Single unit “pauser” characteristics of the globus pallidus pars externa distinguish primary dystonia from secondary dystonia and Parkinson's disease

Abstract

The presence of high frequency discharge neurons with long periods of silence or "pauses" in the globus pallidus pars externa (GPe) are a unique identifying feature of this nucleus. Prior studies have demonstrated that pause characteristics reflect synaptic inputs into GPe. We hypothesized that GPe pause characteristics should distinguish movement disorders whose basal ganglia network abnormalities are different. We examined pause characteristics in 224 GPe units in patients with primary generalized dystonia, Parkinson's disease (PD), and secondary dystonia, undergoing single unit microelectrode recording for DBS placement in the awake state. Pauses in neuronal discharge were identified using the Poisson surprise method. Mean pause length in primary dystonia (606.8 ±373.3) was higher than in PD (557.4±366.6) (p<0.05). Interpause interval (IPI) was lower in primary dystonia (2331.6±3874.1) than PD (3646.4±5894.5) (p<0.01), and mean pause frequency was higher in primary dystonia (0.14±0.10) than PD (0.07±0.12) (p<0.01). Comparison of pause characteristics in primary versus secondary generalized dystonia revealed a significantly longer mean pause length in primary (606.8±373.3) than in secondary dystonia (495.6±236.5) (p<0.01). IPI was shorter in primary (2331.6±3874.1) than in secondary dystonia (3484.5±3981.6) (p<0.01). The results show that pause characteristics recorded in the awake human GPe distinguish primary dystonia from Parkinson's disease and secondary dystonia. The differences may reflect increased phasic input from striatal D2 receptor positive cells in primary dystonia, and are consistent with a recent model proposing that GPe provides capacity scaling for cortical input.

Frequency-dependent effects of electrical stimulation in the globus pallidus of dystonia patients

“…The result would be a regular synchronized, high-frequency output to premotor structures in brain stem and thalamus, which lacks any "pattern-sculpting" by basal ganglia input structures. Given that pauses in GP neuron firing are thought to be related to dystonia (Hutchison et al 2003;Sani et al 2009), the elimination of pathological inhibitory phasic movement-related signals may help to restore more "normal" voluntary movements and the function of reciprocal inhibition to eliminate overflow. These spatial/volume constraints may explain why microstimulation is usually ineffective, whereas macrostimulation is effective on the target premotor structures.…”

Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

“…Detection of pauses in external globus pallidus (GPe) neuronal discharge was performed as described in Sani et al ,18 based on the prior published work of Bergman and colleagues 19. Briefly, pauses were detected using the Poisson surprise method, with a minimum surprise value of 5.…”

Pallidal activity in myoclonus dystonia correlates with motor signs

“…Pauses were detected 24 and the mean pause frequency, duration, and interpause interval calculated. 8 Analysis of oscillatory activity was performed by frequency band using a customized Matlab script (delta: 1-4 Hz, theta: 4-8 Hz, alpha: 8-12 Hz, beta low: 12-20 Hz, beta high: 20-35 Hz, gamma: >35 Hz). 25 …”