Neuroscience

Researchers at Lund University in Sweden have identified the molecular mechanism behind the transformation of one of the components in Alzheimer’s disease. They identified the crucial step leading to formations that kill brain cells.

Alzheimer’s disease is associated with memory loss and personality changes. It is still not known what causes the onset of the disease, but once started it cannot be stopped. The accumulation of plaques in the brain is widely considered a hallmark of the disease. The key discovery identified the chemical reaction that causes the plaques to grow exponentially.

Amyloid beta, a protein fragment that occurs naturally in the fluid around the brain, is one of the building blocks of plaques. However, the processes leading from soluble amyloid beta to the form found in the plaques, known as amyloid fibril, have not been known. In the very early part of the process, two protein fragments can create a nucleus that then grows into a fibril.

In solution this is a slow process, but the rate can be enhanced on surfaces. The current study shows that fibrils present a catalytic surface where new nuclei form and this reaction increases the speed of the process. As soon as the first fibrils are formed, amyloid-beta fragments attach at its surface and form new fibrils that subsequently detach.

This process is thus self-perpetuating, and autocatalytic, and the more fibrils are present, the quicker the new ones are created, says Sara Snogerup Linse, Professor of Chemistry at Lund University and one of the researchers behind the study.

The findings also show that the chemical reaction on the fibril surface creates cell-killing formations. It is hoped that the research could lead to a new type of medication targeting early stages of the disease in the future.

The results have emerged from several years of laboratory work by Professor Snogerup Linse and her colleague in Lund, Erik Hellstrand, including development of extensive methods to obtain amyloid beta in highly pure form and to study its transformation in a highly reproducible manner. Additional methodology based on isotope labelling and spin filters was developed to monitor the surface catalysis and pin-point the origin of the forms that kill brain cells. The collaboration with the theoretical group and cell biologists at Cambridge University has been absolutely crucial for all the findings.

In one of the first successful attempts at genetically engineering mosquitoes, HHMI researchers have altered the way the insects respond to odors, including the smell of humans and the insect repellant DEET. The research not only demonstrates that mosquitoes can be genetically altered using the latest research techniques, but paves the way to understanding why the insect is so attracted to humans, and how to block that attraction.

“The time has come now to do genetics in these important disease-vector insects. I think our new work is a great example that you can do it,” says Leslie Vosshall, an HHMI investigator at The Rockefeller University who led the new research, published May 29, 2013 in the journal Nature.

In 2007, scientists announced the completion of the full genome sequence of Aedes aegypti, the mosquito that transmits dengue and yellow fever. A year later, when Vosshall became an HHMI investigator, she shifted the focus of her lab from Drosophila flies to mosquitoes with the specific goal of genetically engineering the insects. Studying mosquitoes appealed to her because of their importance as disease carriers, as well as their unique attraction to humans.

Vosshall’s first target: a gene called orco, which her lab had deleted in genetically engineered flies 10 years earlier. “We knew this gene was important for flies to be able to respond to the odors they respond to,” says Vosshall. “And we had some hints that mosquitoes interact with smells in their environment, so it was a good bet that something would interact with orco in mosquitoes.”

Vosshall’s team turned to a genetic engineering tool called zinc-finger nucleases to specifically mutate the orco gene in Aedes aegypti. They injected the targeted zinc-finger nucleases into mosquito embryos, waited for them to mature, identified mutant individuals, and generated mutant strains that allowed them to study the role of orco in mosquito biology. The engineered mosquitoes showed diminished activity in neurons linked to odor-sensing. Then, behavioral tests revealed more changes.

When given a choice between a human and any other animal, normal Aedes aegypti will reliably buzz toward the human. But the mosquitoes with orco mutations showed reduced preference for the smell of humans over guinea pigs, even in the presence of carbon dioxide, which is thought to help mosquitoes respond to human scent. “By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans,” says Vosshall. But they don’t yet know whether the confusion stems from an inability to sense a “bad” smell coming from the guinea pig, a “good” smell from the human, or both.

Next, the team tested whether the mosquitoes with orco mutations responded differently to DEET. When exposed to two human arms—one slathered in a solution containing 10 percent DEET, the active ingredient in many bug repellants, and the other untreated—the mosquitoes flew equally toward both arms, suggesting they couldn’t smell the DEET. But once they landed on the arms, they quickly flew away from the DEET-covered one. “This tells us that there are two totally different mechanisms that mosquitoes are using to sense DEET,” explains Vosshall. “One is what’s happening in the air, and the other only comes into action when the mosquito is touching the skin.” Such dual mechanisms had been discussed but had never been shown before.

Vosshall and her collaborators next want to study in more detail how the orco protein interacts with the mosquitoes’ odorant receptors to allow the insects to sense smells. “We want to know what it is about these mosquitoes that makes them so specialized for humans,” she says. “And if we can also provide insights into how existing repellants are working, then we can start having some ideas about what a next-generation repellant would look like.”

In some neurodegenerative diseases, and specifically in a devastating inherited condition called spinocerebellar ataxia 1 (SCA1), the answer may not be an “all-or-nothing,” said a collaboration of researchers from Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and the University of Minnesota in a report that appears online in the journal Nature. The problem might be solved with just a little less.

"If you can only decrease the levels of ataxin-1 (the protein involved in SCA1) by 20 percent, you can reduce many symptoms of the disease," said Dr. Huda Zoghbi, professor of molecular and human genetics and pediatrics at BCM and director of the Neurological Research Institute. She is also a Howard Hughes Medical Institute Investigator.

Her long-time colleague Dr. Harry Orr, director of the University of Minnesota Institute for Translational Neuroscience, echoed that sentiment: “Perhaps, if you decrease the levels of the protein, you will decrease the severity of the disease.” In this report, the laboratories of Zoghbi, Dr. Juan Botas, also of BCM and the Neurological Researcher Institute, Dr. Thomas Westbrook, assistant professor of molecular and human genetics at BCM, and Orr identified a molecular pathway in the cell (RAS/MAPK/MSK1) with components that can be modulated slightly to reduce the levels of defective ataxin-1, the protein that causes disease in patients with the disorder.

Spinocerebellar ataxia 1 occurs when the ataxin-1 gene is mutated, with three letters of the DNA alphabet repeating many, many times. The abnormal protein that results cannot fold correctly and piles up in the cell, eventually killing it. As with many neurodegenerative disorders, the process can take over a decade. A person usually does not develop symptoms of this form of ataxia until he or she is 30 years old or older. The person develops gait problems, eventually loses the ability to speak and function and dies. Zoghbi and Orr teamed to find the gene associated with the disorder in 1993. Their work on the disease has spanned 20 years.

