Rapid response of parkinsonian tremor to STN-DBS changes: direct modulation of oscillatory basal ganglia activity?

Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor and other cardinal symptoms in Parkinson's disease (PD), the precise mechanisms of action of DBS are still unclear. We analyzed the time course of resting tremor amplitude and frequency during discontinuation and subsequent reinitiation of STN-DBS in nine PD patients, using a computerized three-dimensional motion analysis combined with surface electromyography. Following discontinuation of STN-DBS, resting tremor amplitude rapidly increased, reaching maximum amplitude after 2 min (mean +/- 95%CI: 34.3 +/- 13.8 mm; P < 0.01), subsequently stabilizing at a medium level. Reinitiation of stimulation after 30 min resulted in rapid, nearly complete suppression of tremor activity within 1 min (1.4 +/- 1.3 mm; P < 0.01) and, furthermore, increased tremor frequency within a few seconds in seven of nine patients. These findings support the hypothesis that STN-DBS acts by direct interference with the neurotransmission of basal ganglia networks involved in tremor.