Posts tagged science
Articles and news from the latest research reports.
Mathematical model shows how the brain remains stable during learning
Complex biochemical signals that coordinate fast and slow changes in neuronal networks keep the brain in balance during learning, according to an international team of scientists from the RIKEN Brain Science Institute in Japan, UC San Francisco (UCSF), and Columbia University in New York.
The work, reported on October 22 in the journal Neuron, culminates a six-year quest by a collaborative team from the three institutions to solve a decades-old question and opens the door to a more general understanding of how the brain learns and consolidates new experiences on dramatically different timescales.
Neuronal networks form a learning machine that allows the brain to extract and store new information from its surroundings via the senses. Researchers have long puzzled over how the brain achieves sensitivity and stability to unexpected new experiences during learning—two seemingly contradictory requirements.
A new model devised by this team of mathematicians and brain scientists shows how the brain’s network can learn new information while maintaining stability.
To address the problem, the team turned to a classic experimental system. After birth, the visual area of the brain’s cortex undergoes rapid modification to match the properties of neurons when seeing the world through the left and right eyes, a phenomenon termed “ocular dominance plasticity,” or ODP. The discovery of this dramatic plasticity was recognized by the 1981 Nobel Prize in Physiology or Medicine awarded to David H. Hubel and Torsten N. Wiesel.
ODP learning contains a paradox that puzzled researchers—it relies on fast-acting changes in activity called “Hebbian plasticity” in which neural connections strengthen or weaken almost instantly depending on their frequency of use. However, acting alone, this process could lead to unstable activity levels.
In 2008, the UCSF team of Megumi Kaneko and Michael P. Stryker found that a second process, termed “homeostatic plasticity,” also controls ODP by tuning the activity of the whole neural network up in a slower manner, resembling the system for controlling the overall brightness of a TV screen without changing its images.
By modeling Hebbian and homeostatic plasticity together, mathematicians Taro Toyoizumi and Ken Miller of Columbia saw a possible resolution to the paradox of brain stability during learning. Dr. Toyoizumi, who is now at the RIKEN Brain Science Institute in Japan, explains, “We were running simulations of ODP using a conventional model. When we failed to reconcile Kaneko and Stryker’s data to the model, we had to develop a new theoretical solution.”
"It seemed important to explore the interactions between these two different types of plasticity to understand the computations performed by neurons in the visual area," Dr. Stryker adds. Testing the new mathematical model in an animal during experimental ODP was necessary, so the teams decided to collaborate.
The theory and experimental findings showed that fast Hebbian and slow homeostatic plasticity work together during learning, but only after each has independently assured stability on its own timescale. “The essential idea is that the fast and slow processes control separate biochemical factors,” said Dr. Miller.
"Our model solves the ODP paradox and may explain in general terms how learning occurs in other areas of the brain," said Dr. Toyoizumi. "Building on our general mathematical model for learning could reveal insights into new principles of brain capacities and diseases."
Bipolar Disorder Discovery at the Nano Level
A nano-sized discovery by Northwestern Medicine® scientists helps explain how bipolar disorder affects the brain and could one day lead to new drug therapies to treat the mental illness.
Scientists used a new super-resolution imaging method — the same method recognized with the 2014 Nobel Prize in chemistry — to peer deep into brain tissue from mice with bipolar-like behaviors. In the synapses (where communication between brain cells occurs), they discovered tiny “nanodomain” structures with concentrated levels of ANK3 — the gene most strongly associated with bipolar disorder risk. ANK3 is coding for the protein ankyrin-G.
“We knew that ankyrin-G played an important role in bipolar disease, but we didn’t know how,” said Northwestern Medicine scientist Peter Penzes, corresponding author of the paper. “Through this imaging method we found the gene formed in nanodomain structures in the synapses, and we determined that these structures control or regulate the behavior of synapses.”
Penzes is a professor in physiology and psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. The results were published Oct. 22 in the journal Neuron.
High-profile cases, including actress Catherine Zeta-Jones and politician Jesse Jackson, Jr., have brought attention to bipolar disorder. The illness causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. About 3 percent of Americans experience bipolar disorder symptoms, and there is no cure.