Totally eliminating the protein would not work. Mice that lack the gene have problems with learning and memory, indicating that ataxin-1 plays a role in those activities. Reducing the levels of ataxin-1 does not cure the disease, but it can significantly delay onset.

A Collaborative Innovation Award from the Howard Hughes Medical Institute enabled Zoghbi to put together the team that could screen for the genes or the gene pathway that could be manipulated to result in less ataxin-1.

"Harry and I had studied the disease and we had animal models. Botas, professor of molecular and human genetics at BCM, had a fruit fly model and Dr. Westbrook had a nice technology that enabled us to monitor ataxin-1 levels."

They began with a screen for genes that could affect the levels of ataxin-1 produced in the cell, said Dr. Ismail Al-Ramahi, a postdoctoral fellow in the lab of Botas. Dr. Jeehye Park, a post-doctoral fellow in Zoghbi’s laboratory, and Al-Ramahi are co-first authors of the report. Park and her colleagues carried out the screen in human cell lines and Al-Ramahi and his colleagues carried out the screen in fruit flies (Drosophila melanogaster).

The screen in human cells focused on forms of enzymes called kinases because they are susceptible to the effects of drugs. Using a special technique called RNA silencing, they targeted each known human kinase. At the same, Botas and Al-Ramahi screened kinase genes in fruit flies with a form of SCA1. When the two laboratories compared results, they found 10 genes in common that when inhibited could reduce the levels of ataxin-1 as well as the toxicity associated with it. The genes were part of the RAS/MAPK/MSKI signaling cascade within the cell.

Then the researchers focused on one protein in this pathway called MSK1 and found that when its levels were decreased in mice that were laboratory models of SCA1, the levels of ataxin-1 dropped and the animals improved. That was the final experiment that proved that reducing levels of the protein could stave off the disease.

"We want to look for more pathways," said Zoghbi. If they find more pathways, they may be able to reduce toxicity. "If you have a pain and you take acetaminophen all the time, you have a risk of toxicity. Similarly, if you took a nonsteroidal anti-inflammatory all the time, you would have another toxicity. If you alternate between them, there is less toxicity. If we hit only one pathway with a big inhibition, we risk some toxicity. If we find two or three pathways and hit each only a little, the rest of the body should not be hurt. Each little hit should help us reduce ataxin-1 by a respectable amount."

"I think what is novel about this paper is the integration of the screen in cells that was done in Huda’s lab and the screen in fruit flies done in our lab to look for targets for genes about which we knew nothing ahead of time," said Botas.

While the finding in spinocerebellar ataxia 1 is exciting, its potential application in other diseases is even more provocative.

"Now that we know that it works with ataxin-1, we can revisit many proteins whose levels drive neurodegeneration in sporadic and inherited diseases such as Alzheimer’s, Parkinson’s, Huntington’s and other neurological disorders," said Zoghbi. "This is a pilot study and the results from it are as important as a new pathway in neurodegenerative disease research."

"These are diseases that take a long time to develop," said Park. "Most Alzheimer’s occurs after the age of 85. If we could delay it until age 95, that would be very helpful."

"This is getting us really close, not only for SCA1, but I think it’s going to be a guidepost for work on a lot of other neurodegenerative diseases," said Orr. "It sets us a beautiful research strategy to get at that goal."

A team of researchers working at the University of California’s Memory and Aging Center has found that emotional contagion appears to increase in a linear progression with patients who have Alzheimer’s disease (AD). In their paper published in the journal Proceedings of the National Academy of Sciences, the team says their findings indicate that emotional contagion grows stronger in patients with both the precursor Mild Cognitive Impairment (MCI) and full-blown AD.

Emotional contagion is where one person mimics the emotions of another. The phenomenon is very common in human infants—upon seeing someone else smile, they tend to smile too. Babies have also been found to cry upon hearing other babies cry. The tendency to mimic others’ emotions regresses as people age, but this new study suggests it makes a reappearance in people who experience some forms of cognitive impairment later on in life.

Prior research has shown that AD causes damage to parts of the brain that are responsible for emotion—thus not all emotional problems with AD patients can be attributed to a natural human response to mental adversity. Both MCI and AD patients have been found to experience higher rates of depression and anxiety. Until now however, little research has been done to find out if people revert to mimicking the emotions of others as a type of response mechanism.

To learn more, the researchers performed psychological surveys on 120 people diagnosed with AD or MCI. Their inquiries focused mostly on emotional empathy. The team also enlisted the assistance of 111 healthy volunteers to serve as a control group. All of the participants also underwent MRI exams to test for levels of disease progression.

The brain scans revealed damage to the medial temporal lobe—known to be associated with emotional control—in those with dementia and also in the hippocampus, the part of the brain responsible for memory and recall.

An analysis of the results of the surveys and brain scans showed that emotional contagion became apparent in patients with MCI and grew more pronounced at each stage of the progression of AD. They also found that there appeared to be more of a connection between the degree of emotional contagion and damage to the right side of the medial temporal lobe, as compared to the left.

The researchers suggest that patients with dementia may mimic the emotions of others as their ability to gauge their own emotional state deteriorates. Doing so, they suggest, may help patients cope with their ailment. They add they it may also help patients hide their condition from others.

Down syndrome, the most common genetic form of intellectual disability, results from an extra copy of one chromosome. Although people with Down syndrome experience intellectual difficulties and other problems, scientists have had trouble identifying why that extra chromosome causes such widespread effects.

In new research published this week, Anita Bhattacharyya, a neuroscientist at the Waisman Center at UW-Madison, reports on brain cells that were grown from skin cells of individuals with Down syndrome.

"Even though Down syndrome is very common, it’s surprising how little we know about what goes wrong in the brain," says Bhattacharyya. "These new cells provide a way to look at early brain development."

The study began when those skin cells were transformed into induced pluripotent stem cells, which can be grown into any type of specialized cell. Bhattacharyya’s lab, working with Su-Chun Zhang and Jason Weick, then grew those stem cells into brain cells that could be studied in the lab.

One significant finding was a reduction in connections among the neurons, Bhattacharyya says. “They communicate less, are quieter. This is new, but it fits with what little we know about the Down syndrome brain.”  Brain cells communicate through connections called synapses, and the Down neurons had only about 60 percent of the usual number of synapses and synaptic activity. “This is enough to make a difference,” says Bhattacharyya. “Even if they recovered these synapses later on, you have missed this critical window of time during early development.”

