Researchers at the Children’s Hospital of Philadelphia (CHOP) have identified a previously unrecognized brain event following electroconvulsive therapy (ECT), a treatment for severe, medication-resistant depression. The study was published in Nature Communications.
Traditionally, ECT’s therapeutic effects were thought to result from inducing a controlled seizure. However, the new research identifies a second phenomenon, cortical spreading depolarization (CSD), occurring immediately after the seizure, which may play a key role in ECT’s effects on the brain.
“For nearly a century, it has been a mystery why inducing a seizure is therapeutic when medications fail,” said Zach Rosenthal, MD, PhD, the study’s first author and postdoctoral fellow in Ethan Goldberg’s lab at CHOP. “CSD has the potential to explain how the brain course-corrects after seizure, as well as why different ECT stimulation parameters influence antidepressant effects. Understanding the role of CSD may open new avenues for optimizing how we deliver ECT.”
For this study, researchers used advanced light-based neuroimaging techniques in a preclinical model to observe brain activity during and after ECT. They found that following an induced seizure, there is a slow-moving wave of electrical activity and increased blood flow through the cortex. This wave is characterized by maximal activation of neurons followed by suppressed brain activity while neurons reset.
To determine if this phenomenon occurs in humans, researchers applied non-invasive optical neuroimaging techniques developed at the University of Pennsylvania to measure cerebral blood flow and oxygenation. In patients undergoing routine ECT treatments, they observed consistent patterns of increased blood flow—hyperemic waves—following seizures that mirrored preclinical CSD responses.
The authors suggest future research will explore whether modulating ECT-induced CSD could improve treatment efficacy and inform future brain stimulation therapies. “Our hope is we will eventually be able to provide more personalized and effective treatment plans for individuals suffering from severe depression and other neuropsychiatric conditions,” Rosenthal added.
The study represents collaboration between CHOP’s Goldberg lab at the Center for Brain Research in Development, Genetics, and Engineering (BRIDGE), CHOP’s Intellectual and Developmental Disabilities Research Center (IDDRC), Departments of Psychiatry, Physics, Biostatistics and Neurology at Penn, as well as collaborators at the University of New Mexico.
Research funding was provided by several NIH grants including R25MH119043 and UL1TR001878 among others.
Rosenthal et al.’s paper titled “Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans” was published online on May 18, 2025.
