Evidence map›Paper›PMID 42449404›Full record

ArticleAlzheimer's research & therapy2026

Three-order interactions in the alpha band of default mode network EEGs based on O-information rate: insights from aging and Alzheimer's disease.

Hamed Azami, Yuri Antonacci, Daniel M Blumberger, Heather Brooks, Luca Faes, Corinne E Fischer, Alastair Flint, Nathan Herrmann, Sanjeev Kumar, Damien Gallagher and 6 more

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In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Hamed AzamiCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Yuri AntonacciDepartment of Engineering, University of Palermo, Viale Delle Scienze, Palermo, 90128, Italy.
Daniel M Blumberger *Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Heather Brooks *Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Luca Faes *Department of Engineering, University of Palermo, Viale Delle Scienze, Palermo, 90128, Italy.
Corinne E Fischer *Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 30 Bond St Toronto, Toronto, ON, M5B 1W8, Canada.
Alastair Flint *Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Nathan Herrmann *Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Sanjeev Kumar *Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Damien Gallagher *Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Linda Mah *Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Benoit H Mulsant *Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Nicole Schoer *Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Bruce G Pollock *Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada.
Tarek K RajjiCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 1025 Queen St W, Toronto, ON, M6J 1H1, Canada. tarek.rajji@utsouthwestern.edu.
PACt-M. D. Study Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlpha-band default mode network (DMN) connectivity declines with aging and Alzheimer's disease (AD), yet most electroencephalography (EEG) connectivity studies used pairwise (two-order) measures, such as mutual information rate (MIR). We leveraged O-information rate (OIR) to quantify three-order interactions and to separate redundant from synergistic information processing across frontal, temporal, and parietal DMN regions. We hypothesized that, extending established findings of reduced pairwise connectivity, (i) OIR (and its components) would be reduced in older versus younger adults and in AD versus healthy controls (HC); (ii) combining MIR with OIR would improve classification compared with MIR alone; and (iii) OIR measures would correlate positively with global cognition (as assessed by the Montreal Cognitive Assessment (MoCA)).

methodsResting-state EEG from two samples-healthy adult lifespan aging (95 younger; 93 older) and AD spectrum (44 HC; 84 amnestic mild cognitive impairment [aMCI]; 41 AD)-was source-localized using eLORETA to DMN regions. Alpha band (8-13 Hz) MIR and OIR were computed through multivariate spectral analysis. Group differences were tested using t-tests or analysis of covariance (ANCOVA) with multiple comparison correction. Classification (OIR, MIR, demographic, and combined feature sets) used cross-validated logistic-regression, linear-SVM, and random-forest models, with bootstrap 95% confidence intervals and DeLong tests for AUC comparisons.

resultsOIR and its redundancy component were significantly reduced in older versus younger adults and in AD versus HC/aMCI, with no HC-aMCI differences. The synergy component showed no group differences. MIR decreased broadly with aging and fronto-parietally in AD. Regarding classification (AD spectrum dataset, cross-validated AUC), OIR-based metrics outperformed MIR (AD vs. HC: 0.93 vs. 0.73; AD vs. aMCI: 0.93 vs. 0.71; aMCI vs. HC: 0.48 vs. 0.46). Combining demographics with all information-theoretic features improved AD vs. HC (0.98; DeLong p = 0.023) but not AD vs. aMCI (0.93), where OIR alone was already at ceiling; no feature set exceeded chance for aMCI vs. HC. After correction, OIR and its redundancy component correlated positively with MoCA scores; MIR and the synergy component did not.

conclusionsAlpha-band three-order DMN interactions-particularly redundant information processing-decline with aging and AD and provide additional information beyond two-order connectivity for diagnostic classification. OIR offers complementary measures to traditional metrics, and future studies should examine its value when combined with more established AD biomarkers.

Indexed as

AgingAlpha RhythmAlzheimer DiseaseBrainDefault Mode NetworkElectroencephalographyAdultAgedAged, 80 and overCognitive DysfunctionFemaleHumansMaleMiddle AgedYoung AdultAgingAlzheimer’s diseaseDefault mode networkEEGHigh-order InteractionsO-information rate

Identifiers

PMID42449404
PMCPMC13656427

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.