The researchers looked at genes that were affected in the Down syndrome stem cells and neurons, and found that genes on the extra chromosome were increased 150 percent, consistent with the contribution of the extra chromosome.

However, the output of about 1,500 genes elsewhere in the genome was strongly affected. “It’s not surprising to see changes, but the genes that changed were surprising,” says Bhattacharyya. The predominant increase was seen in genes that respond to oxidative stress, which occurs when molecular fragments called free radicals damage a wide variety of tissues.

"We definitely found a high level of oxidative stress in the Down syndrome neurons," says Bhattacharyya. "This has been suggested before from other studies, but we were pleased to find more evidence for that. We now have a system we can manipulate to study the effects of oxidative stress and possibly prevent them."

Down syndrome includes a range of symptoms that could result from oxidative stress, Bhattacharyya says, including accelerated aging. “In  their 40s, Down syndrome individuals age very quickly. They suddenly get gray hair; their skin wrinkles, there is rapid aging in many organs, and a quick appearance of Alzheimer’s disease. Many of these processes may be due to increased oxidative stress, but it remains to be directly tested.”

Oxidative stress could be especially significant, because it appears right from the start in the stem cells. “This suggests that these cells go through their whole life with oxidative stress,” Bhattacharyya adds, “and that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer’s.”

Other researchers have created neurons with Down syndrome from induced pluripotent stem cells, Bhattacharyya notes. “However, we are the first to report this synaptic deficit, and to report the effects on genes on other chromosomes in neurons. We are also the first to use stem cells from the same person that either had or lacked the extra chromosome. This allowed us to look at the difference just caused by extra chromosome, not due to the genetic difference among people.”

The research, published the week of May 27 in the Proceedings of the National Academy of Sciences, was a basic exploration of the roots of Down syndrome. Bhattacharyya says that while she did not intend to explore treatments in the short term, “we could potentially use these cells to test or intelligently design drugs to target symptoms of Down syndrome.”

An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study by researchers at the University of Pittsburgh School of Medicine. The findings, reported this week in the early online version of the Proceedings of the National Academy of Sciences, reveal for the first time the reason the chronic and sometimes debilitating condition occurs.

An estimated 5 to 15 percent of Americans hear whistling, clicking, roaring and other phantom sounds of tinnitus, which typically is induced by exposure to very loud noise, said senior investigator Thanos Tzounopoulos, Ph.D., associate professor and member of the auditory research group in the Department of Otolaryngology, Pitt School of Medicine.

"There is no cure for it, and current therapies such as hearing aids don’t provide relief for many patients," he said. "We hope that by identifying the underlying cause, we can develop effective interventions."

The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells — they fire impulses even when there is no actual sound to perceive. For the new experiments, they took a close look at the biophysical properties of tiny channels, called KCNQ channels, through which potassium ions travel in and out of the cell.

"We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity," Dr. Tzounopoulos said. "These KCNQ channels act as effective "brakes" that reduce excitability or activity of neuronal cells."

In the model, sedated mice are exposed in one ear to a 116-decibel sound, about the loudness of an ambulance siren, for 45 minutes, which was shown in previous work to lead to the development of tinnitus in 50 percent of exposed mice. Dr. Tzounopoulos and his team tested whether an FDA-approved epilepsy drug called retigabine, which specifically enhances KCNQ channel activity, could prevent the development of tinnitus. Thirty minutes into the noise exposure and twice daily for the next five days, half of the exposed group was given injections of retigabine.

Seven days after noise exposure, the team determined whether the mice had developed tinnitus by conducting startle experiments, in which a continuous, 70 dB tone is played for a period, then stopped briefly and then resumed before being interrupted with a much louder pulse. Mice with normal hearing perceive the gap in sounds and are aware something had changed, so they are less startled by the loud pulse than mice with tinnitus, which hear phantom noise that masks the moment of silence in between the background tones.

The researchers found that mice that were treated with retigabine immediately after noise exposure did not develop tinnitus. Consistent with previous studies, 50 percent of noise-exposed mice that were not treated with the drug exhibited behavioral signs of the condition.

"This is an important finding that links the biophysical properties of a potassium channel with the perception of a phantom sound," Dr. Tzounopoulos said. "Tinnitus is a channelopathy, and these KCNQ channels represent a novel target for developing drugs that block the induction of tinnitus in humans."

The KCNQ family is comprised of five different subunits, four of which are sensitive to retigabine. He and his collaborators aim to develop a drug that is specific for the two KCNQ subunits involved in tinnitus to minimize the potential for side effects.

"Such a medication could be a very helpful preventive strategy for soldiers and other people who work in situations where exposure to very loud noise is likely," Dr. Tzounopoulos said. "It might also be useful for other conditions of phantom perceptions, such as pain in a limb that has been amputated."

Researchers at the Stanford University School of Medicine have identified mutations in several new genes that might be associated with the development of spontaneously occurring cases of the neurodegenerative disease known as amyotrophic lateral sclerosis, or ALS. Also known as Lou Gehrig’s disease, the progressive, fatal condition, in which the motor neurons that control movement and breathing gradually cease to function, has no cure.

Although researchers know of some mutations associated with inherited forms of ALS, the majority of patients have no family history of the disease, and there are few clues as to its cause. The Stanford researchers compared the DNA sequences of 47 patients who have the spontaneous form of the disease, known as sporadic ALS, with those of their unaffected parents. The goal was to identify new mutations that were present in the patient but not in either parent that may have contributed to disease development.

Several suspects are mutations in genes that encode chromatin regulators — cellular proteins that govern how DNA is packed into the nucleus of a cell and how it is accessed when genes are expressed. Protein members of one these chromatin-regulatory complexes have recently been shown to play roles in normal development and some forms of cancer.

"The more we know about the genetic causes of the disorder, the greater insight we will have as to possible therapeutic targets," said Aaron Gitler, PhD, associate professor of genetics. "Until now, researchers have primarily relied upon large families with many cases of inherited ALS and attempted to pinpoint genetic regions that seem to occur only in patients. But more than 90 percent of ALS cases are sporadic, and many of the genes involved in these cases are unknown."

Gitler is the senior author of the study, published online May 26 in Nature Neuroscience. Postdoctoral scholar Alessandra Chesi, PhD, is the lead author. Gitler and Chesi collaborated with members of the laboratory of Gerald Crabtree, MD, professor of developmental biology and of pathology. Crabtree, a Howard Hughes Medical Institute investigator, is also a co-author of the study.