Recent large-scale human genetic studies have shown that genes can contribute to disease risk along with stress and other environmental factors. However, how these risk genes affect the brain is not known.
This is the first time any psychiatric risk gene has been analyzed at such a detailed level of resolution. As explained in the paper, Penzes used the Nikon Structured Illumination Super-resolution Microscope to study a mouse model of bipolar disorder. The microscope realizes resolution of up to 115 nanometers. To put that size in perspective, a nanometer is one-tenth of a micron, and there are 25,400 microns in one inch. Very few of these microscopes exist worldwide.
“There is important information about genes and diseases that can only been seen at this level of resolution,” Penzes said. “We provide a neurobiological explanation of the function of the leading risk gene, and this might provide insight into the abnormalities in bipolar disorder.”
The biological framework presented in this paper could be used in human studies of bipolar disorder in the future, with the goal of developing therapeutic approaches to target these genes.
(Source: northwestern.edu)
Researchers Identify Key Factor in Transition from Moderate to Problem Drinking
A team of UC San Francisco researchers has found that a tiny segment of genetic material known as a microRNA plays a central role in the transition from moderate drinking to binge drinking and other alcohol use disorders.
Previous research in the UCSF laboratory of Dorit Ron, PhD, Endowed Chair of Cell Biology of Addiction in Neurology, has demonstrated that the level of a protein known as brain-derived neurotrophic factor, or BDNF, is increased in the brain when alcohol consumed in moderation. In turn, experiments in Ron’s lab have shown, BDNF prevents the development of alcohol use disorders.
In the new study, Ron and first author Emmanuel Darcq, PhD, a former postdoctoral fellow now at McGill University in Canada, found that when mice consumed excessive amounts of alcohol for a prolonged period, there was a marked decrease in the amount of BDNF in the medial prefrontal cortex (mPFC), a brain region important for decision making. As reported in the October 21, 2014 online edition of Molecular Psychiatry, this decline was associated with a corresponding increase in the level of a microRNA called miR-30a-5p.
MicroRNAs lower the levels of proteins such as BDNF by binding to messenger RNA, the molecular middleman that carries instructions from genes to the protein-making machinery of the cell, and tagging it for destruction.
Ron and colleagues then showed that if they increased the levels of miR-30a-5p in the mPFC, BDNF was reduced, and the mice consumed large amounts of alcohol. When mice were treated with an inhibitor of miR-30a-5p, however, the level of BDNF in the mPFC was restored to normal and alcohol consumption was restored to normal, moderate levels.
“Our results suggest BDNF protects against the transition from moderate to uncontrolled drinking and alcohol use disorders,” said Ron, senior author of the study and a professor in UCSF’s Department of Neurology. “When there is a breakdown in this protective pathway, however, uncontrolled excessive drinking develops, and microRNAs are a possible mechanism in this breakdown. This mechanism may be one possible explanation as to why 10 percent of the population develop alcohol use disorders and this study may be helpful for the development of future medications to treat this devastating disease.”
One reason many potential therapies for alcohol abuse have been unsuccessful is because they inhibit the brain’s reward pathways, causing an overall decline in the experience of pleasure. But in the new study, these pathways continued to function in mice in which the actions of miR-30a-5p had been tamped down—the mice retained the preference for a sweetened solution over plain water that is seen in normal mice.
This result has significant implications for future treatments, Ron said. “In searching for potential therapies for alcohol abuse, it is important that we look for future medications that target drinking without affecting the reward system in general. One problem with current alcohol abuse medications is that patients tend to stop taking them because they interfere with the sense of pleasure.”
A rich vocabulary can protect against cognitive impairment
Some people suffer incipient dementia as they get older. To make up for this loss, the brain’s cognitive reserve is put to the test. Researchers from the University of Santiago de Compostela have studied what factors can help to improve this ability and they conclude that having a higher level of vocabulary is one such factor.
‘Cognitive reserve’ is the name given to the brain’s capacity to compensate for the loss of its functions. This reserve cannot be measured directly; rather, it is calculated through indicators believed to increase this capacity.
