neuro

A patient with an implanted neural device that connects to a prosthetic arm can sense, while blindfolded, which of the mechanical fingers are being touched.

(A still image of a video provided to leapsmag by DARPA and UPMC/Pitt Health Sciences)


You may not have heard of DARPA, the research branch of the Pentagon. But you're definitely familiar with some of the technology it has pioneered, like the Internet, Siri, and handheld GPS.

"Now we're going to try to go from this proof-of-concept all the way to commercial technologies that can powerfully affect patients' lives."

Last week in National Harbor, Maryland, DARPA celebrated its 60th anniversary by showcasing its latest breakthroughs and emerging research programs, one of which centers around using neurotechnology to enhance the capabilities of the human brain. This technology is initially being developed to help warfighters and veterans, but its success could have enormous implications for civilian patients and, eventually, mainstream consumers.

The field is moving ahead rapidly. Fifteen years ago, a monkey named Aurora used a brain-machine interface to control a cursor on a computer screen. In 2014, DARPA's mind-controlled prosthetic arm for amputees won approval from the Food and Drug Administration.

Since then, DARPA has continued to push neurotechnology to new heights. Here are three of their research programs that are showing promise in early human testing:

1) A NEURAL IMPLANT HELP MANAGE PSYCHIATRIC ILLNESS

More than 2.2 million veterans and 44 million civilians are living with some form of psychiatric illness, and medications don't work for everyone. DARPA set out to create new options for people living with debilitating anxiety, depression, and PTSD.

"We can get somebody back to normal. It's a whole new set of tools for physicians," said Justin Sanchez, Director of the Biological Technologies Office at DARPA.

He told the audience about a woman living with both epilepsy and extreme anxiety, who has a direct neural interface that reads her brain's signals in real time and can be modulated with stimulation. He shared a recent video of her testing the device:

"Now we're going to try to go from this proof-of-concept all the way to commercial technologies that can powerfully affect patients' lives," Sanchez said.

2) A NEURAL IMPLANT TO HELP IMPROVE MEMORY

"We are right at the cusp" of improving memory recall with direct neural interfaces, Sanchez said.

All day long, our brains shift between poor and good memory states. A brain-computer interface can read the signals of populations of neurons in the lateral temporal cortex. The device continuously monitors the state of the brain and delivers stimulation within a fraction of a second after detecting a poor memory state, to improve the person's memory performance.

The improved memory lasts only seconds, so the system "delivers stimulation as needed in a closed loop to keep the performance in a good state, because of this natural variability of performance," said Dan Rizzuto, founder of NiaTherapeutics, whose technology was developed with support from DARPA and the United States BRAIN Initiative.

Check out this recently shot video of a patient testing the device, which Sanchez called "a breakthrough moment":

About 400 patients have been tested with this technology so far. In a pilot study whose data have not yet been published, patients with traumatic brain injury showed improvement in recall of around 28 percent, according to Rizzuto.

He estimates that potential FDA approval of the device for patients with traumatic brain injury is still 7 to 8 years away. The technology holds the potential to help many other kinds of patients as well.

"We believe this device could also be used to treat Alzheimer's because it's not specific to any brain pathology but based on a deep understanding of the way human memory works," Rizzuto said.

3) A NEURAL IMPLANT TO REVOLUTIONIZE PROSTHETICS FOR WARFIGHTERS AND VETERANS

Since 2006, DARPA has run a program to revolutionize prosthetics. The latest advances allow amputees to actually feel again with their bionic limbs.

Sensors in a prosthetic hand relay information to an interface in the brain that allows the person to detect which of their "fingers" are being touched, while their eyes are closed:

WHAT COMES NEXT?

DARPA is now turning its attention to non-surgical, non-invasive neurotechnology. Researchers hope to use advanced sensor technology to detect signals from neurons without putting any electrodes directly inside the brain. Under the direction of program manager Dr. Al Emondi, the N³ program is about to launch soon and plans to run for four or five years.

"We haven't even scratched the surface of what a human brain's capability is," said Dr. Geoffrey Ling, the Founding Director of the Biological Technologies Office. "When we can make this a non-invasive consumer technology, this will explode. It will take on a life of its own."

Then, inevitably, the hard questions will follow.

As Sanchez put it: "Will society consider some form of neural enhancement a personal choice like braces? Could there be a disturbing gap for people who have neurotech and those who don't? We must come together and all think over the horizon. How the story unfolds ultimately depends on all of us."

