Researchers at Stanford Medicine have made a significant breakthrough in treating severe depression by utilizing transcranial magnetic stimulation (TMS) to reverse abnormal brain signals. The study also highlights the potential use of a biomarker for diagnosing depression—the reversal of neural activity between key brain regions.
TMS involves applying powerful magnetic pulses to the skull, stimulating the brain and providing rapid relief to severely depressed individuals who have not responded to traditional treatments.
Until now, the precise mechanism by which transcranial magnetic stimulation alleviated depression remained elusive. However, a team of scientists at Stanford Medicine, led by Anish Mitra, MD, Ph.D., and Mark Raichle, MD, has uncovered that this therapy works by reversing the direction of abnormal brain signals.
The research findings also indicate that the reversed neural activity between crucial brain areas could serve as a biomarker to aid in diagnosing depression.
“The leading hypothesis has been that TMS could change the flow of neural activity in the brain,” explained Mitra. “But to be honest, I was pretty skeptical. I wanted to test it.”
Mitra, along with Raichle and Nolan Williams, MD, conducted the study, combining their expertise in mathematical analysis of functional magnetic resonance imaging (fMRI) and personalized magnetic stimulation techniques for depression treatment.
The FDA-cleared treatment, known as Stanford Neuromodulation Therapy (SNT), incorporates advanced imaging technologies to guide the application of magnetic pulses tailored to each patient’s brain structure. This personalized approach modifies brain activity associated with major depression. Unlike traditional TMS, which necessitates daily sessions over several weeks or months, SNT accelerates the treatment process to ten daily sessions across five days.
“This was the perfect test to see if TMS has the ability to change the way that signals flow through the brain,” said Mitra, the lead author of the study. “If this doesn’t do it, nothing will.”
In the study, 33 patients diagnosed with treatment-resistant major depressive disorder participated, with 23 receiving SNT treatment and 10 receiving a sham treatment without magnetic stimulation. Data from these patients were compared to that of 85 healthy individuals without depression.
The analysis of fMRI data across the entire brain revealed a distinct connection. In a healthy brain, the anterior insula, responsible for integrating bodily sensations, sends signals to the anterior cingulate cortex, which regulates emotions.
However, in three-quarters of the depressed participants, the flow of activity was reversed: the anterior cingulate cortex transmitted signals to the anterior insula. The severity of depression correlated with a higher proportion of signals traveling in the wrong direction.
Mitra explained, “What we saw is that who’s the sender and who’s the receiver in the relationship seems to really matter in terms of whether someone is depressed.”
The study also demonstrated that SNT treatment could restore the normal flow of neural activity within a week, coinciding with the alleviation of depression symptoms. Those with more severe depression and greater misdirected brain signals showed the most significant improvement.
“We’re able to undo the spatiotemporal abnormality so that people’s brains look like those of normal, healthy controls,” said Williams.
Additionally, the reversed flow of neural activity between brain regions serves as a promising biomarker for depression. While not all depressed individuals exhibit this abnormality, it may be rare in less severe cases. Nonetheless, it can play a crucial role in triaging treatment options for depression.
The researchers emphasized that the findings could help determine the likelihood of a positive response to SNT treatment for individuals with severe depression.
The study’s senior authors, Raichle and Williams, plan to replicate the research with a larger group of patients. They also encourage other scientists to adopt their analytical technique to further investigate the direction of brain activity in fMRI data.
The study was supported by various funding sources, including the Brain and Behavior Research Foundation Young Investigator Award, NIMH Biobehavioral Research Awards for Innovative New Scientists, and several philanthropic foundations dedicated to neuromodulation and brain research.
Frequently Asked Questions (FAQs) about Transcranial magnetic stimulation for depression treatment
What is transcranial magnetic stimulation (TMS) and how does it treat depression?
Transcranial magnetic stimulation (TMS) is a treatment for severe depression that involves applying powerful magnetic pulses to stimulate the brain. It works by reversing abnormal brain signals, providing rapid relief to individuals who have not responded to traditional treatments.
What did the Stanford research team discover about TMS and depression?
The research team at Stanford Medicine found that TMS functions by reversing the direction of abnormal brain signals in individuals with depression. They also identified a potential biomarker for diagnosing depression—the backward flow of neural activity between key areas of the brain.
How does the reversal of brain signals relate to depression?
In a healthy brain, certain regions send signals to others, regulating emotions and integrating bodily sensations. However, the study revealed that in individuals with depression, this flow of activity is often reversed, with key regions transmitting signals in the wrong direction. The severity of depression correlated with the extent of this abnormality.
Can TMS treatment restore normal brain activity?
Yes, the study showed that TMS treatment can restore the normal flow of neural activity within a week, coinciding with the alleviation of depression symptoms. Individuals with more severe depression and greater misdirected brain signals were more likely to benefit from the treatment.
How can the findings be used as a biomarker for depression?
The reversed flow of neural activity between key brain regions serves as a potential biomarker for diagnosing depression. While not all depressed individuals exhibit this abnormality, it can be used to triage treatment options and determine the likelihood of a positive response to TMS treatment for those with severe depression.
More about Transcranial magnetic stimulation for depression treatment
- Stanford Medicine News Center
- Proceedings of the National Academy of Sciences
- Brain and Behavior Research Foundation
- National Institute of Mental Health (NIMH)
- Transcranial Magnetic Stimulation (TMS) – Mayo Clinic