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Record W4285394551 · doi:10.1101/2022.07.12.499688

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape

2022· preprint· en· W4285394551 on OpenAlexafffund
Andrea I. Luppi, Justine Y. Hansen, R. Adapa, Robin Carhart‐Harris, Leor Roseman, Christopher Timmermann, Daniel Golkowski, Andreas Ranft, Rüdiger Ilg, Denis Jordan, Vincent Bonhomme, Audrey Vanhaudenhuyse, Athéna Demertzi, Océane Jaquet, Mohamed Ali Bahri, Naji Alnagger, Paolo Cardone, Alexander R. D. Peattie, Anne E. Manktelow, Dráulio Barros de Araújo, Stefano L. Sensi, Adrian M. Owen, Lorina Naçi, David Menon, Bratislav Mišić, Emmanuel A. Stamatakis

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldPsychology
TopicPsychedelics and Drug Studies
Canadian institutionsWestern UniversityMcGill UniversityMontreal Neurological Institute and Hospital
FundersMedical Research CouncilNatural Sciences and Engineering Research Council of CanadaGates Cambridge TrustCambridge TrustWellcome TrustCanada Excellence Research Chairs, Government of CanadaCambridge Commonwealth TrustRoyal College of AnaesthetistsCanada Research ChairsImperial College LondonNational Institute for Health and Care ResearchBeckley FoundationNIHR Cambridge Biomedical Research CentreAlexander Mosley Charitable TrustUniversity of California, San FranciscoCanadian Institute for Advanced Research
KeywordsNeuroscienceNeurotransmitterNeurotransmitter receptorNeurotransmitter systemsPsychologyPharmacologyMedicineCentral nervous systemDopamineReceptorInternal medicine

Abstract

fetched live from OpenAlex

Abstract To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.780
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0050.000

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 head0.046
GPT teacher head0.280
Teacher spread0.234 · 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.

Study designObservational
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

Citations5
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicPsychedelics and Drug StudiesFrench-language works237,207