Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves

Abstract

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.

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Author details

  1. Miriam Schwalm

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Florian Schmid

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Lydia Wachsmuth

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Hendrik Backhaus

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrea Kronfeld

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Felipe Aedo Jury

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Pierre-Hugues Prouvot

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Consuelo Fois

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Franziska Albers

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Timo van Alst

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Cornelius Faber

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7683-7710
  12. Albrecht Stroh

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    For correspondence
    albrecht.stroh@unimedizin-mainz.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9410-4086

Funding

Deutsche Forschungsgemeinschaft (Fa474/5)

  • Cornelius Faber

Deutsche Forschungsgemeinschaft (SFB 1080)

  • Albrecht Stroh

Deutsche Forschungsgemeinschaft (SFB 1193)

  • Albrecht Stroh

Deutsche Forschungsgemeinschaft (SPP 1665)

  • Albrecht Stroh

Focus Program translational Neurosciences

  • Miriam Schwalm
  • Albrecht Stroh

Interdisciplinary Center for Clinical Research Münster (Fa3/1603,PIX)

  • Cornelius Faber

Excellence Cluster Cells in Motion (EXEC 1003)

  • Cornelius Faber

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

Ethics

Animal experimentation: Animal husbandry and experimental manipulation were carried out according to animal welfare guidelines of the Westfalian Wilhelms-University and the Johannes Gutenberg-University Mainz and were approved by the Landesamt für Natur-, Verbraucher- und Umweltschutz Nordrhein-Westfalen, Recklinghausen, Germany (animal protocol number: 84-02.04.2015.A427), and the Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany (animal protocol number: G 14-1-040). All surgery was performed under deep isoflurane anesthesia.

Reviewing Editor

  1. Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States

Publication history

  1. Received: April 7, 2017
  2. Accepted: September 14, 2017
  3. Accepted Manuscript published: September 15, 2017 (version 1)
  4. Accepted Manuscript updated: September 19, 2017 (version 2)
  5. Version of Record published: October 26, 2017 (version 3)

Copyright

© 2017, Schwalm 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. Miriam Schwalm
  2. Florian Schmid
  3. Lydia Wachsmuth
  4. Hendrik Backhaus
  5. Andrea Kronfeld
  6. Felipe Aedo Jury
  7. Pierre-Hugues Prouvot
  8. Consuelo Fois
  9. Franziska Albers
  10. Timo van Alst
  11. Cornelius Faber
  12. Albrecht Stroh
(2017)
Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
eLife 6:e27602.
https://doi.org/10.7554/eLife.27602
  1. Further reading

Further reading

    1. Neuroscience
    Alex TL Leong, Ed X Wu
    Insight

    Simultaneous measurements of neuronal activity and fMRI signals in the rat brain have shed new light on the origins of resting-state fMRI connectivity networks.

    1. Epidemiology and Global Health
    2. Neuroscience
    Lorenza Dall'Aglio, Hannah H Kim ... Henning Tiemeier
    Research Article Updated

    Background:

    Associations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for the intelligence quotient (IQ) and head motion, which are generally corrected for but play ambiguous roles (aim 2).

    Methods:

    Participants were 10-year-old children from the Adolescent Brain Cognitive Development (N = 7722) and Generation R (N = 2531) Studies. Cortical area, volume, and thickness were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.

    Results:

    ADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes further changed when including IQ and head motion (aim 2), however, we argue that adjustments might have introduced bias.

    Conclusions:

    Careful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.

    Funding:

    Authors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.