Electric field causes volumetric changes in the human brain

  1. Miklos Argyelan  Is a corresponding author
  2. Leif Oltedal
  3. Zhi-De Deng
  4. Benjamin Wade
  5. Marom Bikson
  6. Andrea Joanlanne
  7. Sohag Sanghani
  8. Hauke Bartsch
  9. Marta Cano
  10. Anders M Dale
  11. Udo Dannlowski
  12. Annemiek Dols
  13. Verena Enneking
  14. Randall Espinoza
  15. Ute Kessler
  16. Katherine L Narr
  17. Ketil J Oedegaard
  18. Mardien L Oudega
  19. Ronny Redlich
  20. Max L Stek
  21. Akihiro Takamiya
  22. Louise Emsell
  23. Filip Bouckaert
  24. Pascal Sienaert
  25. Jesus Pujol
  26. Indira Tendolkar
  27. Philip van Eijndhoven
  28. Georgios Petrides
  29. Anil K Malhotra
  30. Christopher Abbott
  1. The Zucker Hillside Hospital, United States
  2. University of Bergen, Norway
  3. National Institute of Mental Health, United States
  4. University of California, Los Angeles, United States
  5. The City College of the City University of New York, United States
  6. University of California, San Diego, United States
  7. Bellvitge University Hospital-IDIBELL, Spain
  8. University of Muenster, Germany
  9. GGZinGeest, Old Age Psychiatry, Amsterdam Neuroscience, Netherlands
  10. Keio University School of Medicine, Japan
  11. University Psychiatric Center - KU Leuven, Belgium
  12. Carlos III Health Institute, Spain
  13. Radboud University Medical Center, Netherlands
  14. University of New Mexico School of Medicine, United States

Abstract

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t =3.77, df = 83, r = 0.38, p = 0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p<0.01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.

Data availability

Source data files (.csv) including processed data have been provided for Figures 1-4, Figure 3-figure supplement 1 and Figure 4-figure supplement 1. Raw data cannot be made available publicly because we do not have consent or ethical approval for this and the data cannot be anonymised. The data is stored on a secure centralized server at the Univerity of Bergen, Norway. Participating GEMRIC sites have access to the raw data according to specific data policy and safety rules of the consortium, and in accord with the approval from the ethical committee. The GEMRIC consortium welcomes new members who are interested in the neuroimaging research of ECT. We hold board meetings twice a year when new members can apply to join and gain access to the database available on the GEMRIC servers. For more about the application process please visit https://mmiv.no/how-to-join-gemric/ or write to Leif Oltedal (leif.oltedal@uib.no). General information about the consortium can be found on the following website: https://mmiv.no/gemric/. For transparency and reproducibility, the entire analytical approach is uploaded to the https://github.com/argyelan/Publications/tree/master/ECTEFvsVOLUME (R scripts in org mode), and also was uploaded to eLife.

Article and author information

Author details

  1. Miklos Argyelan

    Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, United States
    For correspondence
    argyelan@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7254-1776
  2. Leif Oltedal

    Department of Clinical Medicine, University of Bergen, Bergen, Norway
    Competing interests
    No competing interests declared.
  3. Zhi-De Deng

    Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  4. Benjamin Wade

    Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  5. Marom Bikson

    Department of Biomedical Engineering, The City College of the City University of New York, New York, United States
    Competing interests
    Marom Bikson, reports that The City University of New York (CUNY) has intellectual property (IP) on neuro-stimulation system and methods with MB as inventor; serves on the scientific advisory boards of Boston Scientific and GSK; has equity in Soterix Medical.
  6. Andrea Joanlanne

    Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, United States
    Competing interests
    No competing interests declared.
  7. Sohag Sanghani

    Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, United States
    Competing interests
    No competing interests declared.
  8. Hauke Bartsch

    Center for Multimodal Imaging and Genetics, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  9. Marta Cano

    Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0675-9483
  10. Anders M Dale

    Center for Multimodal Imaging and Genetics, University of California, San Diego, San Diego, United States
    Competing interests
    Anders M Dale, reports that he is a Founder of and holds equity in CorTechs Labs, Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc.
  11. Udo Dannlowski

    Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
    Competing interests
    No competing interests declared.
  12. Annemiek Dols

    Departement of Psychiatry, GGZinGeest, Old Age Psychiatry, Amsterdam Neuroscience, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  13. Verena Enneking

    Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
    Competing interests
    No competing interests declared.
  14. Randall Espinoza

    Department of Neurology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  15. Ute Kessler