Chesi and Gitler combined deductive reasoning with recent advances in sequencing technology to conduct the work, which relied on the availability of genetic samples from not only ALS patients, but also the patients’ unaffected parents. Such trios can be difficult to obtain for diseases like sporadic ALS that strike well into adulthood when a patient’s parents may no longer be alive. Gitler and Chesi collaborated with researchers from Emory University and Johns Hopkins University to collect these samples.

The researchers compared the sequences of a portion of the genome called the exome, which directly contributes to the amino acid sequences of all the proteins in a cell. (Many genes contain intervening, non-protein-coding regions of DNA called introns that are removed prior to protein production.) Mutations found only in the patient’s exome, but not in that of his or her parents’, were viewed as potential disease-associated candidates - particularly if they affected the composition or structure of the resulting protein made from that gene.

Focusing on just the exome, which is about 1 percent of the total amount of DNA in each human cell, vastly reduced the total amount of DNA that needed to be sequenced and allowed the researchers to achieve relatively high coverage (or repeated sequencing to ensure accuracy) of each sample.

"We wanted to find novel changes in the patients," Chesi said. "These represent a class of mutations called de novo mutations that likely occurred during the production of the parents’ reproductive cells." As a result, these mutations would be carried in all the cells of patients, but not in their parents or siblings.

Using the exome sequencing technique, the researchers identified 25 de novo mutations in the ALS patients. Of these, five are known to be in genes involved in the regulation of the tightly packed form of DNA called chromatin — a proportion that is much higher than would have been expected by chance, according to Chesi.

Furthermore, one of the five chromatin regulatory proteins, SS18L1, is a member of a neuron-specific complex called nBAF, which has long been studied in Crabtree’s laboratory. This complex is strongly expressed in the brain and spinal cord, and affects the ability of the neurons to form branching structures called dendrites that are essential to nerve signaling.

"We found that, in one sporadic ALS case, the last nine amino acids of this protein are missing," Gitler said. "I knew that Gerald Crabtree’s lab had been investigating SS18L1, so I asked him about it. In fact, they had already identified these amino acids as being very important to the function of the protein."

When the researchers expressed the mutant SS18L1 in motor neurons isolated from mouse embryos, they found the neurons were unable to extend and grow new dendrites as robustly as normal neurons in response to stimuli. They also showed that SS18L1 appears to physically interact with another protein known to be involved in cases of familial, or inherited, ALS.

Although the results are intriguing, the researchers caution that more work is necessary to conclusively prove whether and how mutations in SS18L1 contribute to sporadic cases of ALS. But now they have an idea of where to look in other patients, without requiring the existence of patient and parent trios. They are planning to sequence SS18L1 and other candidates in an additional few thousand sporadic ALS cases.

"This is the first systematic analysis of ALS triads for the presence of de novo mutations," Chesi said. "Now we have a list of candidate genes we can pursue. We haven’t proven that these mutations cause ALS, but we’ve shown, at least in the context of SS18L1, that the mutation carried by some patients is damaging to the protein and affects the ability of mouse motor neurons to form dendrites."

The adult brain is far more malleable that we thought, and so learning can be child’s play if you know how.

Some 36-year-olds choose to collect vintage wine, vinyl records or sports memorabilia. For Richard Simcott, it is languages. His itch to learn has led him to study more than 30 foreign tongues – and he’s not ready to give up.

During our conversation in a London restaurant, he reels off sentences in Spanish, Turkish and Icelandic as easily as I can name the pizza and pasta on our menu. He has learned Dutch on the streets of Rotterdam, Czech in Prague and Polish during a house share with some architects. At home, he talks to his wife in fluent Macedonian.

What’s remarkable about Simcott isn’t just the number and diversity of languages he has mastered. It’s his age. Long before grey hairs appear and waistlines expand, the mind’s cogs are meant to seize up, making it difficult to pick up any new skill, be it a language, the flute, or archery. Even if Simcott had primed his mind for new languages while at school, he should have faced a steep decline in his abilities as the years went by – yet he still devours unfamiliar grammars and strange vocabularies to a high level. “My linguistic landscape is always changing,” he says. “If you’re school-aged, or middle-aged – I don’t think there’s a big difference.”

A decade ago, few neuroscientists would have agreed that adults can rival the learning talents of children. But we needn’t be so defeatist. The mature brain, it turns out, is more supple than anyone thought. “The idea that there’s a critical period for learning in childhood is overrated,” says Gary Marcus, a psychologist at New York University. What’s more, we now understand the best techniques to accelerate knowledge and skill acquisition in adults, so can perhaps unveil a few tricks of the trade of super-learners like Simcott. Whatever you want to learn, it’s never too late to charge those grey cells.

The idea that the mind fossilises as it ages is culturally entrenched. The phrase “an old dog will learn no tricks" is recorded in an 18th century book of proverbs and is probably hundreds of years older.

When researchers finally began to investigate the adult brain’s malleability in the 1960s, their results appeared to agree with the saying. Most insights came indirectly from studies of perception, which suggested that an individual’s visual abilities were capped at a young age. For example, restricting young animals’ vision for a few weeks after birth means they will never manage to see normally. The same is true for people born with cataracts or a lazy eye – repair too late, and the brain fails to use the eye properly for life. “For a very long time, it seemed that those constraints were set in stone after that critical period,” says Daphne Bavelier at the University of Rochester, New York.

These are extreme circumstances, of course, but the evidence suggested that the same neural fossilisation would stifle other kinds of learning. Many of the studies looked at language development – particularly in families of immigrants. While the children picked up new tongues with ease, their parents were still stuttering broken sentences. But if there is a critical period for foreign language learning, everyone should be affected equally; Simcott’s ability to master a host of languages should be as impossible as a dog playing the piano.

Bearing this in mind, Ellen Bialystok at York University in Toronto, Canada, recently turned to the US census records, which detailed the linguistic skills of more than 2 million Hispanic and Chinese immigrants. A “critical period” for learning a second language in infancy should have created a sharp difference between those who had moved country in early childhood and those who were uprooted in adolescence. In reality? “There was absolutely no discontinuity,” Bialystok says. Instead, she saw a very gradual decline with age among immigrants – which could reflect differences in environment as much as the adults’ rusty brain circuits. “People talk more slowly and clearly to children in short, simple sentences,” she says. “And the child’s entire social and educational network is organised around that language.”

