Are Brain Implants the Future of Treatment for Depression and Anxiety?
When she woke up after a procedure involving drilling small holes in her skull, a woman suffering from chronic depression reported feeling “euphoric”. The holes were made to fit the wires that connected her brain with a matchbox-sized electrical implant; this would deliver up to 300 short-lived electricity bursts per day to specific parts of her brain.
Over a year later, Sarah, 36, says the brain implant has turned her life around. A sense of alertness and energy have replaced suicidal thoughts and feelings of despair, which had persisted despite antidepressants and electroconvulsive therapy. Sarah is the first person to have received a brain implant to treat depression, a breakthrough that happened during an experimental study published recently in Nature Medicine.
“What we did was use deep-brain stimulation (DBS), a technique used in the treatment of epilepsy,” says Andrew Krystal, professor of psychiatry at University of California, San Francisco (UCSF), and one of the study’s researchers. DBS typically involves implanting electrodes into specific areas of the brain to reduce seizures not controlled with medication or to remove the part of the brain that causes the seizures. Instead of choosing and stimulating a single brain site though, the UCSF team took a different approach.
They first used 10 electrodes to map Sarah’s brain activity, a phase that lasted 10 days, during which they developed a neural biomarker, a specific pattern of brain activity that indicated the onset of depression symptoms (in Sarah, this was detected in her amygdala, an almondlike structure located near the base of the brain). But they also saw that delivering a tiny burst of electricity to the patient’s ventral striatum, an area of the brain that sits in the center, above and behind the ears, dramatically improved these symptoms. What they had to do was outfit Sara’s brain with a DBS-device programmed to propagate small waves of electricity to the ventral striatum only when it discerned the pattern.
“We are not trying to take away normal responses to the world. We are just trying to eliminate this one thing, which is depression, which impedes patients’ ability to function and deal with normal stuff.”
“It was a personalized treatment not only in where to stimulate, but when to stimulate,” Krystal says. Sarah’s depression translated to low amounts of energy, loss of pleasure and interest in life, and feelings of sluggishness. Those symptoms went away when scientists stimulated her ventral capsule area. When the same area was manipulated by electricity when Sarah’s symptoms “were not there” though, she was feeling more energetic, but this sudden flush of energy soon gave way to feelings of overstimulation and anxiety. “This is a very tangible illustration of why it's best to simulate only when you need it,” says Krystal.
We have the tendency to lump together depression symptoms, but, in reality, they are quite diverse; some people feel sad and lethargic, others stay up all night; some overeat, others don’t eat at all. “This happens because people have different underlying dysfunctions in different parts of their brain. Our approach is targeting the specific brain circuit that modulates different kinds of symptoms. Simply, where we stimulate depends on the specific set of problems a person has,” Krystal says. Such tailormade brain stimulation for patients with long-term, drug-resistant depression, which would be easy to use at home, could be transformative, the UCSF researcher concludes.
In the U.S., 12.7 percent of the population is on antidepressants. Almost exactly the same percentage of Australians–12.5–take similar drugs every day. With 13 percent of its population being on antidepressants, Iceland is the world’s highest antidepressant consumer. And quite away from Scandinavia, the Southern European country of Portugal is the world’s third strongest market for corresponding medication.
By 2020, nearly 15.5 million people had been consuming antidepressants for a time period exceeding five years. Between 40 and 60 percent of them saw improvements. “For those people, it was absolutely what they needed, whether that was increased serotonin, or increased norepinephrine or increased dopamine, ” says Frank Anderson, a psychiatrist who has been administering antidepressants in his private practice “for a long time”, and author of Transcending Trauma, a book about resolving complex and dissociative trauma.
Yet the UCSF study brings to the mental health field a specificity it has long lacked. “A lot of the traditional medications only really work on six neurotransmitters, when there are over 100 neurotransmitters in the brain,” Anderson says. Drugs are changing the chemistry of a single system in the brain, but brain stimulation is essentially changing the very architecture of the brain, says James Giordano, professor of neurology and biochemistry at Georgetown University Medical Center in Washington and a neuroethicist. It is a far more elegant approach to treating brain disorders, with the potential to prove a lifesaver for the 40 to 50 percent of patients who see no benefits at all with antidepressants, Giordano says. It is neurofeedback, on steroids, adds Anderson. But it comes with certain risks.
Even if the device generating the brain stimulation sits outside the skull and could be easily used at home, the whole process still involves neurosurgery. While the sophistication and precision of brain surgeries has significantly improved over the last years, says Giordano, they always carry risks, such as an allergic reaction to anesthesia, bleeding in the brain, infection at the wound site, blood clots, even coma. Non-invasive brain stimulation (NIBS), a technology currently being developed by the Defense Advanced Research Projects Agency (DARPA), could potentially tackle this. Patients could wear a cap, helmet, or visor that transmits electrical signals from the brain to a computer system and back, in a brain-computer interface that would not need surgery.
