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Gentle Brain Stimulation Can Improve Memory During Sleep

Gentle Brain Stimulation Can Improve Memory During Sleep

The researchers called this type of stimulation “synced.” They also tested another form of stimulation, called “mixed-phase,” where the electrode delivered pulses into the frontal lobe without regard to activity in the hippocampus.

To see if these types of stimulation would affect memory, the scientists used a test in which the patients were introduced to pictures of famous people, paired with pictures of pets. Each patient subsequently spent one night in which stimulation was given while they were asleep, and one night without any intervention. During the mornings following each night, the patients were shown pictures of the famous people they’d been exposed to the night prior, as well as “lure” images of people they had not seen before. The team assessed whether the patient could recognize the famous person, could match that person to the associated pet, and could reject the lure images.

The researchers found that after the synced stimulation, recognition of the previously learned famous people was better than after the night without intervention. This improvement wasn’t seen in patients who had been exposed to mixed-phase stimulation, indicating that the timing of stimulation was critical to boosting memory.

“The most interesting part that we didn’t predict was that we saw an increase in the ability to correctly reject those falsely introduced images,” says Maya Geva-Sagiv, previously a postdoctoral fellow in Fried’s lab and a study coauthor. This meant that after synced stimulation during a good night’s sleep, the patients didn’t fall for the lure images. Altogether, these results pointed to an increase in memory accuracy after synced stimulation.

This increase in memory accuracy was reflected in the brain’s physiology, too. The team found that the synced stimulation caused an increase in sleep spindles—bursts of neural activity (that look, unsurprisingly, like spindles on an EEG) known to play a role in memory consolidation. According to Geva-Sagiv, patients with the most improvement in memory accuracy also had the largest increase in sleep spindles. The team also found that after the synced stimulation, the brain was more coordinated—hippocampal ripples occurred in tandem with slow waves and sleep spindles.

Nir draws an analogy to two children on a swing set: the hippocampus on one swing and the neocortex on the other. “All we did was look at one of the swings, and based on its movement, time some very delicate pushes to the other swing to make them in sync,” he says. “Really, the way I think about it is that we provided some back wind—we were helping the sleeping brain do what it’s doing anyway, more effectively.”

Michael Zugaro, a neuroscientist at the Center for Interdisciplinary Research in Biology at the College de France, who was unaffiliated with the study, had previously seen improvement in memory consolidation after a related form of synced stimulation in rats. “It’s interesting to see that these general principles that we can find in different species also apply to humans,” he says.

For Buzsaki, more work is needed to see whether this memory consolidation process is similar in healthy humans, and whether a similar improvement in memory accuracy can be achieved. He said the question is whether the quality of improvement was due to regularizing something that is “already perfect in your brain but not so perfect in an epileptic patient” or it’s something that can be optimized in everyone. He and Zugaro both note, though, that implanting electrodes in a person’s brain is an invasive procedure that raises serious ethical concerns when done without demonstrated clinical need.

Regardless, Fried is hopeful that these results can help patients with different types of memory disorders. In the future, he wants to develop this technique as a method for amplifying certain types of memories and possibly even eliminating bad ones—which could be useful for something like PTSD. For Geva-Sagiv, the potential to stimulate further advances for patients has made the publication of the study, which was a long time in the making, worthwhile. “I’m happy that we can now add more knowledge to this very important field,” she says.

The Abortion Pill Legal Standoff Endangers Access to All Drugs

The Abortion Pill Legal Standoff Endangers Access to All Drugs

In a statement, Jim Stansel, executive vice president of the Pharmaceutical Research and Manufacturers of America, or PhRMA, called the FDA the “gold standard for determining whether a medicine is safe and effective” and said the group has “serious concerns with any court substituting its opinion for the FDA’s expert approval decision-making.” 

Marcus Schabacker, president and CEO of ECRI, a global independent nonprofit organization that advances evidence-based medicine, worries about the effect the rulings could have on patient safety. With medication abortion in legal limbo, it creates ambiguity about what health care providers can and cannot do. “When the court steps in and creates that kind of uncertainty, it endangers patients. That’s what we worried about,” he says. “This introduces additional risk.”

Even if mifepristone ultimately becomes unavailable in the US, medication abortion is still possible with just misoprostol, the other half of the two-pill regimen. This drug is typically taken 24 to 48 hours after mifepristone to dilate the cervix and cause contractions, which empties the womb. Though less effective than taking both pills, a misoprostol-only regimen is endorsed by the World Health Organization and the American College of Obstetricians and Gynecologists as an acceptable alternative.

