Abnormal Functional Hierarchies of EEG Networks in Familial and Sporadic Prodromal Alzheimer's Disease During Visual Short-Term Memory Binding

Abstract

Alzheimer's Disease (AD) shows both complex alterations of functional dependencies between brain regions and a decreased ability to perform Visual Short-Term Memory Binding (VSTMB) tasks. Recent advances in network neuroscience toward understanding the complexity of hierarchical brain function here enables us to establish a link between these two phenomena. Here, we study data on two types of dementia at Mild Cognitive Impairment (MCI) stage-familial AD patients (E280A mutation of the presenilin-1 gene) and elderly MCI patients at high risk of sporadic AD, both with age-matched controls. We analyzed Electroencephalogram (EEG) signals recorded during the performance of Visual Short-Term Memory (VSTM) tasks by these participants. Functional connectivity was computed using the phase-lag index in Alpha and Beta; and network analysis was employed using network indices of hierarchical spread (degree variance) and complexity. Hierarchical characteristics of EEG functional connectivity networks revealed abnormal patterns in familial MCI VSTMB function and sporadic MCI VSTMB function. The middle-aged familial MCI binding network displayed a larger degree variance in lower Beta compared to healthy controls (p = 0.0051, Cohen's d = 1.0124), while the elderly sporadic MCI binding network displayed greater hierarchical complexity in Alpha (p = 0.0140, Cohen's d = 1.1627). Characteristics in healthy aging were not shown to differ. These results indicate that activity in MCI exhibits cross-frequency network reorganization characterized by increased heterogeneity of node roles in the functional hierarchy. Aging itself is not found to cause VSTM functional hierarchy differences.

Keywords: Alzheimer's disease; aging; brain networks; electroencephalogram (EEG); working memory.