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Brain Advance Access published online on January 8, 2007

Brain, doi:10.1093/brain/awl358
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 25, 2006
Revised November 6, 2006
Accepted November 28, 2006

Article

Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson's disease

Alexandros G. Androulidakis 1, Andrea A. Kühn 2, Chiung Chu Chen 1, Patric Blomstedt 3, Florian Kempf 4, Andreas Kupsch 4, Gerd-Helge Schneider 5, Louise Doyle 1, Patricia Dowsey-Limousin 6, Marwan I. Hariz 6, and Peter Brown 1 *

1 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK
2 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK; Department of Neurology, Charité Campus Virchow, Humboldt University, Berlin, Germany
3 Department of Neurosurgery, University Hospital of Northern Sweden, Sweden
4 Department of Neurology, Charité Campus Virchow, Humboldt University, Berlin, Germany
5 Department of Neurosurgery, Charité Campus Virchow, Humboldt University, Berlin, Germany
6 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK; Unit of Functional, Institute of Neurology, London, UK

* To whom correspondence should be addressed.
Peter Brown, E-mail: p.brown{at}ion.ucl.ac.uk


   Abstract

Treatment of patients with Parkinson's disease with levodopa has profound effects on both movement and the pattern of movement-related reactivity in the subthalamic nucleus (STN), as reflected in the local field potential (LFP). The most striking change is the promotion of reactivity in the gamma frequency band, but it remains unclear whether the latter is itself a pathological feature, possibly associated with levodopa induced dyskinesias, or is primarily physiological. Gamma band reactivity in the cerebral cortex of humans without Parkinson's disease occurs contralateral to movement, so we posited that lateralization of subcortical gamma reactivity should occur following levodopa if the latter restores a more physiological pattern in patients with Parkinson's disease. Accordingly, we studied movement-related changes in STN LFP activity in 11 Parkinson's disease patients (age 59 ± 2.7 years, three females) while they performed ipsi- and contralateral self-paced joystick movements ON and OFF levodopa. A bilaterally symmetrical gamma band power increase occurred around movement onset in the OFF state. Following levodopa this feature became significantly more pronounced in the subthalamic region contralateral to movement. The physiological nature of this asymmetric pattern of gamma reactivity was confirmed in the STN of two tremor patients without Parkinson's disease. Although levodopa treatment in the Parkinson's disease patients did not lead to lateralization of power suppression at lower frequencies (8-30 Hz), it did increase the degree of power suppression. These findings suggest that dopaminergic therapy restores a more physiological pattern of reactivity in the STN of patients with Parkinson's disease.

Keywords: deep brain stimulation; local field potentials; Parkinson's disease; subthalamic nucleus; synchronous oscillatory activity.
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