Posts Tagged ‘science’

Olorgesailie Basin: the dig site spans an area of 65 square kilometres

This is according to a series of papers published today in Science.

The results come from an archaeological site in Kenya’s rift valley. “Over one million years of time” is represented at the site, according to Rick Potts from the Smithsonian Institution, who was involved in the studies.

There are also signs of developments in toolmaking technologies.

Environmental change may have been a key influence in this evolution of early Homo sapiens in the region of the Olorgesailie dig site.

The world turned upside down

Early humans were in the area for about 700,000 years, making large hand axes from nearby stone, explained Dr Potts.

“[Technologically], things changed very slowly, if at all, over hundreds of thousands of years,” he said.

Then, roughly 500,000 years ago, something did change.

A period of tectonic upheaval and erratic climate conditions swept across the region, and there is a 180,000 year interruption in the geological record due to erosion.

It was not only the landscape that altered, but also the plant and animal life in the region – transforming the resources available to our early ancestors.

When the record resumes, the way of life of these early humans has completely changed.

“The speed of the transition is really remarkable,” Dr Potts said. “Sometime in that [gap] there was a switch, a very rapid period of evolution.”

The obsidian road

New tools appeared at this time – small, sharp blades and points made from obsidian, a dark volcanic glass.

This technology marks the transition to what is known as the Middle Stone Age, explained Dr Eleanor Scerri from the University of Oxford.

Rather than shaping a block of rock, into a hand axe, humans became interested in the sharp flakes that could be chipped off. These were mounted on spears and used as projectile weapons.

Where 98% of the rock previously used by people in the Olorgesailie area had come from within a 5km radius, there were no sources of obsidian nearby.

People were travelling from 25km to 95km across rugged terrain to obtain the material, and “interacting with other groups of early humans over that time period”, according to Dr Potts.

This makes the site the earliest known example of such long distance transport, and possibly of trade.

(l to r) Hand axes, obsidian sharps and colour pigments discovered at the site

There is additional evidence that the inhabitants, who would likely have lived in small groups of 20-25 people, also used pigments like ochre. It is unclear whether these were merely practical or had a ritual social application.

Dr Marta Mirazon Lahr from the University of Cambridge said that being able to “securely date” the continuous occupation of the site using argon techniques on volcanic deposits “makes Olorgesailie a key reference site for understanding human evolution in Africa during [this period]”.

Human origins

Dr Scerri, who was not involved in the studies, emphasised that they are valuable in implying that “Middle Stone Age technology emerged at the same time in both eastern and northwestern Africa.”

Prof Chris Stringer from the Natural History Museum agrees.

“This makes me think that the Middle Stone Age probably already existed in various parts of Africa by 315,000 years ago, rather than originating in one place at that time and then spreading,” he said.

While the behaviours exhibited at the Kenya site are characteristic of Homo sapiens, there are as yet no fossils associated with this time period and location.

The oldest known Homo sapiens fossils were discovered in Morocco, and are dated to between 300,000 and 350,000 years old.


By Tereza Pultarova

About 4 percent of the people on Earth experience a mysterious phenomenon called synesthesia: They hear a sound and automatically see a color; or, they read a certain word, and a specific hue enters their mind’s eye. The condition has long puzzled scientists, but a small new study may offer some clues.

The study, published March 5 in the journal Proceedings of the National Academy of Sciences, offers insight into what might be happening in the brains of people with synesthesia.

Previous “studies of brain function using magnetic resonance imaging confirm that synesthesia is a real biological phenomenon,” said senior study author Simon Fisher, director of the Max Planck Institute for Psycholinguistics in the Netherlands. For example, when people with synesthesia “hear” color, brain scans show that there’s activity in the parts of the brain linked to both sight and sound, he said. (Not all people with the condition “hear” sights, however; the condition can also link other senses.)Indeed, the brains of people with synesthesia previously have been shown to be more connected across different regions than the brains of people whose senses are not cross-linked, Fisher told Live Science. The question, however, was what causes this different brain wiring, he said.

To answer that question, Fisher and his team looked to genetics.