Yet while Bialystok’s study suggested that adult brains are more pliable than had once been imagined, there was still the suspicion that children might have the edge in certain skills. Adult learners sometimes find it harder to learn to sing in tune, hit a home run or mimic an accent convincingly. At first glance, the problem might seem to lie in adults’ perception and motor skills. Learning involving these abilities differs from the acquisition of factual knowledge, because it needs us to rewire the eyes, ears and muscles.

It’s something that Marcus can identify with. At the age of 38, he devoted himself to learning the guitar, an experience he detailed in his book Guitar Zero. “My family’s initial response was laughter – but they soon saw I was making progress,” he says. Still, during his research, he attended a musical summer camp for 8 to 15-year-olds. He says he was quicker to catch on to the structure of songs, but his younger bandmates had better coordination and sense of pitch.

Yet the available evidence hints that children may not always be inherently better at such tasks. One study by Yang Zhang at the University of Minnesota in Minneapolis that focused on the acquisition of foreign accents in adults suggests we may simply be suffering from poor tuition. When the researchers gave them recordings that mimicked the exaggerated baby talk of cooing mothers, the adult learners progressed rapidly.

Nor do adults necessarily fumble over the intricate movements that are crucial for music or sport. When volunteers visiting Virginia Penhune's lab at Concordia University in Montreal, Canada, learned to press keys in a certain sequence, at certain times – essentially a boiled-down version of keyboard practice – the adults tended to outshine the younger volunteers.

During a more challenging test of hand-eye coordination, nearly 1000 volunteers of all age groups learned to juggle over a series of six training sessions. As you might expect, the senior citizens aged 60 to 80 began with some hesitation, but they soon caught up with the 30-year-olds and by the end of the trials all the adults were juggling more confidently than the 5 to 10-year-olds.

Old dogs, then, are much more adaptable than folklore would have it – and if we do have deficits, they aren’t insurmountable. The reason that children appear to be better learners may have more to do with their environment, and factors such as physical fitness (see “Faster body, faster mind”).

Indeed, many researchers believe that an adult’s lifestyle may be the biggest obstacle. “A child’s sole occupation is learning to speak and move around,” says Ed Cooke, a cognitive scientist who has won many memory contests. “If an adult had that kind of time to spend on attentive learning, I’d be very disappointed if they didn’t do a good job.”

A glut of free time and a carefree existence are out of reach for most of us, but there are other behaviours that boost children’s learning, and these habits can be easily integrated into even an adult’s schedule. For example, children are continually quizzed on what they know – and for good reason: countless studies have shown that testing doubles long-term recall, outperforming all other memory tactics. Yet most adults attempting to learn new skills will rely more on self-testing which, let’s be honest, happens less often.

That’s why Cooke developed a website, called Memrise, which helps take some of the pain out of testing and, crucially, can integrate learning into the adult day. It is designed to track your learning curve with cunningly timed tests that force you to retrieve the information just as you are about to forget it.

"Memrise engages your brain to the greatest possible extent," says Cooke, who has himself used the site to learn thousands of words of foreign vocabulary. Users can create their own courses – the topics range from art to zoology – and importantly, it is easy to load the site in the few spare minutes of your lunch break or while you are waiting for a train. Cooke also plans to launch a smartphone app.

What about tasks that involve perceptual learning or motor skills – like battling against a lifetime of tone deafness, or perfecting that golf swing? Here too, there are guiding principles that can help you rediscover the seemingly effortless learning of youth.

Adults can hamper progress with their own perfectionism: whereas children throw themselves into tasks, adults often agonise over the mechanics of the movements, trying to conceptualise exactly what is required. This could be one of our biggest downfalls. “Adults think so much more about what they are doing,” says Gabriele Wulf at the University of Nevada, Las Vegas. “Children just copy what they see.”

Wulf’s work over the past decade shows that you should focus on the outcome of your actions rather than the intricacies of the movements. She applies this finding in her own life: as a keen golfer, she has found it is better to think about the swing of the club, for instance, rather than the position of her hands. “I’m always trying to find where best to focus my attention,” she says. Similarly, if you are learning to sing, then you should concentrate on the tone of the voice, rather than on the larynx or the placement of the tongue. Study after study shows that simply shifting your mindset in this way accelerates your learning– perhaps by encouraging the subconscious, automatic movements that mark proficiency.

Misplaced conscientiousness may also lead adults to rely on overly rigid practice regimes that stifle long-term learning. The adult talent for perseverance, it seems, is not always a virtue. Left to their own devices, most people segment their sessions into separate blocks – when learning basketball, for instance, they may work on each shot in turn, perhaps because they feel a desire to master it. The approach may bring rapid improvements at first, but a host of studies have found that the refined technique is soon forgotten.

Instead, you do better to take a carousel approach, quickly rotating through the different skills to be practised without lingering too long on each one. Although the reason is still unclear, it seems that jumping between skills makes your mind work a little harder when applying what you’ve learned, helping you to retain the knowledge in the long term – a finding that has helped people improve in activities ranging from tennis and kayaking to pistol shooting.

Such an approach might not be to everyone’s taste – with intricate skills, it might feel like you are making no progress. But even if you do revert to stints of lengthy practice, you can still reap some of the same benefits by occasionally trying out your skills in an unfamiliar situation. In tennis, you might move to a different part of the court for a couple of serves before returning to the regular position; while playing scales on a musical instrument, you might switch hands temporarily. According to work by Arnaud Boutin at the Leibniz Research Centre for Working Environment and Human Factors in Dortmund, Germany, venturing out of your comfort zone in this way helps to ensure that you improve your overall performance rather than confining your progress to the single task at hand. “Otherwise, the longer you practise, the harder it becomes to transfer the skills that you’ve learned to new situations,” says Boutin.

If none of that helps you learn like a child, simply adopting the arrogance of youth may do no harm. “As we get older, we lose our confidence, and I’m convinced that has a big impact on performance,” says Wulf. To test the assumption, she recently trained a small group of people to pitch a ball. While half were given no encouragement, she offered the others a sham test, rigged to demonstrate that their abilities were above average. They learned to pitch on target with much greater accuracy than those who didn’t get an ego boost.

Whether your itch to learn will ever match Simcott’s appetite for foreign languages is another matter. “What I do – it’s like an extreme sport. There’s no need to learn that many languages,” he says. He has recently turned to Chinese, and has no plans to stop after that. “I’m like a linguistic butterfly. There’s always another, really far away, that suddenly feels appealing.”

Still, embrace the idea that your mind is as capable as Simcott’s, and the lure of extreme learning might take hold of you too.

-by David Robson, New Scientist

Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.

