Reversal of Rigidity and Improvement in Motor Performance by Subthalamic High‐frequency Stimulation in MPTP‐treated Monkeys

TLDR

Parkinson’s disease is characterized by loss of dopaminergic neurons in the substantia nigra, leading to basal ganglia disorganization and heightened excitatory activity of subthalamic nucleus glutamatergic neurons, and selective lesioning of this nucleus has been shown to alleviate parkinsonian symptoms in MPTP‑treated monkeys. The study aimed to determine whether high‑frequency stimulation of the subthalamic nucleus could produce reversible, gradual, and controllable functional impairment in two unilaterally MPTP‑treated monkeys. High‑frequency stimulation of the subthalamic nucleus was applied to the two monkeys while clinical, mechanographic, and electromyographic parameters were recorded. The stimulation reduced rigidity and bradykinesia without inducing dyskinesia or hemiballismus, supporting the role of the subthalamic nucleus in sustaining parkinsonian motor changes and suggesting its potential as a therapeutic target.

Abstract

Abstract In Parkinson's disease the loss of dopaminergic neurons in the substantia nigra is associated with global disorganization of basal ganglia activity and, in particular, with increased activity of the excitatory glutamatergic neurons of the subthalamic nucleus. Recent experimental studies have shown that parkinsonian symptoms can be alleviated by selective lesioning of the subthalamic nucleus in monkeys treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). We measured the effect of high‐frequency stimulation of the subthalamic nucleus in two unilaterally MPTP‐treated monkeys in order to determine whether it was possible to obtain reversible, gradual and controllable functional impairment of this structure. Clinical, mechanographic and electromyographic results demonstrate that this technique can alleviate parkinsonian rigidity and bradykinesia without causing dyskinesia or hemiballismus. This study supports the hypothesis that the subthalamic nucleus and its excitatory projections have an important role in the mechanisms sustaining the expression of parkinsonian motor changes, and suggests that high‐frequency stimulation of the subthalamic nucleus could be included in treatment for parkinsonism.