Synesthesia frequently runs in families, so the researchers decided to look for genes that might be responsible for the development of the condition. They chose three families, in which multiple members across at least three generations had a specific type of synesthesia, the so-called sound-color synesthesia, meaning that hearing sounds evokes perceptions of colors. Typically, a specific sound or musical tone is consistently associated with a specific color for people who have this type of synesthesia. However, different members of a single family can see different colors when hearing the same sound, Fisher said.

The scientists used DNA sequencing to study the participants’ genes, Fisher said. Then, to identify genes that might be responsible for the condition, the scientists compared the genes of family members with synesthesia to the genes of family members without it, he said.

But the findings didn’t yield a straightforward result: “There was not a single gene that could explain synesthesia in all three families,” Fisher said. Instead, “there were 37 candidate variants,” or possible gene variations, he said.

Because the study included only a small number of people, there wasn’t enough data to single out the specific genes, of the 37 possibilities, that played a role in synesthesia. So, instead, the scientists looked at the biological functions of each gene to see how it could be related to the development of the condition. “There were just a few biological themes that were significantly enriched across the candidate genes identified,” Fisher said. “One of those was axonogenesis, a crucial process helping neurons get wired up to each other in the developing brain.” Axonogenesis refers to the development of neurons.

This is consistent with prior findings of altered connectivity in brain scans of people with synesthesia, Fisher said. In other words, the genes identified in the study play a role in how the brain is wired, offering a potential explanation for why the brains of people with synesthesia appear to be wired differently.


By Richard Kemeny

According to much of the scientific literature, dominance in social animals goes hand-in-hand with healthier lives. Yet leaders of the pack might not be healthier in all aspects, and according to a study published last week (February 26) in Scientific Reports, they are more at risk of parasite infection.

“While high-ranking animals often have the best access to food and mates, these advantages appear to come with strings attached,” says study coauthor Elizabeth Archie, a behavioral and disease ecologist at the University of Notre Dame, in an email to The Scientist. “These strings take the form of higher parasite exposure and susceptibility.”

Lower social status is usually linked to poorer health, according to previous studies. Animals towards the bottom of hierarchies have to struggle more for resources, and are often subjected to aggressive behavior from their superiors. In many species of birds, mice, and nonhuman primates, for instance, poorer physical condition is more common for subordinates. Female macaques of low social status, for example, have been shown to have lower bone density and an increased risk of developing inflammatory diseases.

Yet the relationship between social subordination and infectious disease risk hasn’t been clearly measured, according Archie and her coauthors. To look at the relationship between social status and one particular malady—parasite infections—they carried out a meta-analysis of 39 studies spanning 31 species, searching for patterns of parasitism.

In the majority of studies, those individuals in dominant positions—in particular, dominant males—were found to be more at risk of being infected. The effect was strongest in mammals, and in ordered hierarchical societies where social status is correlated with sexual activity.

These findings support two previous hypotheses about the links between social status and parasitism. One relates infection risk to resource access: exposure to infection is more common when animals feed and mate more. Dominant reindeer, for example, spend more time eating than subordinate individuals, and are more likely to become infected by nematodes. And greater sexual activity brings more risk of transmitted infections. Take, for instance, dominant feral cats, whose sexual proclivity increases the chances of developing Feline Immunodeficiency Virus.

The other hypothesis proposes a trade-off between reproductive effort and immunity to disease. In other words, those in dominant positions expend more energy on mating, and therefore invest less into costly immune defences.

“When you put it in the context [of these hypotheses], it does make a lot of sense,” says Jennifer Koop, a biologist at the University of Massachusetts-Dartmouth, who was not involved in the study.

Archie doesn’t think that individuals will deliberately opt for lower status in order to avoid infection. “High status comes with so many other advantages that the cost of a few more parasites might not be enough for individuals to shun high social status,” she says.

It’s also conceivable that there are benefits to both parasite and host in this relationship, says Nicole Mideo, an evolutionary biologist at the Univeristy of Toronto, who was not involved in the study. “The parasites are exploiting the resources of the host, so if you have a host that doesn’t get access to much food, then the parasite isn’t going to get access to much food,” she says.

