The oscillatory activity in the Parkinsonian subthalamic nucleus investigated using the macro-electrodes for deep brain stimulation

Abstract

Objectives: To investigate the oscillatory activity in the Parkinsonian subthalamic nucleus using the macro-electrodes for deep brain stimulation.

Methods: During bilateral deep brain stimulating electrode implantation, spontaneous and evoked field potentials were recorded from the subthalamic nucleus (STN) in two patients with Parkinson's disease (PD) during spontaneous resting tremor, passive manipulation of the wrist, and following electrical stimulation of the contralateral STN.

Results: Frequency analysis of the STN field potentials recorded during spontaneous resting tremor showed significant coherence with electromyographic activity in the contralateral arm, suggesting a close involvement of the STN in the generation of resting tremor in PD. The STN responded to passive movement of the contralateral wrist, but not to ipsilateral movement. High frequency (100 Hz) electrical stimulation of the STN induced tremor (4 Hz) in both forearms, and also oscillation of the contralateral STN (4 Hz). In contrast, low frequency (5 Hz) stimulation induced contralateral arrhythmic involuntary movement (3 Hz), but without altering the contralateral STN activity.

Conclusions: We propose that the functional connection between the STN and arm muscles is mainly contralateral, but cross talk may occur between bilateral STN via a frequency-dependent pathway.

Introduction

Chronic deep brain stimulation (DBS) has been shown to be an effective treatment for all major symptoms of Parkinson's disease (PD) (Aziz and Bain, 1999, Bejjani et al., 2000, Benabid et al., 1993, Benabid et al., 1994, Benabid et al., 1998, Brown et al., 1999, Krack et al., 1998, Kumar et al., 1998, Limousin et al., 1995a, Starr et al., 1998). It also provides a unique opportunity to investigate the role of basal ganglia nuclei in the pathogenesis of Parkinsonian symptoms by recording neuronal activity from the nuclei in which the DBS electrode being implanted. By recording and correlating single-unit activity across cells, it has been shown that synchronised tremor-related activity appears in the major basal ganglia nuclei: the ventral thalamic nuclear group (Lenz et al., 1994, Levy et al., 2000), the internal segment of the globus pallidus (Hurtado et al., 1999) and the subthalamic nucleus (STN) (Levy et al., 2000). However, single-unit recording can only sample limited numbers of cells in each patient during electrode implantation. It is still unclear that to what extent the larger population of cells is unified by the increased oscillatory activity. The overall activity of a nucleus can be better represented by focal field potentials, which are mostly generated by synaptic potentials from a population of cells in the nucleus. It was shown that intrinsic focal field potentials (FPs) could be recorded from an intended subcortical nucleus (Spiegel and Gildenberg, 1982). If synchronised tremor-related activity was present across a population of cells, then it would sum up to generate focal FPs which could be recorded using the implanted DBS electrode (Brown et al., 2001). To identify the synchronised movement-related activity in the STN, recordings of FPs in the STN via the DBS electrode were carried out in 7 PD patients during implantation. The primary purpose of recording was to functionally localise the STN so that the placement of the electrode can be optimised (Liu et al., 2000, Liu et al., 2001). FPs were correlated to surface electromyographics (EMGs) simultaneously recorded from the contralateral arm during resting tremor, and during passive and active wrist movements in comparison with rest.

In this paper we report two cases of bilateral STN implantation, where evoked FPs were recorded following electrical stimulation of the contralateral STN at different frequencies together with surface EMGs. We aimed to investigate the frequency-dependent effects of STN stimulation on Parkinsonian symptoms (Limousin et al., 1995b, Limousin et al., 1996) and to examine a possible interaction between the two STNs.