Pacing the Brain Quiets Dyskinesia but Triggers Snap Decisions

TUCSON, Oct. 30 -- Deep-brain stimulation can help patients with Parkinson's disease control their limbs, but it may also cause them to lose impulse control, investigators here reported. In a study of decision-making skills, patients with implanted deep-brain stimulation devices tended to make hasty judgments when faced with conflicts, noted Michael J. Frank, Ph.D.,of the University of Arizona, and colleagues. "While on deep-brain stimulation, patients actually sped up under high-conflict conditions. This form of impulsivity was not affected by dopaminergic medication status. Instead, medication impaired patients' ability to learn from negative decision outcomes," the investigators wrote in an early online publication in Sciencexpress.
The finding suggests how deep-brain stimulation of the subthalamic nucleus can simultaneously quiet motor neuron signals and interfere with the timing of decision-making processes, the authors wrote.
One hypothesis holds that "when faced with multiple seemingly good options, the subthalamic nucleus enables one to adaptively 'hold your horses,' buying more time to settle on the best one."
Evidence to support this theory comes from animal studies in which rats with subthalamic nucleus dysfunction made premature choices in a task that would reward them with food, the authors noted.
To see whether a similar effect occurs in humans, they recruited 17 patients with Parkinson's controlled by deep-brain stimulation, 15 controlled on dopaminergic agents, and age-matched controls.
The Parkinson's patients were tested on and off treatment to test whether the forms of therapies had selective effects on conflict-based decisions, and to replicate previous findings that dopaminergic drugs impair the ability of patients to learn from negative outcomes of their decisions, as evidenced by the tendency of some patients on the drugs to become pathological gamblers.
All three groups of participants were tested with a probabilistic selection task, in which patients are presented with three different pairs of symbols presented in random order, and asked to choose one of the symbols.
The patients received feedback about whether the choices were "correct or incorrect," but the feedback itself is probabilistic -- that is, one pair will lead to positive feedback in 80% of trials if one element of a pair is chosen and negative feedback in 80% of trials if the other symbol is chosen.
The testing indicates whether participants learn from positive feedback by choosing the most reliably correct option, or from negative feedback by avoiding the incorrect option.
"We predicted that, compared with controls, Parkinson's disease patients (regardless of treatment) would show reinforcement learning deficits," the investigators wrote. "We further predicted that dopaminergic medication would impair negative feedback learning, whereas deep-brain stimulation would cause impulsive responding in the face of conflict."
They found that patients were generally slower than controls to learn the reinforcements, and that, as other researchers had shown, patients on dopaminergic agents had selective impairments in their ability to learn from the outcomes of the negative decisions.
In the overall sample, the participants slowed down significantly when making high-conflict decisions compared with low-conflict decisions (P<0.001). But patients on deep-brain stimulation did not slow down as decision conflict increased, and, in fact, responded slightly faster under the high-conflict conditions (P=0.06).
Dopaminergic agents had no effect on whether patients slowed down in high conflict situations, and there were no other between-group or conflict differences.
"Notably, the tendency for deep brain stimulation patients to show speeded high-conflict responses was especially pronounced when choosing the less optimal stimulus," the investigators wrote.
"Further," they said, "High-conflict premature responding led to suboptimal choices under deep-brain stimulation."
The investigators said that their findings point to the presence of two distinct roles for basal ganglia in computation during decision making.
"In brief, two main neuronal populations in the striatum have opposing effects on action selection via output projections through globus pallidus, thalamus, and back to cortex," they wrote. "Activity in 'Go' neurons facilitates the execution of a cortical response, whereas 'No Go' activity suppresses competing responses. Dopamine bursts and dips that occur during positive and negative outcomes drive Go learning (via D1 receptors) to seek rewarding actions, and No Go learning (via D2 receptors) to avoid those that are nonrewarding."
The subthalamic nucleus normally acts a temporary brake, the authors suggested, sending out a global "No Go" response that gives the thinker time to think when confronted with conflicting information.
"Maybe the same circuits are involved in gamblers who don't have Parkinson's," Dr. Frank said.
Funding sources and author conflicts of interest were not listed.Primary source: SciencexpressSource reference: Frank MJ, et al "Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism" Sciencexpress doi: 10.1126/science.1146157.