This study mostly focused on parasitic worms, a limitation the researchers want to expand beyond. Additionally, the toll on dominant animals’ health of the increased risk of parasite infections was not explored. Mideo explains that there could be subtle advantages here, as research has shown worms can alter immune systems, and might protect against other infections. “It’s entirely possible that having worm infections does confer some sort of advantage in the context of other potential diseases,” she says.

Habig et al., “Social status and parasitism in male and female vertebrates: a meta-analysis,” Scientific Reports, doi:10.1038/s41598-018-21994-7, 2018.


A group of genes and genetic switches involved in age-related brain deterioration have been identified by scientists at the Babraham Institute, Cambridge and Sapienza University, Rome. The research, published online today (5th March) in Aging Cell, found that changes to one of these genes, called Dbx2, could prematurely age brain stem cells, causing them to grow more slowly. The study was led jointly by Giuseppe Lupo and Emanuele Cacci in Italy and Peter Rugg-Gunn in the UK.

Cells in the brain are constantly dying and being replaced with new ones produced by brain stem cells. As we age, it becomes harder for these stem cells to produce new brain cells and so the brain slowly deteriorates. By comparing the genetic activity in brain cells from old and young mice, the scientists identified over 250 genes that changed their level of activity with age. Older cells turn some genes, including Dbx2, on and they turn other genes off.

By increasing the activity of Dbx2 in young brain stem cells, the team were able to make them behave more like older cells. Changes to the activity of this one gene slowed the growth of brain stem cells. These prematurely aged stem cells are not the same as old stem cells but have many key similarities. This means that many of the genes identified in this study are likely to have important roles in brain ageing.

The research also identified changes in several epigenetic marks – a type of genetic switch – in the older stem cells that might contribute to their deterioration with age. Epigenetic marks are chemical tags attached to the genome that affect the activity of certain genes. The placement of these marks in the genome change as we age and this alters how the cells behave. The researchers think that some of these changes that happen in the brain may alter causing brain stem cells to grow more slowly.

First author on the paper, Dr Giuseppe Lupo, Assistant Professor at Sapienza University said: “The genes and gene regulators that we identified are corrupted in neural stem cells from older mice. By studying the Dbx2 gene we have shown that these changes may contribute to ageing in the brain by slowing the growth of brain stem cells and by switching on the activity of other age-associated genes.”

Co-lead scientist Dr Peter Rugg-Gunn at the Babraham Institute said: “Ageing ultimately affects all of us and the societal and healthcare burden of neurodegenerative diseases is enormous. By understanding how ageing affects the brain, at least in mice, we hope to identify ways to spot neural stem cell decline. Eventually, we may find ways to slow or even reverse brain deterioration – potentially by resetting the epigenetic switches – helping more of us to stay mentally agile for longer into old age.”

Co-lead scientist Dr Emanuele Cacci at Sapienza University said: “We hope this research will lead to benefits for human health. We have succeeded in accelerating parts of the ageing process in neural stem cells. By studying these genes more closely, we now plan to try turning back the clock for older cells. If we can do this in mice, then the same thing could also be possible for humans.”

This article has been republished from materials provided by the Babraham Institute. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Lupo, G., Nisi, P. S., Esteve, P., Paul, Y.-L., Novo, C. L., Sidders, B., … Rugg-Gunn, P. J. (n.d.). Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline. Aging Cell, n/a-n/a.


For the first time, an international team of scientists, led by researchers at University of California San Diego School of Medicine, have determined that an Alzheimer’s disease (AD) polygenic risk score can be used to correctly identify adults with mild cognitive impairment (MCI) who were only in their 50s. MCI is considered a precursor to AD.

Findings were published in the February 27 online edition of Molecular Psychiatry.

The AD polygenic risk score was created from genome-wide association studies of AD with a combination of genes weighted according to the association of single nucleotide polymorphisms (SNPs) with AD. SNPs are variations of a single nucleotide or DNA-building block that occur at a specific position in the genome. There is some SNP variation in genomic information in all humans, which affects individual susceptibility to disease.

“Current studies of the AD polygenic risk score typically occur in adults in their 70s, but the AD pathological process begins decades before the onset of dementia,” said William S. Kremen, PhD, professor of psychiatry and co-director of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine. “By focusing on a younger population with cognitive impairment, we may be better able to identify patients for critical early interventions and clinical trials.”

