Depression Relief: Brain Signal Reversal by Magnetic Pulses – Neuroscience News

Summary: Transcranial magnetic stimulation (TMS), a treatment involving strong magnetic pulses applied to the scalp, alleviates severe depression by reversing the flow of neural activity in the brain.

The treatment, known as Stanford neuromodulation therapy (SNT), modifies brain activity related to depression, with effects seen after 10 sessions over five days.

The research shows that in many patients with depression, neural signals between key areas of the brain are sent in the opposite direction to that of a normal brain, which changes after SNT. This abnormal flow of neural activity could serve as a biomarker for diagnosing depression.

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Source: Stanford

Powerful magnetic pulses applied to the scalp to stimulate the brain can bring fast relief to many severely depressed patients for whom standard treatments have failed. Yet its been a mystery exactly how transcranial magnetic stimulation, as the treatment is known, changes the brain to dissipate depression.

Now, research led by Stanford Medicine scientists has found that the treatment works by reversing the direction of abnormal brain signals.

The findings also suggest that backward streams of neural activity between key areas of the brain could be used as a biomarker to help diagnosedepression.

The leading hypothesis has been that TMS could change the flow of neural activity in the brain, said Anish Mitra, MD, Ph.D., a postdoctoral fellow in psychiatry andbehavioral sciences. But to be honest, I was pretty skeptical. I wanted to test it.

Mitra had just the tool to do it. As a graduate student at Washington University in Saint Louis, in the lab of Mark Raichle, MD, he developed a mathematical tool to analyzefunctional magnetic resonance imaging, or fMRIcommonly used to locate active areas in the brain. The new analysis used minute differences in timing between the activation of different areas to also reveal the direction of that activity.

In the new study, published May 15 in theProceedings of the National Academy of Sciences, Mitra and Raichle teamed up with Nolan Williams, MD, associate professor of psychiatry and behavioral sciences, whose team has advanced the use of magnetic stimulation, personalized to each patients brain anatomy, to treat profound depression.

The FDA-cleared treatment, known as Stanford neuromodulation therapy, incorporates advanced imaging technologies to guide stimulation with high-dose patterns of magnetic pulses that can modify brain activity related tomajor depression.

Compared with traditional TMS, which requires daily sessions over several weeks or months, SNT works on an accelerated timeline of 10 sessions each day for just 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, who is lead author of the study. If this doesnt do it, nothing will.

The researchers recruited 33 patients who had been diagnosed with treatment-resistant major depressive disorder. Twenty-three received SNT treatment, and 10 received a sham treatment that mimicked SNT but without magnetic stimulation. They compared data from these patients with that of 85 healthy controls without depression.

When they analyzed fMRI data across the whole brain, one connection stood out. In the normal brain, the anterior insula, a region that integrates bodily sensations, 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 bodylike heart rate or temperatureand then deciding how to feel on the basis of all these signals, Mitra said.

In three-quarters of the participants with depression, however, the typical flow of activity was reversed: Theanterior cingulate cortexsent signals to the anterior insula. The more severe the depression, the higher the proportion of signals that traveled the wrong way.

What we saw is that whos the sender and whos the receiver in the relationship seems to really matter in terms of whether someone is depressed, Mitra said.

Its almost as if youd already decided how you were going to feel, and then everything you were sensing was filtered through that, he said. The mood has become primary.

Thats consistent with how a lot of psychiatrists see depression, he added. Even things that are quite joyful to a patient normally are suddenly not bringing them any pleasure.

When depressed patients were treated with SNT, the flow of neural activity shifted to the normal direction within a week, coinciding with a lifting of their depression.

Those with the most severe depressionand the most misdirected brain signalswere the most likely to benefit from the treatment.

Were able to undo the spatio-temporal abnormality so that peoples brains look like those of normal, healthy controls, Williams said.

A challenge of treating depression has been the lack of insight into its biological mechanisms. If a patient has a fever, there are various testsfor a bacterial or viral infection, for examplethat could determine the appropriate treatment. But for a patient with depression, there are no analogous tests.

This is the first time in psychiatry where this particular change in a biologythe flow of signals between these two brain regionspredicts the change in clinical symptoms, Williams said.

Not everyone with depression has this abnormal flow of neural activity, and it may be rare in less severe cases of depression, Williams said, but it could serve as an important biomarker for triaging treatment for the disorder.

The fMRI data that allows precision treatment with SNT can be used both as a biomarker for depression and a method of personalized targeting to treat its underlying cause, he said.

When we get a person with severe depression, we can look for this biomarker to decide how likely they are to respond well to SNT treatment, Mitra said.

Behavioral conditions like depression have been difficult to capture with imaging because, unlike an obvious brain lesion, they deal with the subtlety of relationships between various parts of the brain, said Raichle, who has studied brain imaging for more than four decades.

Its incredibly promising that the technology now is approaching the complexity of the problems were trying to understand.

The researchers plan to replicate the study in a larger group of patients. They also hope others will adopt their analytic technique to uncover more clues about the direction ofbrain activityhidden in fMRI data. As long as you have good clean fMRI data, you can study this property of the signals, Mitra said.

Author: Nina BaiSource: StanfordContact: Nina Bai StanfordImage: The image is credited to Neuroscience News

Original Research: Open access.Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression by Anish Mitra et al. PNAS

Abstract

Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression

Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information.

We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT).

We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC).

Directional signaling shifts in the ACC, but not the DLPFC, predict improvement in depression symptoms, and moreover, pretreatment ACC signaling predicts both depression severity and the likelihood of SNT treatment response.

Taken together, our findings suggest that ACC-based directed signaling patterns in rs-fMRI are a potential biomarker of MDD.

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Depression Relief: Brain Signal Reversal by Magnetic Pulses - Neuroscience News