A research project at the University of Santiago de Compostela (USC) has studied how having a wide vocabulary influences cognitive reserve in the elderly.
As Cristina Lojo Seoane, from the USC, co-author of the study published in the journal ‘Anales de Psicología’(Annals of Psychology), explains to SINC: “We focused on level of vocabulary as it is considered an indicator of crystallised intelligence (the use of previously acquired intellectual skills). We aimed to deepen our understanding of its relation to cognitive reserve.”
The research team chose a sample of 326 subjects over the age of 50 – 222 healthy individuals and 104 with mild cognitive impairment. They then measured their levels of vocabulary, along with other measures such as their years of schooling, the complexity of their jobs and their reading habits.
They also analysed the scores they obtained in various tests, such as the vocabulary subtest of the ‘Wechsler Adult Intelligence Scale’(WAIS) and the Peabody Picture Vocabulary Test.
“With a regression analysis we calculated the probability of impairment to the vocabulary levels of the participants,” Lojo Seoane continues.
The results revealed a greater prevalence of mild cognitive impairment in participants who achieved a lower vocabulary level score.
“This led us to the conclusion that a higher level of vocabulary, as a measure of cognitive reserve, can protect against cognitive impairment,” the researcher concludes.
Memory decline — a frequent complaint of menopausal women — potentially could be lessened by hypnotic relaxation therapy, say Baylor University researchers, who already have done studies showing that such therapy eases hot flashes, improves sleep and reduces stress in menopausal women.
Their review — “Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body Medicine to Improve Cognitive Performance” — is published in the journal Integrative Medicine Insights. October has been designated World Menopause Month by the International Menopause Society.
Initial research by Baylor, funded by the National Institutes of Health, focused on hot flashes, finding that hypnotic relaxation therapy lessened them, but “along the way, we discovered there are a lot of secondary benefits, including significantly improved sleep and mood,” said Jim R. Sliwinski, a doctoral student in the department of psychology and neuroscience in Baylor’s College of Arts & Sciences.
Co-researcher Gary Elkins, Ph.D., theorizes that sleep, mood and hot flashes associated with decreased estrogen also have a bearing on memory. Their publication, which reviews previous research by other scholars, proposes a framework for how mind-body interventions may improve memory, which could prove fruitful in doing future research.
“Memory decline may not be solely about decreased estrogen,” said Elkins, director of Baylor’s Mind-Body Medicine Research Laboratory and a professor of psychology and neuroscience.
Peri- and post-menopausal women may find mind-body therapies attractive for many reasons, among them that they do not have the side effects of medications or hormone therapy, said Elkins, author of “Relief from Hot Flashes: The Natural, Drug-Free Program to Reduce Hot Flashes, Improve Sleep and Ease Stress.”
While hormone therapy can increase estrogen, it also is associated with an increased risk of breast cancer and cardiovascular disease for some women, he said.
Researchers have noted that while memory decline can occur with aging in both men and women, women are more likely to report a greater number of memory problems, associating it with estrogen decline. Women also report more concerns about memory than pre-menopausal women do, according to several large-scale survey studies.
A factor that may impact memory is that women are dealing with increased responsibilities, stress or depression over such issues as caring for aging parents. In addition, their concern about memory problems may cause them to be more aware of memory lapses, Sliwinski said.
Even women who can safely be treated with estrogen do not necessarily have improved memory. “It sometimes even is associated with cognition problems,” he said.
Although there are questions about sleep’s specific role in forming and storing memories, researchers generally agree that consolidated sleep throughout a whole night is optimal for learning and memory.
Memory tests and scores over time with study participants — both pre-and post-menopausal — could help shed light on how menopause affects recollection, the Baylor researchers said.
(Image: Shutterstock)
(Image caption: Pictured is a mouse hippocampal neuron studded with thousands of synaptic connections (yellow). The number and location of synapses — not too many or too few — is critical to healthy brain function. The researchers found that MHCI proteins, known for their role in the immune system, also are one of the only known factors that ensure synapse density is not too high. The protein does so by inhibiting insulin receptors, which promote synapse formation. Credit: Lisa Boulanger)
Immune proteins moonlight to regulate brain-cell connections
When it comes to the brain, “more is better” seems like an obvious assumption. But in the case of synapses, which are the connections between brain cells, too many or too few can both disrupt brain function.