The latest ruling isn’t the final word, however. The FDA could choose to exercise its enforcement discretion, meaning it would not enforce the restrictions set by the Kacsmaryk ruling. If that happens, it would allow providers to continue to prescribe the pill up to 10 weeks into pregnancy and dispense the pill through the mail. 

“Enforcement discretion is a normal part of the American justice system,” Cohen says. “Just think of all the times you’ve driven over 55 miles an hour on the highway and police officers haven’t pulled you over because they’re using their enforcement discretion.”

There’s no clarity on what happens next. One week ago—on the same day that the Kacsmaryk opinion landed—a federal judge in Washington state ruled that the FDA must keep mifepristone available in that state, 16 others, and the District of Columbia. Washington state lies in the Ninth Circuit, and that puts rulings from two separate circuits of the court system into direct conflict. That kind of conflict usually must be decided by the Supreme Court, and scholars now assume the battle over mifepristone access is headed there. 

This morning, US Attorney General Merrick Garland said the US Justice Department would seek emergency relief from the Supreme Court to block the restrictions on mifepristone created by the Kacsmaryk opinion, possibly bringing the issue before the court immediately. With things moving so fast, experts said, it is impossible to predict what the next ruling might be. 

WIRED will continue to update this story as it develops.

Mental Health Apps Won’t Get You Off the Couch

Mental Health Apps Won’t Get You Off the Couch

“Everyone’s so gung ho about therapy these days. I’ve been curious myself, but I’m not ready to commit to paying for it. A mental health app seems like it could be a decent stepping stone. But are they actually helpful?”

—Mindful Skeptic


Dear Mindful,

The first time you open Headspace, one of the most popular mental wellness apps, you are greeted with the image of a blue sky—a metaphor for the unperturbed mind—and encouraged to take several deep breaths. The instructions that appear across the firmament tell you precisely when to inhale, when to hold, and when to exhale, rhythms that are measured by a white progress bar, as though you’re waiting for a download to complete. Some people may find this relaxing, although I’d bet that for every user whose mind floats serenely into the pixelated blue, another is glancing at the clock, eyeing their inbox, or worrying about the future—wondering, perhaps, about the ultimate fate of a species that must be instructed to carry out the most basic and automatic of biological functions.

Dyspnea, or shortness of breath, is a common side effect of anxiety, which rose, along with depression, by a whopping 25 percent globally between 2020 and 2021, according to a report from the World Health Organization. It’s not coincidental that this mental health crisis has dovetailed with the explosion of behavioral health apps. (In 2020, they garnered more than $2.4 billion in venture capital investment.) And you’re certainly not alone, Mindful, in doubting the effectiveness of these products. Given the inequality and inadequacy of access to affordable mental health services, many have questioned whether these digital tools are “evidence-based,” and whether they serve as effective substitutes for professional help.

I’d argue, however, that such apps are not intended to be alternatives to therapy, but that they represent a digital update to the self-help genre. Like the paperbacks found in the Personal Growth sections of bookstores, such apps promise that mental health can be improved through “self-awareness” and “self-knowledge”—virtues that, like so many of their cognates (self-care, self-empowerment, self-checkout), are foisted on individuals in the twilight of public institutions and social safety nets.

Helping oneself is, of course, an awkward idea, philosophically speaking. It’s one that involves splitting the self into two entities, the helper and the beneficiary. The analytic tools offered by these apps (exercise, mood, and sleep tracking) invite users to become both scientist and subject, taking note of their own behavioral data and looking for patterns and connections—that anxiety is linked to a poor night’s sleep, for example, or that regular workouts improve contentedness. Mood check-ins ask users to identify their feelings and come with messages stressing the importance of emotional awareness. (“Acknowledging how we’re feeling helps to strengthen our resilience.”) These insights may seem like no-brainers—the kind of intuitive knowledge people can come to without the help of automated prompts—but if the breathing exercises are any indication, these apps are designed for people who are profoundly alienated from their nervous systems.

Of course, for all the focus on self-knowledge and personalized data, what these apps don’t help you understand is why you’re anxious or depressed in the first place. This is the question that most people seek to answer through therapy, and it’s worth posing about our society’s mental health crisis as a whole. That quandary is obviously beyond my expertise as an advice columnist, but I’ll leave you with a few things to consider.