The results suggest a monthly window of opportunity that could potentially be targeted in efforts to prevent common mental health problems developing in women. The research is the first to show a potential link between psychological vulnerability and the timing of a biological cycle, in this case ovulation.

A common symptom of mood and anxiety problems is the tendency to experience repetitive and unwanted thoughts. These ‘intrusive thoughts’ often occur in the days and weeks after a stressful experience.

In this study, the researchers examined whether the effects of a stressful event are linked to different stages of the menstrual cycle. The participants were 41 women aged between 18 and 35 who had regular menstrual cycles and were not using the pill as a form of contraception. Each woman watched a 14-minute stressful film containing death or injury and provided a saliva sample so that hormone levels could be assessed. They were then asked to record instances of unwanted thoughts about the video over the following days.

“We found that women in the ‘early luteal’ phase, which falls roughly 16 to 20 days after the start of their period, had more than three times as many intrusive thoughts as those who watched the video in other phases of their menstrual cycle,” explains author Dr Sunjeev Kamboj, Lecturer in UCL’s Department of Clinical, Educational and Health Psychology.

“This indicates that there is actually a fairly narrow window within the menstrual cycle when women may be particularly vulnerable to experiencing distressing symptoms after a stressful event.”

The findings could have important implications for mental health problems and their treatment in women who have suffered trauma.

“Asking women who have experienced a traumatic event about the time since their last period might help identify those at greatest risk of developing recurring symptoms similar to those seen in psychological disorders such as depression and post-traumatic stress disorder (PTSD),” said Dr Kamboj.

“This work might have identified a useful line of enquiry for doctors, helping them to identify potentially vulnerable women who could be offered preventative therapies,” continued Dr Kamboj.

“However, this is only a first step. Although we found large effects in healthy women after they experienced a relatively mild stressful event, we now need to see if the same pattern is found in women who have experienced a real traumatic event. We also need further research to investigate how using the contraceptive pill affects this whole process.”

In Parkinson’s disease, the protein “alpha-synuclein” aggregates and accumulates within neurons. Specific areas of the brain become progressively affected as the disease develops and advances. The mechanism underlying this pathological progression is poorly understood but could result from spreading of the protein (or abnormal forms of it) along nerve projections connecting lower to upper brain regions. Scientists at the German Center for Neurodegenerative Diseases (DZNE) in Bonn have developed a novel experimental model that reproduces for the first time this pattern of alpha-synuclein brain spreading and provides important clues on the mechanisms underlying this pathological process. They triggered the production of human alpha-synuclein in the lower rat brain and were able to trace the spreading of this protein toward higher brain regions. The new experimental paradigm could promote the development of ways to halt or slow down disease development in humans. The research team headed by Prof. Donato Di Monte presents these results in the scientific journal “EMBO Molecular Medicine”.

Parkinson’s disease is a disorder of the nervous system. It typically manifests itself with motor disturbances, such as an uncontrollable trembling of the limbs, as well as non-motor symptoms, including sleep disorders and depression.

At the present, no cure exists for Parkinson’s disease, although symptomatic intervention, including treatment with dopamine agonists, can alleviate patients’ motor impairment. Parkinson’s is the second most common neurodegenerative disorder, after Alzheimer’s disease; it is estimated that 100,000 to 300,000 patients are affected by Parkinson’s disease in Germany alone.

In a small percentage of cases, Parkinson’s disease is due to genetic abnormalities carried within families. For the vast majority of patients, however, the cause of the disease remains unknown; the development of this sporadic form of the disease is likely promoted by both environmental and genetic risk factors. An intriguing characteristic of the brain of patients with sporadic Parkinson’s disease is the progressive accumulation of intraneuronal inclusions that were first described by a German neurologist, Friedrich Lewy, and are therefore called Lewy bodies.

“A major discovery in the late 90’s was that Lewy bodies are formed when the protein alpha-synuclein becomes aggregated,” says Di Monte. “Since then, it was also found that aggregates of alpha-synuclein are progressively accumulated within the patients’ brains during the course of the disease”.

Pathology studies from human brains show that the deposits usually start forming in the lower part of the brain, in an area named “medulla oblongata”. In subsequent disease stages, alpha-synuclein aggregates are observed in progressively higher (more rostral) brain regions, including the midbrain and cortical areas.

“This spreading appears to follow a typical pattern based on anatomical connections between regions of the brain,” says the neuroscientist. “For this reason, it has been hypothesized that alpha-synuclein or abnormal forms of it can be transferred between two interconnected neurons and hence migrate throughout the brain. But until now, there was no way of targeting the medulla oblongata to reproduce this spreading of alpha-synuclein in the laboratory. It is also unclear what conditions could trigger the inter-neuronal passage of the protein or its aggregates. We have now developed a new experimental paradigm which enables investigations on these fundamental issues.”

From the neck into the brain
The researchers’ concept is based on reproducing alpha-synuclein spreading in rats: for this, they transferred the blueprint of the human form of alpha-synuclein into the rat brain. The blueprint was transported by specifically engineered viral particles that the scientists injected into nerve fibres in the neck of the animals. The genetic code for the protein passed along these fibres into the medulla oblongata, where transfected rat neurons began producing high quantities of human alpha-synuclein.

“We have good reasons to believe that the medulla oblongata is a primary site of early disease development. This is why we wanted to activate production of alpha-synuclein specifically in this part of the brain. The medulla oblongata is difficult to reach via surgical procedures. For this reason, we injected the viral particles into the vagus nerve. This is a long nerve stretching from the abdomen via the neck to the medulla oblongata. The nerve consequently served as an entrance into the brain and, in particular, the medulla oblongata,” Di Monte explains.

A migrating protein
The researchers monitored the production and localization of human alpha-synuclein in rats’ brains over a period of four and a half months after injection of the viral particles. As predicted, the exogenous protein was synthesized only within neurons of the medulla oblongata connected to the vagus nerve. Starting at two months, however, human alpha-synuclein was observed also in brain areas more and more distant from the medulla oblongata. Caudo-rostral spreading involved inter-neuronal passage of the protein along specific nerve tracts and was accompanied by morphological alterations (such as swellings) of the neuronal projections taking up human alpha-synuclein.

The study, sponsored in part by the Blanche A. Paul Foundation, bears a number of critical implications. It reproduces a pattern of protein propagation that resembles the progressive spreading of pathological alpha-synuclein in Parkinson’s disease. As importantly, the process of protein transmission was triggered by overproduction of alpha-synuclein within a specific brain region.