“This could counter the implantation of hardware into the brain and body, around which there is also a lot of public hesitance,” says Giordano, who is working on such techniques at DARPA.
Embedding a chip in your head is one of the finest examples of biohacking, an umbrella word for all the practices aimed at hacking one’s body and brain to enhance performance –a citizen do-it-yourself biology. It is also a word charged enough to set off a public backlash. Large segments of the population will simply refuse to allow that level of invasiveness in their heads, says Laura Cabrera, an associate professor of neuroethics at the Center for Neural Engineering, Department of Engineering Science and Mechanics at Penn State University. Cabrera urges caution when it comes to DBS’s potential.
“We've been using it for Parkinson's for over two decades, hoping that now that they get DBS, patients will get off medications. But people have continued taking their drugs, even increasing them,” she says. What the UCSF found is a proof of concept that DBS worked in one depressed person, but there’s a long way ahead until we can confidently say this finding is generalizable to a large group of patients. Besides, as a society, we are not there yet, says Cabrera. “Most people, at least in my research, say they don't want to have things in their brain,” she says. But what could really go wrong if we biohacked our own brains anyway?
In 2014, a man who had received a deep brain implant for a movement disorder started developing an affection for Johnny Cash’s music when he had previously been an avid country music fan. Many protested that the chip had tampered with his personality. Could sparking the brain with electricity generated by a chip outside it put an end to our individuality, messing with our musical preferences, unique quirks, our deeper sense of ego?
“What we found is that when you stimulate a region, you affect people’s moods, their energies,” says Krystal. You are neither changing their personality nor creating creatures of eternal happiness, he says. “’Being on a phone call would generally be a setting that would normally trigger symptoms of depression in me,’” Krystal reports his patient telling him. ‘I now know bad things happen, but am not affected by them in the same way. They don’t trigger the depression.’” Of the research, Krystal continues: “We are not trying to take away normal responses to the world. We are just trying to eliminate this one thing, which is depression, which impedes patients’ ability to function and deal with normal stuff.”
Yet even change itself shouldn't be seen as threatening, especially if the patient had probably desired it in the first place. “The intent of therapy in psychiatric disorders is to change the personality, because a psychiatric disorder by definition is a disorder of personality,” says Cabrera. A person in therapy wants to restore the lost sense of “normal self”. And as for this restoration altering your original taste in music, Cabrera says we are talking about rarities, extremely scarce phenomena that are possible with medication as well.
Maybe it is the allure of dystopian sci-fi films: people have a tendency to worry about dark forces that will spread malice across the world when the line between human and machine has blurred. Such mind-control through DBS would probably require a decent leap of logic with the tools science has--at least to this day. “This would require an understanding of the parameters of brain stimulation we still don't have,” says Cabrera. Still, brain implants are not fully corrupt-proof.
“Hackers could shut off the device or change the parameters of the patient's neurological function enhancing symptoms or creating harmful side-effects,” says Giordano.
There are risks, but also failsafe ways to tackle them, adds Anderson. “Just like medications are not permanent, we could ensure the implants are used for a specific period of time,” he says. And just like people go in for checkups when they are under medication, they could periodically get their personal brain implants checked to see if they have been altered or not, he continues. “It is what my research group refers to as biosecurity by design,” says Giordano. “It is important that we proactively design systems that cannot be corrupted.”
Two weeks after receiving the implant, Sarah scored 14 out of 54 on the Montgomery-Åsberg Depression Rating Scale, a ten-item questionnaire psychiatrists use to measure the severity of depressive episodes. She had initially scored 36. Today she scores under 10. She would have had to wait between four and eight weeks to see positive results had she taken the antidepressant road, says Krystal.
He and his team have enrolled two other patients in the trials and hope to add nine more. They already have some preliminary evidence that there's another place that works better in the brain of another patient, because that specific patient had been experiencing more anxiety as opposed to despondency. Almost certainly, we will have different biomarkers for different people, and brain stimulation will be tailored to a person’s unique situation, says Krystal. “Each brain is different, just like each face is different.”
Some hospitals are pioneers in ditching plastic, turning green
This is part 2 of a three part series on a new generation of doctors leading the charge to make the health care industry more sustainable - for the benefit of their patients and the planet. Read part 1 here and part 3 here.
After graduating from her studies as an engineer, Nora Stroetzel ticked off the top item on her bucket list and traveled the world for a year. She loved remote places like the Indonesian rain forest she reached only by hiking for several days on foot, mountain villages in the Himalayas, and diving at reefs that were only accessible by local fishing boats.
