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Induction of parkinsonian resting tremor by stimulation of the caudal zona incerta nucleus: a clinical study
  1. P Plaha1,
  2. S Filipovic2,3,
  3. S S Gill1
  1. 1
    Institute of Neurosciences, Department of Neurosurgery, Frenchay Hospital, Bristol, UK
  2. 2
    Institute of Neurosciences, Department of Neurology, Frenchay Hospital, Bristol, UK
  3. 3
    Burden Neurological Institute, Bristol, UK
  1. Prof Steven Gill, Consultant Neurosurgeon, Institute of Neurosciences, Department of Neurosurgery, Frenchay Hospital, Bristol BS16 1LE, UK; steven.gill{at}


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 α 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 γ-aminobutyric acid (GABA)-ergic α 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 α 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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  • Funding: PP was supported by a grant from the UK Medical Research Council (G9900797).

  • Competing interests: None.