Inferring Progressive Disconnection in Alzheimer’s Disease with Probabilistic Boolean Networks

The modern understanding of Alzheimer’s disease as a disconnection syndrome presents the challenge of quantifying the directed influence between brain regions. To address this, we apply probabilistic Boolean networks to model effective brain connectivity for the first time, introducing a novel framework for analyzing functional magnetic resonance imaging data from a cohort comprising normal controls, individuals with mild cognitive impairment (MCI), and Alzheimers patients. Our robust statistical analysis identified five significant connections, each exhibiting a linear decline in influence throughout the disease spectrum. We observed a progressive disruption of pathways from the Default Mode Network to the Medial Temporal Lobe, capturing a key psychophysiological mechanism underlying Alzheimers disease. These findings demonstrate the potential of our framework as a powerful tool for modeling network-level dynamics in neurodegeneration.