Identification and characterization of neurons with tremor-frequency activity in human globus pallidus.

Abstract

Many previous studies have demonstrated the existence of neurons with tremor-frequency activity ("tremor cells") in the thalamus of Parkinson's disease (PD) patients and these neurons are presumed to play a role in the pathogenesis of tremor. Since a major input to motor thalamus (Voa and Vop) is from the internal segment of the globus pallidus (GPi), neurons with tremor-frequency activity in motor thalamus may receive input from neurons in GPi. The aim of this study was to quantify the characteristics of tremor cells in human globus pallidus. In three PD patients with tremor undergoing microelectrode exploration of the globus pallidus prior to pallidotomy, 228 neurons were sampled, and 28 (12.3%) were identified to fire at the same frequency as the tremor. These "tremor cells" were located in the ventral portion of GPi. Autocorrelogram analysis of the sampled spike trains of these 28 tremor cells was carried out over sequential 10-s time segments, and autocorrelograms showing maximal oscillatory activity were graded from 0 to 10. Average tremor cell oscillation grades ranged from 6.8 to 7.8, similar to those reported in the MPTP-induced primate model of parkinsonism. The average tremor cell oscillation grade varied between patients, as did the clinical measures of tremor severity. Tremor cells had oscillations in spike discharges at the same average frequency (4.2-5.2 Hz) as the patient's tremor determined from the electromyogram and accelerometry records of one or more limbs (4.0-5.4 Hz), and the individual values were correlated (r2=0.73) over the total range (3.7-5.6 Hz). The results of this study demonstrate the presence of neurons with 4-6 Hz tremor-frequency activity in GPi, supporting a role of the globus pallidus in the production of rest tremor in PD patients.