Researchers from Princeton University and the University of California-San Diego (UCSD) recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons. The researchers report in the Journal of Neuroscience that in the brain MHCI could play an unexpected role in conditions such as Alzheimer’s disease, type II diabetes and autism.
MHCI proteins are known for their role in the immune system where they present protein fragments from pathogens and cancerous cells to T cells, which are white blood cells with a central role in the body’s response to infection. This presentation allows T cells to recognize and kill infected and cancerous cells.
In the brain, however, the researchers found that MHCI immune molecules are one of the only known factors that limit the density of synapses, ensuring that synapses form in the appropriate numbers necessary to support healthy brain function. MHCI limits synapse density by inhibiting insulin receptors, which regulate the body’s sugar metabolism and, in the brain, promote synapse formation.
Senior author Lisa Boulanger, an assistant professor in the Department of Molecular Biology and the Princeton Neuroscience Institute (PNI), said that MHCI’s role in ensuring appropriate insulin signaling and synapse density raises the possibility that changes in the protein’s activity could contribute to conditions such Alzheimer’s disease, type II diabetes and autism. These conditions have all been associated with a complex combination of disrupted insulin-signaling pathways, changes in synapse density, and inflammation, which activates immune-system molecules such as MHCI.
Patients with type II diabetes develop “insulin resistance” in which insulin receptors become incapable of responding to insulin, the reason for which is unknown, Boulanger said. Similarly, patients with Alzheimer’s disease develop insulin resistance in the brain that is so pronounced some have dubbed the disease “type III diabetes,” Boulanger said.
"Our results suggest that changes in MHCI immune proteins could contribute to disorders of insulin resistance," Boulanger said. "For example, chronic inflammation is associated with type II diabetes, but the reason for this link has remained a mystery. Our results suggest that inflammation-induced changes in MHCI could have consequences for insulin signaling in neurons and maybe elsewhere."
MHCI levels also are “dramatically altered” in the brains of people with Alzheimer’s disease, Boulanger said. Normal memory depends on appropriate levels of MHCI. Boulanger was senior author on a 2013 paper in the journal Learning and Memory that found that mice bred to produce less functional MHCI proteins exhibited striking changes in the function of the hippocampus, a part of the brain where some memories are formed, and had severe memory impairments.
"MHCI levels are altered in the Alzheimer’s brain, and altering MHCI levels in mice disrupts memory, reduces synapse number and causes neuronal insulin resistance, all of which are core features of Alzheimer’s disease," Boulanger said.
Links between MHCI and autism also are emerging, Boulanger said. People with autism have more synapses than usual in specific brain regions. In addition, several autism-associated genes regulate synapse number, often via a signaling protein known as mTOR (mammalian target of rapamycin). In their study, Boulanger and her co-authors found that mice with reduced levels of MHCI had increased insulin-receptor signaling via the mTOR pathway, and, consequently, more synapses. When elevated mTOR signaling was reduced in MHCI-deficient mice, normal synapse density was restored.
Thus, Boulanger said, MHCI and autism-associated genes appear to converge on the mTOR-synapse regulation pathway. This is intriguing given that inflammation during pregnancy, which alters MHCI levels in the fetal brain, may slightly increase the risk of autism in genetically predisposed individuals, she said.
"Up-regulating MHCI is essential for the maternal immune response, but changing MHCI activity in the fetal brain when synaptic connections are being formed could potentially affect synapse density," Boulanger said.
Ben Barres, a professor of neurobiology, developmental biology and neurology at the Stanford University School of Medicine, said that while it is known that both insulin-receptor signaling increases synapse density, and MHCI signaling decreases it, the researchers are the first to show that MHCI actually affects insulin receptors to control synapse density.
