Oct. 25, 2007 -- Michael Frank did what any thoughtful person would. He asked a patient suffering from Parkinson's disease if he would like to sit in a more comfortable chair across the room.
However, instead of taking a moment to think about it, the patient immediately stood up and tried to get to the chair -- completely ignoring the fact he was unable to walk.
"He couldn't walk without a wheelchair, and I had to help to prevent him from falling down," says Frank, an assistant professor of psychology at the University of Arizona at Tucson. "He saw the chair, thought it was a good idea, and got up to walk toward it without really thinking about his condition."
This kind of impulsive behavior may be a side effect of deep brain stimulation that is used to treat Parkinson's disease. Deep brain stimulation helps some patients control debilitating tremors, but new research suggests it may also impair decision making.
In a new study to be published in the journal Science, researchers found that when Parkinson's patients received brain stimulation, they had trouble making hard decisions. However, when the stimulation was turned off, patients responded like the healthy individuals in the control study.
"From a scientific point of view, this research provides light on how some of the circuitry involved in decision making works in the brain," says study co-author Scott Sherman, a professor of neuroscience at the University of Arizona.
"For Parkinson's patients, this study highlights the fact that there are side effects to most interventions," he says. "Even though patients know they have balance problems and are at risk for falling, they may still act impulsively. Patients may gain more mobility with deep brain stimulation, only to experience more falls."
A Shock to Block Tremors
Parkinson's disease is caused by the degradation of nerve cells in the brain that produce dopamine, a signaling chemical that is necessary for smooth and controlled muscular movement.
When these dopamine-containing cells are destroyed, people experience tremors, muscle rigidity and difficulty walking and balancing -- symptoms that only worsen with time.
However, because the disease progresses slowly, medications, physical therapy and surgical procedures can help most people live for many years after diagnosis. Deep brain stimulation is one surgical treatment option available for patients who do not experience relief from medications.
Doctors implant a neurostimulator, which is similar to a heart pacemaker, to deliver electrical stimulation to a specific area of the brain, called the subthalamic nucleus, or STN, effectively blocking the abnormal nerve signals that cause tremors.
For many patients, this device provides considerable relief and also helps researchers study the parts of the brain that are important in the decision-making process.
"Deep brain stimulation is a surgical technique that has been an important advance in the treatment of movement disorders such as Parkinson's disease," says Sherman. "This has allowed our research group to take advantage of an unusual situation of patients having stimulating electrodes implanted in the brains and to carry out a scientific study that explores how certain brain regions control the decision making process."
Impulsive Side Effects?
In the experiment, participants first went through a learning phase where they chose between two different Japanese characters on a screen and received positive or negative feedback about their choices. For example, they learned to always choose A over B and to choose C over D.
In the test phase of the experiment, all the symbols were combined. When healthy participants saw A and C together, they weren't sure which one to choose because they knew both letters were rewarding. In this win-win situation, deciding between options can be difficult, and healthy participants slowed down to deliberate before choosing an answer.
However, patients receiving deep brain stimulation didn't hesitate and, in fact, answered these types of questions more quickly.
"We found that one specific aspect of decision making is impaired," says study co-author Frank. "The 'hold-your-horses' aspect of being able to slow down when faced with conflicting information is inhibited in these patients."
Researchers also found that medications can impair decision making, but in a different way. Patients taking medications were unable to learn from their past mistakes. In the Japanese alphabet test, they learned that A was very rewarding, but they did not learn to avoid choosing B.
"Medication can also cause impulsive behavior such as pathological gambling habits," says Frank. "These patients have the ability to slow down, but the medication prevents them from learning from negative feedback about their decisions. They show an insensitivity to losses and don't learn from their past mistakes."
Treatment Still Beneficial
Experts caution that this new research does not mean that patients should stop taking medications or turn off their stimulators.
"I don't recommend that this article change anyone's mind about whether or not to have deep brain stimulation," says Sherman. "For some patients who have uncontrollable tremor or rapid fluctuation in response to medications, deep brain stimulation is an excellent treatment option."
What this new research does do is lay the foundations for further clinical studies to try to eliminate the impulsive side effects of deep brain stimulation.
"Understanding the role of the [subthalamic nucleus] in this regard will help us further refine the surgical technique of deep brain stimulation and will advance the general scientific study of the decision making," says Sherman.
Experts think that optimizing the amount of stimulation for each patient may be one solution.
"I believe that it will be possible to program most deep brain stimulators to allow most patients to achieve the benefits in their movements without experiencing any decrease in quality of life due to increased impulsivity," says Dr. Stephen Tatter, a professor of neurosurgery at the Wake Forest University School of Medicine. "I have had several patients with problems with impulsivity after deep brain stimulation. We have always been able to solve the problem by reprogramming the deep brain stimulator."
Sherman agrees. "The advantage of deep brain stimulation is that it is adjustable. There are a range of voltages that can be modified after surgery. If certain settings cause problems, physicians can change the level of stimulation to avoid behavioral problems."
Alternatively, stimulating a different area in the brain may be able to reduce tremors but not affect decision making.
"There is more than one anatomical region of the brain that can be stimulated," says Sherman. "The most popular site is the STN, but the second most popular site, the globus pallidus, may have fewer side effects."
For patients experiencing any impulsive side effects, doctors recommend patients talk to their physicians.
"If patients feel they are experiencing impulsivity, they could try turning off their deep brain stimulation system, and of course should contact the clinician who does programming for them," say Dr. Karen E. Anderson, an assistant professor of psychiatry and neurology at the University of Maryland School of Medicine. "Patients should not make any medication change without consulting with their treating clinician."