"Neural Dust" Could Enable a Fitbit for the Nervous System

A technology with the potential to blur the boundaries between biology and electronics has just leaped a major hurdle in the race to demonstrate its feasibility.

A team at the University of California, Berkeley, led by neuroscientist Jose Carmena and electrical and computer engineer Michel Maharbiz, has provided the first demonstration of what the researchers call “ultrasonic neural dust” to monitor neural activity in a live animal. They recorded activity in the sciatic nerve and a leg muscle of an anesthetized rat in response to electrical stimulation applied to its foot. “My lab has always worked on the boundary between biology and man-made things,” Maharbiz says. “We build tiny gadgets to interface synthetic stuff with biological stuff.” The work was published this week in the journal Neuron.

The system uses ultrasound for both wireless communication and the device’s power source, eliminating both wires and batteries. It consists of an external transceiver and what the team calls a “dust mote” about 0.8x1x3 mm size, which is implanted inside the body. The transceiver sends ultrasonic pulses to a piezoelectric crystal in the implant, which converts them into electricity to provide power. The implant records electrical signals in the rat via electrodes, and uses this signal to alter the vibration of the crystal. These vibrations are reflected back to the transceiver, allowing the signal to be recorded—a technique known as backscatter. “This is the first time someone has used ultrasound as a method of powering and communicating with extremely small implantable systems,” says one of the paper’s authors, Dongjin Seo. “This opens up a host of applications in terms of embodied telemetry: being able to put something super-tiny, super-deep in the body, which you can park next to a nerve, organ, muscle or gastrointestinal tract, and read data out wirelessly.”

The team also plans to develop implants that can stimulate as well as monitor nerves, allowing closed-loop control of nervous system activity. This has potential applications in the emerging field of bioelectric medicine, which promises to deliver a whole new class of therapies called electroceuticals. For example, on Monday GlaxoSmithKline announced it is teaming up with Google sister company Verily Life Sciences to create Galvani Bioelectronics, which will develop implants that can modify nerve signals in an effort to treat chronic illnesses. Animal studies already suggest the technology could be used to treat type 2 diabetes, and there are many other possibilities. Seo says they are looking into treating bladder control problems and bowel disease.

“While the technology is still in its infancy, initial results clearly demonstrate the potential of the ultrasonic backscatter approach,” says Victor Pikov, head of research platforms at GSK Bioelectronics, who was not involved in the Berkeley team’s research. “The Berkeley group is on the exciting path towards developing a completely novel type of sensors that would have widespread uses in bioelectronic medicines.”

The next steps are to test whether the dust motes remain viable for long periods after implantation, and to conduct experiments in awake and freely moving animals. The team then plans to make various improvements. “As we validate these platforms are stable for chronic use, we'll be making them smaller, adding additional functionality like stimulation, and other types of sensors,” Maharbiz says. “The idea that you could use these to take data about pH, oxygen, chemicals, tumors, all sorts of things, deep in your body, and communicate robustly, is extremely exciting.”

The team also plans to use multiple transceivers to keep better track of motes if they move. This would also allow steering the ultrasonic beam to communicate with multiple implants. “The vision is to implant a bunch of these motes anywhere in the body and have a patch that sends ultrasonic waves to wake up the sensors and receive information for any desired therapy,” Seo says. “Everything would be sealed in, with one patch over the site that can talk to the implants individually or simultaneously.”

The original aim of the project was to develop the next generation of brain-machine interfaces, Seo says. The group published a theoretical analysis in 2013 showing the technique could work with implants as small as 50 microns, a scale comparable to neurons. One of the biggest challenges facing neuroscientists is how to put things inside the brain without damaging or disrupting tissue, and part of the problem is anything bigger than a couple of cells tends to provoke biological responses including inflammation.

Not only do standard implants damage tissue, which slowly degrades performance; the wires they need also run a risk of infection. Previous wireless implants have also suffered critical drawbacks such as limited depth and a lifespan that ranges between months and two years. These drawbacks are mainly blamed on the fact that the devices use electromagnetism (EM). EM waves travel much faster than sound, which means wavelengths are longer for a given frequency. This limits how small the implants can be, since wireless communication needs receivers of similar dimensions to the wavelengths used. EM wavelengths short enough to communicate with tiny implants would be extremely high frequency, which would cause tissue damage and not penetrate as far. Ultrasonics solves these problems. “Walking in a parking lot one day, it occurred to me that ultrasound might be the answer, because soft tissue is relatively transparent to ultrasound, and the wavelengths are perfect,” Maharbiz says. “I got very excited; a sort of eureka moment.”