“Overproduction of alpha-synuclein accompanies a variety of conditions, such as aging, neuronal injury or genetic polymorphisms, that could promote the development of Parkinson’s disease.” concludes Di Monte. “Thus, our results suggest a mechanistic link between disease risk factors, enhanced levels of alpha-synuclein, spreading of the protein and its pathological accumulation.”

Insight into the early stages of Parkinson’s
The new model mimics events that likely occur in the early stages of alpha-synuclein pathology in the absence of overt behavioural (in rats) or clinical (in patients) manifestations. “It will therefore become a valuable tool to investigate early mechanisms of disease pathogenesis that could be targeted for therapeutic intervention. Early intervention would have a greater probability to prevent or halt the spreading of pathology and progression of the disease,” says Di Monte.

The first symptoms of major depression may be behavioral, but the common mental illness is based in biology — and not limited to the brain.

In recent years, some studies have linked major, long-term depression with life-threatening chronic disease and with earlier death, even after lifestyle risk factors have been taken into account.

Now a research team led by Owen Wolkowitz, MD, professor of psychiatry at UC San Francisco, has found that within cells of the immune system, activity of an enzyme called telomerase is greater, on average, in untreated individuals with major depression. The preliminary findings from his latest, ongoing study was reported Wednesday at the annual meeting of the American Psychiatric Association in San Francisco.

Telomerase is an enzyme that lengthens protective end caps on the chromosomes’ DNA, called telomeres. Shortened telomeres have been associated with earlier death and with chronic diseases in population studies.

The heightened telomerase activity in untreated major depression might represent the body’s attempt to fight back against the progression of disease, in order to prevent biological damage in long-depressed individuals, Wolkowitz said.

The researchers made another discovery that may suggest a protective role for telomerase. Using magnetic resonance imaging (MRI), they found that, in untreated, depressed study participants, the size of the hippocampus, a brain structure that is critical for learning and memory, was associated with the amount of telomerase activity measured in the white blood cells. Such an association at a single point in time cannot be used to conclude that there is a cause-and-effect relationship with telomerase helping to protect the hippocampus, but it is plausible, Wolkowitz said.

Telomerase Activity and Antidepressants

Remarkably, the researchers also found that the enzyme’s activity went up when some patients began taking an antidepressant. In fact, depressed participants with lower telomerase activity at baseline — as well as those in whom enzyme activity increased the most with treatment — were the most likely to become less depressed with treatment.

“Our results are consistent with the beneficial effect of telomerase when it is boosted in animal studies, where it has been associated with the growth of new nerve cells in the hippocampus and with antidepressant-like effects, evidenced by increased exploratory behavior,” Wolkowitz said. He cautions that his new findings are preliminary due to the small size of the study and must be confirmed through further research.

The researchers also measured telomere length in the same immune cells. Only very chronically depressed individuals showed telomere shortening, Wolkowitz said.

“The longer people had been depressed, the shorter their telomeres were,” he said. “Shortened telomere length has been previously demonstrated in major depression in most, but not all, studies that have examined it. The duration of depression may be a critical factor.”

Ongoing Study

The 20 depressed participants enrolled in the study had been untreated for at least six weeks and had an average lifetime duration of depression of about 13 years. After baseline evaluation and laboratory measures, 16 of the depressed participants were treated with sertraline, a member of the most popular class of antidepressants, the serotonin-selective-reuptake-inhibitors (SSRIs), and then evaluated again after eight weeks. There were 20 healthy participants who served as controls.

The ongoing study still is accepting depressed participants who are not now taking antidepressants.

Wolkowitz’s team also studies chronic inflammation and the biochemical phenomenon of oxidative stress, which he said have often been reported in major depression. Wolkowitz is exploring the hypothesis that inflammation and oxidative stress play a role in telomere shortening and accelerated aging in depression.

“New insights into the mechanisms of these processes may well lead to new treatments — both pharmacological and behavioral — that will be distinctly different from the current generation of drugs prescribed to treat depression,” he said. “Additional studies might lead to simple blood tests that can measure accelerated immune-cell aging.”

Researchers at Lund University have succeeded in preventing very early symptoms of Huntington’s disease, depression and anxiety, by deactivating the mutated huntingtin protein in the brains of mice.

“We are the first to show that it is possible to prevent the depression symptoms of Huntington’s disease by deactivating the diseased protein in nerve cell populations in the hypothalamus in the brain. This is hugely exciting and bears out our previous hypotheses”, explains Åsa Petersén, Associate Professor of Neuroscience at Lund University.

Huntington’s is a debilitating disease for which there is still neither cure nor sufficient treatment. The dance-like movements that characterise the disease have long been the focus for researchers, but the emotional problems affect the patient earlier than the motor symptoms. These are now believed to stem from a different part of the brain – the small emotional centre called the hypothalamus.

“Now that we have been able to show in animal experiments that depression and anxiety occur very early in Huntington’s disease, we want to identify more specifically which nerve cells in the hypothalamus are critical in the development of these symptoms. In the long run, this gives us better opportunities to develop more accurate treatments that can attack the mutated huntingtin where it does the most damage”, says Åsa Petersén.

As the role of the hypothalamus in Huntington’s disease is gradually mapped, knowledge might be gained from drug research for other psychiatric diseases. It is likely that similar mechanisms control different types of depression, according to Åsa Petersén.

Publication:
Hypothalamic expression of mutant huntingtin contributes to the development of depressive-like behavior in the BAC transgenic mouse model of Huntington’s disease
Human Molecular Genetics
Sofia Hult Lundh, Nathalie Nilsson, Rana Soylu, Deniz Kirik and Åsa Petersén

An anti-cancer drug about to be tested in a clinical trial by a biomedical company in Ohio as a possible treatment for Alzheimer’s disease has failed to work with the same type of brain plaques that plague Alzheimer’s patients, according to results of a study by University of Florida researchers.

David Borchelt, Ph.D., a professor of neuroscience affiliated with the Evelyn F. and William L. McKnight Brain Institute of the University of Florida, emphasized the importance of verifying promising research results before investing in clinical studies or testing potential therapies in people. Bexarotene has known side effects that include effects on the liver, blood and other metabolic systems.

“We wanted to repeat the study to see if we could build on it, and we couldn’t,” he said. “We thought it was important that something like this, which got a lot of publicity and patients were immediately looking to try to get access to this drug, that it was important to publish the fact that we couldn’t reproduce the most exciting part of the study. Maybe there should be some caution going forward in regard to patients.”

