Microstimulation-induced inhibition of neuronal firing in human globus pallidus

Neurosurgical treatment of Parkinson's disease (PD) frequently employs chro nic high-frequency deep brain stimulation (DBS) within the internal segment of globus pallidus (GPi) and can very effectively reduce L-dopa-induced dy skinesias and bradykinesia, but the mechanisms are unknown. The present stu dy examined the effects of microstimulation in GPi on the activity of neuro ns close to the stimulation site. Recordings were made from GPi using two f ixed or independently controlled microelectrodes, with the electrode tips u sually similar to 250 or >600 mu m apart in PD patients undergoing stereota ctic exploration to localize the optimal site for placement of a lesion or DBS electrode. The spontaneous activity of nearly all of the cells (22/23) recorded in GPi in three patients was inhibited by microstimulation at curr ents typically <10 mu A (0.15-ms pulses at 5 Hz). The inhibition had a dura tion of 10-25 ms at threshold. These findings suggest that microstimulation within GPi preferentially excites the axon terminals of striatal and/or ex ternal pallidal neurons causing release of GABA and inhibition of GPi neuro ns.