Alterations in Globus Pallidus Internus Firing Patterns are Associated with Different Movement Disorders

Abstract

Differences in neuronal firing rates of the globus pallidus internus (GPi) in hypokinetic and hyperkinetic movement disorders are thought to play an important role in mediating the contrasting motor symptoms. However, deep brain stimulation (DBS) in the GPi can alleviate both types of disturbances. This suggests that DBS might work by changing the pattern of GPi output, instead of the overall rate. In this study we examined whether GPi firing patterns are altered in various movement disorders involving basal ganglia pathology. We analyzed the neuronal firing patterns in the GPi of 14 Parkinson's disease (PD; n = 188) patients, 3 patients with multiple system atrophy (MSA; n = 26) and 10 patients with varying degrees of hyperkinetic disorders. This hyperkinetic group consisted of six cervical dystonia (CD; n = 183) patients, two idiopathic generalized dystonia (GD; n = 72) patients with the DYT1 mutation and two Huntington's disease (HD; n = 42) patients. The studies were approved by the local research ethics board and patients gave informed consent. Comparisons using different measurements of burstiness such as the burst index (131), coefficient of variation (COV) and percentage of spikes in bursts (%SB) showed that the burstiness was lowest in the HD group (2.1 +/- 0.2, 0.7 +/- 0.05, and 6.3 +/- 1.3; BI, COV, and %SB, respectively; mean +/- SEM), followed by PD (2.6 +/- 0.1, 0.9 +/- 0.02, and 12.7 +/- 0.9), MSA (2.9 +/- 0.7, 0.9 +/- 0.1, and 12.6 +/- 3.4), CD (3.4 +/- 0.1, 1.0 +/- 0.02, and 15.5 +/- 1.0) and GD (3.4 +/- 0.3, 1.2 +/- 0.07, and 22.4 +/- 2.6), which had the highest burstiness. This demonstrates that each disease is associated with a different degree of neuronal firing burstiness and supports the hypothesis that differences in neuronal firing patterns are related to the different movement disorders.