"The idea that there could be a direct interaction between these two signaling systems comes as a great surprise," said Barres, who was not involved in the research. "This discovery not only will lead to new insight into how brain circuitry develops but to new insight into declining brain function that occurs with aging."
Particularly, the research suggests a possible functional connection between type II diabetes and Alzheimer’s disease, Barres said.
"Type II diabetes has recently emerged as a risk factor for Alzheimer’s disease but it has not been clear what the connection is to the synapse loss experienced with Alzheimer’s disease," he said. "Given that type II diabetes is accompanied by decreased insulin responsiveness, it may be that the MHCI signaling becomes able to overcome normal insulin signaling and contribute to synapse decline in this disease."
Research during the past 15 years has shown that MHCI lives a prolific double-life in the brain, Boulanger said. The brain is “immune privileged,” meaning the immune system doesn’t respond as rapidly or effectively to perceived threats in the brain. Dozens of studies have shown, however, that MHCI is not only present throughout the healthy brain, but is essential for normal brain development and function, Boulanger said. A 2013 paper from her lab published in the journal Molecular and Cellular Neuroscience showed that MHCI is even present in the fetal-mouse brain, at a stage when the immune system is not yet mature.
"Many people thought that immune molecules like MHCI must be missing from the brain," Boulanger said. "It turns out that MHCI immune proteins do operate in the brain — they just do something completely different. The dual roles of these proteins in the immune system and nervous system may allow them to mediate both harmful and beneficial interactions between the two systems."
New Research on Walnuts and the Fight Against Alzheimer’s Disease
A new animal study published in the Journal of Alzheimer’s Disease indicates that a diet including walnuts may have a beneficial effect in reducing the risk, delaying the onset, slowing the progression of, or preventing Alzheimer’s disease.
Research led by Abha Chauhan, PhD, head of the Developmental Neuroscience Laboratory at the New York State Institute for Basic Research in Developmental Disabilities (IBR), found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet.
The researchers suggest that the high antioxidant content of walnuts (3.7 mmol/ounce) may have been a contributing factor in protecting the mouse brain from the degeneration typically seen in Alzheimer’s disease. Oxidative stress and inflammation are prominent features in this disease, which affects more than five million Americans.
“These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease – a disease for which there is no known cure,” said lead researcher Dr. Abha Chauhan, PhD. “Our study adds to the growing body of research that demonstrates the protective effects of walnuts on cognitive functioning.”
The research group examined the effects of dietary supplementation on mice with 6 percent or 9 percent walnuts, which are equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. This research stemmed from a previous cell culture study led by Dr. Chauhan that highlighted the protective effects of walnut extract against the oxidative damage caused by amyloid beta protein. This protein is the major component of amyloid plaques that form in the brains of those with Alzheimer’s disease.
Someone in the United States develops Alzheimer’s disease every 67 seconds, and the number of Americans with Alzheimer’s disease and other dementias are expected to rapidly escalate in coming years as the baby boom generation ages. By 2050, the number of people age 65 and older with Alzheimer’s disease may nearly triple, from five million to as many as 16 million, emphasizing the importance of determining ways to prevent, slow or stop the disease. Estimated total payments in 2014 for all individuals with Alzheimer’s disease and other dementias are $214 billion.
Walnuts have other nutritional benefits as they contain numerous vitamins and minerals and are the only nut that contains a significant source of alpha-linolenic acid (ALA) (2.5 grams per ounce), an omega-3 fatty acid with heart and brain-health benefits. The researchers also suggest that ALA may have played a role in improving the behavioral symptoms seen in the study.
Tarantula Toxin is Used to Report on Electrical Activity in Live Cells
Crucial experiments to develop a novel probe of cellular electrical activity were conducted in the Neurobiology course at the Marine Biological Laboratory (MBL) in 2013. Today, that optical probe, which combines a tarantula toxin with a fluorescent compound, is introduced in a paper in the Proceedings of the National Academy of Sciences.
The lead authors of the paper are Drew C. Tilley of University of California-Davis and the late Kenneth Eum, who was a teaching assistant in the Neurobiology course and a Ph.D. candidate at UC-Davis.
