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The Journal of Neuroscience, June 11, 2008, 28(24):6165-6173; doi:10.1523/JNEUROSCI.0282-08.2008

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Neurobiology of Disease
High-Frequency Stimulation of the Subthalamic Nucleus Suppresses Oscillatory β Activity in Patients with Parkinson's Disease in Parallel with Improvement in Motor Performance

Andrea A. Kühn,^1,3 Florian Kempf,³ Christof Brücke,³ Louise Gaynor Doyle,¹ Irene Martinez-Torres,^1,2 Alek Pogosyan,¹ Thomas Trottenberg,³ Andreas Kupsch,³ Gerd-Helge Schneider,⁴ Marwan I. Hariz,^1,2 Wim Vandenberghe,⁵ Bart Nuttin,⁶ and Peter Brown¹

¹Sobell Department of Motor Neuroscience and Movement Disorders and ²Unit of Functional Neurosurgery, Institute of Neurology, London WC1N 3BG, United Kingdom, ³Departments of Neurology and ⁴Neurosurgery, Charité Campus Virchow, Humboldt University, 13353 Berlin, Germany, and ⁵Division of Experimental Neurology and ⁶Laboratory for Experimental Neurosurgery and Neuroanatomy, Katholieke Universiteit Leuven, Bus 5005 3000 Leuven, Belgium

Correspondence should be addressed to Prof. Andrea A. Kühn, Department of Neurology, Charité, University Medicine Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Email: andrea.kuehn{at}charite.de

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the β (13–30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local β activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP β activity for 12 s after the end of stimulation and a decrease in motor cortical–STN coherence in the β band over the same time period. The reduction in LFP β activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of β activity was associated with better task performance. These features were absent when power in the 5–12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological β activity in PD.

Key words: DBS; mechanism; β oscillation; STN; Parkinson's disease; motor

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Received Jan. 22, 2008; revised April 7, 2008; accepted April 8, 2008.

Correspondence should be addressed to Prof. Andrea A. Kühn, Department of Neurology, Charité, University Medicine Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Email: andrea.kuehn{at}charite.de

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