Work

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

Year: 2025

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-025-59900-1

Authors: 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, Ethan M. Goldberg

Institutions: University of Pennsylvania, Children's Hospital of Philadelphia, University of New Mexico, University of California, San Francisco

Language: English

Topic: Electroconvulsive Therapy Studies

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: U.S. Department of Health and Human Services, 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

Awards: G1353440949, G1574713008, G2083866179, G226818447, G2447268582, G2549326750, G2788747769, G2859360560, G3191539631, Adenosine receptor activation in spreading depolarization and ischemic injury, G3840334392, Center for Advanced Metabolic Imaging in Precision Medicine (CAMIPM), G3970329492, G4207471524, G4570705582, G471519714, G5377247008, G6100615285, Educating Physician Scientists in Psychiatry (EPSP): Firing up the next generation of translational and clinical neuroscientists, NINDS Research Education Programs for Residents and Fellows in Neurology, Neurosurgery, Neuropathology, Neuroradiology and Emergency Medicine (R25), Spreading Depolarizations and Neuronal Vulnerability, Spreading Depolarizations and Post-Ischemic Injury, G769385088, G7768549844, G8617835366, G9000025887, G9000043450, G9000067683, G9000116279, G9000149996, G9000280402, The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/Penn, G952518113

OpenAlex ID: W4410469017

FWCI: 12.91

Cites: 106

Cited by: 21

Related to: 10