Local signal variability and functional connectivity: Sensitive measures of the excitation-inhibition ratio?

A novel network version of permutation entropy, the inverted joint permutation entropy (JPEinv), holds potential as non-invasive biomarker of abnormal excitation-inhibition (E-I) ratio in Alzheimer's disease (AD). In this computational modelling study, we test the hypotheses that this metric, and related measures of signal variability and functional connectivity, are sensitive to altered E-I ratios. The E-I ratio in each neural mass of a whole-brain computational network model was systematically varied. We evaluated whether JPEinv, local signal variability (by permutation entropy) and functional connectivity (by weighted symbolic mutual information (wsMI)) were related to E-I ratio, on whole-brain and regional level. The hub disruption index can identify regions primarily affected in terms of functional connectivity strength (or: degree) by the altered E-I ratios. Analyses were performed for a range of coupling strengths, filter and time-delay settings. On whole-brain level, higher E-I ratios were associated with higher functional connectivity (by JPEinv and wsMI) and lower local signal variability. These relationships were nonlinear and depended on the coupling strength, filter and time-delay settings. On regional level, hub-like regions showed a selective decrease in functional degree (by JPEinv and wsMI) upon a lower E-I ratio, and non-hub-like regions showed a selective increase in degree upon a higher E-I ratio. These results suggest that abnormal functional connectivity and signal variability, as previously reported in patients across the AD continuum, can inform us about altered E-I ratios. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-10003-x.

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

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.