Quasi-Periodic Patterns of Neural Activity improve Classification of Alzheimer\u2019s Disease in Mice

Abstract

Resting state (rs)fMRI allows measurement of brain functional connectivity and has identified default mode (DMN) and task positive (TPN) network disruptions as promising biomarkers for Alzheimer’s disease (AD). Quasi-periodic patterns (QPPs) of neural activity describe recurring spatiotemporal patterns that display DMN with TPN anti-correlation. We reasoned that QPPs could provide new insights into AD network dysfunction and improve disease diagnosis. We therefore used rsfMRI to investigate QPPs in old TG2576 mice, a model of amyloidosis, and age-matched controls. Multiple QPPs were determined and compared across groups. Using linear regression, we removed their contribution from the functional scans and assessed how they reflected functional connectivity. Lastly, we used elastic net regression to determine if QPPs improved disease classification. We present three prominent findings: (1) Compared to controls, TG2576 mice were marked by opposing neural dynamics in which DMN areas were anti-correlated and displayed diminished anti-correlation with the TPN. (2) QPPs reflected lowered DMN functional connectivity in TG2576 mice and revealed significantly decreased DMN-TPN anti-correlations. (3) QPP-derived measures significantly improved classification compared to conventional functional connectivity measures. Altogether, our findings provide insight into the neural dynamics of aberrant network connectivity in AD and indicate that QPPs might serve as a translational diagnostic tool.