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Brain Stimulation Is the Future of Medicine

Personalized shockwaves can be an alternative to medication

Illustration: Keith Rankin

LLaura Soloway tried to end her own life for the first time when she was 12, using her childhood chemistry set. She remembers lining up all the bottles that read “fatal if swallowed,” but she couldn’t open their childproof caps. She tried again at age 18 and was rushed to the emergency room by her parents.

After years in and out of hospitals and on and off various medications, Soloway and her doctors finally settled on a cocktail of drugs that kept her stable. But, she says, “it worked just enough to keep me functional. I never felt like I could ever really be happy about anything or even be extremely sad about anything. I was just a zombie sleepwalking.”

It wasn’t until she was 40 that Soloway found a better solution for her depression: transcranial magnetic stimulation (TMS). The procedure involves zapping the brain through the skull using a high-powered magnetic burst. After three weeks of the treatment, Soloway says she no longer considered suicide.

“I constantly had this thought in the back of my head that if I swerve the car this way, I’ll die, and that’ll be fine,” she says. “It wasn’t until after TMS when that thought was gone.”

For many people like Soloway, medication does not adequately control their disease. It’s estimated that between 30 and 40 percent of people with depression don’t respond to available treatments. In return, doctors are turning to new technology that builds on an old idea — that altering patterns of brain activity using electricity or magnetic stimulation can treat psychiatric and neurological disorders.

Like most complex machines, your brain runs on electricity. Neurons communicate with each other through electrical and chemical signals; adding high or low amounts of electricity to the brain can make these neurons more or less likely to fire. By changing whether or not a neuron releases its electrochemical pulse, scientists can alter the brain’s overall connectivity, strengthening pathways between some neurons while suppressing connections in other areas. Shocking the brain in this way can disrupt harmful patterns of activity associated with depression, block pain signals from the spinal cord, or stop dysfunctional electrical firing during a seizure.

“I constantly had this thought in the back of my head that if I swerve the car this way, I’ll die, and that’ll be fine.”

Electrically stimulating the body is not new. Pacemakers that monitor and zap heart muscles through electrodes have been used for decades and saved millions of lives. In the brain, psychiatrists in the 1960s used electroconvulsive therapy to treat severe depression. The practice fell out of favor due to its potentially severe side effects, but the therapy is still considered effective at improving treatment-resistant depression, and it is used — with better safety measures — in some extreme cases today.

Newer brain-stimulating therapies are much more precise in both the location and intensity of the electrical current. And as research continues, neuromodulation, as the field is called, has become smarter, less intrusive, and more personalized.

TTMS is emerging as a leading alternative to medication for severe depression. The treatment involves stimulating the brain with a giant magnet held to the scalp. The magnetic pulses have a similar effect on brain cells as an electrical current, making the neurons more or less likely to fire depending on the frequency applied.

In depression, some parts of the brain are hyperactive, meaning the neurons fire too easily, while other parts of the brain are hypoactive and don’t fire enough. It’s believed that this mismatch may underlie people’s depressive symptoms. TMS works to correct the imbalance by ramping up hypoactive areas and toning down hyperactive ones.

For example, a part of the brain called the subgenual anterior cingulate is believed to be hyperactive in most patients with depression. “Successful treatment of depression across classes — whether you’re using medications or therapy or ECT or TMS — ends up leading to a normalization of that part of the brain,” says Adam Stern, an assistant professor of psychiatry at Harvard Medical School and director of psychiatric applications at the Berenson-Allen Center for Noninvasive Brain Stimulation.

The magnetic pulses from TMS can’t actually reach the subgenual anterior cingulate, which is located deep within the brain. The signal penetrates only a few centimeters through the scalp. Doctors instead target a brain region called the dorsolateral prefrontal cortex, which is located just under the hairline and tends to be hypoactive in depression. This area is connected to the subgenual anterior cingulate; turning up one region turns down the other. Doctors think that, together, these changes create an antidepressant response.

