Scans displaying neuronal fluorescence and hemoglobin absorption. Credit score: College of Pennsylvania
Throughout his third-year psychiatry clerkship as a medical pupil, Zach Rosenthal, MD, Ph.D., was a part of a crew offering care to a younger man with schizophrenia and extreme catatonia.
“He was stuck frozen in bed and had stopped speaking or eating,” recalled Rosenthal, now a third-year resident in Psychiatry at Penn. “His symptoms weren’t responding to medication.”
Catatonia is a neuropsychiatric situation related to motor dysfunction, behavioral change, and withdrawal. When unresponsive to remedy, it could possibly grow to be medically harmful, and even deadly.
“After discussing with his family, our team recommended trying ECT,” Rosenthal mentioned.
ECT, or electroconvulsive remedy, makes use of temporary, noninvasive electrical stimulation of the mind to induce a seizure. Regardless of an outdated popular culture moniker (electroshock remedy) that usually paints the remedy in a unfavourable gentle, ECT has been confirmed to be a secure and extremely efficient remedy, providing speedy reduction from extreme signs when medicines have failed.
“People don’t think of ECT as ‘modern medicine,’ but it remains the gold standard intervention for treatment-resistant depression, psychosis, catatonia, bipolar mania, and more,” Rosenthal mentioned.
And now, Rosenthal is main a bunch that printed new findings which problem a long-held assumption that the seizure induced by ECT is the remedy’s final end result, probably altering the best way the remedy is run and considered.
‘Arduous reset’
The group’s findings, printed in Nature Communications, discovered that instantly after a seizure, ECT induces a second main mind occasion, often called cortical spreading depolarization (CSD), a slow-moving, high-amplitude touring wave of neuronal depolarization that resets nearly each neuron in its path.
“A CSD wave is a kind of hard reset for the brain and has the potential to explain many of the clinical effects of ECT,” Rosenthal mentioned.
Utilizing a contemporary neuroscience instrument known as optical neuroimaging (a non-invasive instrument that makes use of gentle to measure mind exercise), the crew was capable of exhibit that CSD happens after ECT in each a mouse mannequin and human sufferers. The waves had not beforehand been reported in the complete 86-year historical past of ECT as a result of they require newly created, specialised instruments like optical neuroimaging to detect them.
It is a part of an evolution of ECT the place establishments like Penn are main the best way.
“ECT is moving toward a precision medicine approach, using brain-based biomarkers to guide individualized treatment decisions,” Rosenthal mentioned.
“We’ve known for decades that stimulation parameters and seizure intensity can predict the therapeutic efficacy of ECT, but we didn’t know why. Now we are testing whether modern tools like optical CSD detection, neuroimaging, and computational modeling can guide us towards personalized ECT dosing to target specific outcomes in the brain.”
To check what position CSD performs within the scientific results of ECT, Rosenthal’s crew is now becoming a member of forces with a state-of-the-art ECT scientific trial led by Yvette I. Sheline, MD, the McLure Professor of Psychiatry and Behavioral Analysis and Director of the Penn Heart for Neuromodulation in Despair and Stress (CNDS).
“This model gives us the opportunity to understand the mechanism of ECT in a radically new way: that it is not the seizure but instead the subsequent inhibition from CSD that accounts for treatment effects. We are looking forward to testing this idea in the combined data from our multi-center trial,” Sheline mentioned.
Potential to broaden use of ECT
Rosenthal described the early ECT remedies for the younger man with extreme catatonia from his medical faculty clerkship as “a seemingly miraculous transformation.”
“After a single treatment, he could speak in full sentences and move well enough to feed himself. After a few more treatments, he walked out of the hospital and returned to living independently,” Rosenthal mentioned, including that the expertise was a part of what impressed him to grow to be a psychiatrist and research why electrically induced seizures are therapeutic.
“As I learned more about ECT, I realized that, despite decades of data demonstrating that it is highly effective and safe across the lifespan, there is so much to be learned about the underlying neurobiology, as well as how we can further optimize and improve treatment,” Rosenthal mentioned.
The undertaking took “a village,” together with mentorship from Ethan Goldberg MD, Ph.D., a pediatric neurologist with Youngsters’s Hospital of Philadelphia, in addition to Sheline, the ECT scientific crew led by Mario Cristancho, MD, an assistant professor of Medical Psychiatry, and Arjun Yodh, Ph.D., the Penn Physics division chair, whose lab developed the optical monitoring expertise used for CSD detection throughout ECT.
Setting a brand new customary
Rosenthal hopes ECT good points extra widespread public acceptance and accessibility as a medical process, transferring away from its largely unfavourable portrayal in common media. He famous that ECT is carried out below basic anesthesia and muscle relaxants. A crew of medical doctors and nurses intently displays, so sufferers are asleep, stay nonetheless, and don’t expertise ache in the course of the process.
“After ECT, most patients experience rapid improvement from previously severe, disabling neuropsychiatric symptoms when other treatments have failed, yet these outcomes are rarely represented in popular narratives,” he mentioned.
“The stigma of mental illness and ECT have real consequences, preventing patients and their families from accessing a treatment that can be life-saving.”
Extra info:
Zachary P. Rosenthal et al, Electroconvulsive remedy generates a postictal wave of spreading depolarization in mice and people, Nature Communications (2025). DOI: 10.1038/s41467-025-59900-1
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Electroconvulsive remedy’s ‘exhausting reset’ impact: Mind wave discovery challenges long-held assumption (2025, Could 29)
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