Network-level permutation entropy of resting-state MEG recordings: A novel biomarker for early-stage Alzheimer’s disease?

Elliz P. Scheijbeler, Anne M. van Nifterick, Cornelis J. Stam, Arjan Hillebrand, Alida A. Gouw, Willem de Haan

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7 Citations (Scopus)


Increasing evidence suggests that measures of signal variability and complexity could present promising biomarkers for Alzheimer’s disease (AD). Earlier studies have however been limited to the characterization of local activity. Here, we investigate whether a network version of permutation entropy could serve as a novel biomarker for early-stage AD. Resting-state source-space magnetoencephalography was recorded in 18 subjects with subjective cognitive decline (SCD) and 18 subjects with mild cognitive impairment (MCI). Local activity was characterized by permutation entropy (PE). Network-level interactions were studied using the inverted joint permutation entropy ( JPEinv ), corrected for volume conduction. The JPEinv showed a reduction of nonlinear connectivity in MCI subjects in the theta and alpha band. Local PE showed increased theta band entropy. Between-group differences were widespread across brain regions. Receiver operating characteristic (ROC) analysis of classification of MCI versus SCD subjects revealed that a logistic regression model trained on JPEinv features (78.4% [62.5–93.3%]) slightly outperformed PE (76.9% [60.3–93.4%]) and relative theta power–based models (76.9% [60.4–93.3%]). Classification performance of theta JPEinv was at least as good as the relative theta power benchmark. The JPEinv is therefore a potential biomarker for early-stage AD that should be explored in larger studies.
Original languageEnglish
Pages (from-to)382-400
Number of pages19
JournalNetwork Neuroscience
Issue number2
Publication statusPublished - 1 Jun 2022


  • Biomarker
  • Early-stage Alzheimer’s
  • Functional brain networks
  • Joint permutation entropy
  • Magnetoencephalography

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