Kremen and team found that someone with an AD polygenic risk score in the upper quartile was 2.5 to 3 times more likely to have MCI than someone with a score in the lowest quartile. Signs of MCI may include difficulty with word recall, forgetting appointments, or often losing personal belongings. The type of MCI most associated with memory loss is called amnestic MCI.

According to the National Institute on Aging, more people with MCI than those without it go on to develop Alzheimer’s. Approximately eight of every 10 persons who fit the definition of amnestic MCI develop Alzheimer’s disease within seven years.

“Our research team found that the polygenic score could differentiate individuals with mild cognitive impairment from those who were cognitively normal,” said Kremen. “We also noticed that for study participants who had cognitive deficits other than memory problems, diabetes was three-fold more likely.”

Kremen added that while this test is not yet available to primary care physicians, it may be an important tool to aid researchers in predicting MCI and AD, and, eventually, reducing the number of future cases.

“The Alzheimer’s Association and others have modeled how the impact of delaying the onset of AD by five years could reduce the number of cases by nearly 50 percent by 2050. We want to do what we can to make this projection a reality,” said Kremen.

Data for this study were collected from 1,329 men who participated in the Vietnam Era Twin Study of Aging (VESTA.). VESTA constitutes a national sample comparable to U.S. men in their age range with respect to health and lifestyle characteristics. Approximately 90 percent of subjects in this analysis were in their 50s. Diagnosis of AD was based on the Jak-Bondi actuarial/neuropsychological approach.

This article has been republished from materials provided by UCSD. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Logue, M. W., Panizzon, M. S., Elman, J. A., Gillespie, N. A., Hatton, S. N., Gustavson, D. E., … Kremen, W. S. (2018). Use of an Alzheimer’s disease polygenic risk score to identify mild cognitive impairment in adults in their 50s. Molecular Psychiatry, 1.


3D reconstruction of a serotonin receptor generated by cryo-electron microscopy

by Rebecca Pool

Claiming a world first and using cryo-electron microscopy, researchers from Case Western Reserve University School of Medicine, US, have observed full-length serotonin receptors. The proteins are common drug targets, and the new images provide details about molecular binding sites that could lead to more precise drug design. Serotonin receptors, which reside in cell membranes throughout the body, are highly dynamic and difficult to image. In the past, the receptors have been sectioned into pieces to study, but by capturing full-length samples, researchers have revealed how different portions interact.

Dr Sandip Basak from Physiology and Biophysics, and colleagues, describe ‘a finely tuned orchestration of three domain movements’ that allows the receptors to elegantly control passageways across cell membranes. “The serotonin receptor acts as a gateway, or channel, from outside the cell to inside,” he says. “When serotonin binds onto the receptor, the channel switches conformation from closed to open. It eventually twists into a ‘desensitized’ state, where the channel closes but serotonin remains attached,” he adds. “This prevents it from being reactivated.”

For this study, the researchers used a FEI Titan Krios microscope, operating at 300 kV, and equipped with a Gatan K2-Summit direct detector camera, at the National Cryo-Electron Microscopy Facility in Frederick, Maryland.

“Successful design of safer therapeutics [for cancer therapies and gastrointestinal diseases] has slowed because there is currently a limited understanding of the structure of the serotonin receptor itself, and what happens after serotonin binds,” says research leader, Professor Sudha Chakrapani. “Our new structure of the serotonin receptor in the resting state has the potential to serve as a structural blueprint to drive targeted drug design and better therapeutic strategies.”

This research is published in Nature Communications.


Illustration by Paweł Jońca

by Helen Thomson

In March 2015, Li-Huei Tsai set up a tiny disco for some of the mice in her laboratory. For an hour each day, she placed them in a box lit only by a flickering strobe. The mice — which had been engineered to produce plaques of the peptide amyloid-β in the brain, a hallmark of Alzheimer’s disease — crawled about curiously. When Tsai later dissected them, those that had been to the mini dance parties had significantly lower levels of plaque than mice that had spent the same time in the dark.

