Altered Neuronal Firing Pattern of the Basal Ganglia Nucleus Plays a Role in Levodopa-Induced Dyskinesia in Patients with Parkinson’s Disease

Abstract

Background: Levodopa therapy alleviates the symptoms of Parkinson’s disease (PD), but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID).Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID.Methods: Thirty patients with idiopathic PD (age, 55.1 ± 11.0 years; disease duration, 8.7 ± 5.6 years) were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr (1967) scores ranged from 2–4 and their UPDRS III scores were 28.5 ± 5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7 ± 1.6). Microelectrode recording was performed in the globus pallidus internus (GPi) and subthalamic nucleus (STN) during pallidotomy (n = 12) or STN deep brain stimulation (DBS; bilateral, n = 12; unilateral, n = 6). The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs) and the corresponding coefficient of variation (CV).Results: A total of 295 neurons were identified from the GPi (n = 12) and STN (n = 18). These included 26 (8.8%) highly grouped discharge, 30 (10.2%) low frequency firing, 78 (26.4%) rapid tonic discharge, 103 (34.9%) irregular activity, and 58 (19.7%) tremor-related activity. There were significant differences between the two groups (p < 0.05) for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing.Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID.