Elsevier

Neuroscience

Volume 88, Issue 1, January 1999, Pages 201-212
Neuroscience

High-frequency stimulation of the subthalamic nucleus suppresses experimental resting tremor in the monkey

https://doi.org/10.1016/S0306-4522(98)00235-8Get rights and content

Abstract

The effect of high-frequency stimulation of the subthalamic nucleus on parkinsonian-like resting tremor was investigated in two monkeys (Macaca fascicularis). Unilateral tremor of the arm and leg was induced by electrical coagulation of the brainstem area including the substantia nigra and the red nucleus. The tremor was only seen at rest condition with a very stable frequency of 4.46±0.59 Hz (mean±S.D.). Apomorphine (0.1–0.4 mg/kg, s.c.) completely blocked the tremor, suggesting that it was a dopaminergic-dependent symptom just like the parkinsonian tremor. When the stimulating frequency varied from 20 to 1 000 Hz, both mono- and bipolar stimulation (square pulses, 0–5 mA, 0.06 ms) of the subthalamic nucleus suppressed resting tremor in a frequency-dependent manner but monopolar stimulation was more effective. These effects remained stable for more than two years.

The present results suggest that the subthalamic nucleus is involved in the control and mechanism of resting tremor and that the high-frequency stimulation of the subthalamic nucleus can be used as an alternative therapy in parkinsonian patients with akinesia, rigidity and resting tremor.

Section snippets

Induction of chronic resting tremor

Two male Macaca fascicularis monkeys (Primatologic Rechearch Center, Port Louis, Ile Maurice) with weights ranging from 4 to 6 kg were used in this study. Under general anaesthesia with ketamine (10 mg/kg, i.m., Imalgene, Rhone Merieux, Lyon, France), the monkey's head was fixed in a Kopf stereotaxic apparatus. All operations were performed under sterile conditions. Imalgene was injected at 1-h intervals to maintain basic anaesthesia.

Ventriculography was performed by injecting a contrast medium

Results

Results of both embryonic day (E)15 and postnatal day (P)2 animals are reported here. It was not possible obviously to pool them statistically, but when possible numerical data will be provided for both animals. Behavioural and clinical observations were similar and are described here regardless of the animal number, except when a specific feature was observed in one of the two monkeys.

Resting tremor model

Since its discovery, MPTP was the toxic substance of choice to reproduce motor symptoms resembling those of Parkinson's disease in subhuman primate.[28]MPTP, when injected intramuscularly,[11]intravenously[3]or into the internal carotid artery,7, 8, 9induced mainly akinesia and muscular rigidity, but tremor was never or rarely seen. A stable parkinsonian syndrome with tremor was developed recently following chronic MPTP administration in baboons.[23]Both action and resting tremor were

Conclusion

Our results show that both mono- and bipolar STN-HFS can effectively suppress experimental resting tremor induced by electrical coagulation of the brainstem area including the substantia nigra and the red nucleus. This arrest of tremor was frequency dependent, but monopolar stimulation was better than bipolar one. This approach could be used as a suitable treatment for Parkinson's disease, especially in those parkinsonian patients who suffer from resting tremor, as well as akinesia and muscular

Acknowledgements

This work was supported by grants from Institut National de la Santé et de la Recherche Médicale, Université Joseph Fourier Grenoble 1, Medtronic Inc. and Region Rhône-Alpes.

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