Tsai, a neuroscientist at Massachusetts Institute of Technology (MIT) in Cambridge, says she checked the result; then checked it again. “For the longest time, I didn’t believe it,” she says. Her team had managed to clear amyloid from part of the brain with a flickering light. The strobe was tuned to 40 hertz and was designed to manipulate the rodents’ brainwaves, triggering a host of biological effects that eliminated the plaque-forming proteins. Although promising findings in mouse models of Alzheimer’s disease have been notoriously difficult to replicate in humans, the experiment offered some tantalizing possibilities. “The result was so mind-boggling and so robust, it took a while for the idea to sink in, but we knew we needed to work out a way of trying out the same thing in humans,” Tsai says.

Scientists identified the waves of electrical activity that constantly ripple through the brain almost 100 years ago, but they have struggled to assign these oscillations a definitive role in behaviour or brain function. Studies have strongly linked brainwaves to memory consolidation during sleep, and implicated them in processing sensory inputs and even coordinating consciousness. Yet not everyone is convinced that brainwaves are all that meaningful. “Right now we really don’t know what they do,” says Michael Shadlen, a neuroscientist at Columbia University in New York City.

Now, a growing body of evidence, including Tsai’s findings, hint at a meaningful connection to neurological disorders such as Alzheimer’s and Parkinson’s diseases. The work offers the possibility of forestalling or even reversing the damage caused by such conditions without using a drug. More than two dozen clinical trials are aiming to modulate brainwaves in some way — some with flickering lights or rhythmic sounds, but most through the direct application of electrical currents to the brain or scalp. They aim to treat everything from insomnia to schizophrenia and premenstrual dysphoric disorder.

Tsai’s study was the first glimpse of a cellular response to brainwave manipulation. “Her results were a really big surprise,” says Walter Koroshetz, director of the US National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. “It’s a novel observation that would be really interesting to pursue.”

A powerful wave

Brainwaves were first noticed by German psychiatrist Hans Berger. In 1929, he published a paper describing the repeating waves of current he observed when he placed electrodes on people’s scalps. It was the world’s first electroencephalogram (EEG) recording — but nobody took much notice. Berger was a controversial figure who had spent much of his career trying to identify the physiological basis of psychic phenomena. It was only after his colleagues began to confirm the results several years later that Berger’s invention was recognized as a window into brain activity.

Neurons communicate using electrical impulses created by the flow of ions into and out of each cell. Although a single firing neuron cannot be picked up through the electrodes of an EEG, when a group of neurons fires again and again in synchrony, it shows up as oscillating electrical ripples that sweep through the brain.

Those of the highest frequency are gamma waves, which range from 25 to 140 hertz. People often show a lot of this kind of activity when they are at peak concentration. At the other end of the scale are delta waves, which have the lowest frequency — around 0.5 to 4 hertz. These tend to occur in deep sleep (see ‘Rhythms of the mind’).

At any point in time, one type of brainwave tends to dominate, although other bands are always present to some extent. Scientists have long wondered what purpose, if any, this hum of activity serves, and some clues have emerged over the past three decades. For instance, in 1994, discoveries in mice indicated that the distinct patterns of oscillatory activity during sleep mirrored those during a previous learning exercise. Scientists suggested that these waves could be helping to solidify memories.

Brainwaves also seem to influence conscious perception. Randolph Helfrich at the University of California, Berkeley, and his colleagues devised a way to enhance or reduce gamma oscillations of around 40 hertz using a non-invasive technique called transcranial alternating current stimulation (tACS). By tweaking these oscillations, they were able to influence whether a person perceived a video of moving dots as travelling vertically or horizontally.

The oscillations also provide a potential mechanism for how the brain creates a coherent experience from the chaotic symphony of stimuli hitting the senses at any one time, a puzzle known as the ‘binding problem’. By synchronizing the firing rates of neurons responding to the same event, brainwaves might ensure that the all of the relevant information relating to one object arrives at the correct area of the brain at exactly the right time. Coordinating these signals is the key to perception, says Robert Knight, a cognitive neuroscientist at the University of California, Berkeley, “You can’t just pray that they will self-organize.”