Kira Peikoff
Kira Peikoff is the editor-in-chief of Leaps.org. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.

A doctor looking at MRI scan results.

(© zinkevych/Fotolia)


When was the last time you made a pro-con list? Carefully considered all factors and weighed them against each other before you made a choice?

Chances are that most of your decisions do not follow this rigorous process. They are made quickly, subconsciously, and often do not adhere to any strict logic. Rather, your decisions are influenced by your mood, your relatives and friends, and a range of other factors that scientists are still unraveling.

When the shoppers were asked why they chose that bottle of wine, almost none of them noticed the music or believed it influenced their decision.

Influencing your choices is also the holy grail of marketing. Companies spend vast amounts of time and money creating product designs and ads. These ads are often tested in focus groups or individual interviews to ensure that they will do well in the market.

Traditional methods of market research rely on self-reports. The participants are asked which ad they find more appealing and why. But there are a few problems with this approach.

For one, the participants might not fully understand their true preferences. They might think that the green design looks more appealing when they compare choices, but then pick up the orange one when they mindlessly wander through the supermarket. It's well known that we humans often do not act rationally, so why would we accurately predict our own behavior?

Another issue is that we like to think of ourselves as logical. Even though our choices are at least partially made subconsciously, we have a tendency to rationalize them after the fact. For example, when supermarkets play French music, the shoppers are 3-4 times more likely to buy French wine. Play German music and German wine sales go up. But when the shoppers are asked why they chose that bottle of wine, almost none of them notice the music or believe it influenced their decision. Instead, they say that they preferred the label or price.

Finally, participants might truly know their preference but choose not to disclose it. Imagine sitting in a focus group watching a TV spot that makes fun of somebody's misfortune. You might be too embarrassed to admit that this is the funnier and more appealing spot, because you're afraid of being judged.

Results from traditional market research are therefore unavoidably subjective and biased.

In the hope of overcoming these limitations, newer ways of market research have been developed, among them neuromarketing, which applies neuroscience to marketing.

Today, neuromarketers focus their efforts on three main stages: to aid product ideation, evaluate the finished product or prototypes, and develop the best marketing strategy. In all cases, they want to find the option with the most "favorable" brain response – but exactly how this brain response is defined varies vastly between studies.

Perhaps the most promising of all non-traditional techniques is functional magnetic resonance imaging (fMRI). This neuroimaging technique measures brain activity indirectly by tracking changes in blood flow. In short, active brain areas receive more oxygen-rich blood. The fMRI scanner picks up the difference between oxygen-rich and oxygen-poor blood and can therefore measure which brain areas are more active than others. But is there truly an untapped potential in the human brain that can be unlocked using neuroimaging?

A number of studies claim that functional neuroimaging has been successfully applied to marketing scenarios. For example, when researchers tried to predict the success of 6 different ads for chocolate bars, the brain response of 18 women was reportedly more predictive than their self-reported preference. The ad that was rated best in interviews was actually the least successful in a real supermarket. In contrast, the neuroimaging algorithm correctly predicted the top two selling ads.

One of the biggest fears is that the potential insights from neuromarketing studies could be used in new, disturbing ways for consumer manipulation.

This study has a number of limitations, which are representative of the majority of neuromarketing research. The field is full of experiments that are conducted with small samples or using suboptimal protocols, with a lack of appropriate control conditions. While a small number of academic researchers are using rigorous protocols, most studies are conducted by neuromarketing companies or funded by the corporations whose products were tested. Such set-ups raise the risk of biased reporting, calling into question the reliability of the findings. Publication bias – the tendency to publish only positive results which leads to a skewing of reported results in the literature – is especially common for industry-funded studies.

One of the biggest fears is that the potential insights from neuromarketing studies could be used in new, disturbing ways for consumer manipulation. If a new product or ad campaign is designed to target our subconscious decision-making better than ever before, are we less able to resist the purchase? We might believe that we all have a healthy amount of self-control, but when we're in the supermarket after a stressful day or we're struggling to manage the self-control of someone else, like a small child, is it ethical for corporations to tap our unconscious decision-making?

As with any technology, the deciding factor is how it will be used. While there are many dangerous applications that might make unhealthy products one day impossible to resist, there are also some more optimistic scenarios. For example, brain scans have been used to predict the success of an antismoking campaign. If such public health interventions that are notoriously ineffective could encourage more people to make healthier lifestyle choices, don't we all benefit? Or is this still a step too far toward manipulation and propaganda?

