N C ] 3 J an 2 01 7 Loss of inter-frequency brain hubs in Alzheimer ’ s disease

Alzheimer’s disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. We used the multi-participation coefficient (MPC) to quantify the tendency of brain regions to facilitate information propagation across different frequencies. Main results showed that regional connectivity of AD subjects was abnormally distributed across frequency bands as compared to controls. This loss of inter-frequency centrality was mainly localized in association areas exhibiting fewer interactions with higher sensory rhythms (> 20 Hz) and more connections to lower attentional ones (< 13 Hz). MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-β deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings suggest that multi-layer network frameworks reveal complementary information that can be used to identify inter-frequency neural mechanisms of brain diseases.