“But no matter how far from civilization I ventured, one thing was already there: plastic,” Stroetzel says. “Plastic that would stay there for centuries, on 12,000 foot peaks and on beaches several hundred miles from the nearest city.” She saw “wild orangutans that could be lured by rustling plastic and hermit crabs that used plastic lids as dwellings instead of shells.”
While traveling she started volunteering for beach cleanups and helped build a recycling station in Indonesia. But the pivotal moment for her came after she returned to her hometown Kiel in Germany. “At the dentist, they gave me a plastic cup to rinse my mouth. I used it for maybe ten seconds before it was tossed out,” Stroetzel says. “That made me really angry.”
She decided to research alternatives for plastic in the medical sector and learned that cups could be reused and easily disinfected. All dentists routinely disinfect their tools anyway and, Stroetzel reasoned, it wouldn’t be too hard to extend that practice to cups.
It's a good example for how often plastic is used unnecessarily in medical practice, she says. The health care sector is the fifth biggest source of pollution and trash in industrialized countries. In the U.S., hospitals generate an estimated 6,000 tons of waste per day, including an average of 400 grams of plastic per patient per day, and this sector produces 8.5 percent of greenhouse gas emissions nationwide.
“Sustainable alternatives exist,” Stroetzel says, “but you have to painstakingly look for them; they are often not offered by the big manufacturers, and all of this takes way too much time [that] medical staff simply does not have during their hectic days.”
When Stroetzel spoke with medical staff in Germany, she found they were often frustrated by all of this waste, especially as they took care to avoid single-use plastic at home. Doctors in other countries share this frustration. In a recent poll, nine out of ten doctors in Germany said they’re aware of the urgency to find sustainable solutions in the health industry but don’t know how to achieve this goal.
After a year of researching more sustainable alternatives, Stroetzel founded a social enterprise startup called POP, short for Practice Without Plastic, together with IT expert Nicolai Niethe, to offer well-researched solutions. “Sustainable alternatives exist,” she says, “but you have to painstakingly look for them; they are often not offered by the big manufacturers, and all of this takes way too much time [that] medical staff simply does not have during their hectic days.”
In addition to reusable dentist cups, other good options for the heath care sector include washable N95 face masks and gloves made from nitrile, which waste less water and energy in their production. But Stroetzel admits that truly making a medical facility more sustainable is a complex task. “This includes negotiating with manufacturers who often package medical materials in double and triple layers of extra plastic.”
While initiatives such as Stroetzel’s provide much needed information, other experts reason that a wholesale rethinking of healthcare is needed. Voluntary action won’t be enough, and government should set the right example. Kari Nadeau, a Stanford physician who has spent 30 years researching the effects of environmental pollution on the immune system, and Kenneth Kizer, the former undersecretary for health in the U.S. Department of Veterans Affairs, wrote in JAMA last year that the medical industry and federal agencies that provide health care should be required to measure and make public their carbon footprints. “Government health systems do not disclose these data (and very rarely do private health care organizations), unlike more than 90% of the Standard & Poor’s top 500 companies and many nongovernment entities," they explained. "This could constitute a substantial step toward better equipping health professionals to confront climate change and other planetary health problems.”
Compared to the U.K., the U.S. healthcare industry lags behind in terms of measuring and managing its carbon footprint, and hospitals are the second highest energy user of any sector in the U.S.
Kizer and Nadeau look to the U.K. National Health Service (NHS), which created a Sustainable Development Unit in 2008 and began that year to conduct assessments of the NHS’s carbon footprint. The NHS also identified its biggest culprits: Of the 2019 footprint, with emissions totaling 25 megatons of carbon dioxide equivalent, 62 percent came from the supply chain, 24 percent from the direct delivery of care, 10 percent from staff commute and patient and visitor travel, and 4 percent from private health and care services commissioned by the NHS. From 1990 to 2019, the NHS has reduced its emission of carbon dioxide equivalents by 26 percent, mostly due to the switch to renewable energy for heat and power. Meanwhile, the NHS has encouraged health clinics in the U.K. to install wind generators or photovoltaics that convert light to electricity -- relatively quick ways to decarbonize buildings in the health sector.
Compared to the U.K., the U.S. healthcare industry lags behind in terms of measuring and managing its carbon footprint, and hospitals are the second highest energy user of any sector in the U.S. “We are already seeing patients with symptoms from climate change, such as worsened respiratory symptoms from increased wildfires and poor air quality in California,” write Thomas B. Newman, a pediatrist at the University of California, San Francisco, and UCSF clinical research coordinator Daisy Valdivieso. “Because of the enormous health threat posed by climate change, health professionals should mobilize support for climate mitigation and adaptation efforts.” They believe “the most direct place to start is to approach the low-lying fruit: reducing healthcare waste and overuse.”
