High frequency deep brain stimulation: what are the therapeutic mechanisms?

High frequency deep brain stimulation (HFS) used to treat the symptoms of Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation in GPi might produce this directly by mechanisms such as depolarization block or activation of presynaptic inhibitory fibers, and the same mechanisms evoked by HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on GPi neurons. Although somatic recordings from neurons near the stimulation site may appear to support this potential mechanism, the action downstream from the site of stimulation often is not consistent with this interpretation. A more parsimonious explanation for the similar effects of HFS in STN or GPi and a lesion of either of these structures is that both HFS and pallidotomy interrupt an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that is responsible for the symptoms of PD.