Directional information flow in patients with Alzheimer's disease. A source-space resting-state MEG study.

In a recent magnetoencephalography (MEG) study, we found posterior-to-anterior information flow over the cortex in higher frequency bands in healthy subjects, with a reversed pattern in the theta band. A disruption of information flow may underlie clinical symptoms in Alzheimer's disease (AD). In AD, highly connected regions (hubs) in posterior areas are mostly disrupted. We therefore hypothesized that in AD the information flow from these hub regions would be disturbed. We used resting-state MEG recordings from 27 early-onset AD patients and 26 healthy controls. Using beamformer-based virtual electrodes, we estimated neuronal oscillatory activity for 78 cortical regions of interest (ROIs) and 12 subcortical ROIs of the AAL atlas, and calculated the directed phase transfer entropy (dPTE) as a measure of information flow between these ROIs. Group differences were evaluated using permutation tests and, for the AD group, associations between dPTE and general cognition or CSF biomarkers were determined using Spearman correlation coefficients. We confirmed the previously reported posterior-to-anterior information flow in the higher frequency bands in the healthy controls, and found it to be disturbed in the beta band in AD. Most prominently, the information flow from the precuneus and the visual cortex, towards frontal and subcortical structures, was decreased in AD. These disruptions did not correlate with cognitive impairment or CSF biomarkers. We conclude that AD pathology may affect the flow of information between brain regions, particularly from posterior hub regions, and that changes in the information flow in the beta band indicate an aspect of the pathophysiological process in AD.

Alzheimer's disease: The state of the art in resting-state magnetoencephalography.

Alzheimer's disease (AD) is accompanied by functional brain changes that can be detected in imaging studies, including electromagnetic activity recorded with magnetoencephalography (MEG). Here, we systematically review the studies that have examined resting-state MEG changes in AD and identify areas that lack scientific or clinical progress. Three levels of MEG analysis will be covered: (i) single-channel signal analysis, (ii) pairwise analyses over time series, which includes the study of interdependencies between two time series and (iii) global network analyses. We discuss the findings in the light of other functional modalities, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Overall, single-channel MEG results show consistent changes in AD that are in line with EEG studies, but the full potential of the high spatial resolution of MEG and advanced functional connectivity and network analysis has yet to be fully exploited. Adding these features to the current knowledge will potentially aid in uncovering organizational patterns of brain function in AD and thereby aid the understanding of neuronal mechanisms leading to cognitive deficits.