Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans
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.
Authors
- Mario A. Cristancho (ORCID: https://orcid.org/0009-0005-3100-5677)
- Mary E. Putt (ORCID: https://orcid.org/0000-0001-7954-1288)
- Wesley B. Baker (ORCID: https://orcid.org/0000-0002-3025-6061)
- Arjun G. Yodh (ORCID: https://orcid.org/0000-0003-4744-2706)
- Britta E. Lindquist (ORCID: https://orcid.org/0000-0002-7913-9034)
- Ethan M. Goldberg (ORCID: https://orcid.org/0000-0002-7404-735X)
- Ala Somarowthu (ORCID: https://orcid.org/0000-0001-8109-3816)
- Joseph B. Majeski (ORCID: https://orcid.org/0000-0001-5504-5423)
- Davin K. Quinn
- Zachary P. Rosenthal (ORCID: https://orcid.org/0000-0001-8787-0858)
- Yvette I. Sheline (ORCID: https://orcid.org/0000-0002-6929-9659)
- C. William Shuttleworth (ORCID: https://orcid.org/0000-0002-0237-4888)
- Christopher G. Favilla (ORCID: https://orcid.org/0000-0003-0871-9549)
- Chris Abbott (ORCID: https://orcid.org/0000-0001-6884-2464)
- Juan Carlos Rodríguez‐Aldama (ORCID: https://orcid.org/0000-0001-8664-9879)
- Golkoo Hosseini (ORCID: https://orcid.org/0009-0005-3987-8608)
- Antoneta Karaj
Institutions
- Children's Hospital of Philadelphia (US)
- University of New Mexico (US)
- University of California, San Francisco (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-18
- DOI
- https://doi.org/10.1038/s41467-025-59900-1
- Citations
- 8
- Primary Topic
- Electroconvulsive Therapy Studies
- Type
- article
- Field-Weighted Citation Impact
- 11.77
Funders
- University of Pennsylvania
- Institute for Translational Medicine and Therapeutics
- National Institutes of Health
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- National Institute of Biomedical Imaging and Bioengineering
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development