How Does Electroconvulsive Therapy Change the Brain?

By Lauren Ingeno

The Findings

Researchers at Children’s Hospital of Philadelphia and the University of Pennsylvania uncovered an electrophysiological phenomenon in the brain that may explain the clinical effects of electroconvulsive therapy (ECT), a treatment for medication-resistant depression.

ECT delivers brief electrical pulses to the brain to elicit a controlled seizure while a patient is asleep under general anesthesia. The CHOP-Penn team demonstrated that a second event in the brain follows the initial ECT-induced seizure: cortical spreading depolarization (CSD). CSD is a slow-moving, high-amplitude wave of electrical disturbance that travels across the brain, resetting neurons in its path and inducing lasting plasticity.

Why It Matters

The discovery has implications for understanding how ECT works and could guide researchers toward developing more personalized ECT therapies in the future.

For decades, it was widely believed that seizures were essential for ECT to improve clinical symptoms. Yet not all seizures lead to clinical improvement, and evidence suggests that electrical stimulation below the seizure threshold also can be therapeutic. There is a need, therefore, for more reliable brain activity biomarkers to predict treatment response, monitor side effects, and guide stimulation settings.

Who Conducted the Study

Ethan Goldberg, MD, PhD, an attending physician and director of the Epilepsy Neurogenetics Initiative (ENGIN), served as the study’s principal investigator. Zachary Rosenthal, MD, PhD, a psychiatry resident at Penn’s Perelman School of Medicine and postdoctoral researcher in the Goldberg Laboratory at CHOP, was the study’s lead author.

How They Did It

The researchers created a new animal model of ECT using non-invasive optical neuroimaging — a tool that uses light to visualize brain network activity during ECT stimulation. A genetically encoded calcium indicator in the brain allowed the researchers to image neuronal dynamics through the skull and identify CSD as a new biomarker for ECT. The team then validated the results by using noninvasive optical neuroimaging in human patients to demonstrate that CSD also occurs in routine ECT treatments.

Quick Thoughts

“Nearly a century since it was discovered, ECT remains a safe, highly effective treatment for severe depression. Despite its effectiveness, ECT’s mode of action is understudied and poorly understood,” Dr. Goldberg said. “Dr. Rosenthal’s hypothesis, supported by data in human patients, is that post-seizure spreading depolarization might be driving the efficacy of ECT by inducing brain plasticity.”

What’s Next

The team plans to conduct larger-scale, longitudinal studies to determine if CSD influences clinical trajectories in patients receiving ECT, as well as in animal models of psychiatric disease. If CSD proves to be part of the therapeutic mechanism of ECT, this would allow clinicians to possibly bypass seizure and directly trigger CSD, leading to more targeted clinical effects.

Where the Study Was Published

The findings appeared in Nature Communications. Read more in this CHOP press release.