Linda Stone, a researcher and former Apple and Microsoft executive, coined the term “screen apnea” to describe the tendency to hold one’s breath or breathe more shallowly while using screens. The phenomenon occurs across many digital activities (see “email apnea” and “Zoom apnea”) and can lead to sleep disruption, lower energy levels, or increased depression and anxiety. There are many theories about why extended device use puts the body into a state of stress—psychological stimulation, light exposure, the looming threat of work emails and doomsday headlines—but the bottom line seems to be that digital technologies trigger a biological state that mirrors the fight-or-flight response.

It’s true that many mental health apps recommend activities or “missions” that involve getting off one’s phone. But these tend to be tasks performed in isolation (pushups, walks, guided meditations), and because they are completed so as to be checked off, tracked, and subsumed into one’s overall mental health stats, the apps end up ascribing a utility value to activities that should be pleasurable for their own sake. This makes it more difficult to practice those mindfulness techniques—living in the moment, abandoning vigilant self-monitoring—that are supposed to relieve stress. By attempting to instill more self-awareness, in other words, these apps end up intensifying the disunity that so many of us already feel on virtual platforms.

In the Next Pandemic, Let’s Pay People to Get Vaccinated

In the Next Pandemic, Let’s Pay People to Get Vaccinated

It’s a truth universally acknowledged that people like money. If you show them the cash, they’re generally more likely to do what you want, whether that be to stop smoking, work out, or keep up with their medication.  

As vaccines started to roll out of labs during the pandemic, governments began wondering: How can we encourage as many people as possible to get vaccinated against Covid-19? Countries tried a mishmash of approaches: They rolled out rigorous public health messaging, engaged with hard-to-reach communities, got celebrities to plug the vaccines, and made them compulsory. 

But policymakers and academics also suggested another, controversial approach—why not just offer people cold, hard cash? This reignited a thorny debate. 

Those on the utilitarian side say that if more people get vaccinated, the public benefit outweighs all other harms. But there’s no guarantee that offering people money to do a good deed convinces them to do it—it might even suggest the opposite, that the action isn’t worth doing otherwise. A 2000 study conducted with Israeli high school students found that when they were paid a small commission to collect money for charity on a certain day, the group earning a commission actually collected less than the group that was paid zilch—suggesting monetary incentives had a detrimental effect on the urge to do good. 

A big worry is that cash incentive programs might have unintended long-term consequences. Offering people money to do a public good deed might reduce their willingness to do the same thing for free in the future. It could also trigger distrust. Unlike blood donation or other public health interventions, vaccines are divisive. And research has shown that in paid clinical trials, people associate higher payments with greater risk. Paying people to get vaccinated—when it’s previously been done for free—might make them overestimate the risks involved.

Finally, the ethics are nebulous. Ethicists argue that a monetary reward does not mean the same thing to a cash-strapped single parent who lost their job during the pandemic as it does to a comfortably employed middle-class person. Offering the money could be seen as a form of coercion or exploitation, as the single parent can’t reasonably decline it. “A gun to the back works, but should we use it?” says Nancy Jecker, a professor at the University of Washington School of Medicine. 

But in a new paper published in the journal Nature, researchers Florian Schneider, Pol Campos-Mercade, Armando Meier, and others addressed these concerns. 

In 2021, Meier and his colleagues conducted a randomized trial to see if financial incentives increased vaccine uptake. In their study, published in the journal Science in October 2021, Meier and his coauthors recruited over 8,000 people in Sweden and offered a portion of them $24 to get vaccinated within the next 30 days, while the others were offered nothing. The researchers found that the cash incentive boosted the proportion of people who got vaccinated by about 4 percent. That number didn’t change significantly when factoring in age, race, ethnicity, education, or income. Other research during the pandemic also found that financial incentives were effective.

‘Blood Washing’ Is the Latest Dubious—and Pricey—Long-Covid Trend

‘Blood Washing’ Is the Latest Dubious—and Pricey—Long-Covid Trend

The Covid-19 pandemic is considered by many experts to be a mass disabling event. Though most people fully recover from a battle with the highly infectious coronavirus, a significant chunk of patients develop lingering, sometimes debilitating symptoms—aka long Covid. Estimates of how many Covid patients endure long-term symptoms vary considerably. But the US Centers for Disease Control and Prevention recently estimated that nearly one in five Covid patients report persistent symptoms. With hundreds of millions of Covid-19 cases reported around the globe, even the more modest estimates still suggest that tens of millions have lasting effects.