Healthy oscillations

But these oscillations can become disrupted in certain disorders. In Parkinson’s disease, for example, the brain generally starts to show an increase in beta waves in the motor regions as body movement becomes impaired. In a healthy brain, beta waves are suppressed just before a body movement. But in Parkinson’s disease, neurons seem to get stuck in a synchronized pattern of activity. This leads to rigidity and movement difficulties. Peter Brown, who studies Parkinson’s disease at the University of Oxford, UK, says that current treatments for the symptoms of the disease — deep-brain stimulation and the drug levodopa — might work by reducing beta waves.

People with Alzheimer’s disease show a reduction in gamma oscillations5. So Tsai and others wondered whether gamma-wave activity could be restored, and whether this would have any effect on the disease.

They started by using optogenetics, in which brain cells are engineered to respond directly to a flash of light. In 2009, Tsai’s team, in collaboration with Christopher Moore, also at MIT at the time, demonstrated for the first time that it is possible to use the technique to drive gamma oscillations in a specific part of the mouse brain6.

Tsai and her colleagues subsequently found that tinkering with the oscillations sets in motion a host of biological events. It initiates changes in gene expression that cause microglia — immune cells in the brain — to change shape. The cells essentially go into scavenger mode, enabling them to better dispose of harmful clutter in the brain, such as amyloid-β. Koroshetz says that the link to neuroimmunity is new and striking. “The role of immune cells like microglia in the brain is incredibly important and poorly understood, and is one of the hottest areas for research now,” he says.

If the technique was to have any therapeutic relevance, however, Tsai and her colleagues had to find a less-invasive way of manipulating brainwaves. Flashing lights at specific frequencies has been shown to influence oscillations in some parts of the brain, so the researchers turned to strobe lights. They started by exposing young mice with a propensity for amyloid build-up to flickering LED lights for one hour. This created a drop in free-floating amyloid, but it was temporary, lasting less than 24 hours, and restricted to the visual cortex.

To achieve a longer-lasting effect on animals with amyloid plaques, they repeated the experiment for an hour a day over the course of a week, this time using older mice in which plaques had begun to form. Twenty-four hours after the end of the experiment, these animals showed a 67% reduction in plaque in the visual cortex compared with controls. The team also found that the technique reduced tau protein, another hallmark of Alzheimer’s disease.

Alzheimer’s plaques tend to have their earliest negative impacts on the hippocampus, however, not the visual cortex. To elicit oscillations where they are needed, Tsai and her colleagues are investigating other techniques. Playing rodents a 40-hertz noise, for example, seems to cause a decrease in amyloid in the hippocampus — perhaps because the hippo-campus sits closer to the auditory cortex than to the visual cortex.

Tsai and her colleague Ed Boyden, a neuro-scientist at MIT, have now formed a company, Cognito Therapeutics in Cambridge, to test similar treatments in humans. Last year, they started a safety trial, which involves testing a flickering light device, worn like a pair of glasses, on 12 people with Alzheimer’s.

Caveats abound. The mouse model of Alzheimer’s disease is not a perfect reflection of the disorder, and many therapies that have shown promise in rodents have failed in humans. “I used to tell people — if you’re going to get Alzheimer’s, first become a mouse,” says Thomas Insel, a neuroscientist and psychiatrist who led the US National Institute of Mental Health in Bethesda, Maryland, from 2002 until 2015.

Others are also looking to test how manipulating brainwaves might help people with Alzheimer’s disease. “We thought Tsai’s study was outstanding,” says Emiliano Santarnecchi at Harvard Medical School in Boston, Massachusetts. His team had already been using tACS to stimulate the brain, and he wondered whether it might elicit stronger effects than a flashing strobe. “This kind of stimulation can target areas of the brain more specifically than sensory stimulation can — after seeing Tsai’s results, it was a no-brainer that we should try it in Alzheimer’s patients.”

His team has begun an early clinical trial in which ten people with Alzheimer’s disease receive tACS for one hour daily for two weeks. A second trial, in collaboration with Boyden and Tsai, will look for signals of activated microglia and levels of tau protein. Results are expected from both trials by the end of the year.