In addition to resulting in waste, the plastic in hospitals ultimately harms patients, who may be even more vulnerable to the effects due to their health conditions. Microplastics have been detected in most humans, and on average, a human ingests five grams of microplastic per week. Newman and Valdivieso refer to the American Board of Internal Medicine's Choosing Wisely program as one of many initiatives that identify and publicize options for “safely doing less” as a strategy to reduce unnecessary healthcare practices, and in turn, reduce cost, resource use, and ultimately reduce medical harm.
A few U.S. clinics are pioneers in transitioning to clean energy sources. In Wisconsin, the nonprofit Gundersen Health network became the first hospital to cut its reliance on petroleum by switching to locally produced green energy in 2015, and it saved $1.2 million per year in the process. Kaiser Permanente eliminated its 800,000 ton carbon footprint through energy efficiency and purchasing carbon offsets, reaching a balance between carbon emissions and removing carbon from the atmosphere in 2020, the first U.S. health system to do so.
Cleveland Clinic has pledged to join Kaiser in becoming carbon neutral by 2027. Realizing that 80 percent of its 2008 carbon emissions came from electricity consumption, the Clinic started switching to renewable energy and installing solar panels, and it has invested in researching recyclable products and packaging. The Clinic’s sustainability report outlines several strategies for producing less waste, such as reusing cases for sterilizing instruments, cutting back on materials that can’t be recycled, and putting pressure on vendors to reduce product packaging.
The Charité Berlin, Europe’s biggest university hospital, has also announced its goal to become carbon neutral. Its sustainability managers have begun to identify the biggest carbon culprits in its operations. “We’ve already reduced CO2 emissions by 21 percent since 2016,” says Simon Batt-Nauerz, the director of infrastructure and sustainability.
The hospital still emits 100,000 tons of CO2 every year, as much as a city with 10,000 residents, but it’s making progress through ride share and bicycle programs for its staff of 20,000 employees, who can get their bikes repaired for free in one of the Charité-operated bike workshops. Another program targets doctors’ and nurses’ scrubs, which cause more than 200 tons of CO2 during manufacturing and cleaning. The staff is currently testing lighter, more sustainable scrubs made from recycled cellulose that is grown regionally and requires 80 percent less land use and 30 percent less water.
The Charité hospital in Berlin still emits 100,000 tons of CO2 every year, but it’s making progress through ride share and bicycle programs for its staff of 20,000 employees.
Wiebke Peitz | Specific to Charité
Anesthesiologist Susanne Koch spearheads sustainability efforts in anesthesiology at the Charité. She says that up to a third of hospital waste comes from surgery rooms. To reduce medical waste, she recommends what she calls the 5 Rs: Reduce, Reuse, Recycle, Rethink, Research. “In medicine, people don’t question the use of plastic because of safety concerns,” she says. “Nobody wants to be sued because something is reused. However, it is possible to reduce plastic and other materials safely.”
For instance, she says, typical surgery kits are single-use and contain more supplies than are actually needed, and the entire kit is routinely thrown out after the surgery. “Up to 20 percent of materials in a surgery room aren’t used but will be discarded,” Koch says. One solution could be smaller kits, she explains, and another would be to recycle the plastic. Another example is breathing tubes. “When they became scarce during the pandemic, studies showed that they can be used seven days instead of 24 hours without increased bacteria load when we change the filters regularly,” Koch says, and wonders, “What else can we reuse?”
In the Netherlands, TU Delft researchers Tim Horeman and Bart van Straten designed a method to melt down the blue polypropylene wrapping paper that keeps medical instruments sterile, so that the material can be turned it into new medical devices. Currently, more than a million kilos of the blue paper are used in Dutch hospitals every year. A growing number of Dutch hospitals are adopting this approach.
Another common practice that’s ripe for improvement is the use of a certain plastic, called PVC, in hospital equipment such as blood bags, tubes and masks. Because of its toxic components, PVC is almost never recycled in the U.S., but University of Michigan researchers Danielle Fagnani and Anne McNeil have discovered a chemical process that can break it down into material that could be incorporated back into production. This could be a step toward a circular economy “that accounts for resource inputs and emissions throughout a product’s life cycle, including extraction of raw materials, manufacturing, transport, use and reuse, and disposal,” as medical experts have proposed. “It’s a failure of humanity to have created these amazing materials which have improved our lives in many ways, but at the same time to be so shortsighted that we didn’t think about what to do with the waste,” McNeil said in a press release.
Susanne Koch puts it more succinctly: “What’s the point if we save patients while killing the planet?”
The Friday Five: A surprising health benefit for people who have kids
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- Kids stressing you out? They could be protecting your health.
- A new device unlocks the heart's secrets
- Super-ager gene transplants
- Surgeons could 3D print your organs before operations
- A skull cap looks into the brain like an fMRI