Borchelt and Kevin Felsenstein, Ph.D., an associate professor of neuroscience, said a drug called bexarotene that their team orally administered to mice did not reduce amyloid plaques, waxy buildups on the brain that are a key culprit in Alzheimer’s disease. Their findings will be published in the May 24, 2013 issue of the journal Science magazine, with two additional articles (1, 2) detailing similar results from other researchers.

The research follows up on a 2012 Science article that claimed bexarotene had reversed Alzheimer’s-like symptoms in mice afflicted with the plaques. Authors of that study also administered the drug orally.

The paper “indicated that with as little as three days of treatment, they basically cleared the amyloid deposits from these animals, as well as restored cognitive abilities,” Felsenstein said of the 2012 paper.He said the results of the original study were surprising, given decades of research that had failed to find a therapy successful in dismantling amyloid plaques.

“We can shut down the production of amyloid in these animal models and the deposits in these animal models don’t disappear,” Felsenstein said. “These deposits have been described by some as cement, and it will take a lot to get rid of them. The fact that something could actually make them disappear in literally a couple of days is — again — very remarkable.”

Interested to see how bexarotene might work to break down amyloid plaques, Felsenstein and Borchelt selected mice approximately the same age as those used in the 2012 study and orally administered the drug to the mice. Tests confirmed the drug had reached its target genes in the mice, and that it elevated levels of a protein called apolipoprotein E. Some scientists believe one of the forms of this protein may prevent the buildup of amyloid brain plaques in people who don’t have Alzheimer’s disease.

But elevated levels of the protein in the mice studied by UF researchers seemed to have no effect on the animals’ amyloid plaques. Samples taken after seven days of treatment with bexarotene showed no significant difference in the number or size of plaques in the animals’ brains. Two teams of researchers from other institutions also were unable to replicate the breakdown of amyloid plaques.

Felsenstein emphasized that his team does not claim the previous study indicating bexarotene’s effectiveness is “totally wrong.”

“We’re just saying right now it’s extremely difficult to replicate and there may be little nuances, that there’s something that we don’t quite understand,” he added. Felsenstein and Borchelt both work at UF’s Center for Translational Research in Neurodegenerative Disease.

Until now, little was scientifically known about the human potential to cultivate compassion — the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.

A new study by researchers at the Center for Investigating Healthy Minds at the Waisman Center of the University of Wisconsin-Madison shows that adults can be trained to be more compassionate. The report, recently published online in the journal Psychological Science, is the first to investigate whether training adults in compassion can result in greater altruistic behavior and related changes in neural systems underlying compassion.

"Our fundamental question was, ‘Can compassion be trained and learned in adults? Can we become more caring if we practice that mindset?’" says Helen Weng, a graduate student in clinical psychology and lead author of the paper. "Our evidence points to yes."

In the study, the investigators trained young adults to engage in compassion meditation, an ancient Buddhist technique to increase caring feelings for people who are suffering. In the meditation, participants envisioned a time when someone has suffered and then practiced wishing that his or her suffering was relieved. They repeated phrases to help them focus on compassion such as, “May you be free from suffering. May you have joy and ease.”

Participants practiced with different categories of people, first starting with a loved one, someone whom they easily felt compassion for like a friend or family member. Then, they practiced compassion for themselves and, then, a stranger. Finally, they practiced compassion for someone they actively had conflict with called the “difficult person,” such as a troublesome coworker or roommate.

"It’s kind of like weight training," Weng says. "Using this systematic approach, we found that people can actually build up their compassion ‘muscle’ and respond to others’ suffering with care and a desire to help."

Compassion training was compared to a control group that learned cognitive reappraisal, a technique where people learn to reframe their thoughts to feel less negative. Both groups listened to guided audio instructions over the Internet for 30 minutes per day for two weeks. “We wanted to investigate whether people could begin to change their emotional habits in a relatively short period of time,” says Weng.

The real test of whether compassion could be trained was to see if people would be willing to be more altruistic — even helping people they had never met. The research tested this by asking the participants to play a game in which they were given the opportunity to spend their own money to respond to someone in need (called the “Redistribution Game”). They played the game over the Internet with two anonymous players, the “Dictator” and the “Victim.” They watched as the Dictator shared an unfair amount of money (only $1 out of $10) with the Victim. They then decided how much of their own money to spend (out of $5) in order to equalize the unfair split and redistribute funds from the Dictator to the Victim.

"We found that people trained in compassion were more likely to spend their own money altruistically to help someone who was treated unfairly than those who were trained in cognitive reappraisal," Weng says.

"We wanted to see what changed inside the brains of people who gave more to someone in need. How are they responding to suffering differently now?" asks Weng. The study measured changes in brain responses using functional magnetic resonance imaging (fMRI) before and after training. In the MRI scanner, participants viewed images depicting human suffering, such as a crying child or a burn victim, and generated feelings of compassion towards the people using their practiced skills. The control group was exposed to the same images, and asked to recast them in a more positive light as in reappraisal.

The researchers measured how much brain activity had changed from the beginning to the end of the training, and found that the people who were the most altruistic after compassion training were the ones who showed the most brain changes when viewing human suffering. They found that activity was increased in the inferior parietal cortex, a region involved in empathy and understanding others. Compassion training also increased activity in the dorsolateral prefrontal cortex and the extent to which it communicated with the nucleus accumbens, brain regions involved in emotion regulation and positive emotions.

"People seem to become more sensitive to other people’s suffering, but this is challenging emotionally. They learn to regulate their emotions so that they approach people’s suffering with caring and wanting to help rather than turning away," explains Weng.

Compassion, like physical and academic skills, appears to be something that is not fixed, but rather can be enhanced with training and practice. “The fact that alterations in brain function were observed after just a total of seven hours of training is remarkable,” explains UW-Madison psychology and psychiatry professor Richard J. Davidson, founder and chair of the Center for Investigating Healthy Minds and senior author of the article.

"There are many possible applications of this type of training," Davidson says. "Compassion and kindness training in schools can help children learn to be attuned to their own emotions as well as those of others, which may decrease bullying. Compassion training also may benefit people who have social challenges such as social anxiety or antisocial behavior."

Weng is also excited about how compassion training can help the general population. “We studied the effects of this training with healthy participants, which demonstrated that this can help the average person. I would love for more people to access the training and try it for a week or two — what changes do they see in their own lives?”

Both compassion and reappraisal trainings are available on the Center for Investigating Healthy Minds’ website. “I think we are only scratching the surface of how compassion can transform people’s lives,” says Weng.