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

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.