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    How a ‘Brain Pacemaker’ Can Help Treat Depression

    After 16 years of battling “demons,” one patient says he has been given a second chance at life by a brain-computer interface developed in Shanghai.

    “Can you tell I’m a robot?” Wu Xiaotian asks his taxi driver as he’s heading home to his apartment one day. “It’s true. I have a chip in my head that lets me control my emotions.”

    Wu’s experience will sound to some like science fiction. On the right side of his chest, just under the skin, is a device known as a “brain pacemaker,” which sends tiny electrical pulses to electrodes implanted in his head. With just the press of a button, his mood can switch in a moment from despair to delight.

    After struggling with severe and debilitating depression for more than a decade, Wu underwent the operation to fit the device last year in a last-ditch effort to save his life.

    Sun Bomin, head of functional neurosurgery at Shanghai’s Ruijin Hospital, carried out Wu’s procedure as part of his clinical research into a brain-computer interface for treatment-resistant depression. The smart technology works by looking for patterns in brain activity linked to depression and then automatically interrupts them by stimulating target points in the nucleus accumbens, an area deep inside the brain known for its role in feelings of pleasure and reward.

    Using the technology, researchers believe they can reliably create “mood settings” that patients can apply depending on their state of mind, allowing them to alleviate their symptoms almost immediately.

    Since receiving the implant surgery, Wu has mostly relied on two settings for his device, which he controls with an app on his phone. He activates “work mode” in the morning, which “powers him up,” giving him a renewed interest in the things around him, and he uses “rest mode” before going to bed, when he begins to feel low and loses his desire to communicate.

    Emotional control

    In August, Wu was scheduled to return to the neurosurgery center at Ruijin Hospital for follow-up tests. He put a few bottles of an electrolyte drink in his backpack, as he tends to feel exhausted after examinations, and carefully packed his external wireless charger for the brain pacemaker. The device must not run out of power — Sun says that one patient this happened to said it felt like falling from a cliff.

    Wu, now in his mid-30s, likes to keep the charger strapped to his chest, as he says its bright-green light makes him feel like the Marvel hero Iron Man.

    At the hospital, Wu was met by Wang Yuhan, a physician in Sun’s research team, who started by asking him if he was taking any medicine. She then had him complete a clinical research evaluation to learn about his psychological and emotional state over the previous month.

    During their conversation, she remarked how she thought Wu seemed over-excited and more talkative than usual. “That’s only because you didn’t know me before the depression,” he replied.

    With the survey, Wu was like a schoolboy in an exam — he placed one arm across the paper and buried his head as he filled out the answers. He was able to answer most questions quickly, but when he came to one on whether he’d thought about death or suicide he hesitated. After ruling out two possible options that mentioned suicidal ideation, he chose “I feel that life is empty or doubt whether living is worthwhile.”

    Before receiving the surgery, Wu underwent extensive physical and psychological testing, the results of which showed that he had severe depression. The doctors warned him about the potential risks of the procedure, including paralysis, being left in a vegetative state, and even death. Wu listened calmly but didn’t show a trace of fear, according to the doctors.

    Wu is among 29 patients who have received the surgery as part of the clinical trial, in which Sun leads a team of more than 10 researchers responsible for data analysis, imaging, and clinical evaluation. It was initiated by the hospital’s Brain-Computer Interface and Neuromodulation Center.

    Sun explains that the selection process for the first set of participants was extremely strict. The initial step was to determine that they did in fact have depression through the use of a survey and face-to-face evaluations by doctors. Candidates were required to also have previously received some level of treatment, and both their age and any related diseases were taken into account.

    Out of more than 100 potential participants, less than a third met the criteria. Shen Xia, a master’s student in applied psychology at Shanghai Jiao Tong University who is part of the research team, says each had severe depression, were unresponsive to medication, had been ill for longer than two years, and either had suicidal thoughts or had previously attempted suicide.

    “This technology is only deployed after the maximum dosage of recognized first-line drugs and psychotherapy have been attempted and treatment has been unsuccessful,” explains Shen.

    Wu tried to kill himself by inhaling carbon monoxide from burning charcoal. He also has two faint scars on his wrist from another attempt.

    Right up until the operation, his parents couldn’t understand why he wanted to undergo brain surgery. His mother cried and begged him not to go through with it, promising to support him for the rest of his life. In response, he told her that he lived every day trapped inside a prison built by “demons” — existing in the same way was just stretching out his sentence. In his mind, surgery was his only hope.

