It has been proposed that parkinsonian tremor is produced either by the activity of an intrinsic thalamic pacemaker or by the oscillation of an unstable long loop reflex arc. The former (central) hypothesis proposes that overactivity of neurons in the internal segment of the globus pallidus inhibits or hyperpolarizes thalamic neurons. When hyperpolarized, thalamic cells oscillate with bursting of the type associated with low threshold calcium spikes (low threshold spike-bursts). Low threshold spike-bursts can be identified by particular patterns of interspike intervals within the burst. The alternative (peripheral) hypothesis proposes that tremor results from oscillation of a reflex arc transmitting activity from muscle stretch receptors to thalamus, motor cortex, and back to the stretched muscle. When the gain of this reflex is increased, the arc may become unstable and oscillate. Oscillations produced by peripheral inputs may produce an acceleration-deceleration pattern within the burst which results in sinusoidal modulation of a spike train if bursting is periodic. We have assessed these two hypotheses by studying the pattern of interspike intervals occurring within bursts recorded in patients with parkinsonian tremor. The spike trains were analysed for 118 cells located in the ventral nuclear group including ventralis intermedius (thalamic cerebellar relay nucleus, n=48) and ventralis oralis posterior (thalamic pallidal relay nucleus, n=39) of patients with parkinsonian tremor. Two cells recorded in ventralis intermedius of a sleeping patient with chronic pain showed bursting activity similar to the low threshold spike-bursts recorded in sleeping animals, suggesting a common mechanism for low threshold spike-bursts across species. Forty-two cells recorded in patients with parkinsonian tremor (ventralis intermedius, n=19; ventralis oralis posterior, n=12) were classified as tremor-related cells because their activity was characterized by both a concentration of power at tremor frequency and significant correlation with tremor. Eleven tremor-related cells, 10 located in ventralis intermedius or ventralis oralis posterior and most responding to sensory inputs, had an acceleration-deceleration pattern of intraburst firing. Only one cell, a tremor-related cell in ventralis intermedius, showed the pattern expected of presumed low threshold spike-bursts. Therefore, intraburst interspike interval patterns consistent with either the central or the peripheral hypothesis were recorded in the thalamus of patients with parkinsonian tremor. Twenty-one tremor-related cells (15 cells in ventralis intermedius or ventralis oralis posterior) had bursts with intraburst interspike intervals which were independent of position of the interspike interval within the burst. Therefore, the activity of the majority of cells was not consistent with either hypothesis, suggesting that another oscillatory process may contribute to parkinsonian tremor.
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