While some people with Parkinson's disease have obtained great relief by using deep brain stimulation (DBS), a few also grow more impulsive, as though they have lost the ability to stop and consider their options before making a decision. Researchers at the University of Arizona have devised an experiment that may shed some light on how DBS interferes with what they call the brain’s “hold-your-horses” signal.
For the past five years, many Parkinson’s patients have experienced a decrease in tremors and muscle rigidity through deep brain stimulation, in which a pacemaker-like device sends pulses of electricity through wires running to the core of the brain. But in a few cases, they also lost a bit of their self-control.
Michael J. Frank, an assistant professor of psychology at the University of Arizona, had seen signs of this side effect among the people he treated. One patient who could no longer walk was positioned in front of a computer in preparation for a test. When Frank suggested that a chair across the room might be more comfortable for him, all of a sudden the man got up out of the wheelchair and tried to dart towards the chair. He was saved from falling only by the quick action of Frank and the man’s wife.
“That chair was something he desired,” Frank said. “It was as though he could not pause and tell himself, ‘This is not something I should do.’ ”
Seeking the source of the change
Frank, director of the university’s Laboratory for Neural Computation and Cognition, attributes the impulsivity to changes in the subthalamic nucleus, which modulates decision making. When a person is confronted with two or more choices, the subthalamic nucleus sends a signal that temporarily prevents a selection. DBS sometimes seems to act like a lesion on the subthalamic nucleus, disrupting that signal, he says, which could lead to a failure to put on the brake.
In a paper published in the November of Science, Frank and his colleagues described a study in which they found that DBS does indeed cause Parkinson's patients to become more impulsive in their decision making. They tested three groups: 17 Parkinson's patients with DBS implants, 15 Parkinson's patients on medication only, and 27 healthy controls. Each group of Parkinson's patients was tested both while on treatment (DBS or medication) and while off treatment.
The participants sat in front of a computer screen that displayed pairs of Japanese characters and were asked to select which one was “correct.” Through trial and error, they were expected to learn which characters were more likely to be designated as correct. Then they were tested again without feedback and told to select the character that “feels” more correct. “Go with your gut instinct,” they were told.
Some choices demanded more thought and caused healthy controls and the Parkinson's patients on medication to slow down before choosing. In contrast, the patients receiving deep brain stimulation not only did not slow down but sped up their decision making in such cases, indicating that their “hold-your-horses” signal was impaired.
Frank thinks the electrical impulses of deep brain stimulation disrupt the subthalamic nucleus. But Mahlon DeLong, an expert in Parkinson's and the basal ganglia (which include the subthalamic nucleus) at Emory University, urges caution in drawing such a conclusion. Although he calls the study fascinating and important, he points out that the subthalamic nucleus is part of highly complex “loops” and that DBS could be disrupting the functions of the loops rather than just the subthalamic nucleus.
“When you put an electrode into the subthalamic nucleus you are almost certainly inadvertently stimulating nearby structures and passing fiber systems, and not just the sensory-motor areas,” DeLong said. “You have to think of network function rather than focusing on particular node of the circuit. The subthalamic nucleus is a messy target.”