Alterations in resting-state network dynamics along the Alzheimer's disease continuum: a combined MEG-PET/MR approach

Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimers disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with Subjective Cognitive Decline (SCD), 10 patients with amnestic Mild Cognitive Impairment (aMCI) and 10 patients with typical Alzheimers disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. HMM patterns were related to participants cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores. However, it correlated positively with the whole hippocampal volume and regional glucose consumption in the right temporo-parietal junctions and dorsolateral prefrontal cortex, and negatively with glucose consumption in the cerebellum. In AD patients, alterations of posterior DMN power activation dynamics at rest correlate with structural and neurometabolic abnormalities. These findings represent an additional electrophysiological correlate of AD-related synaptic and neural dysfunction.