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Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans

Author

Listed:
  • Zachary P. Rosenthal

    (University of Pennsylvania)

  • Joseph B. Majeski

    (University of Pennsylvania)

  • Ala Somarowthu

    (The Children’s Hospital of Philadelphia)

  • Davin K. Quinn

    (University of New Mexico School of Medicine)

  • Britta E. Lindquist

    (University of California San Francisco School of Medicine)

  • Mary E. Putt

    (University of Pennsylvania)

  • Antoneta Karaj

    (University of Pennsylvania)

  • Chris G. Favilla

    (University of Pennsylvania)

  • Wesley B. Baker

    (The Children’s Hospital of Philadelphia)

  • Golkoo Hosseini

    (University of Pennsylvania)

  • Jenny P. Rodriguez

    (University of Pennsylvania)

  • Mario A. Cristancho

    (University of Pennsylvania
    University of Pennsylvania)

  • Yvette I. Sheline

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • C. William Shuttleworth

    (University of New Mexico School of Medicine)

  • Christopher C. Abbott

    (University of New Mexico School of Medicine)

  • Arjun G. Yodh

    (University of Pennsylvania)

  • Ethan M. Goldberg

    (The Children’s Hospital of Philadelphia
    University of Pennsylvania
    University of Pennsylvania)

Abstract

Electroconvulsive therapy (ECT) is a fast-acting, highly effective, and safe treatment for medication-resistant depression. Historically, the clinical benefits of ECT have been attributed to generating a controlled seizure; however, the underlying neurobiology is understudied and unresolved. Using optical neuroimaging of neural activity and hemodynamics in a mouse model of ECT, we demonstrated that a second brain event follows seizure: cortical spreading depolarization (CSD). We found that ECT pulse parameters and electrode configuration directly shaped the wave dynamics of seizure and subsequent CSD. To translate these findings to human patients, we used non-invasive diffuse optical monitoring of cerebral blood flow and oxygenation during routine ECT treatments. We observed that human brains reliably generate hyperemic waves after ECT seizure which are highly consistent with CSD. These results challenge a long-held assumption that seizure is the primary outcome of ECT and point to new opportunities for optimizing ECT stimulation parameters and treatment outcomes.

Suggested Citation

  • Zachary P. Rosenthal & Joseph B. Majeski & Ala Somarowthu & Davin K. Quinn & Britta E. Lindquist & Mary E. Putt & Antoneta Karaj & Chris G. Favilla & Wesley B. Baker & Golkoo Hosseini & Jenny P. Rodri, 2025. "Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59900-1
    DOI: 10.1038/s41467-025-59900-1
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