Posts tagged memory
Articles and news from the latest research reports.
Compound Reverses Symptoms of Alzheimer’s Disease in Mice
A molecular compound developed by Saint Louis University scientists restored learning, memory and appropriate behavior in a mouse model of Alzheimer’s disease, according to findings in the May issue of the Journal of Alzheimer’s Disease. The molecule also reduced inflammation in the part of the brain responsible for learning and memory.
The paper, authored by a team of scientists led by Susan Farr, Ph.D., research professor of geriatrics at Saint Louis University, is the second mouse study that supports the potential therapeutic value of an antisense compound in treating Alzheimer’s disease in humans.
"It reversed learning and memory deficits and brain inflammation in mice that are genetically engineered to model Alzheimer’s disease," Farr said. "Our current findings suggest that the compound, which is called antisense oligonucleotide (OL-1), is a potential treatment for Alzheimer’s disease."
Farr cautioned that the experiment was conducted in a mouse model. Like any drug, before an antisense compound could be tested in human clinical trials, toxicity tests need to be completed.
Antisense is a strand of molecules that bind to messenger RNA, launching a cascade of cellular events that turns off a certain gene.
In this case, OL-1 blocks the translation of RNA, which triggers a process that keeps excess amyloid beta protein from being produced. The specific antisense significantly decreased the overexpression of a substance called amyloid beta protein precursor, which normalized the amount of amyloid beta protein in the body. Excess amyloid beta protein is believed to be partially responsible for the formation of plaque in the brain of patients who have Alzheimer’s disease.
Scientists tested OL-1 in a type of mouse that overexpresses a mutant form of the human amyloid beta precursor gene. Previously they had tested the substance in a mouse model that has a natural mutation causing it to overproduce mouse amyloid beta. Like people who have Alzheimer’s disease, both types of mice have age-related impairments in learning and memory, elevated levels of amyloid beta protein that stay in the brain and increased inflammation and oxidative damage to the hippocampus — the part of the brain responsible for learning and memory.
"To be effective in humans, OL-1 would need to be effective at suppressing production of human amyloid beta protein," Farr said.
Scientists compared the mice that were genetically engineered to overproduce human amyloid beta protein with a wild strain, which served as the control. All of the wild strain received random antisense, while about half of the genetically engineered mice received random antisense and half received OL-1.
The mice were given a series of tests designed to measure memory, learning and appropriate behavior, such as going through a maze, exploring an unfamiliar location and recognizing an object.
Scientists found that learning and memory improved in the genetically engineered mice that received OL-1 compared to the genetically engineered mice that received random antisense. Learning and memory were the same among genetically engineered mice that received OL-1 and wild mice that received random antisense.
They also tested the effect of administering the drug through the central nervous system, so it crossed the blood brain barrier to enter the brain directly, and of giving it through a vein in the tail, so it circulated through the bloodstream in the body. They found where the drug was injected had little effect on learning and memory.
"Our findings reinforced the importance of amyloid beta protein in the Alzheimer’s disease process. They suggest that an antisense that targets the precursor to amyloid beta protein is a potential therapy to explore to reversing symptoms of Alzheimer’s disease," Farr said.
(Source: slu.edu)
Structurally-Constrained Relationships between Cognitive States in the Human Brain
The anatomical connectivity of the human brain supports diverse patterns of correlated neural activity that are thought to underlie cognitive function. In a manner sensitive to underlying structural brain architecture, we examine the extent to which such patterns of correlated activity systematically vary across cognitive states. Anatomical white matter connectivity is compared with functional correlations in neural activity measured via blood oxygen level dependent (BOLD) signals. Functional connectivity is separately measured at rest, during an attention task, and during a memory task. We assess these structural and functional measures within previously-identified resting-state functional networks, denoted task-positive and task-negative networks, that have been independently shown to be strongly anticorrelated at rest but also involve regions of the brain that routinely increase and decrease in activity during task-driven processes. We find that the density of anatomical connections within and between task-positive and task-negative networks is differentially related to strong, task-dependent correlations in neural activity. The space mapped out by the observed structure-function relationships is used to define a quantitative measure of separation between resting, attention, and memory states. We find that the degree of separation between states is related to both general measures of behavioral performance and relative differences in task-specific measures of attention versus memory performance. These findings suggest that the observed separation between cognitive states reflects underlying organizational principles of human brain structure and function.
How your brain works during meditation
Mindfulness. Zen. Acem. Meditation drumming. Chakra. Buddhist and transcendental meditation. There are countless ways of meditating, but the purpose behind them all remains basically the same: more peace, less stress, better concentration, greater self-awareness and better processing of thoughts and feelings.
But which of these techniques should a poor stressed-out wretch choose? What does the research say? Very little – at least until now.
Nondirective or concentrative meditation?
A team of researchers at the Norwegian University of Science and Technology (NTNU), the University of Oslo and the University of Sydney is now working to determine how the brain works during different kinds of meditation.
Different meditation techniques can actually be divided into two main groups. One type is concentrative meditation, where the meditating person focuses attention on his or her breathing or on specific thoughts, and in doing so, suppresses other thoughts. The other type may be called nondirective meditation, where the person who is meditating effortlessly focuses on his or her breathing or on a meditation sound, but beyond that the mind is allowed to wander as it pleases. Some modern meditation methods are of this nondirective kind.
“No one knows how the brain works when you meditate. That is why I’d like to study it,” says Jian Xu, who is a physician at St. Olavs Hospital and a researcher at the Department of Circulation and Medical Imaging at NTNU.
