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 disease 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, microinjections of
lidocaine (n = 4) and
muscimol, a
GABA(A) 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 lead to an improvement in
tremor,
bradykinesia and rigidity. We also report the first use of
microelectrode recording of the effects of microinjections on neuronal activity in the human brain (n = 2). Microinjections of 10-23 microl of
lidocaine produced striking improvements in
bradykinesia,
limb tremor and rigidity in three out of three patients. These improvements were correlated 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 appearance of dyskinetic limb movements. In one patient, simultaneous
microelectrode recording during an injection of 3.5 microl of
lidocaine demonstrated a suppression of neuronal activity at distances of < 0.9 mm from the injection site, but no suppression was observed at > or = 1.2 mm from the injection site. Microinjections of 5-10 microl of
muscimol in a region with
tremor-related activity resulted in suppression of
limb tremor in two out of two patients. Interestingly, in one of these patients, 4 Hz oscillatory activity was diminished in a neurone recorded 1.3 mm from the injection site, but there was no reduction in the mean firing rate or 20 Hz oscillatory activity. These results demonstrate that inactivation of neuronal activity 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 oscillatory activity of neurones located beyond the inhibited region.