High-frequency stimulation in Parkinson's disease: more or less?

Deep-brain stimulation at high frequency is now considered the most effective neurosurgical therapy for movement disorders. An electrode is chronically implanted in a particular area of the brain and, when continuously stimulated, it significantly alleviates motor symptoms. In Parkinson's disease, common target nuclei of high-frequency stimulation (HFS) are ventral thalamic nuclei and basal ganglia nuclei, such as the internal segment of the pallidum and the subthalamic nucleus (STN), with a preference for the STN in recent years. Two fundamental mechanisms have been proposed to underlie the beneficial effects of HFS: silencing or excitation of STN neurons. Relying on recent experimental data, we suggest that both are instrumental: HFS switches off a pathological disrupted activity in the STN (a 'less' mechanism) and imposes a new type of discharge in the upper gamma-band frequency that is endowed with beneficial effects (a 'more' mechanism). The intrinsic capacity of basal ganglia and particular STN neurons to generate oscillations and shift rapidly from a physiological to a pathogenic pattern is pivotal in the operation of these circuits in health and disease.