If the team can develop sufficiently small implants, it may pave the way for treating neurological disorders including epilepsy. It will also fall within the remit of President Barack Obama's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, which encourages the development of new tools for communicating with the brain. “What's exciting about this is it uses an old technique we already know much about, that's used in clinical settings every day,” says Miyoung Chun, executive vice president of science programs at The Kavli Foundation, a major player in the BRAIN initiative. “A lot of new tools developed in animals, like optogenetics, are not ready for human application, but there are different opportunities here; this looks really exciting.”

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Simon Makin

Simon J Makin is an auditory perception researcher turned science writer and journalist. Originally from Liverpool in the north of England, he has a bachelor's in engineering, a masters in Speech and Hearing Sciences, and a PhD in computational auditory modelling from The University of Sheffield. He spent several years working as a research fellow in the psychology dept at The University of Reading, before recently branching out and retraining in journalism.

A Q&A with the Scientist Who Helped Create the "Cortex in a Dish" System

Neuroscientists desperately need better tools to develop drugs for treating mental illness and neurodegenerative diseases. Experiments in lab animals more often than not produce drug candidates that ultimately fail in clinical trials. If a laboratory cell culture existed that accurately mimicked the intricate cellular networks that make up the cerebral cortex, it would provide a reality check and help answer the persistent question every drug developer wants to know: if this chemical works in mice that mimic some of the effects of schizophrenia or autism, will it work in humans?

A team from Johns Hopkins Medical School and Nanjing University has just created a microcosm of the cerebral cortex that fits inside a lab dish. The “cortex in a dish” consists of an interwoven mesh of neurons that transmit electrical signals and other cells that damp down this activityThe cultured neurons may expand the toolkit needed to lift neurological and psychiatric drug development out of its present rut.

Scientific American talked with Valina Dawson, co-director of the Institute for Cell Engineering at Johns Hopkins University School of Medicine, about a paper published April 6 in Science Translational Medicine on which she was the senior author.

Scientific American: Describe what a 'cortex in a dish' is?

Valina Dawson: The brain is divided into different structures and regions. The cerebral cortex is the largest part of the brain and manages higher brain functions such as thought and actions, language, sensory processing such as hearing and vision. One way to study how the neurons in the cortex function is to grow them in culture, “in a dish.” 

SA: Why have researchers wanted to create this laboratory model of the cortex?

VD: Having human neurons in culture allows experimental investigations into signaling events at the chemical, protein and genetic levels that underlie normal and diseased actions in a manner that would not be possible or ethical in an intact human brain. Understanding how the neurons in the cortex work and what goes wrong when disease occurs will provide, we hope, new therapeutic opportunities to treat patients who suffer from brain injury and disease.

SA: Why has it been so difficult to build this and how did you overcome hurdles along the way?

VD: The ability to create human neurons from stem cells is relatively new. Established protocols to make different types of neurons from stem cells are limited to a few types of neurons out of the hundreds that exist in the human brain. Most of our understanding about the carefully controlled and elegantly choreographed events in the development of the cortex are from less complex organisms. Thus some of the key elements necessary to generate a protocol to produce the complex network of neuronal populations had to be guessed and identified by trial and error.

SA:. What will scientists be able to do with your system?

VD: We hope they will use this system to understand important mechanisms in cortical function and communication. We hope these cultures will also be useful in understanding how to provide neuroprotection against stroke and trauma and to investigate what goes wrong in diseases such as schizophrenia, autism and epilepsy.

SA: Didn’t you show in the paper just published how this might work?

Yes, in a model of stroke. Stroke is a common cause of death, disability and loss of quality of life world-wide but unfortunately there are few treatments to reduce the brain injury suffered. During a stroke there is a loss of blood flow to brain tissue. This can be mimicked in a culture dish by removing oxygen and glucose or by activating with the chemical NMDA a specific protein on the surface of neurons, an excitatory receptor. We have used our cortical culture system to study the cellular signaling events that occur and lead to neuronal cell death. Previously we found in rodent systems, that a member of a biochemical pathway, poly(ADP-Ribose) polymerase-1 (PARP-1) is pathologically activated and serves as a switch, directing the cell away from DNA repair towards cell death.

Preventing PARP-1 activation protects neurons from ischemic cell death. For the first time we were able to determine using our cortical culture if human neurons respond in a similar manner, and they do! Inhibitors of PARP have been developed for the treatment of patients with certain types of cancer and some of these clinically useful drugs cross the blood brain barrier. Finding agents that can gain access to the brain has been a major hurdle in developing good treatments for neurologic disease and injury. Our studies raise the potential that these drugs could also be useful in the treatment of stroke.

SA: What are the next steps?

VD: Besides using these cultures to study how cortical neurons protect themselves from injury, we are also using these cultures to probe the molecular signaling events that underlie a form of autism with the hopes of finding a way to intervene. Additionally, other brain regions connect to the cortex, providing important information or receiving instructions from cortical regions. In the future, cultures could be established so that these connections could be studied at the cellular and sub-cellular level. One could also envision using sophisticated bioengineered scaffolds to permit the normal layering of the cortex so that interconnectivity between layers could be studied. In the science fiction future, perhaps cortical plugs would be developed that could be implanted into patients with stroke or trauma to replace the brain material that was damaged and lost.

