The neuronal basis of
hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to
dyskinesias induced by low doses of
apomorphine in patients with advanced
Parkinson's disease (PD). During
pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of
apomorphine at doses just adequate to induce
dyskinesias (21 neurons, 17 patients). After the
apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of
dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with
dyskinesias. Among the three neurons in which the onset of on occurred before that of
dyskinesias, the firing rate did not change at the time of onset of
dyskinesias. After injection of
apomorphine,
dyskinesias during on with
dyskinesias often fluctuated between transient periods with
dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with
dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with
dyskinesias. These results suggest that mild
dyskinesias resulting from low doses of
apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.