1. Neuroscience

Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing

  1. Thomas Pfeffer  Is a corresponding author
  2. Christian Keitel  Is a corresponding author
  3. Daniel S Kluger
  4. Anne Keitel
  5. Alena Russmann
  6. Gregor Thut
  7. Tobias H Donner
  8. Joachim Gross
  1. Universitat Pompeu Fabra, Spain
  2. University of Stirling, United Kingdom
  3. University of Münster, Germany
  4. University of Dundee, United Kingdom
  5. University Medical Center Hamburg-Eppendorf, Germany
  6. University of Glasgow, United Kingdom
  7. University of Muenster, Germany
https://doi.org/10.7554/eLife.71890
Share this article
Cite this article
  1. Thomas Pfeffer
  2. Christian Keitel
  3. Daniel S Kluger
  4. Anne Keitel
  5. Alena Russmann
  6. Gregor Thut
  7. Tobias H Donner
  8. Joachim Gross
(2022)
Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing
eLife 11:e71890.
https://doi.org/10.7554/eLife.71890
  2. Download BibTeX
  3. Download .RIS

Abstract

Fluctuations in arousal, controlled by subcortical neuromodulatory systems, continuously shape cortical state, with profound consequences for information processing. Yet, how arousal signals influence cortical population activity in detail has so far only been characterized for a few selected brain regions. Traditional accounts conceptualize arousal as a homogeneous modulator of neural population activity across the cerebral cortex. Recent insights, however, point to a higher specificity of arousal effects on different components of neural activity and across cortical regions. Here, we provide a comprehensive account of the relationships between fluctuations in arousal and neuronal population activity across the human brain. Exploiting the established link between pupil size and central arousal systems, we performed concurrent magnetoencephalographic (MEG) and pupillographic recordings in a large number of participants, pooled across three laboratories. We found a cascade of effects relative to the peak timing of spontaneous pupil dilations: Decreases in low-frequency (2-8 Hz) activity in temporal and lateral frontal cortex, followed by increased high-frequency (>64 Hz) activity in mid-frontal regions, followed by monotonic and inverted-U relationships with intermediate frequency-range activity (8-32 Hz) in occipito-parietal regions. Pupil-linked arousal also coincided with widespread changes in the structure of the aperiodic component of cortical population activity, indicative of changes in the excitation-inhibition balance in underlying microcircuits. Our results provide a novel basis for studying the arousal modulation of cognitive computations in cortical circuits.

Data availability

The ethics protocol(s) disallow sharing raw and preprocessed MEG and MRI data via a public repository. Data may be shared however within the context of a collaboration.No proposal is needed. However, the results presented in the manuscript are based on three separate datasets, collected independently in three different laboratories. As such, in order to obtain the data, an (informal) email to the authors responsible for the respective data sets is required (Hamburg: Thomas Pfeffer, thms.pfffr@gmail.com; Glasgow: Anne Keitel, a.keitel@dundee.ac.uk; Münster: Daniel Kluger, daniel.kluger@wwu.de).The code and data immediately underlying all main and supplementary figures has been made publicly available. Source data has been uploaded to a public repository (https://osf.io/fw4bt), along with MATLAB code that was used to generate the main and supplementary figures.

The following data sets were generated

Article and author information

Author details

  1. Thomas Pfeffer

    Department of Neurophysiology and Pathophysiology, Universitat Pompeu Fabra, Barcelona, Spain
    For correspondence
    thms.pfffr@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9561-3085

  2. Christian Keitel

    Department of Psychology, University of Stirling, Stirling, United Kingdom
    For correspondence
    christian.keitel@stir.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2597-5499

  3. Daniel S Kluger

    Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, Münster, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0691-794X

  4. Anne Keitel

    Department of Psychology, University of Dundee, Dundee, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4498-0146

  5. Alena Russmann

    Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    No competing interests declared.

  6. Gregor Thut

    Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.

  7. Tobias H Donner

    Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    Tobias H Donner, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7559-6019

  8. Joachim Gross

    Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Muenster, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3994-1006

Funding

Alexander von Humboldt-Stiftung (Feodor-Lynen Fellowship)

  • Thomas Pfeffer

Interdisciplinary Center for Clinical Research of the Medical Faculty of Münster (Gro3/001/19)

  • Joachim Gross

Deutsche Forschungsgemeinschaft (GR 2024/5-1)

  • Joachim Gross

Wellcome Trust (Senior Investigator Grant #098433)

  • Joachim Gross

Wellcome Trust (Senior Investigator Grant #98434)

  • Gregor Thut

University of Glasgow (BBSRC Flexible Talent Mobility funding (BB/R506576/1))

  • Christian Keitel

Deutsche Forschungsgemeinschaft (DO 1240/3-1)

  • Tobias H Donner

Deutsche Forschungsgemeinschaft (DO 1240/4-1)

  • Tobias H Donner

Deutsche Forschungsgemeinschaft (SFB 936 A7/Z3)

  • Tobias H Donner

Bundesministerium für Bildung und Forschung (01GQ1907)

  • Tobias H Donner

Bundesministerium für Bildung und Forschung (01EW2007B)

  • Tobias H Donner

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

Ethics

Human subjects: Human subjects were recruited and participated in the experiments in accordance with the ethics committee responsible for the University Medical Center Hamburg-Eppendorf (Hamburg MEG data) approval number PV4648, the ethics committee of the University of Glasgow, College of Science and Engineering (Glasgow MEG data) approval number 300140078, and the ethics committee of the University of Muenster (Muenster MEG data) approval number 2018-068-f-S. All participants gave written informed consent prior to all experimental procedures and received monetary compensation for their participation.

