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. 2016 May;89:213-22.
doi: 10.1016/j.nbd.2016.02.015. Epub 2016 Feb 14.

Subthalamic Local Field Potentials in Parkinson's Disease and Isolated Dystonia: An Evaluation of Potential Biomarkers

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Free PMC article

Subthalamic Local Field Potentials in Parkinson's Disease and Isolated Dystonia: An Evaluation of Potential Biomarkers

Doris D Wang et al. Neurobiol Dis. .
Free PMC article

Abstract

Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13-30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non-parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers.

Keywords: Beta oscillation; Cross frequency interaction; Deep brain stimulation; Electrophysiology; Phase amplitude coupling.

Conflict of interest statement

Authors’ contributions and conflict of interest disclosures: Authors report no conflict of interest.

Figures

Figure 1
Figure 1. lead locations and STN LFP example recordings
A) Top: Axial T2-weighted MRI showing DBS lead locations for a patient with PD (left) and dystonia (right). Bottom: axial and coronal planes showing the location of the recording contact, in mm from the midpoint between the anterior and posterior commissures in PD (left) and Dystonia (right). B) Top: one second sample resting state raw LFP signals recorded from the STN in PD (left, patient 8) and dystonia (right, patient 7). Bottom: Corresponding power spectra of a 30 second resting state LFP recording from PD and dystonia patients (from top).
Figure 2
Figure 2. STN LFP spectral power characteristics in PD vs. dystonia
A) Log-transformed individual spectral power density graphs for 28 PD (left) and 14 dystonia LFP recordings (right). All signals were notch-filtered at 60 Hz. B) Boxplots (median and 25–75th quartiles) of non-normalized spectral power, averaged in specified frequency ranges for PD and dystonia showing no differences in spectral power between groups (PD vs. dystonia: theta: p=0.2948, alpha: p=0. 0.8710, low beta: p= 0.8019; high beta: p= 0.5257, broadband gamma: p=0.2948, HFO: p=0.4879; Wilcoxon rank sum test). C) Example of method used for characterizing the alpha-beta peak (PD patient 8), to account for baseline power variations across subjects. The log spectral power (excluding the alpha-beta range) is fitted using a polynomial function to find the power baseline (red line). The resulting alpha beta peak is then fitted using Gaussian function (blue line). The power peak is indicated by *. D) Boxplots showing characteristics of the alpha-beta peak frequency, amplitude, and width. There was no significant difference between PD and dystonia (PD vs. dystonia: frequency: p =0.7552; amplitude: p= 0.0954; width: p= 0.1077; Wilcoxon rank sum test). E) Boxplots showing similar alpha-beta peak characteristics between focal/segmental and generalized dystonia (Focal vs. generalized: frequency: p=0.5563; amplitude: p= 0.8182; width: p= 0.9172; Wilcoxon rank sum test).
Figure 2
Figure 2. STN LFP spectral power characteristics in PD vs. dystonia
A) Log-transformed individual spectral power density graphs for 28 PD (left) and 14 dystonia LFP recordings (right). All signals were notch-filtered at 60 Hz. B) Boxplots (median and 25–75th quartiles) of non-normalized spectral power, averaged in specified frequency ranges for PD and dystonia showing no differences in spectral power between groups (PD vs. dystonia: theta: p=0.2948, alpha: p=0. 0.8710, low beta: p= 0.8019; high beta: p= 0.5257, broadband gamma: p=0.2948, HFO: p=0.4879; Wilcoxon rank sum test). C) Example of method used for characterizing the alpha-beta peak (PD patient 8), to account for baseline power variations across subjects. The log spectral power (excluding the alpha-beta range) is fitted using a polynomial function to find the power baseline (red line). The resulting alpha beta peak is then fitted using Gaussian function (blue line). The power peak is indicated by *. D) Boxplots showing characteristics of the alpha-beta peak frequency, amplitude, and width. There was no significant difference between PD and dystonia (PD vs. dystonia: frequency: p =0.7552; amplitude: p= 0.0954; width: p= 0.1077; Wilcoxon rank sum test). E) Boxplots showing similar alpha-beta peak characteristics between focal/segmental and generalized dystonia (Focal vs. generalized: frequency: p=0.5563; amplitude: p= 0.8182; width: p= 0.9172; Wilcoxon rank sum test).
Figure 3
Figure 3. STN phase amplitude coupling (PAC) in PD vs dystonia
A) Example comodulograms for PD (left) and dystonia (right) showing high modulation index (MI) between beta phase frequency and high frequency oscillation (HFO) amplitude. Warmer color demonstrates higher MI values. B) Boxplots of beta-HFO PAC in subjects who had detectable PAC (19/28 PD patients, 6/12 dystonia patients). There was no significant difference between groups (PD vs. dystonia: alpha: p= 0.4011; low beta, p=0.2035; high beta p=0.3547; Wilcoxon rank sum test). C) (Left) Scatter plot of the phase and amplitude where maximal MI occurs (PD vs. dystonia: phase frequency, p=0.7718; amplitude frequency, p=0.9769; Wilcoxon rank sum test). (Right) Boxplots of maximal modulation index for PD and dystonia (PD vs. dystonia: p=0.5632; Wilcoxon rank sum test). D) Polar histograms showing averaged phase angle for those phase and amplitude frequency pairs showing significant PAC in 19 PD patients (top) and 6 dystonia (bottom). Red line indicates median phase angle and shaded area indicates standard deviation. There is no statistical difference among the groups in phase preference (PD vs. dystonia, p>0.1 for alpha and low beta phase, p=0.1000 high beta phase, Kuiper’s test).
Figure 3
Figure 3. STN phase amplitude coupling (PAC) in PD vs dystonia
A) Example comodulograms for PD (left) and dystonia (right) showing high modulation index (MI) between beta phase frequency and high frequency oscillation (HFO) amplitude. Warmer color demonstrates higher MI values. B) Boxplots of beta-HFO PAC in subjects who had detectable PAC (19/28 PD patients, 6/12 dystonia patients). There was no significant difference between groups (PD vs. dystonia: alpha: p= 0.4011; low beta, p=0.2035; high beta p=0.3547; Wilcoxon rank sum test). C) (Left) Scatter plot of the phase and amplitude where maximal MI occurs (PD vs. dystonia: phase frequency, p=0.7718; amplitude frequency, p=0.9769; Wilcoxon rank sum test). (Right) Boxplots of maximal modulation index for PD and dystonia (PD vs. dystonia: p=0.5632; Wilcoxon rank sum test). D) Polar histograms showing averaged phase angle for those phase and amplitude frequency pairs showing significant PAC in 19 PD patients (top) and 6 dystonia (bottom). Red line indicates median phase angle and shaded area indicates standard deviation. There is no statistical difference among the groups in phase preference (PD vs. dystonia, p>0.1 for alpha and low beta phase, p=0.1000 high beta phase, Kuiper’s test).

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