    Feeling things out

    Scientists overseas have been testing brain-computer interface technologies to treat depression for a few years. Known as deep-brain stimulation, the technique regulates neural activity in order to intervene in behavior, mood, and cognition. “Neurotechnology has been in development for some time, and it’s now possible to identify the parts of the brain that need to be targeted for a certain disorder, and to precisely position the stimulation device in the target area with relatively little medical risk,” Shen says.

    However, while many researchers in other countries apply a single-target interface, the team at Ruijin Hospital uses technology that can stimulate 16 specific points in the brain.

    The operation to implant the chest pulse generator, or brain pacemaker, and electrodes is minimally invasive, according to Sun. Wu’s surgery lasted from 9 a.m. to about 3 p.m. For several hours after waking from the anesthetic he experienced nausea and vomiting but otherwise suffered no side effects.

    The day the device was first turned on, Wu and several researchers were in one of the hospital’s conference rooms. In an instant, Wu says, he felt as if the vitality he had lost over the past 16 years had suddenly been reinjected into his body; his sadness vanished and his eyes welled up from happiness. The doctors ran a series of tests to see which combination of the 16 targets worked best for him. His nerves were relatively sensitive, and Wu could feel an obvious difference each time the targets changed — some made him excited and tearful, others felt like he had been stabbed in the back or made him want to curse and pound the table.

    For a few days, Wu felt happier than ever. But then the “demons” returned, and questions began swimming around in his head: Had the operation been for nothing? Were the doctors lying to me? Am I just a guinea pig? Although concerned, he realized that there was nothing to do but wait.

    Receiving the implants is just the first step — constant stimulation of different points in various combinations is required to refine the interface’s parameters and achieve the desired therapeutic effect. Through trial and error, the doctors ran electrical currents back and forth across the 16 targets in Wu’s brain to find out how each made him feel. He says most of the targets made him uncomfortable.

    After three months of debugging, the team had refined Wu’s device to four modes, although in April he ultimately discovered switching between “work” and “rest” on mornings and evenings suited him best. He considers that moment the start of his second life.

    Sun says that patients with depression who undergo a long period of electrical stimulation tend to develop mania, demonstrated by overactive or high-energy behaviors. However, Wu’s hypomania fell within the acceptable limits, as he describes it as “similar to the happy feeling of hanging out and having drinks with friends.”

    Generally, Sun doesn’t let patients adjust their own mood settings, but Wu is an exception. “He’s sensitive and able to control himself — he’s able to switch depending on his condition,” Sun says.

    Sun believes his research represents a breakthrough in terms of ethics, although his technology has proved controversial, with some arguing that if a brain-computer interface is in control of a person’s emotions, that could impact their privacy. “The ethics committee at Ruijin Hospital looked very closely in advance at the clinical study and was very cautious. It took a year of back-and-forth, submitting additional materials, and demonstrations to get it approved,” he says.

    From the perspective of the treatment’s efficacy, he explains that the results from the multi-target stimulation method are better than the single-target method used primarily overseas, and that many patients can reach the clinical standard of being cured. However, as for the associated risks, Shen concedes that these remain largely unknown, as the technology is still in the development stage. Too few people have undergone the surgery, so there’s simply insufficient data.

    Beating the “demons”

    Wu was 15 years old when his “demons” first appeared. After moving with his parents from Nantong to the relatively prosperous Suzhou, both in the eastern Jiangsu province, while at elementary school, he first began to develop an inferiority complex and feared that bullies would target him for being from out of town, especially as he had witnessed two classmates making fun of someone from the suburbs.

    He hid his origins for several years, until one day he was “found out” when some classmates heard him talking with his parents at a restaurant in the Nantong dialect. The next day, one of them remarked that Wu wasn’t from Suzhou. Although their tone wasn’t harsh, Wu’s heart skipped a beat — he had been exposed.

    Wu felt at the time that something didn’t feel right inside, but he couldn’t express what it was. One night, he lost control, kicking his father in the stomach during an argument. After experiencing pain for several days, his father went to the hospital and was diagnosed with liver cancer. Wu cried hysterically, blaming himself and wishing he could trade his own life for his father’s health. No one had explained to him at the time that none of it was his fault, leaving him with a lingering sense of shame.

