Cortical effects of deep brain stimulation: implications for pathogenesis and treatment of Parkinson disease.

High-frequency electrical stimulation that targets the subthalamic nucleus has proved to be beneficial in alleviating the motor symptoms in many patients with Parkinson disease. The mechanism of action for this paradigm of deep brain stimulation is still not fully understood, and this is, in part, attributed to the fact that there are diverse cellular elements at the stimulation site that could bring about local and distal effects. Recent studies in both human and animal models strongly suggest that the activity in the cortex, especially in the motor cortical areas, is directly altered by deep brain stimulation by signals traveling in an antidromic fashion from the subthalamic nucleus. Herein, we discuss the evidence for this proposition, as well as the mechanism by which antidromic activation desynchronizes motor cortical activity. The implications of these new findings for the pathogenesis and treatment of Parkinson disease are highlighted.