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Gary Stix

Gary Stix, a senior editor, commissions, writes, and edits features, news articles and Web blogs for SCIENTIFIC AMERICAN. His area of coverage is neuroscience. He also has frequently been the issue or section editor for special issues or reports on topics ranging from nanotechnology to obesity. He has worked for more than 20 years at SCIENTIFIC AMERICAN, following three years as a science journalist at IEEE Spectrum, the flagship publication for the Institute of Electrical and Electronics Engineers. He has an undergraduate degree in journalism from New York University. With his wife, Miriam Lacob, he wrote a general primer on technolo

Controversial New Push to Tie Microbes to Alzheimer's DiseaseNEU

Scientists have long puzzled over the root causes of Alzheimer's disease, a devastating and typically fatal condition that currently denies more than five million Americans their cognition and memory. But in a provocativeeditorial soon to be published in the Journal of Alzheimer’s Disease, a cadre of scientists argue that the complex disease may have a surprisingly simple trigger: tiny brain-infecting microbes. This controversial view, which is not new, has long been dismissed as outlandish, but a growing body of work suggests it may be worth considering and further studying. If researchers can prove the theory and iron out the many argued-over details—both formidable tasks, as brain infections are difficult to study—Alzheimer's could become a preventable illness.

The editorial, signed by 31 scientists around the world, argues that in certain vulnerable individuals—such as those with the APOE ε4 gene variant, a known Alzheimer’s risk factor—common microbial infections can infect the aging brain and cause debilitating damage. These microbes may include herpes simplex virus 1 (HSV-1), the ubiquitous virus that causes cold sores as well as Chlamydophila pneumoniae and Borrelia burgdorferi, the bacteria that cause pneumonia and Lyme disease, respectively.

The controversial idea butts heads with the long-standing theory that amyloid-beta proteins and tau tangles, both of which build up inside the brains of those with Alzheimer’s, are the main drivers of disease-induced cell death. Instead, supporters of the pathogen hypothesis, as it is called, posit that either pathogens induce brain cells to produce the amyloid proteins and tau tangles or that nerve cells that have been damaged by infection produce them as part of an immune response. “We think the amyloid story does come into play, but it’s secondary to the initial inflammation,” says editorial co-author Brian Balin, who directs the Center for Chronic Disorders of Aging at the Philadelphia College of Osteopathic Medicine.

Critics of the pathogen theory point out that much of the supportive human research does not establish cause and effect. In a study published in The Lancet in 1997, a team led by Ruth Itzhaki, one of the editorial’s co-authors and a molecular neurobiologist at the University of Manchester in England, reported that people whose brains were infected with HSV-1 and who also had the APOE ε4 gene variant were 12 times more likely to develop Alzheimer’s than those with either the gene variant or the infection alone. One hypothesis is that the APOE ε4 variant makes it easier for HSV-1 to infect brain cells—but, critics say, it could also be that the gene variant and the infection are associated with Alzheimer’s in ways that are not causal.

Scientists have tried to nail down the mechanics of the relationship using animals. Researchers in Spain have found, for instance, that mice whose brains have been infected with HSV-1 produce nearly 14 times as much viral DNA when they have the APOE ε4 variant compared with when they do not. And after infecting the brains of mice with HSV-1, Itzhaki’s groupshowed that their brains accumulated amyloid plaques. But these studies are criticized, too—after all, what happens in a mouse’s brain may not happen in a human’s.

The burden of proof is formidable for this theory, in part because it is impossible to detect infections like HSV-1 in the brains of living people—they can only be seen postmortem. “‘Proof of causation is a major, critical and very complex issue,” says David Relman, an infectious disease specialist at Stanford University. Itzhaki agrees, noting that one cannot just inject people with the virus and wait to see if they develop Alzheimer’s. (That said, Australian microbiologist Barry Marshall finally convinced skeptics that Heliobactor pylori bacteria cause gastric ulcers by infecting himself.) Itzhaki says that one potential solution would be to conduct a pilot clinical trial that evaluates whether HSV-1-infected individuals with mild Alzheimer’s and the APOE ε4 variant improve if they are treated with antiviral drugs. They have already shown in the lab that these drugs inhibit amyloid plaque production in HSV-1 infected cells. But she has applied for funding for a human study multiple times and has so far has been unsuccessful.

