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

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. Rodriguez, Mario A. Cristancho, Yvette I. Sheline, C. William Shuttleworth, Christopher C. Abbott, Arjun G. Yodh and Ethan M. Goldberg
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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
Yvette I. Sheline: 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

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59900-1

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