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Hold your horses…How the Brain works with Parkinson’s patients with Deep Brain Stimulation

For those who suffer with the debilitating symptoms of Parkinson's disease, Deep Brain Stimulation offers relief from the tremors and rigidity that can't be controlled by medicine.

A particularly troublesome downside, though, is that these patients often exhibit compulsive behaviors that healthy people, and even those taking medication for Parkinson's, can easily manage.

Michael Frank, an assistant professor of psychology and director of the Laboratory for Neural Computation and Cognition at The University of Arizona, and his research colleagues have shed some light on how DBS interferes with the brain's innate ability to deliberate on complicated decisions. Their results are published in the current (Oct. 26) issue of the journal Science.

DBS implants affect the region of the brain called the subthalamic nucleus (STN), which also modulates decision-making.

"This particular area of the brain is needed for what's called a 'hold-your-horses' signal," Frank said. "When you're making a difficult choice, with a conflict between two or more options, an adaptive response for your system to do is to say 'Hold on for a second. I need to take a little more time to figure out which is the best option.'"

The STN, he said, detects conflict between two or more choices and reacts by sending a neural signal to temporarily prevent the selection of any response. It's this response that DBS seems to interrupt. DBS acts much like a lesion on the subthalamic nucleus. Frank's hypothesis predicted that DBS would negate the "hold-your-horses" response to high-conflict choices. Surprisingly, it actually sped up the decision-making process, a signature, he said, indicated of impulsive decision making.

The tendency toward impulsive behavior in Parkinson's patients is well-documented but only dimly understood. How is the STN involved in decision-making and why should things go awry when you stimulate it"

For those taking them, medications did not slow down decision-making conflict. Regardless of whether these patients are on or off medication, for the purposes of the experiment they looked like healthy people or people who are off DBS.

But what Frank found was that medications prevent people from learning from negative outcomes of their choices. That could be one explanation for why patients develop gambling habits. If you learn from the positive outcomes instead of the negative, it could cause you to become a gambler.

"Whereas the DBS had no effect on positive v. negative learning, but it had an effect on your ability to 'hold your horses,' so it was a dissociation between two treatments which we think reveal different mechanisms of the circuit of the brain that we're interested in.

Frank said the results of his experiments are a test of a basic science mechanism for how the brain makes adaptive decisions. The same basal ganglia is involved in other disorders. People who are addicts, for example, are more likely to make impulsive choices, and DBS and medication used to treat Parkinson's have been shown to cause pathological gambling to some degree.

"We may be able to use this to understand that from this more basic sciences perspective. Maybe the same circuits are involved in gamblers who don't have Parkinson's," Frank said.

He also hinted that the study might also offer clues to consumer behavior.

"I think that you can have the opposite effect, where the hold-your-horses signal is too strong in responding to decision conflict. One thing that has been shown in healthy people who have been presented with too many options exhibit is a kind of 'decision paralysis,'" he said.

For example, if shoppers are exposed to two dozen varieties of essentially the same product, research shows very few will actually make a purchase. Employees faced with too many options for 401k plans are less likely to invest in any of them, even though their employer is going to match their contributions.

Frank is interested in whether impulsive decision making can be prevented in DBS patients. One long-range goal, he said, is to be able to test the STN during the implant surgery, avoiding the decision-making areas and target only the brain's motor function.

We hope that in the operating room we can actually when they record this brain area, we can determine selective parts of it that respond to this conflict-based decision-making and use that as a potential way of avoiding stimulating that area and have it be selective to just the pure motor function.

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Frank's collaborators include Johan Samanta (UA Neurology Department and Banner Good Samaritan Medical Center in Phoenix), Ahmed A. Mousafa (UA Psychology Department) and Scott J. Sehrman (UA Neurology Department).