Rudolph Tanzi, a neurologist at Harvard University who directs the Genetics and Aging Research Unit at Massachusetts General Hospital, agrees that microbes likely play a role in Alzheimer’s—but his work suggests that the brain’s response to the infection is more dangerous than the infection itself. “We do need to take the role of microbes in the brain seriously, but it’s going to be a lot more involved than simply saying ‘infection causes Alzheimer’s disease,’” he notes. (He was not involved in the editorial.) In a 2010 study Tanzi and his colleagues reported that the amyloid protein strongly inhibits microbial growth in the brain, which suggests that it accumulates as a protective response to infection. “Over the last five years, following up from that 2010 paper, we’ve showed that in every Alzheimer’s model tested—from cells to flies to dirt worms to mice—beta amyloid potently protects from infection,” he explains. The presence of even just a few microbes in the brain, he says, triggers its accumulation.

Infections induce potent immune responses, too, and they likely worsen the problem. Normally, brain immune cells called microglia clear amyloid proteins from the brain. But when these cells get fired up in response to infection, they stop, causing the proteins to build up even faster. As Tanzi’s team showed in a 2014 Nature paper, the amyloid proteins that fill up the brain then spark the creation of tau tangles, which cause more brain cell death. “And now, you have the full-blown disease,” he says. (Scientific American is part of Springer Nature.)

As for which pathogens might be triggers, HSV-1 is a contender, Tanzi says, but it is too soon to know for sure. “I think we have to take a couple of steps back and say, ‘What types of bacteria, viruses and fungus accumulate in the brain as we age?’ and study this systematically in an unbiased, agnostic way,” he says. He is leading a consortium funded by the nonprofit Cure Alzheimer’s Fund to map the microbiome of the human brain; once potentially important microbes are identified, it might be possible to develop neuroimaging techniques to track them in the brains of living individuals, he says.

Other Alzheimer’s scientists still are not convinced, however. David Holtzman, chair of the department of neurology at Washington University School of Medicine in St. Louis and associate director of its Knight Alzheimer's Disease Research Center, told Scientific American that although more research on the idea is warranted, “there is not clear or conclusive evidence of whether or how different infections influence risk for Alzheimer’s disease.” Tanzi says that when he presents his findings and ideas at scientific meetings, reactions are indeed mixed. One comment Itzhaki often hears is that HSV-1 cannot cause Alzheimer’s if it is also found, as it is, in the brains of elderly healthy people. But she points out that other pathogens, including tuberculosis, only cause symptoms in subset of vulnerable individuals, too.

If microbes do turn out to be a potential trigger for Alzheimer’s—and to most in the field, this is still a big “if”—the implications would be huge: It might be possible to vaccinate against the debilitating disease simply by inoculating against offending infections. At the very least, doctors might be able to treat infections with antimicrobial drugs before they harm the brain. But building enough evidence to prove the theory could take decades. Among other challenges, researchers working in the area complain of funding woes. “Over the 50-plus years that I’ve been doing the work, our group has had extreme difficulties nearly all the time—we’ve been working on a shoestring,” Itzhaki says.

But given that hundreds of clinical trials for Alzheimer’s drugs have failed based on the prevailing dogma, those working on the various versions of the pathogen theory believe it is worth pushing forward. More than anything, they hope their editorial will encourage skeptics to at least consider the possibility that microbes could play a role in Alzheimer’s disease and support their desire to study it more. “We’re saying ‘wait a minute, folks—we have a body of evidence here from decades of work that we have to stop ignoring,’” Balin says.

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Melinda Wenner Moyer

Melinda Wenner Moyer is a freelance science writer and frequent contributor to Scientific American Mind.

New Estimate Boosts the Human Brain's Memory Capacity 10-Fold

The human brain’s memory-storage capacity is an order of magnitude greater than previously thought, researchers at the Salk Institute for Biological Studies reported last week. The findings, recently detailed ineLife, are significant not only for what they say about storage space but more importantly because they nudge us toward a better understanding of how, exactly, information is encoded in our brains.

The question of just how much information our brains can hold is a longstanding one. We know that the human brain is made up of about 100 billion neurons, and that each one makes 1,000 or more connections to other neurons, adding up to some 100 trillion in total. We also know that the strengths of these connections, or synapses, are regulated by experience. When two neurons on either side of a synapse are active simultaneously, that synapse becomes more robust; the dendritic spine (the antenna on the receiving neuron) also becomes larger to support the increased signal strength. These changes in strength and size are believed to be the molecular correlates of memory. The different antenna sizes are often compared with bits of computer code, only instead of 1s and 0s they can assume a range of values. Until last week scientists had no idea how many values, exactly. Based on crude measurements, they had identified just three: small, medium and large.

But a curious observation led the Salk team to refine those measurements. In the course of reconstructing a rat hippocampus, an area of the mammalian brain involved in memory storage, they noticed some neurons would form two connections with each other: the axon (or sending cable) of one neuron would connect with two dendritic spines (or receiving antennas) on the same neighboring neuron, suggesting that duplicate messages were being passed from sender to receiver. Because both dendrites were receiving identical information, the researchers suspected they would be similar in size and strength. But they also realized that if there were significant differences between the two, it could point to a whole new layer of complexity. If the spines were of a different shape or size, they reasoned, the message they passed along would also be slightly different, even if that message was coming from the same axon.

