Bilateral symmetry and coherence of subthalamic nuclei beta band activity in Parkinson's disease

Abstract

Abnormal synchronization of neuronal activity in the basal ganglia has been associated with the dysfunction of sensorimotor circuits in Parkinson's disease (PD). In particular, oscillations at frequencies within the beta range (13–35 Hz) are specifically modulated by dopaminergic medication and are correlated with the clinical state of the subjects. While these oscillations have been shown to be coherent ipsilaterally within the basal ganglia and between the basal ganglia nuclei and the ipsilateral motor cortex in PD, the bilateral extent of their coherence has never been characterized. Here we demonstrate for the first time that the beta band oscillations recorded in the local field potential of the subthalamic nuclei (STN), while appearing different across subjects, are occurring at the same frequencies bilaterally (p < 0.001) and are coherent between the two STNs of individual PD subjects (11/12 cases, p < 0.05). These findings suggest the existence of a bilateral network controlling the beta band activity in the basal ganglia in PD.

Introduction

In Parkinson's disease (PD), the loss of dopamine neurons is associated with the appearance of excessive synchronization of oscillatory activity in the basal ganglia and associated circuits (Hammond et al., 2007). The use of deep brain stimulation (DBS) therapy has provided a unique opportunity to record these abnormal oscillations in the local field potential (LFP) of the subthalamic nuclei (STN). These rhythms are usually classified according to their frequency band: < 8 Hz, 8–12 Hz, 13–35 Hz and > 60 Hz. In particular, most research in the field has concentrated on oscillations in the beta range (13–35 Hz), as they are modulated by dopaminergic medication (Levy et al., 2002, Priori et al., 2004, Kuhn et al., 2006). There is growing evidence that they are also attenuated by deep brain stimulation (Wingeier et al., 2006, Kuhn et al., 2008, Bronte-Stewart et al., 2009), and are correlated with the severity of bradykinesia and rigidity (Kuhn et al., 2006, Kuhn et al., 2008, Ray et al., 2008).

Simultaneous recordings from multiple nuclei of the basal ganglia and in the ipsilateral cortex in PD subjects have led to the conclusion that the excessive beta synchrony is a feature of the entire ipsilateral basal ganglia-cortical network in PD. Populations of neurons not only synchronize their activity locally in the basal ganglia nuclei, but also between these nuclei and the ipsilateral cortex (Brown et al., 2001, Marsden et al., 2001).

Furthermore, some experiments of stimulation in PD subjects have shown small but measurable ipsilateral effects of unilateral STN stimulation (Liu et al., 2002, Chung et al., 2006, Slowinski et al., 2007, Tabbal et al., 2008). Gaynor et al. (2008) have shown that unilateral cortical stimulation with trans-cranial magnetic stimulation (TMS) could affect STN beta rhythm bilaterally. The possibility of a common rhythm in bilateral basal ganglia has also been recently suggested by Bronte-Stewart et al. (2009), who demonstrated that the beta band profile at rest in one STN is a stationary phenomenon and proposed that it was similar within both STNs of an individual subject while varied between subjects.

However, no bilateral connections are known between the two hemispheres at the level of the basal ganglia in the human and the bilateral effects of unilateral DBS or TMS do not necessarily imply a bilateral neural network connecting the two STNs. Indeed both stimulation techniques affect all neurons and neurites in the area surrounding the stimulating probe. Hence, stimulation could affect two independent networks which would lie within the volume of activation but with one projecting ipsilaterally and the other one contralaterally. Therefore, there is a need for further insight into the spatial extent of the synchronized network and in particular to ask whether there is a bilateral organization of the beta rhythm.

Here we investigate this issue by first comparing the frequency of LFP spectral peaks in the beta range in bilateral STNs of PD subjects. We hypothesize that the beta band oscillations in the LFP of each STN of an individual subject with PD are characterized by the same peak frequencies. This result would suggest that there is either a similarity in the local circuit characteristics underlying beta oscillations within each STN of an individual or that there is a bilateral network, which allows resonance or synchrony between hemispheres in subjects with PD. The second goal of this study was hence to investigate the possible existence of coherence between bilateral beta band oscillations in the two STNs of individual subjects.