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Record W4393304642 · doi:10.1101/2024.03.26.586837

EEG biomarkers of α5-GABA positive allosteric modulators in rodents

2024· preprint· en· W4393304642 on OpenAlexafffund
Frank Mazza, Alexandre Guet-McCreight, Thomas D. Prévot, Taufik A. Valiante, Etienne Sibille, Etay Hay

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsCentre for Addiction and Mental HealthUniversity of Toronto
FundersKrembil Foundation
KeywordsAnxiolyticElectroencephalographyAllosteric regulationAllosteric modulatorGABAA receptorNeuroscienceDiazepamAnxietyPharmacologyElectrophysiologyAlpha (finance)PsychologyAntidepressantgamma-Aminobutyric acidReceptorChemistryBiologyMedicineInternal medicineHippocampusDevelopmental psychologyPsychiatry

Abstract

fetched live from OpenAlex

Abstract Reduced cortical inhibition mediated by gamma-aminobutyric acid (GABA) is reported in depression, anxiety disorders, and aging. Novel positive allosteric modulator that specifically target α5-GABA A receptor subunit (α5-PAM), ligand GL-II-73, shows anxiolytic, antidepressant, and pro-cognitive effects without the common side effects associated with non-specific modulation by benzodiazepines such as diazepam (DZP), thus suggesting novel therapeutic potential. However, it is unknown if α5-PAM has detectable signatures in clinically-relevant brain electroencephalography (EEG). We analyzed EEG in freely moving rats at baseline and following injections of α5-PAM and DZP. We showed that α5-PAM specifically decreased theta peak power whereas DZP shifted peak power from high to low theta, while increasing beta and gamma power. EEG decomposition showed that these effects were periodic and corresponded to changes in theta oscillation event duration. Our study thus shows that α5-PAM has robust and distinct EEG biomarkers in rodents, indicating that EEG could enable non-invasive monitoring of α5-PAM treatment efficacy.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.029
GPT teacher head0.289
Teacher spread0.261 · 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 source (direct Gemma or distilled Codex), 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

Citations2
Published2024
Admission routes2
Has abstractyes

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