Brain activity ‘stimulator’ helps woman recover from severe depression

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After all available treatments failed, a patient with severe depression found relief with an implanted device that delivers short electrical impulses to specific places in her brain.

The battery-powered device, called the NeuroPace RNS System, not only stimulates the brain but also monitors electrical activity from inside the organ. Thus, the device can be programmed to turn on in response to specific brain activity patterns. The United States Food and Drug Administration (FDA) had previously approved the system as a treatment for epilepsy, but now a team at the University of California at San Francisco (UCSF) is testing whether the technology could also benefit people with resistance to treatment depression.

And so far the idea looks promising, the team reported in a new proof-of-concept study, published Monday (October 4) in the journal. Natural medicine. The study involved a single patient, a 36-year-old woman named Sarah, who underwent various tests to determine where her implant should be placed and what specific patterns of electrical activity should turn on the device. A few months after receiving the implant, Sarah went from suicidal thoughts several times an hour to disappearing those thoughts and having her depression in remission, she told reporters at a press conference on the 30th. September.

Related: 7 ways to recognize depression in people 20 and over

SUICIDE HOTLINE

If you’re thinking about suicide, worrying about a friend or loved one, or want emotional support, the National Suicide Prevention Lifeline is available 24/7 in the United States. You can call Lifeline at 1-800-273-8255 or chat with someone online.

And now, after over a year, “my device has kept my depression at bay and allowed me to resume a life worth living,” she said. At this point, Sarah’s symptoms are almost gone and when negative thoughts arise, they no longer consume her.

“This is a really exciting study,” said Dr Paul Holtzheimer, associate professor of psychiatry and surgery at the Geisel School of Medicine in Dartmouth and deputy director of research at the National Center for PTSD, who was not involved. in the study. “The caveat being… this is what we call an ‘N of one’, a one-participant study,” and therefore has yet to be validated in a large trial with a placebo group to see if the same approach will work. reliably in other people, he says.

Before the study, Sarah’s depression did not respond to multiple combinations of antidepressants, as well as electroconvulsive therapy (ECT), which stimulates one or both halves of the brain with electricity, rather than target only specific parts of the brain. The process of trying treatment after treatment, to no avail, “made me feel like I was the worst patient in the world – that it was my own moral failure,” Sarah said at the press conference.

But after taking the UCSF trial and receiving targeted brain stimulation for the first time, something clicked. Once the implant was lodged in her brain, “within a few weeks, the suicidal thoughts just disappeared,” Sarah said. And over the next several months, her “focus on the world changed” and she was able to apply the lessons she had learned in talk therapy meaningfully.

Sarah’s treatment is a type of deep brain stimulation (DBS), which uses surgically implanted electrodes, or thin insulated wires, to stimulate the brain with electricity. Other forms of DBS have already been tested as a treatment for depression in various clinical testing, especially for people who do not respond to antidepressants, psychotherapy or ECT, but these trials have shown limited success. In some trials, patients who received DBS showed more significant improvement compared to those who received placebo treatment, but in other trials no such difference appeared.

“We believe that one of the reasons for this is that traditional DBS provides continuous stimulation, 24 hours a day,” rather than triggering when a patient’s symptoms worsen, said the first author, the Dr. Katherine Scangos, Assistant Professor of Psychiatry at UCSF. press conference. “And the location of the stimulation is not personalized to each individual’s depression.”

Related: 10 things you didn’t know about the brain

Sarah, the clinical trial patient, in her garden;  she wears a floppy hat and surgical mask and seems to be smiling

(Image credit: John Lok; UCSF 2021)

“The other approaches to DBS have all been kind of cookie-cutter,” Holtzheimer told Live Science. The new study sets itself apart from previous work with DBS because researchers matched Sarah’s implant to her brain, taking into account the unique characteristics of her depression. If validated, the study would represent a “huge breakthrough” in the way brain stimulation is used for neuropsychiatric treatment, in general, Holtzheimer said.