    Later, Wu studied vehicle maintenance at a vocational school in Suzhou. For the first two years he dreamed of studying in Japan and would spend five hours every evening learning Japanese. He breezed through the level three Japanese proficiency exam, but in subsequent tests he felt like his brain was “rusted shut.”

    His behavior began to get more erratic, too. When he felt hot, he found himself saying he was cold, and when he wanted to open the door, he’d say to close it. Some of his classmates called him an idiot, and he eventually began to believe them. He kept his head down and his mouth shut. Every day, when he got back home, he would hide in his room and cry.

    After finishing school, Wu shut himself away in the warehouse of his parents’ small business, which sold embroidery products. Thinking he was simply lazy, his mother encouraged him to look for work, so he wrote a résumé of only a few lines and went to a job fair. When a recruiter asked him questions, he became tongue-tied and was unable to respond.

    Whenever he heard the phone ring, he would shake uncontrollably and a sense of dread would surge through his body. He didn’t know what was wrong with him, but sometimes he’d feel a little better and would reach out to friends. After meeting with them, he would relax, but before long his mind would become muddled and he wouldn’t want to talk anymore. He’d then stop answering their calls. The “demons” would again beat him back down and he’d lock himself away.

    Like many in his generation, Wu is an only child. His parents, who had lived through hard times, were unable to understand why a child who didn’t have to worry about food or clothing could be depressed. As far as they could see, there was no reason for him to feel bad, and he never spoke about any kind of trauma.

    Wu didn’t understand either. When he first heard the word “depression,” he searched online but couldn’t find the information he needed, and since his symptoms were not obvious, he didn’t associate himself with the illness. However, as his symptoms got worse he was unable to think straight and felt lethargic.

    To try and alleviate his constant feelings of sadness, Wu went to Hangzhou, the capital of Zhejiang province, in 2009 to study under a master of qigong, a traditional Chinese practice involving rhythmic breathing and moving meditation. He also traveled to Shenzhen and Shanghai, tried acupuncture, hypnosis, and the Buddhist practice of releasing live animals (he unleashed 10,000 earthworms), and even underwent electroconvulsive therapy. Yet the “demons” continued to have him in their grasp.

    When he went for a general health checkup at a hospital in 2011, his results came back normal. The doctor told him he might be neurotic, which Wu took to mean crazy. He had seen mental patients in movies but couldn’t understand how he could possibly be in the same category.

    After experiencing symptoms of depression for eight years, Wu decided to visit a specialist. When the doctor diagnosed him with depression, he felt numb. “I knew then that I was no longer the person I once was,” he says.

    He borrowed money to see a therapist, making 12 visits at a cost of 800 yuan ($109) a time. The drugs they prescribed had some effect at first, but they soon stopped working. He frequently tried different medicines and would get a new prescription before he’d finished the previous course.

    Throughout 2014 and 2015, he joined various support groups for people with depression. He believed most people were there to just blow off steam like him, but then a woman in one group killed herself.

    Last year, Wu saw that Sun’s team was recruiting participants for his clinical trial. Wu could have directly contacted the group by phone, but he was struggling to form full sentences at the time, so instead got in touch using the Good Doctor app, an online medical consultation platform.

    Sun has treated many people with depression, and has experienced the illness himself. He understands that even if they get better, patients don’t want others to know that they have had the condition. However, Wu didn’t care. And when the first clinical trial ended after a year, Sun considered him to be such a representative case that he decided to continue with their explorations.

    Wu was more than happy to keep participating, believing that the technology would “give him freedom and dignity.” He now visits the hospital once a month to complete a survey designed to assess his mood and to meet with doctors. He believes that the operation has allowed him to recover 80% of himself, with the remaining 20% still in the hands of his “demons.”

    A few months ago, Wu moved to a new neighborhood where he lives on his own. Looking out from the apartment’s balcony, he can enjoy a clear blue sky and lush flowers and trees. He feels he’s now able to manage his emotions and experience the vitality of life. Every night he goes to bed with one thought: What will tomorrow bring?

    Reported by Yuan Lu.

    (Due to privacy concerns, Wu Xiaotian and Shen Xia are pseudonyms.)

    A version of this article originally appeared in The Paper. It has been translated and edited for brevity and clarity, and is republished here with permission.

    Translator: David Ball; editors: Xue Ni and Craig McIntosh.

    (Header image: VCG)