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Published Online First: 23 November 2007. doi:10.1136/jnnp.2006.112342
Journal of Neurology, Neurosurgery, and Psychiatry 2008;79:514-521
Copyright © 2008 by the BMJ Publishing Group Ltd.
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RESEARCH PAPERS

Induction of parkinsonian resting tremor by stimulation of the caudal zona incerta nucleus: a clinical study

P Plaha1, S Filipovic2,3, S S Gill1

1 Institute of Neurosciences, Department of Neurosurgery, Frenchay Hospital, Bristol, UK
2 Institute of Neurosciences, Department of Neurology, Frenchay Hospital, Bristol, UK
3 Burden Neurological Institute, Bristol, UK

Correspondence to:
Prof Steven Gill, Consultant Neurosurgeon, Institute of Neurosciences, Department of Neurosurgery, Frenchay Hospital, Bristol BS16 1LE, UK; steven.gill{at}nbt.nhs.uk

Introduction: We hypothesise that parkinsonian tremor arises when the caudal zona incerta (cZI) and subthalamic nucleus (STN) are deprived of dopamine and become increasingly responsive to motor cortical {alpha} and β frequency oscillations. These oscillations are synchronised and amplified through the basal ganglia thalamocortical loop and entrained into the cerebello-thalamocortical loop via the cZI. On receiving potent {gamma}-aminobutyric acid (GABA)-ergic {alpha} and β frequency oscillations in cZI afferents, ventrolateral (VL) thalamocortical neurons become hyperpolarised and rebound burst fire, generating 4–6 Hz tremor oscillations. We test this hypothesis by stimulating the cZI at {alpha} and β frequencies using deep brain stimulation (DBS) in non-tremulous parkinsonian patients to see whether a 4–6 Hz tremor can be induced.

Method: This study included 11 patients with non-tremulous Parkinson’s disease (PD), who had DBS leads implanted in a range of targets, including the cZI, STN, VL nucleus, globus pallidus internus (GPi), centromedian and parafascicular nucleus (CM/Pf), and the pedunculopontine nucleus (PPN). All patients underwent stimulation of active contacts within their respective targets at a standard pulse width, with frequencies ranging from 5 to 80 Hz up to a maximum tolerated voltage. The frequency of the tremor induced in the hands was recorded by accelerometry.

Result: Resting tremor in the 4–6 Hz range could be readily induced following stimulation of the cZI and the VL nucleus between 5 and 40 Hz. Tremor was also seen following STN stimulation; however, this was only at high stimulation voltages (>5 volts). No tremor could be induced following CM/Pf, PPN or GPi stimulation.

Conclusion: We discuss the implications of these findings and argue that resting tremor in PD is generated in the cortico-ZI-VL-thalamocortical loop rather than in the cortico-basal-ganglia-thalamocortical loop.






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