They successfully treat severe depression by reversing brain signals

The most frequent mental health problem in Spain is anxiety disorder, which affects 6.7% of the population (8.8% in women, 4.5% in men), according to data from the Ministry of Health, while the depressive disorder 4.1% of the population suffers from it (5.9% in women and 2.3% in men), and its incidence increases progressively with age, affecting 12% of women and 5% of men from 75 to 84 years.

Many patients with severe depression do not respond to available treatments, but a new study led by Stanford Medicine scientists could offer new hope for them because it has revealed why the magnetic stimulation transcraneal may be a very useful therapeutic strategy to combat this psychiatric disorder, upon discovering that the secret of its effectiveness is based on the fact that it achieves correct the abnormal flow of brain signals in these people.

Powerful magnetic pulses applied to the scalp to stimulate the brain can provide quick relief for many people with severe depressive symptoms where traditional treatments have failed. Until now, however, it was unknown how transcranial magnetic stimulation (TMS) worked to treat depression and what the authors of the paper have discovered is that this therapy works reversing the direction of abnormal brain signals.

When depressed patients were treated with SNT, the flow of neural activity changed to the normal direction within a week, and this coincided with the disappearance of their depression.

Their findings have been published in Proceedings of the National Academy of Sciences (PNAS) and also suggest that the regressive currents of neural activity between key areas of the brain could be used as a biomarker that will facilitate the diagnosis of depression. “The main hypothesis has been that TMS could change the flow of neural activity in the brain,” said the Dr. Anish Mitra, postdoctoral fellow in psychiatry and behavioral sciences. “But to be honest, he was pretty skeptical. He wanted to prove it”.

Modify brain activity related to major depression

Mitra had developed a mathematical tool for analyzing functional magnetic resonance imaging, or fMRI, in Mark Raichle’s lab at Washington University in Saint Louis, which is typically used to locate active areas in the brain. The new analysis used minute differences in time between the activation of different areas to also reveal the direction of that activity.

Mitra and Raichle were associated with the Dr. Nolan Williams, associate professor of psychiatry and behavioral sciences, whose team has advanced the use of personalized magnetic stimulation based on each patient’s brain anatomy to treat major depression. The treatment has been approved by the FDA (United States Food and Drug Administration), it is known as Stanford neuromodulation therapy (SNT), and incorporates advanced imaging technologies to guide stimulation with high-dose patterns of magnetic pulses that can modify brain activity related to major depression. Compared to traditional EMT, which requires daily sessions for several weeks or months, SNT works on an accelerated schedule of 10 sessions each day for just five days.

The research involved 33 patients diagnosed with a treatment-resistant major depressive disorder. Twenty-three of them received SNT treatment and the other 10 received a sham treatment mimicking SNT, but without magnetic stimulation. Data from these patients were compared with that of 85 healthy individuals without depression who served as a control group.

When the researchers looked at the fMRI data across the whole brain, one connection stood out. In the normal brain, the anterior insula—an area that integrates bodily sensations—sends signals to a region that controls emotions, the anterior cingulate cortex. “You might think that the anterior cingulate cortex receives this information about the body, like heart rate or temperature, and then decides how to feel based on all these signals,” says Mitra.

However, in three quarters of the participants with depression, the typical flow of activity was reversed: the anterior cingulate cortex sent signals to the anterior insula. They found that the more severe the depression, the greater the proportion of signals traveling in the opposite direction. “What we saw is that who is the sender and who is the receiver in the relationship seems to really matter in terms of whether someone is depressed,” Mitra said, adding: “It’s almost like you already decided how you were going to feel, and then everything you were feeling seeped through that.” “That’s consistent with how many psychiatrists view depression.” “Even things that are usually quite pleasant to a patient suddenly don’t bring them any pleasure at all.”

When the depressed patients were treated with SNT, the flow of neural activity changed to the normal direction within a week, and this coincided with the disappearance of their depression. Patients with the most severe depression and the worst-directed brain signals were most likely to benefit from treatment. “We can undo the spatiotemporal anomaly so that the patients’ brains behave like those of normal, healthy controls,” Williams says.

A challenge in the treatment of depression has been the ignorance of its biological mechanisms, since there is no medical test to help determine the best therapy in each case. “This is the first time in psychiatry where this particular change in biology, the signal flow between these two brain regions, predicts change in clinical symptoms,” Williams said.

Although not all people with depression have this abnormal flux of neural activity and it may be rare in patients with less severe depression, Williams said, it could still serve as an important biomarker for classifying treatment of the disorder. “fMRI data that enables precision treatment with SNT can be used as a biomarker for depression and as a personalized guidance method to treat its underlying cause.” “When we find a person with severe depression, we can look for this biomarker to decide how likely they are to respond well to SNT treatment,” concludes Mitra.


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