Bilateral symmetry and coherence of subthalamic nuclei beta band activity in Parkinson's disease
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.
Section snippets
Patient assessment
Intra-operative local field potential (LFP) recordings were collected immediately after STN DBS bilateral implantation from 56 subthalamic nuclei in 28 subjects with PD, who were off medication. All subjects signed a written consent for the study, which was approved by the Stanford Institutional Review Board. The pre-operative selection criteria and assessment of subjects have been previously described (Taylor Tavares et al., 2005, Bronte-Stewart et al., 2009). Long-acting dopaminergic
Results
Bilateral recordings were made from 28 subjects with PD. The subjects' average ± standard deviation are given: age 62.8 ± 8.6 years, disease duration 10.1 ± 4.5 years, pre-operative mean UPDRS III (motor) score 38.9 ± 9.5 off medication and 17.6 ± 9.3 on medication.
Beta oscillations occur at the same frequency and are coherent between bilateral STN in individual subjects with PD
In this study we have shown that the frequencies of spectral peaks in the beta band of the LFP are similar between the left and right STNs of 28 individual subjects with PD. The demonstration of both stationarity of beta band power (Bronte-Stewart et al., 2009) and bilateral similarity of spectral peaks between bilateral STN LFP strengthens the hypothesis that STN LFP spectral profiles recorded from the DBS lead may be considered as a “signature” for each individual PD subject, as suggested
Conclusion
Our study demonstrates for the first time that beta oscillations occurring in the STN of PD subjects are characterized by a similar frequency of oscillation, specific to the subject, and are coherent between the two hemispheres of a subject. These results show that the spatial extent of beta synchrony is greater than previously known, and that further insight into the basal ganglia network and in particular into their cortical inputs is required to understand the connections underlying the
Funding
This work was supported by grants from the Robert and Ruth Halperin Foundation, The Peggy K Cahill Family Research Foundation and the John A Blume Foundation.
Acknowledgments
We thank Gary Heit and Brett Wingeier for helpful discussion, and Stephanie Louie for help with the manuscript.
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