Copyright

© 2022, Pfeffer 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.

Metrics

  • 2,910
    views
  • 459
    downloads
  • 38
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Thomas Pfeffer
  2. Christian Keitel
  3. Daniel S Kluger
  4. Anne Keitel
  5. Alena Russmann
  6. Gregor Thut
  7. Tobias H Donner
  8. Joachim Gross
(2022)
Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing
eLife 11:e71890.
https://doi.org/10.7554/eLife.71890

Share this article

https://doi.org/10.7554/eLife.71890

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Language experience shapes predictive coding of rhythmic sound sequences

    Piermatteo Morucci, Sanjeev Nara ... Nicola Molinaro
    Research Article

    Perceptual systems heavily rely on prior knowledge and predictions to make sense of the environment. Predictions can originate from multiple sources of information, including contextual short-term priors, based on isolated temporal situations, and context-independent long-term priors, arising from extended exposure to statistical regularities. While the effects of short-term predictions on auditory perception have been well-documented, how long-term predictions shape early auditory processing is poorly understood. To address this, we recorded magnetoencephalography data from native speakers of two languages with different word orders (Spanish: functor-initial vs Basque: functor-final) listening to simple sequences of binary sounds alternating in duration with occasional omissions. We hypothesized that, together with contextual transition probabilities, the auditory system uses the characteristic prosodic cues (duration) associated with the native language’s word order as an internal model to generate long-term predictions about incoming non-linguistic sounds. Consistent with our hypothesis, we found that the amplitude of the mismatch negativity elicited by sound omissions varied orthogonally depending on the speaker’s linguistic background and was most pronounced in the left auditory cortex. Importantly, listening to binary sounds alternating in pitch instead of duration did not yield group differences, confirming that the above results were driven by the hypothesized long-term ‘duration’ prior. These findings show that experience with a given language can shape a fundamental aspect of human perception – the neural processing of rhythmic sounds – and provides direct evidence for a long-term predictive coding system in the auditory cortex that uses auditory schemes learned over a lifetime to process incoming sound sequences.

    1. Cell Biology
    2. Neuroscience

    Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis

    Luting Yang, Chunqing Hu ... Yaping Yan
    Research Article

    Reactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. However, the role and molecular mechanism of metabolic reprogramming in activation of astrocytes have not been clarified. Here, we found that PKM2, a rate-limiting enzyme of glycolysis, displayed nuclear translocation in astrocytes of EAE (experimental autoimmune encephalomyelitis) mice, an animal model of multiple sclerosis. Prevention of PKM2 nuclear import by DASA-58 significantly reduced the activation of mice primary astrocytes, which was observed by decreased proliferation, glycolysis and secretion of inflammatory cytokines. Most importantly, we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. TRIM21 interacted with PKM2, promoted its nuclear translocation and stimulated its nuclear activity to phosphorylate STAT3, NF-κB and interact with c-myc. Further single-cell RNA sequencing and immunofluorescence staining demonstrated that TRIM21 expression was upregulated in astrocytes of EAE. TRIM21 overexpressing in mice primary astrocytes enhanced PKM2-dependent glycolysis and proliferation, which could be reversed by DASA-58. Moreover, intracerebroventricular injection of a lentiviral vector to knockdown TRIM21 in astrocytes or intraperitoneal injection of TEPP-46, which inhibit the nuclear translocation of PKM2, effectively decreased disease severity, CNS inflammation and demyelination in EAE. Collectively, our study provides novel insights into the pathological function of nuclear glycolytic enzyme PKM2 and ubiquitination-mediated regulatory mechanism that are involved in astrocyte activation. Targeting this axis may be a potential therapeutic strategy for the treatment of astrocyte-involved neurological disease.

    1. Neuroscience

    Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

    Felix Michaud, Ruggiero Francavilla ... Lisa Topolnik
    Research Article

    Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal CA1 region, regulating incoming inputs and memory formation. However, it remains unclear whether AD pathology induces changes in the activity of I-S3 cells, impacting the hippocampal network motifs. Here, using young adult 3xTg-AD mice, we found that while the density and morphology of I-S3 cells remain unaffected, there were significant changes in their firing output. Specifically, I-S3 cells displayed elongated action potentials and decreased firing rates, which was associated with a reduced inhibition of CA1 INs and their higher recruitment during spatial decision-making and object exploration tasks. Furthermore, the activation of CA1 PCs was also impacted, signifying early disruptions in CA1 network functionality. These findings suggest that altered firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.