doi:10.1016/j.expneurol.2005.03.014 
Copyright © 2005 Elsevier Inc. All rights reserved.
Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease
Paul Silbersteina, b, Antonio Olivieroc, Vincenzo Di Lazzarod, Angelo Insolae, Paolo Mazzonef and Peter Browna, 
, 
aSobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London WCIN 3BG, UK
bUnit of Functional Neurosurgery, Institute of Neurology, London, UK
cFENNSI Group, Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain
dInstitute of Neurology, Università Cattolica, Rome, Italy
eOperative Unit of Neurophysiology, CTO “A. Alesini” Hospital, Rome, Italy
fOperative Unit of Functional and Stereotactic Neurosurgery, CTO “A. Alesini” Hospital, Rome, Italy
Received 30 January 2005;
revised 28 March 2005;
accepted 30 March 2005.
Available online 30 April 2005.
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Abstract
Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = −0.65, P < 0.001 and r = −0.33, P < 0.001 for activities over 13–30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.
Keywords: Dyskinesia; Pallidum; Local field potentials; Parkinson's disease
Fig. 1. Post-operative MRI of case 1 showing pallidal localization of macroelectrodes. Recordings were only made from the right pallidal electrode (arrowed). The medial electrodes on either side are located in the thalamus.
Fig. 2. Polarity reversal in pallidal LFPs in case 2. Cross-correlation between LFPs from contact pair 01 (reference) and 12 after first pass-band filtering signals in the beta (13–30 Hz) band. Cross-correlograms from two separate records of 285 and 249 s are superimposed and show a negative wave centered at zero, indicative of a generator very near to contact 1, where cathodal stimulation afforded maximal suppression of dyskinesias (using bipolar stimulation 1–2+).
Fig. 3. (A) Correlation between log LFP 13–30 Hz power (x axis, arbitrary units) at contact pair 01 in case 1 and rectified log total sEMG power (y axis, arbitrary units). Each point represents log power over a 1.024 s epoch. (B) Reciprocal relationship between right pallidal (contact 01) log LFP power in the beta (13–30 Hz) band and log power (4–200 Hz) of rectified sEMG from left forearm extensor muscles during involuntary dyskinesias in case 1. Note that there is an increase in pallidal beta activity when the dyskinesia briefly settles (long arrow), but there are also peaks in pallidal beta activity at the same time as smaller fluctuations in EMG level (see shorter arrows). Fluctuations occur over seconds rather than minutes.
Fig. 4. Correlation coefficient between 13–30 Hz log pallidal LFP power and log total sEMG power by pallidal contact pair and subject. Correlation coefficients for case 1 in black and correlations for case 2 in white. Significant correlations after Bonferroni correction (i.e., P < 0.016) are marked with a star.
Fig. 5. Correlation coefficient between log total sEMG power and pallidal power in different frequency bands at the contact with the highest correlation (01 and 12 in cases 1 and 2, respectively). Case 1 is in black. Case 2 is in white. Significant correlations after Bonferroni correction (i.e., P < 0.01) are marked with a star.
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