The globus pallidus, deep brain stimulation, and Parkinson's disease

Parkinson's disease (PD) is caused by the degeneration of the dopaminergic neurons in the substantia nigra. Loss of dopaminergic innervation leads to hyperactivity in the internal segment of the globus pallidus (GPi), the main output nucleus of the basal ganglia and to a profound disturbance in the function of motor circuits. Lesions of the GPi (or in its upstream modulator, the subthalamic nucleus) can greatly improve the motor symptoms of PD presumably by reducing this pathological activity. Paradoxically, high-frequency electrical stimulation of the GPi (deep brain stimulation, DBS) mimics the effects of pallidotomy and has become an accepted therapeutic technique. The mechanisms underlying the beneficial effects of pallidal DBS are not known. Various mechanisms that might account for inhibiting or disrupting the pathological pallidal outflow by high-frequency DBS have been proposed ranging from depolarization block to stimulation-evoked release of GABA, and these are discussed.