So they decided to measure the synapse pairs. And sure enough, they found an 8 percent size difference between dendritic spines connected to the same axon of a signaling neuron. That difference might seem small, but when they plugged the value into their algorithms, they calculated a total of 26 unique synapse sizes. A greater number of synapse sizes means more capacity for storing information, which in this case translated into a 10-fold greater storage capacity in the hippocampus as a whole than the previous three-size model had indicated. “It’s an order of magnitude more capacity than we knew was there,” says Tom Bartol, a staff scientist at the Salk Institute and the study’s lead author.

But if our memory capacity is so great, why do we forget things? Because capacity is not really the issue, says Paul Reber, a memory researcher at Northwestern University who was not involved in the study, “Any analysis of the number of neurons will lead to a sense of the tremendous capacity of the human brain. But it doesn’t matter because our storage process is slower than our experience of the world. Imagine an iPod with infinite storage capacity. Even if you can store every song ever written, you still have to buy and upload all that music and then pull individual songs up when you want to play them.”

Reber says that it is almost impossible to quantify the amount of information in the human brain, in part because it consists of so much more information than we’re consciously aware of: not only facts and faces and measurable skills but basic functions like how to speak and move and higher order ones like how to feel and express emotions. “We take in much more information from the world than ‘what do I remember from yesterday?’” Reber says. “And we still don’t really know how to scale up from computing synaptic strength to mapping out these complex processes.”

The Salk study brings us a bit closer, though. “They’ve done an amazing reconstruction,” Reber says. “And it adds significantly to our understanding of not only memory capacity but more importantly of how complex memory storage actually is.” The findings might eventually pave the way toward all manner of advances: more energy-efficient computers that mimic the human brain’s data-transmission strategies, for example, or a better understanding of brain diseases that involve dysfunctional synapses.

But first scientists will have to see if the patterns found in the hippocampus hold for other brain regions. Bartol’s team is already working to answer this question. They hope to map the chemicals, which pass from neuron to neuron, that have an even greater capacity than the variable synapses to store and transmit information. As far as a precise measurement of whole-brain capacity, “we are still a long way off,” Bartol says. “The brain still holds many, many more mysteries for us to discover.”

A Single Concussion May Triple the Long-Term Risk of Suicide

As the Panthers and Broncos faced off in the third quarter of last night’s Super Bowl, wide receiver Philly Brown suffered a possible concussion—and to the disappointment of Panthers fans, he never returned to the game. But for good reason: concussions are now known to be much more serious injuries than once thought. And the danger may not be limited to the immediate repercussions. Researchers have already linked more severe traumatic brain injury to later suicide—particularly in military veterans and professional athletes—and have more recently explored the connection between concussion and depression.

Now, new research published in the Canadian Medical Association Journal shows that even mild concussions sustained in ordinary community settings might be more detrimental than anyone anticipated; the long-term risk of suicide increases threefold in adults if they have experienced even one concussion. That risk increases by a third if the concussion is sustained on a weekend instead of a weekday—suggesting recreational concussions are riskier long-term than those sustained on the job. “The typical patient I see is a middle-aged adult, not an elite athlete,” says Donald Redelmeier, a senior scientist at the University of Toronto and one of the study’s lead authors. “And the usual circumstances for acquiring a concussion are not while playing football; it is when driving in traffic and getting into a crash, when missing a step and falling down a staircase, when getting overly ambitious about home repairs—the everyday activities of life.”

Redelmeier and his team wanted to examine the risks of the concussions acquired under those circumstances. They identified nearly a quarter of a million adults in Ontario who were diagnosed with a mild concussion over a timespan of 20 years—severe cases that resulted in hospital admission were excluded from the study—and tracked them for subsequent mortality due to suicide. It turned out that more than 660 suicides occurred among these patients, equivalent to 31 deaths per 100,000 patients annually—three times the population norm. On average, suicide occurred almost six years after the concussion. This risk was found to be independent of demographics or previous psychiatric conditions, and it increased with additional concussions.

For weekend concussions, the later suicide risk increased to four times the norm. Redelmeier and his fellow researchers had wondered whether the risk would differ between occupational and recreational concussions. They did not have information about how the concussions happened, so they used day of the week as a proxy. Although they do not know why weekend risk is indeed higher, they suspect it may be because on weekends medical staff may not be as available or accessible or people may not seek immediate care.

