New advances are letting scientists use electrodes instead of drugs to treat dozens of diseases affecting millions of people.
By Emma Yasinski June 3, 2022 • 15 min readSharon Laudisi, who runs a green energy consulting company, was driving to see a client in Brooklyn, New York, in 2019, when she was rear-ended. She wound up in the hospital, but was discharged the next day, sent home to tend her bruised arm. Once she was at home, she made her way to the restroom. That’s when she realized she couldn’t button her pants. Her left thumb wouldn’t move, and she’d lost the ability to feel anything with it.
“I went to 15 doctors, all telling me, ‘Forget your thumb. It's not gonna work. It's not gonna bend. Just adapt,’” Laudisi says. But life without the use of her thumb meant she struggled to get dressed, hold her keys, open a bottle, or use a flat iron or blow dryer to style her hair. Before long, she resorted to wearing wigs.
More than a year after her accident, an orthopedic specialist told her about a clinical trial at the Feinstein Institutes of Medical Research in Manhasset, New York, that might help her. In November 2020, Laudisi met with researchers who explained that rather than using drugs or physical therapy, they might be able to heal her thumb with electricity. “They didn’t promise anything,” she says, but at least they gave her hope.
Recent advances in engineering and biology suggest that electricity could treat such conditions as paralysis, depression, and autoimmune conditions. Physicians have demonstrated for decades that it is possible to treat some patients with epilepsy or Parkinson’s disease using deep brain stimulation (DBS)—in which an electrode is surgically implanted deep in the brain to electrically stimulate specific neurons. What’s different now is that there is a growing repertoire of diseases that scientists believe may also respond to electrical stimulation, delivered from both the inside and outside of the body.
The idea of using electricity to modulate brain activity in diseases like severe depression gained new momentum in the 2010s. “It got to a tipping point about ten years ago,” says Kevin Tracey, a neurosurgeon and the CEO at the Feinstein Institutes for Medical Research. But after several small studies had shown promising results, two large clinical trials of DBS for severe depression failed to demonstrate efficacy.
Those trials “let all the air out of the room,” says Sameer Sheth, a neurosurgeon at the Baylor College of Medicine. “It was a big bummer.”
The larger of the two trials stopped enrolling patients after six months. No announcement was published at the time, but several bloggers publicized a scoop that St. Jude, the study sponsor, had halted enrollment. Nonetheless, St. Jude Medical and Abbott, which had purchased St. Jude, agreed to continue following the patients, who already had had the electrodes surgically implanted, for any adverse effects or changes in mood.
Though it took up to two years, half of the patients with implants eventually experienced dramatic improvements in their depressive symptoms, but by then it was too late; the trial had already ended.
In 2020, the researchers at the Feinstein Institutes hoped that they might be able to reactivate Laudisi’s thumb, without surgery, by delivering electrical stimulation from the outside of her body. They fashioned a credit card-sized patch with about 100 electrodes and attached it to the surface of Laudisi’s skin at the back of her neck. There it stimulated nerves traveling down her spinal cord and radiating to her thumb. She felt the sensation in her head at first. “It feels like vibrations or little, teeny pins,” she says. Satisfied with the positioning and the effect, the physicians scheduled her for regular appointments.
Once a week for eight weeks she visited the lab for an hour for bioelectric therapy during which the scientists stuck the electrode patch to her neck and sent electrical signals down her spine.
The treatment began working within the first few weeks, allowing Laudisi to wiggle her thumb. Nine months later, she remembers she was at her regular appointment at the nail salon when suddenly she could feel the technician filing her left thumb nail. Her thumb isn’t as strong as it was before the accident, but today she can use it to open bottles of soda. She can feel sensations again.
“I’m not 100 percent, but I can pick things up,” she says while demonstrating over Zoom how she unscrews and tightens the cap on a soda bottle. She considers the electrical treatment “a modern-day miracle.”
How electricity modifies neurons and helps them work again seems to vary for different diseases.
Parkinson’s disease attacks a specific population of neurons that produce the neurotransmitter dopamine in a small part of the brain called the substantia nigra. As these neurons die, the decline in dopamine causes Parkinson’s symptoms such as tremors. Inserting an electrode into this area to deliver periodic bursts of electricity, like a pacemaker, can stimulate the remaining neurons to release more dopamine than they typically would to offset the loss and help ease symptoms.
For epilepsy, the electrodes can help quiet the overactive neurons that initiate seizures.
But when it comes to treating other diseases, the methods aren’t as straightforward. “There’s a number of mechanisms evolving,” says Sheth the Baylor College neurosurgeon. “And we don’t understand them fully.”
Sheth and his colleagues weren’t ready to give up on the idea of deep brain stimulation for depression after hearing about the aborted trials in 2013. Like many scientists, they still believed the treatment had potential. Maybe one of the reasons those trials were not a universal success was because “it was a very one size fits all therapy that was applied to those patients. And, you know, depression is not one size fits all,” he says.
Although patients with Parkinson’s all have damaged neurons in the same area of the brain, epilepsy patients are far more diverse. Before using the treatment to reduce seizures, scientists must use electrodes to map and record each patient’s brain activity over the course of several days to determine where their seizures are originating. Only then will they know where to modulate electrical activity.
Sheth and his team wondered if they could use a similar technique identify dysregulated brain circuits in patients with severe depression and launched a clinical trial to find out.
As the COVID-19 pandemic broke out in the United States in March 2020, Sheth and his team were in the hospital working with their first trial patient, a 37-year-old man whose severe depression had persisted for years and had resisted a variety of treatments. To identify which areas of the man’s brain were triggering depression they implanted 10 electrodes in several regions previously implicated in the disease. Then they monitored and recorded the electrical impulses between neurons for 10 days while they kept him in the hospital.
“Those recordings really individualized our understanding of that single patient’s depression networks—networks regulating mood and affective cognitive processes to really drill down on what’s wrong,” says Sheth. Next, they started delivering periodic pulses of electricity to two specific brain regions thought to be involved in regulating positive and negative feelings: the subcallosal singulate and the ventral striatum.
Within the first few days of treatment the man reported more than a 50 percent reduction in depression symptoms. After 22 weeks, doctors said his depression was in remission. After 37 weeks, the scientists reduced the stimulation by 25 percent per week, all the way to zero, to see if his symptoms changed. He reported a steady increase in anxiety and worsening mood. When the researchers reactivated the electrodes, his symptoms dissipated once again, suggesting that the ongoing stimulation was responsible for his improved mood, and that if it continued, he was likely to remain in remission.
“He's doing great,” says Sheth. “He's living a much fuller life. He's working. His social relationships are just going really well.” Last year he visited Sheth’s doctoral students to help deliver a lecture on depression.