The conduct of the studies themselves is another problematic area. Academic researchers must go through a rigorous process before they can start a study, which involves review by an ethics board. In contrast, there are barely any regulations for corporate studies. This is not only relevant for the experience of the participants, but also for how the data are being used. Take an extreme case – the brain scan reveals that the participant has a tumor. Universities have protocols in place for how to deal with these situations – often, the scans would be reviewed by a neuro-radiologist and the participant would be informed. Commercial organizations are under no such obligation.

Neuromarketing carries great potential to nudge positive behavioral change, though it also carries the risk of abuse.

Neuromarketing is now a highly competitive field with many different vendors. The Advertising Research Foundation compared 8 vendors that used neuroscientific methods or biometrics for the research of ad campaigns and found that there were differences in methodology and approach; most were proprietary and vendors were not willing to disclose what they measured and how. This lack of transparency is slowing down progress, as researchers cannot contrast and compare different approaches to optimize them.

Despite these methodological challenges, neuromarketing carries great potential to nudge positive behavioral change, though it also carries the risk of abuse. Where one ends and the other starts will need to be clearly defined. It's time to start a public debate now to inform future laws and regulations for the neuromarketing industry, as these technologies will eventually affect us all.

Julia Gottwald
Julia Gottwald is the co-author of “Sex, Lies, and Brain Scans”, which won the BPS Popular Science Book Award 2017. She completed her PhD in Psychiatry at the University of Cambridge and also holds degrees in Neuroscience from the University of Oxford and Biochemistry from Free University (Germany). In 2016, she won the BAP Public Communication Prize. In 2017, she was awarded the Association of British Science Writers Best Student Journalist Award. She now works for the healthcare communications agency Havas Lynx in Manchester, UK.
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Eric Kandel.

(Courtesy of Columbia University Medical Center)


Eric Kandel, 88, is a living legend. A specialist in the neurobiology of learning and memory, he received a Nobel Prize in 2000 for his work on the physiological basis of memory storage. Kandel is the Director of the Kavli Institute for Brain Science and Co-Director of the Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University, where he has taught and conducted research for 44 years.

"If you walk two or three miles a day, you will release sufficient osteocalcin from your bones to combat non-Alzheimer's age-related memory loss."

And he's still going strong. Leapsmag Editor-in-Chief Kira Peikoff recently caught up with Dr. Kandel about his latest research, his advice for fellow seniors, and his opinions on some of the biggest challenges in neuroscience today.

What are working on these days?

I'm working on three problems: one is age-related memory loss, the second is post-traumatic stress disorder, and the third is the beholder's share: how a viewer responds to works of art. The beholder's share is a term that Alois Riegl created. He said there are two shares to a painting: the painter creates it, but it's not meaningful until somebody responds to it: the viewer, the beholder.

That's fascinating. As far as age-related memory loss, what are you learning in that area?

I'm learning that there are two forms of age-related memory loss. One is Alzheimer's disease, which we've known about for a long time. But the second is a more benign form which I call just age-related memory loss, which begins actually somewhat earlier and has a very different anatomical locus in the brain. It is caused by a different anatomical defect and responds to different therapeutic measures. It critically involves an area in the hippocampus called the dentate gyrus and it responds to a hormone released by bone called osteocalcin.

It therefore seems likely that one very effective way of combatting age-related memory loss is walking. If you walk two or three miles a day, you are likely to release sufficient osteocalcin from your bones to combat non-Alzheimer's age-related memory loss. In collaboration with Gerard Karsenty at Columbia, my lab at Columbia has been exploring this over the last year and a half.

Have you published anything about this yet?

We are just getting ready to do so.

"I think at the moment we should stick with trying to just reverse abnormalities."

Another question I have is about brain-computer interfaces to help cure disease or even provide cognitive enhancements. What do you think of companies like Kernel and Neuralink that are trying to push this new technology?

I think if it works it would be very nice. We have to see some direct evidence first, but it's certainly an encouraging approach. I think there are a number of directions we could take. The one I think at the moment is most profitable is to try to use the brain as it is and try to enhance it, restore it, refurbish it, make it function better from its age-related condition.

You mean, without some kind of machine interface?

Without necessarily introducing anything from the outside world. Although I have no objection whatsoever to introducing ancillary aids if they're beneficial and not harmful.

