Microstimulation near fast-spiking human substantia nigra neurons impairs reinforcement learning

Neuronal firing in the substantia nigra (SN) immediately following reward is thought to play a crucial role in human reinforcement learning however direct evidence for this relation is lacking. We applied microstimulation in the SN of patients undergoing deep brain stimulation (DBS) for the treatment of Parkinson’s disease as they engaged in reinforcement learning. Microstimulation during the 500-ms post-reward interval impaired learning, particularly when the electrode was positioned near fast-spiking, putative GABA neurons. These results demonstrate a causal relation between post-reward SN firing and human reinforcement learning, and suggest that SN GABA firing may reduce the e↵ect of reward on subsequent behavior.