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19 January, 2022
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A ‘Pacemaker for the Brain’: No Treatment Helped Her Depression — Until This

It’s the first study of individualized brain stimulation to treat severe depression. Sarah’s case raises the possibility the method may help people who don’t respond to other therapies.

Source: The New York Times

By Pam Belluck

Driving home from work in Northern California five years ago, Sarah was so overwhelmed with depression that all she could think about was ending her life.

Within a few weeks, the suicidal thoughts just disappeared

She made it home, but soon after, moved in with her parents because doctors considered it unsafe for her to live alone. No longer able to function at work, she quit her health technology job.

She tried nearly every treatment: roughly 20 different medications, months in a hospital day program, electroconvulsive therapy, transcranial magnetic stimulation. But as with nearly a third of the more than 250 million people with depression worldwide, her symptoms persisted.

Then Sarah became the first participant in an unusual study of an experimental therapy. Now, her depression is so manageable that she’s taking data analysis classes, has moved to her own place and helps care for her mother, who suffered a fall.  “Within a few weeks, the suicidal thoughts just disappeared,” said Sarah.

Researchers at the University of California, San Francisco surgically implanted a battery-operated, matchbook-sized device in Sarah’s brain — a “pacemaker for the brain” some call it — calibrated to detect the neural activity pattern that occurs when she is becoming depressed. It then delivers pulses of electrical stimulation to stave off depression.

Twelve days after Sarah’s device was fully operational in August 2020, her score on a standard depression scale dropped to 14 from 33, and several months later, it fell below 10, essentially signaling remission, the researchers reported.

Sarah’s is the first documented case of personalizing a technique called deep brain stimulation to successfully treat depression. Much more research is needed before it’s clear how effective the approach could be and for how many patients. But several teams of scientists are now working on ways to essentially match the electrical stimulation to what happens in an individual patient’s brain.

Deep brain stimulation is used to treat Parkinson’s disease and several other disorders, but isn’t approved by federal regulators for depression because results have been inconsistent. While some previous studies suggested benefits, two trials sponsored by U.S. device companies were stopped in the last decade because stimulation seemed no better than the placebo effect of a “sham” implant that provided no stimulation.

But those studies didn’t target individualized locations or patterns of electrical activity in people’s brains. It was “one size fits all,” said Dr. Darin Dougherty, director of neurotherapeutics at Massachusetts General Hospital, who worked on one of the halted trials. He called the personalized approach with Sarah, which he wasn’t involved in, “very exciting.”

To identify the specific brain activity pattern linked to Sarah’s depression, researchers conducted an intensive 10-day exploration of Sarah’s brain, placing multiple electrodes in it and asking about her feelings when they applied stimulation to different locations in varying doses. 

Eventually, the team identified a specific pattern of electrical activity that coincided with Sarah becoming depressed.

The exploratory phase guided the researchers to place the stimulation device in Sarah’s right brain hemisphere linked to electrodes in two regions. One was the ventral striatum, involved in emotion, motivation and reward, where stimulation “consistently eliminated her feelings of depression,” and the other the amygdala, where changes could “predict when her symptoms were most severe,” Dr. Scangos said.

While deep brain stimulation is typically delivered continuously, Sarah’s device is set to supply only a six-second burst when it recognizes her depression-linked brain activity pattern.

The goal, said Dr. Dougherty, is that stimulation will disrupt or shift the neural activity to produce a healthier pattern that will ease depressive symptoms.

Sarah has continued taking psychiatric medications, and the stimulation hasn’t eliminated depression-causing activity in her brain. But she can manage her illness much better, she said, instead of being unable to make even the smallest decisions, like what to eat.

About 30 percent of people with depression don’t respond to standard treatments or find the side effects intolerable. Deep brain stimulation wouldn’t be appropriate for all because it costs tens of thousands of dollars and brain surgery to implant the device carries risks like infection. But if the new attempts work, it might help a significant number, experts said. Dr. Chang said the research may also lead to noninvasive approaches that would help more people.

[The New York Times]

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