Do you have any opinion on whether neuroscience and technology should aim to provide an enhancement to the brain or just return it to baseline and cure disease?

I would be perfectly satisfied if we just cured diseases. I think at the moment we should stick with trying to just reverse abnormalities, but certainly … having the capability of becoming more intelligent, more attentive, capable of remembering things better than normal, that would be nice.

What do you think is the most important challenge facing the field of neuroscience today?

It's hard to say. I think the biology of consciousness is one fantastic problem. Trying to understand and successfully reverse some of the abnormalities of the brain, like age-related memory loss, schizophrenia, depression, manic depressive illness would be wonderful.

To be able to reverse memory loss, to allow people in their 70s, 80s, and 90s to live free and independent lives, is a major challenge for brain science.

Absolutely. Is there anything else you'd like to share with our readers about your research or the field more broadly?

I'd emphasize that brain science is a relatively young discipline but it's moving ahead in a very responsible and a very effective fashion, making progress in a number of areas, and is clearly sensitive to, and responsive to, the demands of the social situation. Right now, number one, the population is aging dramatically. In 1900, the average life expectancy was 50, and now the average life expectancy is 78 for men, and 82 for women.

So people are living longer and therefore are having age-related diseases, including memory loss. To be able to reverse it, to allow people in their 70s, 80s, and 90s to live free and independent lives, is a major challenge for brain science in both its basic and its clinically applied fashion. I think this is very important and serious effort should be put into this.

Kira Peikoff
Kira Peikoff is the editor-in-chief of Leaps.org. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.

Magnetic resonance imaging of the brain.

(© Maxim Pavlov/Fotolia)


This past March, headlines suddenly flooded the Internet about a startup company called Nectome. Founded by two graduates of the Massachusetts Institute of Technology, the new company was charging people $10,000 to join a waiting list to have their brains embalmed, down to the last neuron, using an award-winning chemical compound.

While the lay public presumably burnt their wills and grew ever more excited about the end of humanity's quest for immortality, neurologists let out a collective sigh.

Essentially, participants' brains would turn to a substance like glass and remain in a state of near-perfect preservation indefinitely. "If memories can truly be preserved by a sufficiently good brain banking technique," Nectome's website explains, "we believe that within the century it could become feasible to digitize your preserved brain and use that information to recreate your mind." But as with most Faustian bargains, Nectome's proposition came with a serious caveat -- death.

That's right, in order for Nectome's process to properly preserve your connectome, the comprehensive map of the brain's neural connections, you must be alive (and under anesthesia) while the fluid is injected. This way, the company postulates, when the science advances enough to read and extract your memories someday, your vitrified brain will still contain your perfectly preserved essence--which can then be digitally recreated as a computer simulation.

Almost immediately this story gained buzz with punchy headlines: "Startup wants to upload your brain to the cloud, but has to kill you to do it," "San Junipero is real: Nectome wants to upload your brain," and "New tech firm promises eternal life, but you have to die."

While the lay public presumably burnt their wills and grew ever more excited about the end of humanity's quest for immortality, neurologists let out a collective sigh -- hype had struck the scientific community once again.

The truth about Nectome is that its claims are highly speculative and no hard science exists to suggest that our connectome is the key to our 'being,' nor that it can ever be digitally revived. "We haven't come even close to understanding even the most basic types of functioning in the brain," says neuroscientist Alex Fox, who was educated at the University of Queensland in Australia. "Memory storage in the brain is only a theoretical concept [and] there are some seriously huge gaps in our knowledge base that stand in the way of testing [the connectome] theory."

After the Nectome story broke, Harvard computational neuroscientist Sam Gershman tweeted out:

"Didn't anyone tell them that we've known the C Elegans (a microscopic worm) connectome for over a decade but haven't figured out how to reconstruct all of their memories? And that's only 7000 synapses compared to the trillions of synapses in the human brain!"

Hype can come from researchers themselves, who are under an enormous amount of pressure to publish original work and maintain funding.

How media coverage of Nectome went from an initial fastidiously researched article in the MIT Technology Review by veteran science journalist Antonio Regalado to the click-bait frenzy it became is a prime example of the 'science hype' phenomenon. According to Adam Auch, who holds a doctorate in philosophy from Dalhousie University in Nova Scotia, Canada, "Hype is a feature of all stages of the scientific dissemination process, from the initial circulation of preliminary findings within particular communities of scientists, to the process by which such findings come to be published in peer-reviewed journals, to the subsequent uptake these findings receive from the non-specialist press and the general public."

