Subthalamic local field potentials in Parkinson's disease and isolated dystonia: An evaluation of potential biomarkers

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.

Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms

“…Despite being common across nodes, β-HFO PAC in the current analysis seems to carry little clinical significance, not correlating with symptom severity. Furthermore, β-HFO PAC is present in dystonia patients in both STN (Wang et al, 2016) and GPi, (in the current report). Given the lack of clinical correlation and its presence across diseases, more work is needed to define whether β-HFO PAC is still valuable as a specific biomarker of PD.…”

“…Recent reports in the literature suggest that coupling and not merely the power of β oscillations may be an important underpinning of PD pathophysiology (de Hemptinne et al, 2015; Swann et al, 2015; Wang et al, 2016). So far, the literature has been largely focused on analysis of STN and motor cortical LFPs.…”

A localized pallidal physiomarker in cervical dystonia

“…Crucially, our results demonstrate a spectrally highly focal association of peak theta activity with clinical symptom severity in a large cohort of cervical dystonia patients. 38 Given our findings on pallidal coherence and the previously described presence of theta activity in the subthalamic nucleus in dystonia patients, [11][12][13] we hypothesize that subcortical theta synchronization may represent a "noisy signal" as proposed by Marsden and Obeso 39 in the cortex-basal ganglia-thalamic loop that may interfere with physiological motor network function, leading to the generation of dystonic muscle contractions. 18 Both neuroimaging and electrophysiological studies have revealed structural and functional network changes in dystonic patients that have resulted in the current opinion that dystonia is a circuit disorder.…”

“…20 Before spectral analysis, all data segments with artifacts were rejected after visual inspection. Nine contact pairs from 5 patients (Cases 8, 10,13,14,15) had to be excluded from all analysis because of continuous contamination by artifacts. Nine contact pairs from 5 patients (Cases 8, 10,13,14,15) had to be excluded from all analysis because of continuous contamination by artifacts.…”

Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease

“…We also calculated the height of the beta peak normalized to baseline power using a previously described method 37 . In brief, the log of the PSD was taken and fit to a 5 th order polynomial to approximately remove the 1/f component of the PSD 25 .…”