness.

How different? The drugs leave a subset of patients unlikely to learn from bad experiences, like a losing poker hand.

The brain implant doesn't hinder learning. In contrast, those patients can make hasty decisions as the brain loses its automatic tendency to hesitate when faced with conflict, University of Arizona researchers reported online in the journal Science.

"Deep brain stimulation," or DBS, involves placing electrodes into a small region called the subthalamic nucleus, an area important for controlling movement. But it also is where scientists believe the brain yells: "Stop, weigh your options!"

Frank's theory: When electrodes fire to disrupt excessive movement, they also may block that signal.

"It makes a lot of sense," said Dr. Valerie Voon, a psychiatrist with the National Institutes of Health's neurology center, after reviewing the research.

The study doesn't offer easy solutions. But it could affect how neurologists counsel Parkinson's patients after DBS surgery.

"Because they don't have those brakes in place, you need to teach someone to slow down" when faced with certain decisions, Voon said.

At least 1 million Americans have Parkinson's, suffering increasingly severe tremors and periodically stiff or frozen limbs as brain cells quit producing dopamine, a chemical crucial for movement. There is no cure. Standard treatments include medications to stimulate dopamine and, once those fail, DBS surgery to control tremors.

Doctors have long noticed varying degrees of impulsiveness in Parkinson's patients, from making uncensored remarks to rare cases of extreme behavior such as compulsive gambling, shopping, eating or sex. Changing medications or doses often solves extreme symptoms -- if patients or their families report the worrisome behavior.

Frank wondered what role the brain implant plays.

His team used specialized computer games to probe decision-making in 15 Parkinson's patients taking dopamine drugs, 17 others who received DBS, and 14 healthy older adults.

First, participants were shown pairs of Japanese characters and told to pick the "correct" one. It was baffling -- what makes one symbol better, especially if you don't know Japanese? But as the computer screen beamed back "Correct!" or "Incorrect!" their brains learned to prefer some characters over others.

Then Frank paired the symbols differently: "Correct" ones together to simulate "win-win" decisions; "incorrect" pairings to model choosing the lesser of two evils; and easy "right-wrong" pairs.

Healthy people and Parkinson's patients on dopamine drugs hesitated briefly when faced with win-win or lose-lose choices, allowing time to weigh options. But DBS patients didn't hesitate with lose-lose choices -- and actually sped up win-win decisions.

Remarkably, switch off the brain implant and DBS patients quit rushing the close calls.

As in previous research, medicated patients were less likely to learn which "wrong" symbols to avoid, backing the theory that dopamine drugs can hinder learning from negative feedback.

But do the DBS patients' hasty choices really matter in a win-win situation, where there's no clearly wrong answer?

In the real world, definitely, said Arizona's Frank. Say your job offers a range of 401K options. Sure, any one is better than no investment, but just grabbing the first one might not be the most lucrative.

It hasn't been obvious that different treatments cause different impulsive behaviors, said Dr. Kathleen Shannon of Chicago's Rush University Hospital.

"They all seem to make bad decisions and have trouble making decisions," she said. Now, "I'll start to look at my patients differently."


On the Net:

Information on Parkinson's disease:

www.ninds.nih.gov/disorders/parkinsons--... m


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