Lidocaine and muscimol microinjections in subthalamic nucleus reverse parkinsonian symptoms

Inactivation of neurones in the subthalamic nucleus (STN) of the 1-methyl-4 -phenyl-1,2,3,6-tetrahydropyridine treated monkey model of Parkinson's dise ase has been shown to relieve parkinsonian motor symptoms. In patients with Parkinson's disease, neurones in the STN display hyperactive firing rates and rhythmic discharge activity such as tremor-related oscillations (3-8 Hz ) and synchronous high-frequency oscillations (15-30 Hz). In this study, mi croinjections of lidocaine (n = 4) and muscimol, a GABAA receptor agonist ( n = 2), were performed in the STN of six patients with Parkinson's disease to determine whether the focal suppression of STN neuronal activity can lea d to an improvement in tremor, bradykinesia and rigidity. We also report th e first use of microelectrode recording of the effects of microinjections o n neuronal activity in the human brain (n = 2). Microinjections of 10-23 mu l of lidocaine produced striking improvements in bradykinesia, limb tremor and rigidity in three out of three patients. These improvements were correl ated with good therapeutic effects of subsequent STN deep brain stimulation performed in the same microelectrode trajectories as these injections. The most dramatic observation following lidocaine injections was the appearanc e of dyskinetic limb movements. In one patient, simultaneous microelectrode recording during an injection of 3.5 mul of lidocaine demonstrated a suppr ession of neuronal activity at distances of <0.9 mm from the injection site , but no suppression was observed at <greater than or equal to>1.2 nun from the injection site. Microinjections of 5-10 mul of muscimol in a region wi th tremor-related activity resulted in suppression of limb tremor in two ou t of two patients. Interestingly, in one of these patients, 4 Hz oscillator y activity was diminished in a neurone recorded 1.3 mm from the injection s ite, but there was no reduction in the mean firing rate or 20 Hz oscillator y activity. These results demonstrate that inactivation of neuronal activit y in the STN of patients with Parkinson's disease improves motor symptoms. These findings also suggest that a focal block of the STN might alter the o scillatory activity of neurones located beyond the inhibited region.