A systematic review of MEG-based studies in Parkinson's disease: The motor system and beyond

Abstract

Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD-affected brain. The available articles could be separated into motor network-focused and whole-brain focused studies. Motor network studies revealed PD-related changes in beta band (13-30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole-brain studies PD-related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD-specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care.

Keywords: Parkinson's disease; magnetoencephalography; motor network; network analysis; whole-brain.

Figure 1

Flowchart for inclusion of studies

Figure 2

(in color) Overview of main findings in motor network‐focused research. A schematic representation of a coronal view of the brain, combined with the forearm muscle extensor digitorum communis. All displayed findings involve undirected functional connectivity, depicted using lines with double arrow heads. A: motor cortex; B: subthalamic nucleus; C: forearm muscle; D: temporal cortex. Red and blue represent higher respectively lower values found in PD patients compared with controls; Black lines represent no significant difference between PD patients and controls, or no comparison with a control group. References: (Hall et al., 2014; Heinrichs‐Graham, Kurz, et al., 2014; Hirschmann et al., 2011; Hirschmann, Ozkurt, et al., 2013; Litvak et al., 2011; Litvak et al., 2012; Oswal, Beudel, et al., 2016; Pollok et al., 2012; Pollok et al., 2013; Salenius et al., 2002; van Wijk et al., 2016; Vardy et al., 2011). (b)Overview of main findings in tremor network‐focused research. A schematic representation of a coronal view of the brain, combined with the forearm muscle extensor digitorum communis. All displayed findings involve coherence at tremor frequency and its (sub)harmonics. A: sensorimotor and premotor cortex; B: cingulate motor area; C: thalamus; D: subthalamic Nucleus; E: cerebellum; F: forearm muscle. Not depicted in this figure: Posterior parietal cortex. References: (Hirschmann, Hartmann, et al., 2013; Pollok et al., 2009; Timmermann et al., 2003; Volkmann et al., 1996)

Figure 3

(in color) Overview of main findings in whole brain network‐focused research: Band power. Schematic representation of observed statistical differences in relative band power between groups. Both sensor‐space and source‐space analyses are included in the figure. In case of sensor‐space analysis, the brain region underlying the relevant sensor was colored. In case of source‐space analysis results for each ROI are displayed as a color‐coded map on a parcellated template brain viewed from, in clockwise order, the left, right, and top. An area is colored red when the mean power early PD > controls, late PD > early PD, and PDD > PD and blue when the difference was in the opposite direction. The three color codes of magnitudes (from light to dark) illustrate the effect size of the observed difference. Areas that did not show statistically significant differences are represented in white/gray. In the study by (Ponsen et al., 2012) the alpha1 and alpha2 band were combined. PD, Parkinson's disease without dementia; PDD, Parkinson's disease related dementia; L or R, cortical area on the left (L) or right (R) side of the head; C, central; F, frontal; O, occipital; P, parietal; T, temporal. Figure adapted from (Bosboom et al., 2006; Olde Dubbelink et al., 2013a; Ponsen et al., 2012; Stoffers et al., 2007). (b) (in color) Overview of main findings in whole brain network‐focused research: Functional connectivity. Schematic representation of observed statistical differences. In case of a sensor‐space analysis differences are depicted for local (colored regions) and interregional (arrows) functional connectivity (FC; synchronization likelihood and phase lag index) between groups. In case of a source‐space analysis differences in FC from one ROI to the rest of the brain (using phase lag index) are displayed as a color‐coded map on a parcellated template brain viewed from, in clockwise order, the left, right, and top. An area is colored red when the FC of early PD > controls, moderately advanced PD > controls, and PDD > PD and blue when the difference was in the opposite direction. Areas that did not show statistically significant differences are represented in white/gray. In the study by Ponsen et al. (2012) the alpha1 and alpha2 band were combined. PD, Parkinson's disease without dementia; PDD, Parkinson's disease related dementia; L or R, cortical area on the left (L) or right (R) side of the head; C, central; F, frontal; O, occipital; P, parietal; T, temporal. Figure adapted from (Bosboom, Stoffers, Wolters, et al., 2009; Cao et al., 2018; Olde Dubbelink et al., 2013b; Ponsen et al., 2012; Stoffers, Bosboom, Deijen, et al., 2008)