Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness

  1. Oluwaseun Akeju  Is a corresponding author
  2. Marco L Loggia
  3. Ciprian Catana
  4. Kara J Pavone
  5. Rafael Vazquez
  6. James Rhee
  7. Violeta Contreras Ramirez
  8. Daniel B Chonde
  9. David Izquierdo-Garcia
  10. Grae Arabasz
  11. Shirley Hsu
  12. Kathleen Habeeb
  13. Jacob M Hooker
  14. Vitaly Napadow
  15. Emery Brown
  16. Patrick L Purdon
  1. Massachusetts General Hospital, Harvard Medical School, United States
  2. MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, United States
  3. Massachusetts General Hospital, United States
  4. Massachusetts Institute of Technology, United States

Abstract

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow, and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.

Article and author information

Author details

  1. Oluwaseun Akeju

    Massachusetts General Hospital, Harvard Medical School, Boston, United States
    For correspondence
    oluwaseun.akeju@mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Marco L Loggia

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ciprian Catana

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kara J Pavone

    Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rafael Vazquez

    Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. James Rhee

    Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Violeta Contreras Ramirez

    Massachusetts General Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Daniel B Chonde

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. David Izquierdo-Garcia

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Grae Arabasz

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Shirley Hsu

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Kathleen Habeeb

    Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Jacob M Hooker

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Vitaly Napadow

    MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Emery Brown

    Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Patrick L Purdon

    Massachusetts Institute of Technology, Cambridge,, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jody C Culham, University of Western Ontario, Canada

Ethics

Human subjects: The Human Research Committee and the Radioactive Drug Research Committee at the Massachusetts General Hospital approved the study protocol. After an initial email/phone screen, potential study subjects were invited to participate in a screening visit. At the screening visit, informed consent including the consent to publish was requested after the nature and possible consequences of the study was explained. All subjects provided informed consent and were American Society of Anesthesiology Physical Status I with Mallampati Class I airway anatomy.

Version history

  1. Received: August 25, 2014
  2. Accepted: November 26, 2014
  3. Accepted Manuscript published: November 28, 2014 (version 1)
  4. Version of Record published: January 1, 2015 (version 2)

Copyright

© 2014, Akeju 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. Oluwaseun Akeju
  2. Marco L Loggia
  3. Ciprian Catana
  4. Kara J Pavone
  5. Rafael Vazquez
  6. James Rhee
  7. Violeta Contreras Ramirez
  8. Daniel B Chonde
  9. David Izquierdo-Garcia
  10. Grae Arabasz
  11. Shirley Hsu
  12. Kathleen Habeeb
  13. Jacob M Hooker
  14. Vitaly Napadow
  15. Emery Brown
  16. Patrick L Purdon
(2014)
Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness
eLife 3:e04499.
https://doi.org/10.7554/eLife.04499

Share this article

https://doi.org/10.7554/eLife.04499

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