ECT Generates a Postictal Wave of Spreading Depolarization in Mice and Humans

 Out on PubMed, from authors in the USA, is this paper:

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

Rosenthal ZP, Majeski JB, Somarowthu A, Quinn DK, Lindquist BE, Putt ME, Karaj A, Favilla CG, Baker WB, Hosseini G, Rodriguez JP, Cristancho MA, Sheline YI, William Shuttleworth C, Abbott CC, Yodh AG, Goldberg EM.Nat Commun. 2025 May 18;16(1):4619. doi: 10.1038/s41467-025-59900-1.PMID: 40383825

The abstract is copied below:

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.

The paper is here.

And from the text:

Here is a combination of animal and human research that posits a new theory of the mechanism of action of ECT. If cortical spreading depolarization turns out to be a valid finding in effective ECT, this line of research could lead to progress in both understanding how ECT works and in refining treatment procedures even further.

Big kudos to these authors!

Despite the fact that this paper is dense and complex, I strongly recommend a full and careful read to all ECT health care professionals.

I believe that this paper could become a landmark classic in the field.

I will leave it up on the blog indefinitely, because of its importance...