The probe takes advantage of the potent ability of tarantula toxin to bind to electrically active cells, such as neurons, while the cells are in a resting state. The team discovered that a trace amount of toxin combined with a fluorescent compound would bind to a specific subset of voltage-activated proteins (Kv2-type potassium ion channels) in live cells. The probe lights up cell surfaces with this ion channel, and the fluorescent signal dims when the channel is activated by electrical signals.
This is the first time that researchers have been able to visually observe these ion channels “turning on” without first genetically modifying them. All that is required is a means to detect probe location, suggesting that related probes could potentially one day be used to map neural activity in the human brain.
“This is a demonstration, a prototype probe. But the promise is that we could use it to measure the activity state of the electrical system in an organism that has not been genetically compromised,” says senior author Jon Sack, an assistant professor in the departments of Physiology and Membrane Biology at UC-Davis. Sack is a faculty member in the MBL Neurobiology course.
Since the probe binds selectively to one of the many different kinds of ion channels, it can help scientists disentangle the function of those specific channels in neuronal signaling. This can, in turn, lead to the identification of drug targets for neurological diseases and disorders.
“We have an incredible diversity of ion channels, and even of voltage-activated ion channels. The real trouble has been determining which ones perform which roles. Which ones turn on and when in normal nervous system functioning? Which are involved in abnormal states or syndromes?” Sack says. “The dream is to be able to see what the different types of ion channels are doing and when, to understand what they contribute to physiology and pathophysiology.”
These probes respond to movement of ion channel voltage sensors, and it is particularly fulfilling to have conducted some of this work at the MBL, Sack says. The first measurements of voltage sensor movement were conducted at the MBL in the early 1970s by Clay M. Armstrong and Francisco Bezanilla (Nature 242: 459-461, 1973). Armstrong and Bezanilla used electrophysiological methods to measure the movement of voltage sensors. The spider toxin probe creates an optical signal when voltage sensors move, and no electrophysiology or genetic mutation of the channels is required.
Brain Activity Provides Evidence for Internal “Calorie Counter”
As you glance over a menu or peruse the shelves in a supermarket, you may be thinking about how each food will taste and whether it’s nutritious, or you may be trying to decide what you’re in the mood for. A new neuroimaging study suggests that while you’re thinking all these things, an internal calorie counter of sorts is also evaluating each food based on its caloric density.
The findings are published in Psychological Science, a journal of the Association for Psychological Science.
“Earlier studies found that children and adults tend to choose high-calorie food,” says study author Alain Dagher, neurologist at the Montreal Neurological Institute and Hospital. “The easy availability and low cost of high-calorie food has been blamed for the rise in obesity. Their consumption is largely governed by the anticipated effects of these foods, which are likely learned through experience.”
“Our study sought to determine how people’s awareness of caloric content influenced the brain areas known to be implicated in evaluating food options,” says Dagher. “We found that brain activity tracked the true caloric content of foods.”
For the study, 29 healthy participants were asked to examine pictures of 50 familiar foods. The participants rated how much they liked each food (on a scale from 1 to 20) and were asked to estimate the calorie content of each food. Surprisingly, they were poor at accurately judging the number of calories in the various foods, and yet, the amount participants were willing to bid on the food in a simulated auction matched up with the foods that actually had higher caloric content.
Results of functional brain scans acquired while participants looked at the food images showed that activity in the ventromedial prefrontal cortex, an area known to encode the value of stimuli and predict immediate consumption, was also correlated with the foods’ true caloric content.
Participants’ explicit ratings of how much they liked a food, on the other hand, were associated with activity in the insula, an area of the brain that has been linked to processing the sensory properties of food.
According to Dagher, understanding the reasons for people’s food choices could help to control the factors that lead to obesity, a condition that is linked to many health problems, including high blood pressure, heart disease, and Type 2 diabetes.
