Deep-Brain Stimulation of the Subthalamic Nucleus Selectively Decreases Risky Choice in Risk-Preferring Rats.

ABSTRACT

Deep brain stimulation of the subthalamic nucleus (STN-DBS) can improve the motor symptoms of Parkinson's disease (PD) and negate the problematic side effects of dopamine replacement therapy. Although there is concern that STN-DBS may enhance the development of gambling disorder and other impulse control disorders in this patient group, recent data suggest that STN-DBS may actually reduce iatrogenic impulse control disorders, and alleviate obsessive-compulsive disorder (OCD). Here, we sought to determine whether STN-DBS was beneficial or detrimental to performance of the rat gambling task (rGT), a rodent analogue of the Iowa Gambling Task (IGT) used to assess risky decision making clinically. Rats chose between four options associated with different amounts and probabilities of sugar pellet rewards versus timeout punishments. As in the IGT, the optimal approach was to favor options associated with smaller per-trial gains but lower timeout penalties. Once a stable behavioral baseline was established, electrodes were implanted bilaterally into the STN, and the effects of STN-DBS assessed on-task over 10 consecutive sessions using an A-B-A design. STN-DBS did not affect choice in optimal decision makers that correctly favored options associated with smaller per-trial gains but also lower penalties. However, a minority (∼25%) preferred the maladaptive "high-risk, high-reward" options at baseline. STN-DBS significantly and progressively improved choice in these risk-preferring rats. These data support the hypothesis that STN-DBS may be beneficial in ameliorating maladaptive decision making associated with compulsive and addiction disorders.