Inhibitory control of frontal metastability sets the temporal signature of cognition

  1. Vincent Fontanier
  2. Matthieu Sarazin
  3. Frederic M Stoll
  4. Bruno Delord
  5. Emmanuel Procyk  Is a corresponding author
  1. Inserm, France
  2. Sorbonne Université, CNRS, France
  3. Icahn School of Medicine at Mount Sinai, United States

Abstract

Cortical dynamics are organized over multiple anatomical and temporal scales. The mechanistic origin of the temporal organization and its contribution to cognition remain unknown. Here we demonstrate the cause of this organization by studying a specific temporal signature (time constant and latency) of neural activity. In monkey frontal areas, recorded during flexible decisions, temporal signatures display specific area-dependent ranges, as well as anatomical and cell-type distributions. Moreover, temporal signatures are functionally adapted to behaviorally relevant timescales. Fine-grained biophysical network models, constrained to account for experimentally observed temporal signatures, reveal that after-hyperpolarization potassium and inhibitory GABA-B conductances critically determine areas’ specificity. They mechanistically account for temporal signatures by organizing activity into metastable states, with inhibition controlling state stability and transitions. As predicted by models, state durations non-linearly scale with temporal signatures in monkey, matching behavioral timescales. Thus, local inhibitory-controlled metastability constitutes the dynamical core specifying the temporal organization of cognitive functions in frontal areas.

Data availability

All spike time series from monkey recordings, scripts for temporal signatures extraction and scripts of computational models are freely accessible on the Zenodo repository (https://doi.org/10.5281/zenodo.5707884).

The following data sets were generated

Article and author information

Author details

  1. Vincent Fontanier

    Stem Cell and Brain Research Institute U1208, Inserm, Bron, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2742-0542
  2. Matthieu Sarazin

    Institute of Intelligent Systems and Robotics (ISIR) - UMR 7222, Sorbonne Université, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Frederic M Stoll

    Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8642-8133
  4. Bruno Delord

    Institute of Intelligent Systems and Robotics (ISIR) - UMR 7222, Sorbonne Université, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2912-3405
  5. Emmanuel Procyk

    Stem Cell and Brain Research Institute U1208, Inserm, Lyon, France
    For correspondence
    Emmanuel.Procyk@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7486-4993

Funding

Fondation pour la Recherche Médicale (DEQ20160334905)

  • Emmanuel Procyk

Agence Nationale de la Recherche (ANR-10-SVSE4-1441)

  • Emmanuel Procyk

Agence Nationale de la Recherche (ANR-16-NEUC-0006-01)

  • Bruno Delord

Agence Nationale de la Recherche (ANR-11-LABX-0042)

  • Emmanuel Procyk

Fondation pour la Recherche Médicale (FDT201904008187)

  • Vincent Fontanier

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures followed the European Community Council Directive (2010) (Ministère de l'Agriculture et de la Forêt, Commission nationale de l'expérimentation animale) and were approved by the localethical committee (Comité d'Ethique Lyonnais pour les Neurosciences Expérimentales, CELYNE, C2EA683 #42)

Copyright

© 2022, Fontanier et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Vincent Fontanier
  2. Matthieu Sarazin
  3. Frederic M Stoll
  4. Bruno Delord
  5. Emmanuel Procyk
(2022)
Inhibitory control of frontal metastability sets the temporal signature of cognition
eLife 11:e63795.
https://doi.org/10.7554/eLife.63795

Share this article

https://doi.org/10.7554/eLife.63795

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