Reduced weighted permutation entropy in visual-temporal cortex and altered resting-state brain dynamics in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is increasingly recognized as a disorder of distributed neural dynamics. Resting-state fMRI combined with signal-complexity measures may provide new insights into alterations in spontaneous brain activity. This study investigated whether weighted permutation entropy (WPE), an amplitude-sensitive measure of temporal complexity, could identify regional abnormalities in AD and characterize their temporal and network-level features. Twenty patients with AD and twenty-four healthy controls underwent resting-state fMRI. Regional WPE was calculated using the Brainnetome atlas. Group comparisons included age, sex, years of education, and mean framewise displacement as covariates. Brainnetome findings were evaluated at an exploratory uncorrected threshold of p < 0.001 and checked against Bonferroni correction across 246 regions. Selected regions were used for secondary seed-based functional connectivity analysis. Four complexity-drop cascade intervals were compared without multiplicity correction. Sensitivity analyses examined window length, AAL parcellation, and cascade recruitment thresholds of 8, 10, and 12 regions; Fourier-surrogate analyses provided an additional model-based assessment. At the exploratory Brainnetome threshold, AD was associated with lower WPE in two right inferior temporal subregions and one left fusiform subregion; these findings did not survive Bonferroni correction across 246 regions. The AAL analysis showed a similar regional pattern under FDR correction ( q < 0.05). Secondary seed-based analyses identified increased connectivity with visual, parietal, and sensorimotor regions. Longer Peak-to-End and Start-to-End cascade intervals were observed in AD at nominal p < 0.05, without correction across the four interval tests. The overall pattern of subsequent cascade analyses was retained at the 8- and 12-region thresholds. This small-sample study suggests that AD is associated with regional WPE differences, altered connectivity, and possible prolongation of complexity-drop cascades. The exploratory Brainnetome and temporal findings, together with within-sample AAL convergence, motivate independent replication with prespecified multiplicity control. These measures do not yet establish a clinical biomarker or a specific physiological mechanism.