Yet, as those patients seek effective care, researchers are scrambling to define, understand, and treat this new phenomenon. Many patients have reported uphill battles for finding care and relief, including long waits at clinics and few treatment options when they see a care provider.

Cue the quacks. This situation is ripe for unscrupulous actors to step in and begin offering unproven products and treatments—likely at exorbitant prices. It’s a tried-and-true model: When modern medicine is not able to provide evidence-based treatment, quacks slither in to console the desperate, untreated patients. Amid their sympathetic platitudes, they rebuke modern medicine, scowl at callous physicians, and scoff at the slow pace and high price of clinical trials. With any ill-gotten trust they earn, these bad actors can peddle unproven treatments and false hope.

There are already reports in the US of such unproven long-Covid treatments, such as supplements, vitamins, infusions, fasts, ozone therapy, and off-label drug prescribing. But, a British investigation published this week highlights a growing international trend of pricey “blood washing” treatments.

Costly Cleanse

The investigation, carried out by the British outlet ITV News and The BMJ, revealed that thousands of long-Covid patients are traveling to private clinics in various countries—including Switzerland, Germany, and Cyprus—to receive blood filtering, or apheresis, which is not proven to treat long Covid.

Apheresis is an established medical therapy, but it’s used to treat specific conditions by filtering out known problematic components of blood, such as filtering out LDL (low-density lipoprotein) in people with intractable high cholesterol, or removing malignant white blood cells in people with leukemia.

In the case of long-Covid patients, it seems apheresis treatments are used to remove a variety of things that may or may not be problematic. That includes LDL and inflammatory molecules, a strategy initially designed to treat people with cardiovascular disease. Internal medicine doctor Beate Jaeger, who runs the Lipid Center North Rhine in Germany and has started treating long-Covid patients, touts the method, which involves filtering blood through a heparin filter. She also prescribes long-Covid patients a cocktail of anticoagulant drugs.

Jaeger hypothesizes that the blood of people with long Covid is too viscous and contains small blood clots. She suggests that thinning the blood with drugs and apheresis can improve microcirculation and overall health. But there’s no evidence that this hypothesis is correct or that the treatment is effective. When Jaeger tried to publish her hypothesis in a German medical journal, it was rejected.

Robert Ariens, professor of vascular biology at the University of Leeds School of Medicine, told The BMJ and ITV that the treatment is premature. For one thing, researchers don’t understand how microclots form, if apheresis and anticoagulation drugs reduce them, and if a reduction would even matter for disease. “If we don’t know the mechanisms by which the microclots form and whether or not they are causative of disease, it seems premature to design a treatment to take the microclots away, as both apheresis and triple anticoagulation are not without risks, the obvious one being bleeding,” Ariens said.

False Hope

Jaeger, meanwhile, defended treating patients despite a rejected hypothesis and a lack of evidence. She expressed anger over “dogmatism” in medicine and claimed to have treated patients in her clinic who arrived in wheelchairs but walked out. “If I see a child in a wheelchair suffering for a year, I prefer to treat and not to wait for 100 percent evidence,” she said.

And Jaeger isn’t alone; other clinics have also started offering apheresis for long Covid. The British investigation interviewed a woman in the Netherlands, Gitte Boumeester, who paid more than $60,000—nearly all her savings—for treatment at a new long-Covid clinic in Cyprus after seeing positive anecdotes online. The woman, desperate for relief from her long-Covid symptoms, signed a dubious consent form filled with spelling mistakes, grammatical errors, and half-finished sentences that waived her rights.

Daniel Sokol, a London barrister and medical ethicist, said the form would be invalid under English and Welsh law. “You can’t say, ‘By the way, you agree not to sue us if we cause you horrible injury or kill you, even if it’s through our own negligence,’” he told the investigators. “You can’t do that.”

At the Cyprus clinic, Boumeester received a battery of other unproven treatments along with the apheresis, including vitamin infusions, hyperbaric oxygen treatment, anticoagulants, and hydroxychloroquine, which is notoriously ineffective against Covid-19. After two months in Cyprus, subjecting herself to various treatments and draining her bank account, Boumeester said, she’d seen no improvement in her debilitating symptoms, which include heart palpitations, chest pain, shortness of breath, and brain fog.

“I do think they should emphasize the experimental nature of the treatments more, especially because it’s so expensive,” Boumeester said. “I realized before I started that the outcome was uncertain, but everyone at the clinic is so positive that you start to believe it too and get your hopes up.”

This story originally appeared on Ars Technica.