Knight says that Tsai’s animal studies clearly show that oscillations have an effect on cellular metabolism — but whether the same effect will be seen in humans is another matter. “In the end, it’s data that will win out,” he says.

The studies may reveal risks, too. Gamma oscillations are the type most likely to induce seizures in people with photosensitive epilepsy, says Dora Hermes, a neuroscientist at Stanford University in California. She recalls a famous episode of a Japanese cartoon that featured flickering red and blue lights, which induced seizures in some viewers. “So many people watched that episode that there were almost 700 extra visits to the emergency department that day.”

A brain boost

Nevertheless, there is clearly a growing excitement around treating neurological diseases using neuromodulation, rather than pharmaceuticals. “There’s pretty good evidence that by changing neural-circuit activity we can get improvements in Parkinson’s, chronic pain, obsessive–compulsive disorder and depression,” says Insel. This is important, he says, because so far, pharmaceutical treatments for neurological disease have suffered from a lack of specificity. Koroshetz adds that funding institutes are eager for treatments that are innovative, non-invasive and quickly translatable to people.

Since publishing their mouse paper, Boyden says, he has had a deluge of requests from researchers wanting to use the same technique to treat other conditions. But there are a lot of details to work out. “We need to figure out what is the most effective, non-invasive way of manipulating oscillations in different parts of the brain,” he says. “Perhaps it is using light, but maybe it’s a smart pillow or a headband that could target these oscillations using electricity or sound.” One of the simplest methods that scientists have found is neurofeedback, which has shown some success in treating a range of conditions, including anxiety, depression and attention-deficit hyperactivity disorder. People who use this technique are taught to control their brainwaves by measuring them with an EEG and getting feedback in the form of visual or audio cues.

Phyllis Zee, a neurologist at Northwestern University in Chicago, Illinois, and her colleagues delivered pulses of ‘pink noise’ — audio frequencies that together sound a bit like a waterfall — to healthy older adults while they slept. They were particularly interested in eliciting the delta oscillations that characterize deep sleep. This aspect of sleep decreases with age, and is associated with a decreased ability to consolidate memories.

So far, her team has found that stimulation increased the amplitude of the slow waves, and was associated with a 25–30% improvement in recall of word pairs learnt the night before, compared with a fake treatment7. Her team is midway through a clinical trial to see whether longer-term acoustic stimulation might help people with mild cognitive impairment.

Although relatively safe, these kinds of technologies do have limitations. Neurofeedback is easy to learn, for instance, but it can take time to have an effect, and the results are often short-lived. In experiments that use magnetic or acoustic stimulation, it is difficult to know precisely what area of the brain is being affected. “The field of external brain stimulation is a little weak at the moment,” says Knight. Many approaches, he says, are open loop, meaning that they don’t track the effect of the modulation using an EEG. Closed loop, he says, would be more practical. Some experiments, such as Zee’s and those involving neuro-feedback, already do this. “I think the field is turning a corner,” Knight says. “It’s attracting some serious research.”

In addition to potentially leading to treatments, these studies could break open the field of neural oscillations in general, helping to link them more firmly to behaviour and how the brain works as a whole.

Shadlen says he is open to the idea that oscillations play a part in human behaviour and consciousness. But for now, he remains unconvinced that they are directly responsible for these phenomena — referring to the many roles people ascribe to them as “magical incantations”. He says he fully accepts that these brain rhythms are signatures of important brain processes, “but to posit the idea that synchronous spikes of activity are meaningful, that by suddenly wiggling inputs at a specific frequency, it suddenly elevates activity onto our conscious awareness? That requires more explanation.”

Whatever their role, Tsai mostly wants to discipline brainwaves and harness them against disease. Cognito Therapeutics has just received approval for a second, larger trial, which will look at whether the therapy has any effect on Alzheimer’s disease symptoms. Meanwhile, Tsai’s team is focusing on understanding more about the downstream biological effects and how to better target the hippocampus with non-invasive technologies.

For Tsai, the work is personal. Her grandmother, who raised her, was affected by dementia. “Her confused face made a deep imprint in my mind,” Tsai says. “This is the biggest challenge of our lifetime, and I will give it all I have.”