Inside a surgical suite at UC San Francisco, a patient has been wired for happiness.
After years of struggle with severe and untreatable depression, the woman wears tiny implanted electrodes that stimulate her brain’s errant circuitry, a first-ever experiment that is successfully fending off dark moods that once sent her sinking into despair.
“When negative thoughts come up, they just kind of ‘poof,’ and the cycle stops,” said Sarah, who is 30-something and lives in Wine Country. She asked that her last name not be used.
“I’m a better version of myself,” she said, her voice light and bouncy. “I’m rebuilding my life, one thing at a time.”
The procedure, called deep brain stimulation, is based on the growing recognition that the brain operates via complex electrical circuits – the networks of cells that are activated every time we think, feel or move. UCSF scientists report their results in the Oct. 4 issue of the journal Nature Medicine.
When these circuits malfunction, they can cause depression and other forms of mental illness.
Medication and psychotherapy remain the frontline treatments for depression, a leading cause of disability that affects 350 million people, according to the World Health Organization. But they don’t help everyone. And they take time.
Although the biology of electrical stimulation isn’t completely understood, it appears to improve how the circuits work. Although it takes time to “tune” the device so that it delivers the right amount of stimulation, it is proven to be useful in easing symptoms of Parkinson’s disease, epilepsy and other movement disorders.
For Sarah, the treatment was tailored to her illness. “We identified a circuit in her brain that was specific to her depression, and we delivered therapeutic stimulation to one area of that circuit,” said UCSF assistant professor of psychiatry Dr. Katherine Scangos, who led the research, published in the most recent issue of the journal Nature Medicine.
“And we can monitor and treat it, in an iterative loop, only when she needs it,” Scangos said.
The brain circuits involved in depression are located in the amygdala, an almond-shaped mass of gray matter inside each cerebral hemisphere, which regulates the experience of emotions. It’s challenging to pinpoint the exact location of problem, because not everyone’s depression is the same. In different people, different parts of brain circuitry may be involved.
“They normally operate like a symphony, through coordinated activity,” said Dr. Edward Chang, the patient’s neurosurgeon. “But they can become untuned, or out of sync.”
When electricity is delivered as a repetitive pulse in a series of daily treatments, over several weeks, it’s proven to lift mood. But this approach is expensive and not feasible for ongoing care.
The UCSF team wanted a strategy that was more efficient and practical – and better targeted and fine-tuned for each patient.
The goal was to send pulses “only when a patient needed the stimulation,” said Scangos.
After identifying the spot in Sarah’s brain, they did surgery, carving out an area of her skull to make room for a small battery-powered device, about the size of a matchbook cover. The device is FDA-approved for use in epilepsy.
Two electronic wires – as thin as angel hair pasta – were connected to the device and strategically placed in the wrinkles of her brain.
With the first electrical pulse, “I just involuntarily giggled,” Sarah recalled. “Out of nowhere, I smiled.”
Later, at the hospital cafeteria, she took a sip of soup. “I swear to God, it was the best thing I’d eaten in five years — the crunchy green sprouts, the slurp of the noodles.”
That was two years ago. Now a permanent part of her life, the device monitors the daily electrical activity of her brain, sensing when she’s emotionally upset, such as after seeing a homeless encampment or a grisly crime scene on television.
When it detects trouble, it sends a tiny shock. When all is well, it’s quiet. This feedback system is called “closed loop therapy.”
Tracking the patient’s response, the team reports that her “depression severity score,” a metric for measuring illness, dropped from a high of 33 to much healthier score of 14 after two weeks of stimulation. It dropped below 10 several months later.
She hopes to wear the device for as long as possible, its small scar on her scalp concealed by hair. “It’s a permanent part of me,” she said.
The technology needs further improvement, Chang said. For instance, the device must be specifically designed for treatment of depression, not borrowed from epilepsy care. The electronic signals of a depressive episode are much more subtle and complex than those seen during an epileptic seizure.
The team also seeks to test its efficacy in a larger trial of a dozen patients. Eventually, if authorized by regulatory authorities and insurers, more widespread use is anticipated, said Scangos.
“Now we need to show: Is it going to work in a broader set of people and with different types of depression?” she said.
For Sarah, who has endured repeated hospitalizations and whose family has a generations-long history of depression, there’s hope where there was once nothingness.
“I couldn’t make a decision about anything. I didn’t care about anything. It all just felt overwhelming. I felt so awful about myself — it’s not who I wanted to be,” she said. After losing her house and job, she felt like a burden on her family. “I had exhausted every option. I just couldn’t see myself continuing.”
The treatment is not a magic wand, she said. It doesn’t create constant euphoria; her life still has plenty of the usual challenges. But now she has the energy and focus to tackle them, using techniques she learned in therapy.
“When there are emotional triggers, I approach them rationally,” she said. “During those moments of darkness that we all go through, instead of it just sweeping over me, I think, ‘Hey, be kind to yourself.’ ”
“My best self is able to stay in control. I just get on with my day,” doing errands, cooking, helping her family and studying in online classes, she said. “It’s something I can manage.”