Pallidal burst activity during therapeutic deep brain stimulation

Abstract

Theoretical and experimental analyses of deep brain stimulation (DBS) in the subthalamic nucleus (STN) show both excitatory and inhibitory effects on the neural elements surrounding the electrode. Given these observations, the mechanism underlying the therapeutic effect of STN DBS on parkinsonian motor signs remains under debate. One hypothesis suggests that abnormal levels of bursting activity in the pallidum play a key role in the development of parkinsonian motor signs and that STN DBS may exert its beneficial effect by modifying this type of activity. We quantified the changes in bursting activity of globus pallidus internus (GPi) and externus (GPe) neurons before and during ineffective (subtherapeutic) and effective (therapeutic) STN DBS in two monkeys rendered parkinsonian by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared to pre-stimulation control values, the population mean firing rate increased during therapeutic stimulation significantly in both GPe (from 41.7 Hz ± 2.8 to 71.4 Hz ± 7.8) and GPi (from 58.8 Hz ± 4.2 to 71.5 Hz ± 6.2). The burst rate, however, increased significantly in GPe (from 80.1 bursts/min ± 10.0 to 103.1 bursts/min ± 11.1) and decreased significantly in GPi (from 104.2 bursts/min ± 8.3 to 75.8 bursts/min ± 10.8). Although both animals showed improvement in parkinsonian motor signs, changes in rate and bursting activity in GPi were significant only in one animal. These data suggest that while changes in rate and bursting activity may contribute to the improvement in PD motor signs during STN DBS, one cannot explain the therapeutic effects of stimulation in all cases solely on changes in these parameters. Other physiological changes that contribute to its therapeutic effect must also occur.