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.

Context-dependent modulation of movement-related discharge in the primate globus pallidus.

A selective contribution of the basal ganglia (BG) to memory-contingent motor control has long been hypothesized. The importance of memory context remains an open question, however, for the BG skeletomotor circuit. To investigate this question, we studied the perimovement discharge of a carefully selected group of 74 "arm-related" pallidal cells in two rhesus monkeys.

Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey.

The reduction in symptoms of Parkinson's disease produced by high-frequency stimulation (HFS) in the internal globus pallidus (GPi) has been proposed to be due to stimulus-induced inactivation of pallidal neurons and resulting disinhibition of thalamic neurons. We tested this in awake Macaca fascicularis by stimulating between pairs of electrodes inserted into GPi under electrophysiological control and recording the responses evoked in thalamic neurons. HFS produced a reduction, not an increase, in discharge frequency during the stimulus train in 77% of the responsive thalamic neurons.