Deep brain stimulation entrains local neuronal firing in human globus pallidus internus

Daniel R. Cleary, Ahmed M. Raslan, Jonathan E. Rubin, Diaa Bahgat, Ashwin Viswanathan, Mary M. Heinricher, Kim J. Burchiel

Deep brain stimulation (DBS) in the internal segment of the globus pallidus (GPi) relieves the motor symptoms of Parkinson's disease, yet the mechanism of action remains uncertain. To address the question of how therapeutic stimulation changes neuronal firing in the human brain, we studied the effects of GPi stimulation on local neurons in unanesthetized patients. Eleven patients with idiopathic Parkinson's disease consented to participate in neuronal recordings during stimulator implantation surgery. A recording microelectrode and a DBS macroelectrode were advanced through the GPi in parallel until a single neuron was isolated. After a baseline period, stimulation was initiated with varying voltages and different stimulation sites. The intra-operative stimulation parameters (1-8 V, 88-180 Hz, 0.1-ms pulses) were comparable with the postoperative DBS settings. Stimulation in the GPi did not silence local neuronal activity uniformly, but instead loosely entrained firing and decreased net activity in a voltage-dependent fashion. Most neurons had decreased activity during stimulation, although some increased or did not change firing rate. Thirty-three of 45 neurons displayed complex patterns of entrainment during stimulation, and burst-firing was decreased consistently after stimulation. Recorded spike trains from patients were used as input into a model of a thalamocortical relay neuron. Only spike trains that occurred during therapeutically relevant voltages significantly reduced transmission error, an effect attributable to changes in firing patterns. These data indicate that DBS in the human GPi does not silence neuronal activity, but instead disrupts the pathological firing patterns through loose entrainment of neuronal activity.