Although the underlying causes of the connection between concussion and suicide are not yet known, Redelmeier says that there were at least three potential explanations. A concussion may be a marker but not necessarily a mechanism of subsequent troubles—or, in other words, people who sustain concussions may already have baseline life imbalances that increase their risks for depression and suicide. “But we also looked at the subgroup of patients who had no past psychiatric history, no past problems, and we still found a significant increase in risk. So I don’t think that’s the entire story,” he notes. One of the more likely explanations, he says, is that concussion causes brain injury such as inflammation (as has been found in some studies) from which the patient may never fully recover. Indeed, a study conducted in 2014 found that sustaining a head injury leads to a greater risk of mental illness later in life. The other possibility is that some patients may not give themselves enough time to get better before returning to an ordinary schedule, leading to strain, frustration and disappointment—which, in turn, may result in depression and ultimately even suicide.

Lea Alhilali, a physician and researcher at the Barrow Neurological Institute who did not participate in this study, uses diffusion tensor imaging (an MRI technique) to measure the integrity of white matter in the brain. Her team has found similarities between white matter degeneration patterns in patients with concussion-related depression and noninjured patients with major depressive disorder—particularly in the nucleus accumbens, or the “reward center” of the brain. “It can be difficult to tease out what’s related to an injury and what’s related to the circumstances surrounding the trauma,” Alhilali says. “There could be PTSD, loss of job, orthopedic injuries that can all influence depression. But I do believe there’s probably an organic brain injury.”

Alhilali points to recent studies on chronic traumatic encephalopathy (CTE), a progressive degenerative brain disease associated with repeated head traumas. Often linked to dementia, depression, loss of impulse control and suicide, CTE was recently diagnosed in 87 of 91 deceased NFL players. Why, then, she says, should we not suspect that concussion causes other brain damage as well?

This new study may only represent the tip of the iceberg. “We’re only looking at the most extreme outcomes, at taking your own life,” Redelmeier says. “But for every person who dies from suicide, there are many others who attempt suicide, and hundreds more who think about it and thousands more who suffer from depression.”

More research needs to be done; this study was unable to take into account the exact circumstances under which the concussions were sustained. Redelmeier’s research examined only the records of adults who sought medical attention, it did not include more severe head injuries that required hospitalization or extensive emergency care. To that extent, his findings may have underestimated the magnitude of the absolute risks at hand.

Yet many people are not aware of these risks.

Redelmeier is adamant that people should take concussions seriously. “We need to do more research about prevention and recovery,” he says. “But let me at least articulate three things to do: One, give yourself permission to get some rest. Two, when you start to feel better, don’t try to come back with a vengeance. And three, even after you’re feeling better, after you’ve rested properly, don’t forget about it entirely. If you had an allergic reaction to penicillin 15 years ago, you’d want to mention that to your doctor and have it as a permanent part of your medical record. So, too, if you’ve had a concussion 15 years ago.”

New Estimate Boosts the Human Brain's Memory Capacity 10-Fold

The human brain’s memory-storage capacity is an order of magnitude greater than previously thought, researchers at the Salk Institute for Biological Studies reported last week. The findings, recently detailed ineLife, are significant not only for what they say about storage space but more importantly because they nudge us toward a better understanding of how, exactly, information is encoded in our brains.

The question of just how much information our brains can hold is a longstanding one. We know that the human brain is made up of about 100 billion neurons, and that each one makes 1,000 or more connections to other neurons, adding up to some 100 trillion in total. We also know that the strengths of these connections, or synapses, are regulated by experience. When two neurons on either side of a synapse are active simultaneously, that synapse becomes more robust; the dendritic spine (the antenna on the receiving neuron) also becomes larger to support the increased signal strength. These changes in strength and size are believed to be the molecular correlates of memory. The different antenna sizes are often compared with bits of computer code, only instead of 1s and 0s they can assume a range of values. Until last week scientists had no idea how many values, exactly. Based on crude measurements, they had identified just three: small, medium and large.

But a curious observation led the Salk team to refine those measurements. In the course of reconstructing a rat hippocampus, an area of the mammalian brain involved in memory storage, they noticed some neurons would form two connections with each other: the axon (or sending cable) of one neuron would connect with two dendritic spines (or receiving antennas) on the same neighboring neuron, suggesting that duplicate messages were being passed from sender to receiver. Because both dendrites were receiving identical information, the researchers suspected they would be similar in size and strength. But they also realized that if there were significant differences between the two, it could point to a whole new layer of complexity. If the spines were of a different shape or size, they reasoned, the message they passed along would also be slightly different, even if that message was coming from the same axon.

So they decided to measure the synapse pairs. And sure enough, they found an 8 percent size difference between dendritic spines connected to the same axon of a signaling neuron. That difference might seem small, but when they plugged the value into their algorithms, they calculated a total of 26 unique synapse sizes. A greater number of synapse sizes means more capacity for storing information, which in this case translated into a 10-fold greater storage capacity in the hippocampus as a whole than the previous three-size model had indicated. “It’s an order of magnitude more capacity than we knew was there,” says Tom Bartol, a staff scientist at the Salk Institute and the study’s lead author.

