Large-scale frontoparietal theta, alpha, and beta phase synchronization: A set of EEG differential characteristics for freezing of gait in Parkinson’s disease?

Abstract

Freezing of gait (FOG) is a complex gait disturbance in Parkinson’s disease (PD), during which the patient is not able to effectively initiate gait or continue walking. The mystery of the FOG phenomenon is still unsolved. Recent studies have revealed abnormalities in cortical activities associated with FOG, which highlights the importance of cortical and cortical-subcortical network dysfunction in PD patients with FOG. In this paper, phase-locking value (PLV) of eight frequency sub-bands between 0.05 Hz and 35 Hz over frontal, motor, and parietal areas [during an ankle dorsiflexion (ADF) task] is used to investigate EEG phase synchronization. PLV was investigated over both superficial and deeper networks by analyzing EEG signals preprocessed with and without Surface Laplacian (SL) spatial filter. Four groups of participants were included: PD patients with severe FOG (N = 5, 5 males), PD patients with mild FOG (N = 7, 6 males), PD patients without FOG (N = 14, 13 males), and healthy age-matched controls (N = 13, 10 males). Fifteen trials were recorded from each participant. At superficial layers, frontoparietal theta phase synchrony was a unique feature present in PD with FOG groups. At deeper networks, significant dominance of interhemispheric frontoparietal alpha phase synchrony in PD with FOG, in contrast to beta phase synchrony in PD without FOG, was identified. Alpha phase synchrony was more distributed in PD with severe FOG, with higher levels of frontoparietal alpha phase synchrony. In addition to FOG-related abnormalities in PLV analysis, phase-amplitude coupling (PAC) analysis was also performed on frequency bands with PLV abnormalities. PAC analysis revealed abnormal coupling between theta and low beta frequency bands in PD with severe FOG at the superficial layers over frontal areas. At deeper networks, theta and alpha frequency bands show high PAC over parietal areas in PD with severe FOG. Alpha and low beta also presented PAC over frontal areas in PD groups with FOG. The results introduced significant phase synchrony differences between PD with and without FOG and provided important insight into a possible unified underlying mechanism for FOG. These results thus suggest that PLV and PAC can potentially be used as EEG-based biomarkers for FOG.