Correlations between alterations in resting-state functional dynamics and memory impairments in the TgF344-AD rat model of Alzheimer’s Disease

Motivation: Resting-state fMRI studies of Alzheimer’s disease impact on brain’s function commonly use functional connectivity (FC) ignoring sensitive and dynamic readouts such as the co-activation patterns (CAPs) occurring at short timescales. Goal(s): We aimed to assess changes in CAPs, in addition to network-level FC, in a transgenic rat model of Alzheimer’s disease longitudinally. Approach: We acquired high temporal resolution resting-state fMRI and performed FC and CAP analysis. Results: We found increased lateral cortical network FC that correlated with memory impairments at the plaque stage, and hyper and hypoactivation of the default-mode-like-network and hippocampal regions in two CAPs at the pre-plaque and plaque stages respectively. Impact: Our findings demonstrate that metrics of brain dysfunction of Alzheimer’s disease derived from high temporal resolution resting-state fMRI not only explain behavioural manifestations but also capture alterations preceding plaque formation further validating their translational potential as an early, functional biomarker.