In the case of Nectome, hype was present from the word go. Riding the high of several major wins, including having raised over one million dollars in funding and partnering with well-known MIT neurologist Edward Boyden, Nectome founders Michael McCanna and Robert McIntyre launched their website on March 1, 2018. Just one month prior, they were able to purchase and preserve a newly deceased corpse in Portland, Oregon, showing that vitrifixation, their method of chemical preservation, could be used on a human specimen. It had previously won an award for preserving every synaptic structure on a rabbit brain.

The Nectome mission statement, found on its website, is laced with saccharine language that skirts the unproven nature of the procedure the company is peddling for big bucks: "Our mission is to preserve your brain well enough to keep all its memories intact: from that great chapter of your favorite book to the feeling of cold winter air, baking an apple pie, or having dinner with your friends and family."

This rhetoric is an example of hype that can come from researchers themselves, who are under an enormous amount of pressure to publish original work and maintain funding. As a result, there is a constant push to present science as "groundbreaking" when really, as is apparently the case with Nectome, it is only a small piece in a much larger effort.

Calling out the audacity of Nectome's posited future, neuroscientist Gershman commented to another publication, "The important question is whether the connectome is sufficient for memory: Can I reconstruct all memories knowing only the connections between neurons? The answer is almost certainly no, given our knowledge about how memories are stored (itself a controversial topic)."

The former home page of Nectome's website, which has now been replaced by a statement titled, "Response to recent press."

Furthermore, universities like MIT, who entered into a subcontract with Nectome, are under pressure to seek funding through partnerships with industry as a result of the Bayh-Dole Act of 1980. Also known as the Patent and Trademark Law Amendments Act, this piece of legislation allows universities to commercialize inventions developed under federally funded research programs, like Nectome's method of preserving brains, formally called Aldehyde-Stabilized Cryopreservation.

"[Universities use] every incentive now to talk about innovation," explains Dr. Ivan Oransky, president of the Association of Health Care Journalists and co-founder of retractionwatch.com, a blog that catalogues errors and fraud in published research. "Innovation to me is often a fancy word for hype. The role of journalists should not be to glorify what universities [say, but to] tell the closest version of the truth they can."

In this case, a combination of the hyperbolic press, combined with some impressively researched expose pieces, led MIT to cut its ties with Nectome on April 2nd, 2018, just two weeks after the news of their company broke.

The solution to the dangers of hype, experts say, is a more scientifically literate public—and less clickbait-driven journalism.

Because of its multi-layered nature, science hype carries several disturbing consequences. For one, exaggerated coverage of a discovery could mislead the public by giving them false hope or unfounded worry. And media hype can contribute to a general mistrust of science. In these instances, people might, as Auch puts it, "fall back on previously held beliefs, evocative narratives, or comforting biases instead of well-justified scientific evidence."

All of this is especially dangerous in today's 'fake news' era, when companies or political parties sow public confusion for their own benefit, such as with global warming. In the case of Nectome, the danger is that people might opt to end their lives based off a lacking scientific theory. In fact, the company is hoping to enlist terminal patients in California, where doctor-assisted suicide is legal. And 25 people have paid the $10,000 to join Nectome's waiting list, including Sam Altman, president of the famed startup accelerator Y Combinator. Nectome now has offered to refund the money.

Founders McCanna and McIntyre did not return repeated requests for comment for this article. A new statement on their website begins: "Vitrifixation today is a powerful research tool, but needs more research and development before anyone considers applying it in a context other than research."

The solution to the dangers of hype, experts say, is a more scientifically literate public—and less clickbait-driven journalism. Until then, it seems that companies like Nectome will continue to enjoy at least 15 minutes of fame.

Addison Nugent
Addison Nugent is a professional freelance journalist based out of Paris, France. Like so many Americans before her, she fell in love with the French capital at a young age and never left. She graduated from the Sorbonne's Master of the Arts literary research program with honors in 2016, and has since pursued a career in journalism. She has accumulated a diverse portfolio of published work that includes investigative pieces, in-depth profiles, historical deep dives, and tech news. Her work has been featured in such publications as OZY, Vice Motherboard, Atlas Obscura, Dazed Digital and Messy Nessy Chic.

Brain-computer interfaces are raising big questions about the future of the human species.


Kira Peikoff
Kira Peikoff is the editor-in-chief of Leaps.org. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.