But if our memory capacity is so great, why do we forget things? Because capacity is not really the issue, says Paul Reber, a memory researcher at Northwestern University who was not involved in the study, “Any analysis of the number of neurons will lead to a sense of the tremendous capacity of the human brain. But it doesn’t matter because our storage process is slower than our experience of the world. Imagine an iPod with infinite storage capacity. Even if you can store every song ever written, you still have to buy and upload all that music and then pull individual songs up when you want to play them.”

Reber says that it is almost impossible to quantify the amount of information in the human brain, in part because it consists of so much more information than we’re consciously aware of: not only facts and faces and measurable skills but basic functions like how to speak and move and higher order ones like how to feel and express emotions. “We take in much more information from the world than ‘what do I remember from yesterday?’” Reber says. “And we still don’t really know how to scale up from computing synaptic strength to mapping out these complex processes.”

The Salk study brings us a bit closer, though. “They’ve done an amazing reconstruction,” Reber says. “And it adds significantly to our understanding of not only memory capacity but more importantly of how complex memory storage actually is.” The findings might eventually pave the way toward all manner of advances: more energy-efficient computers that mimic the human brain’s data-transmission strategies, for example, or a better understanding of brain diseases that involve dysfunctional synapses.

But first scientists will have to see if the patterns found in the hippocampus hold for other brain regions. Bartol’s team is already working to answer this question. They hope to map the chemicals, which pass from neuron to neuron, that have an even greater capacity than the variable synapses to store and transmit information. As far as a precise measurement of whole-brain capacity, “we are still a long way off,” Bartol says. “The brain still holds many, many more mysteries for us to discover.”

Is Dementia Risk Falling?

Amid gloomy reports of an impending epidemic of Alzheimer’s and other dementias, emerging research offers a promising twist. Recent studies in North America, the U.K. and Europe suggest that dementia risk among seniors in some high-income countries has dropped steadily over the past 25 years. If the trend is driven by midlife factors such as building “brain reserve” and maintaining heart health, as some experts suspect, this could lend credence to staying mentally engaged and taking cholesterol-lowering drugs as preventive measures.

At first glance, the overall message seems somewhat confusing. Higher life expectancy and falling birth rates are driving up the global elderly population. “And if there are more 85-year-olds, it’s almost certain there will be more cases of age-related diseases,” says Ken Langa, professor of internal medicine at the University of Michigan. According to the World Alzheimer Report 2015 (pdf), 46.8 million people around the globe suffered from dementia last year, and that number is expected to double every 20 years.

Looking more closely, though, new epidemiological studies reveal a surprisingly hopeful trend. Analyses conducted over the last decade in the U.S., Canada, England, the Netherlands, Sweden and Denmark suggest that “a 75- to 85-year-old has a lower risk of having Alzheimer’s today than 15 or 20 years ago,” says Langa, who discussed the research on falling dementia rates in a 2015 Alzheimer’s Research & Therapycommentary (pdf).

Some of the clearest evidence comes from the Cognitive Function and Aging Study (CFAS), led by Carol Brayne, professor of public health medicine at the University of Cambridge. This study surveyed adults in the U.K. 65 or older in Cambridgeshire, Newcastle and Nottingham in the 1990s and again around 2010. During that period, dementia rates in the older population fell 24 percent—from 8.3 to 6.5 percent. Put another way: if the frequency of dementia in seniors had stayed the same across that period, there should have been 214,000 additional people with dementia than the 670,000 documented.

HEALTHY BRAIN VS. BRAIN WITH SEVERE ALZHEIMER'S DISEASE. CREDIT: NATIONAL INSTITUTE ON AGING/NATIONAL INSTITUTES OF HEALTH

Studies in Canada as well as the Netherlands, Sweden and elsewhere in Europe also suggest that dementia risk has declined in the past few decades. In the U.S. Langa and colleagues reported in Alzheimer’s & Dementia that the percent of adults over 70 years of age with cognitive impairment dropped from 12.2 to 8.7 between 1993 and 2002. The seniors were part of an ongoing longitudinal study funded by the National Institute on Aging (NIA), which surveys a representative sample of 20,000 older adults in the U.S. every two years.

But other research does not underscore this trend. A study led by Denis Evans, director of the Rush Institute for Healthy Aging in Chicago sends a more sobering message. The researchers measured new cases of Alzheimer’s between 1997 and 2008 and found no change in disease risk over time. Another study estimated, based on U.S. Census Bureau data, that the number of people with Alzheimer’s will nearly triple by 2050—and the percentage of seniors with dementia will creep upward.

All things considered, Langa agrees it’s very likely that due to higher life expectancy the absolute number of people with Alzheimer’s and other dementias will go up in the coming years. He notes, however, if an older adult’s risk for dementia continues declining as it has in some high-income countries over the last few decades, “that increase in number of cases may be a little less eye-popping than it would be if the risk were staying the same.”

