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Record W4417362080 · doi:10.1111/acel.70329

Linking Age Changes in Human Cortical Microcircuits to Impaired Brain Function and <scp>EEG</scp> Biomarkers

2025· article· en· W4417362080 on OpenAlexafffund
Alexandre Guet-McCreight, Shreejoy J. Tripathy

Bibliographic record

VenueAging Cell · 2025
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersCanadian Institutes of Health Research
KeywordsBrain agingHuman brainElectroencephalographyNeurotransmissionInhibitory postsynaptic potentialBrain functionAging brainGlutamate receptorAgeingNMDA receptor

Abstract

fetched live from OpenAlex

Human brain aging involves a variety of cellular and synaptic changes, but how these changes affect brain function and signals remains poorly understood due to experimental limitations in humans, meriting the use of detailed computational models. We identified key human cellular and synaptic changes occurring with age from previous studies, including a loss of inhibitory cells, NMDA receptors, and spines. We integrated these changes into our detailed human cortical microcircuit models and simulated activity in middle age (~50 years) and older (~70 years) microcircuits, and linked the altered mechanisms to reduced spike rates and impaired signal detection. We then simulated EEG potentials arising from the microcircuit activity and found that the emergent power spectral changes due to these aging cellular mechanisms reproduced most of the resting-state EEG biomarkers seen in human aging, including reduced aperiodic offset, exponent, and periodic peak center frequency. Using machine learning, we demonstrated that the changes to the cellular and synaptic aging mechanisms can be estimated accurately from the simulated EEG aging biomarkers. Our results link cellular and synaptic mechanisms of aging with impaired cortical function and physiological biomarkers in clinically relevant brain signals.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.511
Threshold uncertainty score0.728

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.266
Teacher spread0.240 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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