Aberrant MEG multi-frequency phase temporal synchronization predicts conversion from mild cognitive impairment-to-Alzheimer's disease

Many neuroimaging studies focus on a frequency-specific or a multi-frequency network analysis showing that functional brain networks are disrupted in patients with Alzheimer's disease (AD). Although those studies enriched our knowledge of the impact of AD in brain's functionality, our goal is to test the effectiveness of combining neuroimaging with network neuroscience to predict with high accuracy subjects with mild cognitive impairment (MCI) that will convert to AD.In this study, eyes-closed resting-state magnetoencephalography (MEG) recordings from 27 stable MCI (sMCI) and 27 progressive MCI (pMCI) from two scan sessions (baseline and follow-up after approximately 3 years) were projected via beamforming onto an atlas-based set of regions of interest (ROIs). Dynamic functional connectivity networks were constructed independently for the five classical frequency bands while a multivariate phase-based coupling metric was adopted. Thus, computing the distance between the fluctuation of functional strength of every pair of ROIs between the two conditions with dynamic time wrapping (DTW), a large set of features was extracted. A machine learning algorithm revealed 30 DTW-based features in the five frequency bands that can distinguish the sMCI from pMCI with absolute accuracy (100%). Further analysis of the selected links revealed that most of the connected ROIs were part of the default mode network (DMN), the cingulo-opercular (CO), the fronto-parietal and the sensorimotor network.Overall, our dynamic network multi-frequency analysis approach provides an effective framework of constructing a sensitive MEG-based connectome biomarker for the prediction of conversion from MCI to Alzheimer's disease. Keywords: Mild cognitive impairment, Conversion, Magnetoencephalography, Source reconstruction, Dynamic functional connectivity analysis, Connectomic biomarker