Approximately 60 percent of people who receive TMS respond to the treatment, meaning their symptoms are cut in half. Among those people, 30 to 40 percent experience a full remission. For people who don’t respond, Stern thinks their brains may be less receptive to the stimulation or their doctors may not have found the exact right spot to target.

Although there’s no implant involved, TMS requires a major time commitment. It’s typically administered in a specialized clinic five days a week for four to six weeks, and each session takes 30 to 40 minutes. Most people experience relief from their symptoms within three weeks, and it can last for about a year. After that, they may need to come back for a booster session.

“The treatment is not for the faint of heart,” Soloway says. “It’s time intensive, it’s not the most comfortable thing in the world, but it worked miracles for me.”

AAlthough TMS requires a long treatment timeline, it’s considered noninvasive because it’s applied over the scalp. Other types of neuromodulation require implants in the brain or spinal cord that the patient sometimes controls with a remote.

Neuromodulation industry consultant Ben Pless says that noninvasive devices are very low risk, so more patients are willing to try them. However, he says, implantable devices often “provide a much better therapy to a patient because once they’re out of sight, they’re out of mind.”

For some people with epilepsy, implantable brain-stimulation devices offer this type of hands-off relief. Medical technology company NeuroPace’s responsive neurostimulation device, or RNS system, is called a closed-loop system, meaning that it both detects and corrects the dysfunctional brain activity that causes seizures. The device is implanted in the skull and has electrodes that travel into the brain to the precise location where a person’s seizures originate. The electrodes continuously record neuron activity in that area; when they detect a specific pattern, they deliver a mild electric jolt, stopping the seizure as soon as it starts. People who have the device experience, on average, a 73 percent reduction in seizures, and nearly 30 percent of people are seizure-free for at least six months.

“I’m no longer dealing with epilepsy alone.”

Approximately 3 million people in the United States have epilepsy, and a third don’t respond to medication. “These people are at risk for seizure-related injury, but also they’re at risk for death,” says Martha Morrell, chief medical officer at NeuroPace. People with uncontrolled epilepsy have a sevenfold increased risk of death from all causes, including a phenomenon called “sudden unexpected death in epilepsy,” which kills between six and 10 patients out of 1,000 every year. With the RNS system, that number drops to less than three out of 1,000.

Kimberly Bari is one of those people. She developed epilepsy in her early twenties when she was teaching English in China. The seizures caused her muscles to tighten up, twitch, or go numb; on some occasions, she would even hallucinate or lose consciousness. After six years, more than a dozen anti-epileptic medications, and even surgery to remove part of her brain, Bari was still having multiple seizures a day and could no longer work or lead a normal life.

In 2017, Bari’s doctor in San Francisco recommended the NeuroPace implant, in addition to a second surgery. Now she has just a handful of seizures a month — down from more than 30 a day at her peak — and she says they’re much less intense. But she says the biggest advantage has come from feeling more in control of her disease and in sync with her doctors. The recordings offer her doctors an unprecedented window into her brain. With that knowledge, they’re able to personalize her treatment through changes to her medications and the electrical current of the implant.

“Not only am I more comfortable, I don’t have that terrified feeling I had before,” Bari says. “I’m no longer dealing with epilepsy alone.”

SSome neuromodulation experts predict that implantable devices will have a growing role in public health. Spinal cord stimulation for chronic pain, for example, is gaining in popularity. An estimated 25 million Americans suffer from chronic pain, and many take prescription opioids to manage their condition. However, the addictive nature of the drugs has left people looking for other options, either because they’re worried about dependence or because their doctors want to wean them off.

That was the position Doug Rodd found himself in. An Army veteran, Rodd had a number of knee injuries from his military service that resulted in a knee replacement in his early fifties. A couple years later, he was in a car accident that reinjured his leg and left him with complex regional pain syndrome. Rodd managed for a decade with a high dose of daily morphine, but in recent years he wanted to quit the medication, in large part because of the backlash against opioids.

“I wanted to get off of medicine probably because I was afraid at some point I was going to be told I couldn’t have anymore, and that would really end my career [and] end my life as I know it,” Rodd says. “There wasn’t a psychological dependence to it. It was purely that I needed this to just knock the pain down if I’m going to go to work every day.”

