Tremor-frequency Activity Research Articles

S20-2 Thalamic neurons with tremor-frequency activity in patients with essential tremor

S20-2 Thalamic neurons with tremor-frequency activity in patients with essential tremor

Difference in surgical strategies between thalamotomy and thalamic deep brain stimulation for tremor control

Stereotactic targeting strategies differ between thalamotomy and thalamic deep brain stimulation (DBS) for tremor control. In thalamotomy, a minimal radiofrequency lesion created within the lateral portion of the nucleus ventralis intermedius (Vim) often affords the best control of parkinsonian tremor, supporting the assumption that there is a concentrated cluster of cells within this area which is responsible for tremor. However, this assumption may not always be true; such neural elements sometimes appear to spread out across wide areas. Cells with tremor-frequency activity are widely distributed over the areas extending from the Vim to the nuclei ventralis oralis posterior and anterior (Vop and Voa). All of these cells appear to be more or less involved in tremor generation, especially in patients with essential tremor and post-stroke tremor. In contrast to radiofrequency lesions for thalamotomy, electrodes for DBS can be arranged in such a way that wide areas can be stimulated, if necessary. For this purpose, it is critically important to determine optimal placement and orientation of DBS leads for arranging the electrodes to yield maximal benefits in patients with tremor.

Tremor-frequency (3–6 Hz) activity in the sensorimotor arm representation of the internal segment of the globus pallidus in patients with Parkinson's disease

Neurons in the internal segment of the globus pallidus (GPi) oscillate at approximately the frequency of parkinsonian tremor. However, the correlation of that activity with tremor has not previously been studied. We now describe the relationship between single neuron activity in the arm sensorimotor portion of GPi and upper extremity tremor in patients with Parkinson's disease. There was a significant concentration of power in the tremor-frequency range (3–6 Hz) for 11/44 GPi neurons. However, pallidal tremor-frequency activity correlated significantly with electromyogram (EMG) activity during tremor for only a single GPi neuron. These data are most consistent with the hypothesis that the output of neurons in GPi is transformed in thalamus by a non-linear mechanism, before transmission via the cortex to the spinal motorneurons that drive movement.

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

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.

Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells.

During procedures for parkinsonian tremor, neurons in the thalamic ventral nuclear group show periodic activity at tremor frequency (tremor-frequency activity). The tremor-frequency activity of some cells is significantly correlated with tremor. Cells in this region also display functional properties defined by activity related to somatosensory stimuli and to active movement. Cells with activity related to somatosensory stimulation were termed sensory cells while those with activity related to active movement were termed voluntary cells. Cells with activity related to both somatosensory stimulation and active movement were termed combined cells. Those with activity related to neither somatosensory stimulation nor active movement were termed no-response cells. Combined, voluntary and no-response cells were located in the region of thalamus where a lesion stops tremor and anterior to the region where sensory cells were found. Spectral cross-correlation analysis demonstrated that many combined, voluntary and no-response cells had a peak of activity at tremor frequency which was significantly correlated with electromyogram (EMG). Analysis of the phase of thalamic activity relative to EMG activity indicated that voluntary and combined cell activity usually led EMG during tremor. These results suggest that thalamic cells unresponsive to somatosensory stimulation (voluntary and no-response cells) and those responsive to somatosensory stimulation (combined cells) are involved in the mechanism of parkinsonian tremor. The activity of sensory cells frequently lagged behind tremor while activity of combined cells often led tremor. This finding suggests that the activity of these two cell types, both responding to sensory input, is related to tremor by different mechanisms.

The role of feedback in the tremor frequency activity of tremor cells in the ventral nuclear group of human thalamus.

Close loop system identification techniques have been used to identify the presence of feedback in the firing pattern of thalamic tremor cells recorded in parkinsonian tremor patients.