School of Medicine investigators have found that stimulating the brain’s subthalamic nucleus (STN) to control motor symptoms of Parkinson’s disease has an unintended consequence: It interferes with cognitive function.
When given cognitive tests, patients performed better when their stimulators were turned off than when they were turned on.
“It’s clear that stimulation can provide a great deal of benefit to patients with Parkinson’s disease,” said principal investigator Tamara Hershey, Ph.D., assistant professor of psychiatry. “But when we looked at cognitive function, patients did better when their stimulators were turned off, although these effects were subtle.”
Hershey and her colleagues tested 24 patients with Parkinson’s disease. All had electrodes surgically implanted into the STN, and when the electrodes were stimulated, all had improvements in tremors, stiffness, shaking and other motor symptoms that characterize Parkinson’s disease.
The subjects were given two tests. In one, they looked at a computer screen and were asked to remember the spatial location where a dot appeared on the screen. They had to keep track of either one or two dots. When the task involved remembering the location of more than one dot, subjects performed better when their stimulators were off.
In a second task, subjects were required to press a button when a letter appeared on a computer screen and not to push the button when they saw a number. When subjects saw many letters and very few numbers, their natural tendency was to continue pressing the button whether their stimulator was on or off.
“When a number would appear, they had to try to inhibit the natural tendency to press the button,” Hershey said. “Stimulation interfered with that inhibition — when stimulators were turned on, people had a harder time stopping themselves from pressing the button when they weren’t supposed to.”
Hershey said the STN is very important in motor control and in Parkinson’s disease, but it also has connections to cognitive areas of the brain. When a stimulator is turned on, it clearly changes the behavior and the firing pattern of neurons in the STN, but she said this study suggests that stimulation also may affect cognitive pathways in the brain.
In standard clinical practice, brain stimulators are set as high as they can go without causing motor side effects. But based on these findings, Hershey believes it might be possible to set stimulator parameters lower to provide motor benefit without affecting cognitive function.
“It’s important to note that although the motor benefits of stimulation are very dramatic, the changes in cognitive function tend to be much less obvious,” she said. “Those subtle effects fit with anecdotal reports from patients who sometimes complain that when their stimulators are on, they don’t think quite as clearly.
“It’s not such a dramatic change that everyone complains of it, but it could make things like paying bills or balancing a checkbook more difficult.”
Hershey hopes to continue this research and test people at various stimulation levels to see whether it is possible to get motor benefits without causing declines in cognitive performance. She would also like to learn whether the location of the electrodes within the STN has any effect on cognitive declines, but technical limitations in imaging make that question difficult to study.