    Division of Psychiatry, University of Bergen, Bergen, Norway
    Competing interests
    No competing interests declared.
  16. Katherine L Narr

    Department of Neurology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  17. Ketil J Oedegaard

    Division of Psychiatry, University of Bergen, Bergen, Norway
    Competing interests
    No competing interests declared.
  18. Mardien L Oudega

    Departement of Psychiatry, GGZinGeest, Old Age Psychiatry, Amsterdam Neuroscience, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  19. Ronny Redlich

    Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
    Competing interests
    No competing interests declared.
  20. Max L Stek

    Departement of Psychiatry, GGZinGeest, Old Age Psychiatry, Amsterdam Neuroscience, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  21. Akihiro Takamiya

    Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.
  22. Louise Emsell

    Department of Geriatric Psychiatry, University Psychiatric Center - KU Leuven, Leuven, Belgium
    Competing interests
    No competing interests declared.
  23. Filip Bouckaert

    Department of Geriatric Psychiatry, University Psychiatric Center - KU Leuven, Leuven, Belgium
    Competing interests
    No competing interests declared.
  24. Pascal Sienaert

    Academic center for ECT and Neurostimulation, University Psychiatric Center - KU Leuven, Kortenberg, Belgium
    Competing interests
    No competing interests declared.
  25. Jesus Pujol

    CIBERSAM, Carlos III Health Institute, Barcelona, Spain
    Competing interests
    No competing interests declared.
  26. Indira Tendolkar

    Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  27. Philip van Eijndhoven

    Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  28. Georgios Petrides

    Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, United States
    Competing interests
    No competing interests declared.
  29. Anil K Malhotra

    Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, United States
    Competing interests
    No competing interests declared.
  30. Christopher Abbott

    Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, United States
    Competing interests
    No competing interests declared.

Funding

National Institute of Mental Health (MH092301)

  • Randall Espinoza
  • Katherine L Narr

National Institute of Mental Health (ZIAMH00295)

  • Zhi-De Deng

National Institute of Mental Health (MH119616)

  • Miklos Argyelan

National Institute of Mental Health (MH111826)

  • Christopher Abbott

National Institute of Mental Health (MH110008)

  • Randall Espinoza
  • Katherine L Narr

National Institute of Mental Health (MH102743)

  • Randall Espinoza
  • Katherine L Narr

Western Norway Regional Health Authority (911986)

  • Ketil J Oedegaard

Western Norway Regional Health Authority (912238)

  • Leif Oltedal

Deutsche Forschungsgemeinschaft (DFG FOR2107 DA1151/5-1 and DA1151/5-2)

  • Udo Dannlowski

Deutsche Forschungsgemeinschaft (SFB-TRR58)

  • Udo Dannlowski

Deutsche Forschungsgemeinschaft (Projects C09 and Z02)

  • Udo Dannlowski

Innovative Medical Research (RE111604 and RE111722)

  • Ronny Redlich

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

Reviewing Editor

  1. Klaas Enno Stephan, University of Zurich and ETH Zurich, Switzerland

Ethics

Human subjects: All sites' contributing data received approval by their local ethical committees or institutional review board, and the centralized mega-analysis was approved by the Regional Ethics Committee South-East in Norway (2013/1032 ECT and Neuroradiology, June 1, 2015).

Version history

  1. Received: June 6, 2019
  2. Accepted: October 22, 2019
  3. Accepted Manuscript published: October 23, 2019 (version 1)
  4. Version of Record published: November 22, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Miklos Argyelan
  2. Leif Oltedal
  3. Zhi-De Deng
  4. Benjamin Wade
  5. Marom Bikson
  6. Andrea Joanlanne
  7. Sohag Sanghani
  8. Hauke Bartsch
  9. Marta Cano
  10. Anders M Dale
  11. Udo Dannlowski
  12. Annemiek Dols
  13. Verena Enneking
  14. Randall Espinoza
  15. Ute Kessler
  16. Katherine L Narr
  17. Ketil J Oedegaard
  18. Mardien L Oudega
  19. Ronny Redlich
  20. Max L Stek
  21. Akihiro Takamiya
  22. Louise Emsell
  23. Filip Bouckaert
  24. Pascal Sienaert
  25. Jesus Pujol
  26. Indira Tendolkar
  27. Philip van Eijndhoven
  28. Georgios Petrides
  29. Anil K Malhotra
  30. Christopher Abbott
(2019)
Electric field causes volumetric changes in the human brain
eLife 8:e49115.
https://doi.org/10.7554/eLife.49115

Share this article

https://doi.org/10.7554/eLife.49115

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