Reversing depression

A study led by Stanford Medicine scientists has revealed that transcranial magnetic stimulation treats depression by correcting the abnormal flow of brain signals.

Previously, it was a mystery why the therapy, in which magnetic pulses are used to stimulate neurons, was effective in people with the mental illness. In the brain, the anterior insula, a region that integrates bodily sensations, typically sends signals to a region that governs emotions, the anterior cingulate cortex.

“You could think of it as the anterior cingulate cortex receiving this information about the body — like heart rate or temperature — then deciding how to feel on the basis of these signals,” said Anish Mitra, MD, PhD, a postdoctoral fellow in psychiatry and behavioral sciences and lead author of the study published in May 2023 in the Proceedings of the National Academy of Sciences.

Researchers analyzed brain-imaging data from 33 study participants with depression. In three-quarters of them, the typical activity flow was reversed -— the anterior cingulate cortex sent signals to the anterior insula. The more severe the depression, the higher the proportion of signals that traveled the wrong way.

“It’s almost as if you’d already decided how you were going to feel, and then everything you were sensing was filtered through that,” Mitra said. “The mood has become primary.”

In patients treated with Stanford neuromodulation therapy, a form of transcranial magnetic stimulation -— pioneered by Nolan Williams, MD, the associate professor of psychiatry and behavioral sciences — the neural activity flow shifted to the normal direction within a week, coinciding with a lifting of their depression. Williams was one of the senior authors of the research.