Physical exercise in old age can stimulate brain fitness, but effect decreases with advancing age
Physical exercise in old age can improve brain perfusion as well as certain memory skills. This is the finding of Magdeburg neuroscientists who studied men and women aged between 60 and 77. In younger individuals regular training on a treadmill tended to improve cerebral blood flow and visual memory. However, trial participants who were older than 70 years of age tended to show no benefit of exercise. Thus, the study also indicates that the benefits of exercise may be limited by advancing age. Researchers of the German Center for Neurodegenerative Diseases (DZNE), the University of Magdeburg and the Leibniz Institute for Neurobiology have published these results in the current edition of the journal “Molecular Psychiatry”. Scientists at the Karolinska Institute in Stockholm and the Max Planck Institute for Human Development were also involved in the study.
The 40 test volunteers were healthy for their age, sedentary when the study commenced and divided into two groups. About half of the study participants exercised regularly on a treadmill for 3 months. The other individuals merely performed muscle relaxation sessions. In 7 out of 9 members of the exercise group who were not more than 70 years old, the training improved physical fitness and also tended to increase perfusion in the hippocampus – an area of the brain which is important for memory function. The increased perfusion was accompanied by improved visual memory: at the end of the study, these individuals found it easier to memorize abstract images than at the beginning of the training program. These effects were largely absent in older volunteers who participated in the workout as well as in the members of the control group.
The study included extensive tests of the volunteers’ physical condition and memory. Furthermore, the study participants were examined by magnetic resonance imaging (MRI). This technique enables detailed insights into the interior of the brain.
Exercising against dementia
Physical exercise is known to have considerable health benefits: the effects on the body have been researched extensively, the effects on brain function less so. An increase in brain perfusion through physical exercise had previously only been demonstrated empirically in younger people. The new study shows that some ageing brains also retain this ability to adapt, even though it seems to decrease with advancing age. Furthermore, the results indicate that changes in memory performance resulting from physical exercise are closely linked to changes in brain perfusion.
“Ultimately, we aim to develop measures to purposefully counteract dementia such as Alzheimer’s disease. This is why we want to understand the effects of physical exercise on the brain and the related neurobiological mechanisms. This is essential for developing treatments that are truly effective,” is how Professor Emrah Düzel, site speaker of the DZNE in Magdeburg and director of the Institute of Cognitive Neurology and Dementia Research at the University of Magdeburg, explains the background to the study.
The goal: new brain cells
The researchers’ goal is to cause new nerve cells to grow in the brain. This is how they intend to counter the loss of neurons typical of dementia. “The human brain is able to change and evolve throughout our lives. New nerve cells can form even in adult brains,” says Düzel. “Our aim is to stimulate this so-called neurogenesis. We don’t yet know whether our training methods promote the development of new brain cells. However, fundamental research shows that the formation of new brain cells often goes hand in hand with improved brain perfusion.”
Changes in the hippocampus
Indeed, it did turn out that the treadmill exercise sessions caused more blood to reach the hippocampus in younger participants. “This improves the supply of oxygen and nutrients and may also have other positive effects on the brain’s metabolism,” says the neuroscientist. “However, we have also seen that the effect of the training decreases with age. It is less effective in people aged over 70 than in people in their early 60s. It will be an important goal of our research to understand the causes for this and to find remedies.”
Düzel adds: “It is encouraging to see that visual memory improved as brain perfusion increased. However, effective treatments would also have to affect other brain functions. In our study, the effect was limited to visual short-term memory.”
A combined training for body and mind
Other experiments are now under way in Magdeburg in which test participants are sent on an unusual kind of scavenger hunt: they are assigned the task of finding objects concealed in a computer-generated landscape which is pictured on a large screen. Movement control in this virtual world is done with the help of a treadmill. “This complex situation makes high demands on motor skills and sense of orientation,” explains Düzel. “It challenges both the brain as well as the muscles.”
In the long term, the scientists aim to include people in the early stages of Alzheimer’s disease in their study program. “We are looking for ways of delaying or even stopping the progression of the disease. And we are also researching methods of prevention,” emphasizes Düzel. “Connecting physical activity and mental exercise may have a broad impact, and combined training might become a therapeutic approach. However, this has yet to be shown. In fact, our current results suggest that we may need pharmacological treatments to make exercise more effective.”