MEG Delta Mapping Along the Healthy Aging-Alzheimer's Disease Continuum: Diagnostic Implications

Abstract

New diagnostic criteria for Alzheimer's disease (AD) stress the role of in vivo biomarkers. Neurophysiological markers are usually not considered as such criteria, although theoretical and practical reasons would justify them. In order to assess the value of neurophysiology as an AD biomarker, whole-head magnetoencephalographic (MEG) resting state recordings were obtained from 35 AD patients, 23 mild cognitive impairment (MCI) patients, and 24 healthy controls. The AD group was further split into two groups differing in severity according to the GDS/FAST criteria. A Minimum Norm Estimation procedure was utilized to estimate the cortical origin of slow brain oscillatory activity in the delta band (2-4 Hz). Eight regions of interest (ROIs) discriminated between AD patients and controls. Delta current density (DCD) in all ROIs showed a significant negative correlation with cognitive status (p < 0.001). DCD values in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished reliably between MCI patients, AD patients with different severity scores, and controls. Importantly, an increase of DCD in right parietal cortex and precuneus indexed the transition from MCI to mild dementia and from mild to more severe dementia. MEG delta mapping might be a serious candidate for a "neural degeneration" marker of AD reflecting dysfunctional synaptic transmission. More importantly, the localization of DCD values is in line with functional imaging markers of AD. However, MEG delta mapping is a totally non-invasive technique that directly measures neural activity. We propose that individuals with enhanced DCD in posterior parietal and precuneus cortices are at risk of progression to full dementia.

Disrupted network connectivity in pediatric brain tumor survivors is a signature of injury

“…Increased power and connectivity of slow wave frequency bands (i.e., theta and beta) has consistently been observed in adult brain injury and disease, including TBI and Alzheimer's disease severity (Fernandez et al, ; Hier et al, ; Huang et al, ). This slow‐wave oscillatory activity has been observed both within and between brain regions (Bajo et al, ; Dunkley et al, ; Hier et al, ).…”

Healthy and Pathological Brain Aging: From the Perspective of Oscillations, Functional Connectivity, and Signal Complexity

“…Evidence for this argument is provided by Fernandez et al [38] in an MEG study that reported increased occipital delta current density in individuals with prodromal AD, with this activity likely reflecting dysfunctional synaptic transmission. In patients who have already progressed to full clinical AD, an increase in both delta and theta oscillations was found in the temporoparietal regions, and this correlated with HA [39].…”

MEG spectral analysis in subtypes of mild cognitive impairment

“…Nevertheless, the more important question addressed by our investigation is the potential role of neurophysiological techniques (EEG or MEG) as markers for AD pathology. In a very recent study of our group (Fernandez et al 2013), it was demonstrated that delta current densities in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished among MCI patients, AD patients with different severity scores, and controls. More importantly, an increase in delta activity in posterior regions such as the right posterior parietal cortex and the precuneus indexed the transition from MCI to mild and from mild to more severe dementia.…”