High-Frequency Stimulation of the Globus Pallidus External Segment Biases Behavior Toward Reward

Abstract

Associative learning requires the ability to learn the connections between events. Fundamental to the learning process is acquiring the expectation that certain events lead to certain outcomes. Indeed, studies have shown that when an expected outcome is changed, so does the subsequent behavior. It has also been demonstrated that basal ganglia neuronal activity is highly modulated by the expectation of future reward. However, the direct link between reward expectation, basal ganglia neuronal activity, and the final change in behavior is not clear. Electrical stimulation enables a direct manipulation of neuronal activity and has been shown to cause behavioral changes. From another perspective, high-frequency deep brain electrical stimulation (DBS) is used as treatment of advanced neurological disorders, yet the underlying mechanism is still a topic of debate. We investigated the effect of high-frequency stimulation of the external segment of the globus pallidus, the central nucleus of the basal ganglia networks, on monkey's expectations of both reward and aversive events. We show that long-duration (30 min), high-frequency (130 Hz) stimulation changed the monkey's behavior in a classical conditioning task, enhancing its expectation of reward. The effect we observed was gradual and persisted even after stimulation had ceased, implying a plastic change. The results support the notion of asymmetric coding of the positive vs. negative domains in the basal ganglia and may suggest the GPe as another possible target for DBS therapy of depression.