Journal Article

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

Filipovic, S, Plaha, P, Gill, S S

2008

Overview

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.

• Publisher: BMJ Publishing Group Ltd,BMJ,BMJ Publishing Group LTD
• Subject: Afferent Pathways - physiopathology / Basal Ganglia - physiopathology / Biological and medical sciences / Cerebral Cortex - physiopathology / Cortical Synchronization / Deep Brain Stimulation / Dopamine / Double-Blind Method / Female / Humans / Hypotheses / Intralaminar Thalamic Nuclei / Male / Medical sciences / Motor Neurons - physiology / Nerve Net - physiopathology / Nervous system (semeiology, syndromes) / Nervous system as a whole / Neurologic Examination / Neurology / Neurons / Parkinson Disease - physiopathology / Parkinson Disease - therapy / Parkinson's disease / Pedunculopontine Tegmental Nucleus - physiopathology / Serotonin / Subthalamic Nucleus - physiopathology / Subthalamus - physiopathology / Tremor (Muscular contraction) / Tremor - physiopathology / Tremor - therapy / Ventral Thalamic Nuclei - physiopathology