Use of magnetoencephalography (MEG) to study functional brain networks in neurodegenerative disorders

Abstract

The pathophysiological mechanisms underlying clinical symptoms in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) are incompletely understood. Magnetoencephalography (MEG) is a relatively new functional neuroimaging technique, which allows the simultaneous recording of the brain's magnetic activity from large arrays of sensors covering the whole head. MEG studies in PD and AD have identified characteristic patterns of abnormal oscillatory activity in different frequency bands. Furthermore, MEG studies aimed at the characterization of distributed functional networks have demonstrated distinct patterns of abnormal connectivity in demented and non-demented PD, as well as in AD. In PD abnormal oscillatory activity and disturbed connectivity may respond differently to dopaminergic treatment. Further studies in this field could benefit from new technological developments such as ultra low field MRI and from the application of a well-defined theoretical framework such as graph theory to the study of disturbed brain networks.

Introduction

Neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) constitute a major health burden, especially in the ageing Western population. Although there is a large and increasing body of knowledge on the genetic, molecular and cellular mechanisms involved in these disorders, the exact cause is unknown, except for a few rare genetic variants. The pathophysiological mechanisms that ultimately give rise to the cognitive and motor disturbances are incompletely understood, even though treatment is likely to interact exactly at this level. A better understanding of the neurophysiological changes in neurodegenerative disease could bridge the gap between molecular and cellular levels on the one hand, and clinical symptoms on the other hand. Neurophysiological understanding could guide early and differential diagnosis, and may suggest new ways to monitor treatment response.

Tools from clinical neurophysiology have been used for many years in the study of PD and AD. Since a few years the availability of whole-head magnetoencephalography (MEG) systems has expanded the scope of such studies. MEG can record brain activity directly, and has several advantages compared to conventional EEG recordings. In contrast to EEG, MEG is hardly affected by the skull, and does not require a reference electrode. Therefore, MEG may provide a more accurate image of ongoing brain activity. In addition, significant advances have been made in neuroscience concerning the understanding of oscillatory and synchronized brain activities. In particular it is now assumed that synchronization of neural activity between different brain regions may reflect functional interactions between these regions [1]. Such synchronization processes can be measured at the level of the scalp with EEG and even better with MEG. Interesting patterns of abnormal oscillatory activity and interregional synchronization have now been described in various brain disorders, including PD and AD [2].

In the present review we will give an overview of MEG studies in PD and AD performed in the last decade. First we will briefly introduce MEG as a technique. Next, a short summary of current understanding of oscillations and synchronization will be given. We will then address MEG studies in PD and AD, and consider distinct and overlapping patterns of abnormalities in both disorders. Finally, we will address a number of remaining problems and point out directions for future research.