Two Therapies Release Different Brakes on Impulsive Behavior

Abstract

NEUROSCIENCE To unlock rigid limbs and restore their mobility, people with Parkinson's disease often require strong therapy, such as drugs that boost levels of the neurotransmitter dopamine—and if that fails, stimulating electrodes implanted deep in the brain. Yet these treatments can trigger impulsivity: Pathological gambling and hypersexuality have been associated with dopamine drugs, for example. Impulsive behavior can also accompany deep brain stimulation (DBS), but the electrical treatment promotes it in different ways than the drugs do, according to a study published online this week by Science ([www.sciencemag.org/cgi/content/abstract/1146157][1]). Michael Frank and colleagues at the University of Arizona, Tucson, report that DBS interferes with patients' normal tendency to hesitate when faced with a difficult decision, whereas dopamine drugs interfere with the ability to learn from bad experiences. Although the study doesn't immediately point to ways to counteract such impulsive tendencies, other researchers say that the work does shed light on the neural mechanisms that control our thoughts and actions. “It's an advance towards understanding the architecture of cognitive control in the human brain,” says Adam Aron, a cognitive neuroscientist at the University of California, San Diego. Frank and his team used a computer game to investigate decision-making in 15 people with Parkinson's disease taking dopamine drugs and 17 patients receiving DBS targeted to the subthalamic nucleus, part of the network of brain regions disrupted by the disease. In the initial learning phase, the participants saw pairs of unfamiliar squiggles (actually Japanese hiragana characters) and were told, without further instruction, to pick the one that was “correct.” Unbeknownst to the subjects, each character had a fixed success rate: In one pair, for instance, one character caused the word “Correct!” to flash on the screen 80% of the time, whereas the other was correct the remaining 20% of the time. With practice, the people generally picked the character with the highest success rate. Next, the researchers presented new pairings of the same characters. Healthy subjects and medicated patients hesitated for a split second when faced with a pair of characters with similar success rates. DBS patients, on the other hand, made faster choices when the alternatives were similarly attractive. This tendency to rush close calls vanished when researchers tested the same DBS patients with the stimulating electrodes turned off. The findings, says Frank, bolster his group's suggestion that when a difficult decision presents itself, the normal role of the subthalamic nucleus is to send a “hold your horses” signal to other parts of the brain to allow more time to weigh the options. DBS interferes with this signal, leading to hasty choices, Frank hypothesizes. ![Figure][2] Wired. Deep brain electrodes may stimulate impulsivity as well as mobility in Parkinson's patients. CREDIT: ZEPHYR/PHOTO RESEARCHERS INC. Dopamine-boosting drugs had no effect on the speed of decisions, but they did reduce patients' tendency to avoid bad choices that had burned them in the past (such as picking the character with a 20% success rate). That fits with previous work, and it may help explain why some medicated patients with Parkinson's disease keep gambling despite repeated losses, says cognitive neuroscientist Roshan Cools of Radboud University Nijmegen in the Netherlands. “What's really novel is the argument here that there are multiple pathways by which these impulsive behaviors can occur,” says Cameron Carter, a cognitive neuroscientist at the University of California, Davis. [1]: http://www.sciencemag.org/cgi/content/abstract/1146157 [2]: pending:yes