The different results could have come from different starting assumptions—Evans assumes the number of new dementia cases will stay the same in coming decades, while Langa takes into account the possibility that dementia risk could decline because of changes in lifestyle and health prevention measures in the last quarter century.

What could be driving the apparent downward trend in dementia frequency? Although the question cannot be answered definitively, other analyses have linked lower dementia risk to better control of cardiovascular risk factors such as hypertension and high cholesterol, and by building up “cognitive reserve” with more education. People with chronic health conditions, however, add additional complexity to the picture. Those with type 2 diabetes, for example, are at higher risk for dementia. In light of rising levels of diabetes—as well as obesity—it’s possible these conditions could offset or override the downward dementia trend going forward, Langa says.

Epidemiological studies such as these could be further complicated by an artificial rise in reported dementia cases due to several factors. One is simply a growing awareness of Alzheimer’s disease. As a result, physicians may be more likely to make a diagnosis today, compared with decades ago, even in someone with the same level of cognitive impairment. They may also be more prone to list Alzheimer’s as a cause of mortality on death certificates. Second, neuroimaging and basic science research aimed at identifying potential treatments is shifting the field’s focus to earlier in the disease trajectory, driven by the belief that interventions stand the greatest chance in people who have not become too impaired. There is yet no cure for Alzheimer’s, although some drugs can alleviate symptoms. “From a clinical point of view, the concept of dementia syndrome has changed,” Brayne says. “Using current criteria, people get diagnosed at a much earlier stage.”

Despite the possible influence of growing disease awareness and changing diagnostic standards, bigger problems with assessing dementia rates could be methodological, says John Haaga, NIA deputy director for behavioral and social research. Different labs use different measures; the same group might use two measures 15 years apart. “How much change is real and how much is due to measurement differences?” Haaga says.

Evans sees a more fundamental problem with epidemiological studies of chronic disorders in older people. Although the diseases are scored in a binary fashion—you have it or you don’t—their underlying causes are often a continuous process. “When you diagnose Alzheimer’s disease, what you’re doing is placing a cut point on a bell-shaped curve” of cognitive function, Evans says. “You’re cutting off one tail to separate ‘Alzheimer’s’ from ‘non-Alzheimer’s.’” Putting the cut point in the same place every time is challenging. Well-trained researchers “will vary in how they do it,” Evans says. Yet because it is a point in the curve where the slope is changing sharply, even “a slight difference in where they place the cut can make a big difference in the number of people in the tail.”

On the whole, though, Haaga thinks the epidemiological data on dementia is improving. Whereas in the past “we were often extrapolating from small samples,” he says, “we’re now starting to be able to talk confidently about what the trends are in national populations.” Plus, efforts are underway to harmonize data sets, which should make it easier to compare results across different studies. That will become especially important as data comes in from other parts of the world—such as developing countries where the relative growth in dementia cases is predicted to exceed that of high-income nations.

Two thirds (66 percent) of people with dementia live in low- and middle-income countries, where less than 10 percent of population-based research has been conducted. Aptly named, the 10/66 study is investigating dementia and aging trends in these very regions. In India, for example, people do not live as long as they do in many developed countries, but life expectancy is continuing to go up, prompting a sharper rise in the number of dementia cases among the elderly. “In order to get Alzheimer’s or other dementias, you have to live long enough,” Langa says.

But changes in average life span can have different effects on different diseases. Eileen Crimmins, a gerontologist at the University of Southern California, studies how life expectancy influences chronic disease burden, as measured by the time one needs help and care. Two factors contribute to this: changes in mortality and changes in disease onset. “It is possible to end up with more people sick for a longer time when you are delaying death,” Crimmins told Scientific American via e-mail. “This is what has happened with heart disease.” More people in the U.S. are living with heart disease today, compared with decades ago, even though rates of death due to heart disease have gone down. Mortality and disease onset trends have played out more favorably for dementia, however. Nowadays fewer people have cognitive impairment, and people are not living as long with cognitive impairment, Crimmins says.

Crimmins, Brayne and Langa will discuss the research on falling dementia risk in a February 13 panel at the annual meeting of the American Association for the Advancement of Science in Washington, D.C. The trend is “intriguing and wonderful,” says NIA’s Haaga, who will moderate the panel. However, “I don’t want to give the impression that somehow the problem is now solved.” Even if progressively smaller percentages of the growing elderly population develop dementia in years to come, Haaga says, Alzheimer’s “is already the most expensive disease in the U.S., and it will continue to grow.”

Worldwide, the cost of dementia in 2015 was estimated at $818 billion. By 2030, it is expected to become a $2-trillion disease. As far as individual risk is concerned, however, “things are not getting worse,” Crimmins says. “Even if it is only a start of a trend, the likelihood of your getting dementia is getting smaller.”