In 2017, his doctor suggested a new type of treatment: dorsal root ganglion stimulation. The technology, which is manufactured by Abbott, delivers a small electrical current to a bundle of nerves — the dorsal root ganglion — located in the periphery of the spinal cord. For people like Rodd, this nerve bundle becomes dysfunctional and starts generating its own pain signals that are interpreted in the brain as coming from the site of the injury. Interrupting those signals with a very low level of electrical current can often stop the pain.

“We commonly think of [chronic pain] as being a neurological disorder, one in which the nervous system is not working appropriately and is out of balance,” says Lawrence Poree, a professor of anesthesia at UC San Francisco. “We’re trying to regain that balance.”

Dorsal root ganglion stimulation is just one type of spinal cord stimulation, a procedure that’s been around since the 1960s to treat chronic pain. One or two electrodes are inserted into the epidural space around the spine to stimulate and override the nerves responsible for the pain signal. A battery pack that provides the energy and can control the stimulation is implanted into the lower back or upper buttock, depending on what’s most convenient for the patient. Although it requires a small surgical procedure, patients are awake the entire time and typically leave the hospital the same day.

For Rodd, the implant worked wonders. He now manages his pain with just the device and the occasional ibuprofen. And he’s back to hiking in the woods with his wife and sons.

Poree estimates that 20 percent of chronic pain patients are treated with some sort of neuromodulation, although many more would likely benefit from the procedure. Amid concerns about the opioid crisis, doctors and insurance companies are starting to get onboard as well.

“Spinal cord stimulation is very safe and can be extremely effective in treating chronic pain, but it’s much easier for a patient to get a prescription for opioids than to get a spinal cord stimulator,” Pless says.

TThe biggest question doctors face is when to try these devices. For epilepsy and depression, people must be considered treatment refractory, meaning they’ve failed to respond to several different medications. However, the more drugs a person has cycled through, the less chance they have of responding to either medication or neuromodulation.

One reason for this dilemma is that insurance providers will not cover the treatments earlier. These technologies aren’t cheap, and even though they can provide long-term relief and prevent people from incurring more expensive costs, like hospitalization, in the future, it’s cheaper in the short term to keep cycling people through different drugs.

Another challenge is doctor knowledge and acceptance of the technology. Even though spinal cord stimulation has been around since the 1960s, doctors don’t learn about the devices in medical school unless they go through a specific pain fellowship, says UC San Francisco’s Poree.

Patients may also balk at the invasiveness of the treatments. Even minor surgeries for implantable devices come with risks of infection, not to mention pain and inconvenience during the recovery. Those working in the field, however, argue that neuromodulation is less invasive than pharmaceutical drugs, which affect the entire body and are associated with more side effects.

“The neuromodulation that exists five or 10 or 20 years from now will hardly resemble what we’re doing today.”

“I think neuromodulation really should be considered much earlier. There’s the thought, ‘Well it’s very invasive,’” says Morrell of NeuroPace. But “medications are not trivial.”

These devices are not cures. Most people who get them remain on their medications, albeit often fewer of them and at lower doses. And just like with pharmaceutical drugs, in pain management there is concern about developing tolerance to the stimulation as the nervous system adapts. Researchers are working to address this issue by making the timing and intensity of the stimulation more adaptable.

Others worry that these types of devices are not subject to rigorous enough regulation, putting people at risk of unanticipated side effects or device failures. The Implant Files, an exposé by the International Consortium of Investigative Journalists, recently published a scathing series of reports on medical device malfunctions, recalls, and shoddy communication. None of the devices included in this article were named in the consortium’s reporting, but concerns remain about the industry at large.

Despite these challenges, doctors and researchers say they’re optimistic that this is just the beginning for brain stimulation therapies.

“The neuromodulation that exists five or 10 or 20 years from now will hardly resemble what we’re doing today, in my opinion,” says Stern, the psychiatrist. “The ability to stimulate parts of the brain is an invaluable tool.”

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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