To properly tune the NeuroPace RNS system on Sarah’s brain, the study authors first conducted an exploratory study in which they temporarily bonded 10 electrodes into key components of her brain’s emotional circuitry. Parts of the brain known as the orbitofrontal cortex, amygdala, and hippocampus are found in this circuit, along with the subgenual cingulate cortex and ventral capsule / ventral striatum (VC / VS).

With the electrodes plugged in, the team sent electrical impulses into each of these brain structures, one at a time, and tracked Sarah’s mood changes using multiple clinical scales for depression. After performing these tests for 10 days, they identified VC / SV as the point of stimulation that provided the most “consistent” and “lasting” improvement in her symptoms, the authors wrote in their report.

Specifically, the VC / VS stimulation coincided with a huge increase in Sarah’s energy and arousal levels; during the stimulation, Sarah said that she would suddenly experience an “intensely happy feeling” and sometimes burst into involuntary laughter. And even after the stimulation ended, the benefits seemed to persist; During the 10-day study, Sarah’s symptoms improved steadily, and after this initial study ended, she went into remission for six weeks.

How does it work and will it work for others?

Why would skipping the VC / VS relieve Sarah’s depression? The answer may lie in how the VC / VS calibrates the amygdala, an almond-shaped structure that connects to the VC / VS through a dense bundle of wires, the team found.

Based on the electrical activity picked up by the temporary electrodes, when Sarah experienced her most severe episodes of depressive symptoms, her tonsil activity skyrocketed. This increased activity was marked by a specific pattern of so-called gamma waves – the fastest type of brain wave – emanating from the almond-shaped structure of the brain. But when the VC / VS received an electric shock, this uncontrolled tonsil activity subsided and, in turn, Sarah’s symptoms abated.

Seeing this diagram, the team then knew how to program the NeuroPace RNS system to bypass Sarah’s depression, and she underwent surgery for the implant in June 2020.

Related: 8 tips for parents of teens with depression

During the procedure, the team drilled several 0.06 inch wide (1.5 mm) holes in the skull to insert electrodes into the amygdala and VC / VS. The amygdala’s electrodes track its electrical activity, and when the device detects telltale gamma waves in the amygdala, it delivers a 6 second electrical pulse to the VC / VS, to reduce this activity. So the system works by registering one brain structure and sending electricity to another.

In total, Sarah can receive up to 300 stimulation pulses per day, for a total of 30 minutes.

In addition to inserting electrodes, the team removed a small portion of the skull bone and plugged it in with a matchbox-sized battery, which powers the device, said the lead author Dr. Edward Chang, professor of neurological surgery at UCSF. conference. Integrating the battery into the skull – rather than outside the bone – prevents the patient from feeling the device under their scalp, he noted. And at current usage levels, Sarah’s device battery is expected to last around 10 years, Scangos said.

At this point, the team cannot say how long Sarah might need the implant. As the trial continues, the team will monitor if and how their brain circuits change over time, while also monitoring their psychiatric symptoms. In the meantime, two more patients have been enrolled in the trial and the team plans to enroll nine more. Some of the patients might look like Sarah, in that their tonsil activity is a red flag for their depression; but then again, each patient can turn out to be very different from the next, said Scangos.

While the new study is an exciting start, the research is still in its early stages, Holtzheimer noted. With the exception of data from a large, placebo-controlled study, “this is definitely not ready for prime time.” But if large trials show it works, the therapy could be of benefit to a large number of patients, he said.

It is estimated that 30% of people with depression do not respond to medication or psychotherapy, and although ECT works for some people, it comes with potential side effects like memory loss, according to UCSF. And ECT doesn’t work for one in 10 people who try it. For these patients, the NeuroPace RNS System may represent a viable option where it did not previously exist.

Having said that, “I think in order for this to help more people, it’s going to require some simplification,” Chang said of the new system. With that in mind, the team has already started exploring methods to make the treatment completely non-invasive, rather than requiring surgery. “I think we’re a long way from something like that, but you can imagine it,” Holtzheimer said.

Originally posted on Live Science.


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