Two different ways to meditate
Fourteen people who had extensive experience with the Norwegian technique Acem meditation were tested in an MRI machine. In addition to simple resting, they undertook two different mental meditation activities, nondirective meditation and a more concentrative meditation task. The research team wanted to test people who were used to meditation because it meant fewer misunderstandings about what the subjects should actually be doing while they lay in the MRI machine.
The results were recently published in the journal “Frontiers in Human Neuroscience”.
Nondirective meditation led to higher activity than during rest in the part of the brain dedicated to processing self-related thoughts and feelings. When test subjects performed concentrative meditation, the activity in this part of the brain was almost the same as when they were just resting.
A place for the mind to rest
“I was surprised that the activity of the brain was greatest when the person’s thoughts wandered freely on their own, rather than when the brain worked to be more strongly focused,” said Xu. “When the subjects stopped doing a specific task and were not really doing anything special, there was an increase in activity in the area of the brain where we process thoughts and feelings. It is described as a kind of resting network. And it was this area that was most active during nondirective meditation.”
Provides greater freedom for the brain
“The study indicates that nondirective meditation allows for more room to process memories and emotions than during concentrated meditation,” says Svend Davanger, a neuroscientist at the University of Oslo, and co-author of the study.
“This area of the brain has its highest activity when we rest. It represents a kind of basic operating system, a resting network that takes over when external tasks do not require our attention. It is remarkable that a mental task like nondirective meditation results in even higher activity in this network than regular rest,” says Davanger.
Meditating researchers
Most of the research team behind the study do not practice meditation, although three do: Professors Are Holen and Øyvind Ellingsen from NTNU and Professor Svend Davanger from the University of Oslo.
Acem meditation is a technique that falls under the category of nondirective meditation. Davanger believes that good research depends on having a team that can combine personal experience with meditation with a critical attitude towards results.
“Meditation is an activity that is practiced by millions of people. It is important that we find out how this really works. In recent years there has been a sharp increase in international research on meditation. Several prestigious universities in the US spend a great deal of money to research in the field. So I think it is important that we are also active,” says Davanger.
Brain May Never Fully Recover from Exposure to Paint, Glue, Degreasers
People who are exposed to paint, glue or degreaser fumes at work may experience memory and thinking problems in retirement, decades after their exposure, according to a study published in the May 13, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology.
“Our findings are particularly important because exposure to solvents is very common, even in industrialized countries like the United States.” said study author Erika L. Sabbath, ScD, of Harvard School of Public Health in Boston. “Solvents pose a real risk to the present and future cognitive health of workers, and as retirement ages go up, the length of time that people are exposed is going up, too.”
The study involved 2,143 retirees from the French national utility company. Researchers assessed the workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene, including the timing of last exposure and lifetime dosage. Benzene is used to make plastics, rubber, dye, detergents and other synthetic materials. Chlorinated solvents can be found in dry cleaning solutions, engine cleaners, paint removers and degreasers. Petroleum solvents are used in carpet glue, furniture polishes, paint, paint thinner and varnish. Of the participants, 26 percent were exposed to benzene, 33 percent to chlorinated solvents and 25 percent to petroleum solvents.
Participants took eight tests of their memory and thinking skills an average of 10 years after they had retired, when they were an average age of 66. A total of 59 percent of the participants had impairment on one to three of the eight tests; 23 percent had impairment on four or more tests; 18 percent had no impaired scores.
The average lifetime solvent exposure was determined based on historical company records, and the participants were categorized as having no exposure, moderate exposure if they had less than the average and high exposure if they had higher than the average. They were also divided by when the last exposure occurred, with those last exposed from 12 to 30 years prior to the testing considered as recent exposure and those last exposed 31 to 50 years prior considered as more distant exposure.
The research found that people with high, recent exposure to solvents were at greatest risk for memory and thinking deficits. For example, those with high, recent exposure to chlorinated solvents were 65 percent more likely to have impaired scores on tests of memory and visual attention and task switching than those who were not exposed to solvents. The results remained the same after accounting for factors such as education level, age, smoking and alcohol consumption.
“The people with high exposure within the last 12 to 30 years showed impairment in almost all areas of memory and thinking, including those not usually associated with solvent exposure,” Sabbath said. “But what was really striking was that we also saw some cognitive problems in those who had been highly exposed much longer ago, up to 50 years before testing. This suggests that time may not fully lessen the effect of solvent exposure on some memory and cognitive skills when lifetime exposure is high.”
Sabbath said the results may have implications for policies on workplace solvent exposure limits. “Of course, the first goal is protecting the cognitive health of individual workers. But protecting workers from exposure could also benefit organizations, payers, and society by reducing workers’ post-retirement health care costs and enabling them to work longer,” said Sabbath. “That said, retired workers who have had prolonged exposure to solvents during their career may benefit from regular cognitive screening to catch problems early, screening and treatment for heart problems that can affect cognitive health, or mentally stimulating activities like learning new skills.”
Study of neurogenesis in mice may have solved mystery of childhood amnesia in humans
A team of researchers working at the University of Toronto in Canada may have found the answer to the question of why we humans tend to have little to no memory of the first few years of our lives. In their paper published in the journal Science, the team describes several experiments they ran on mice and other small mammals that revealed the impact of neurogenesis on memory and how what they learned might be applied to memory retention in people. Lucas Mongiat and Alegandro Schinder offer a review of memory studies and how the research by the team in Toronto fits in with what has already been learned in a Perspective piece in the same journal edition.
Your brain on speed: Walking doesn’t impair thinking and multitasking
When we’re strolling down memory lane, our brains recall just as much information while walking as while standing still—findings that contradict the popular science notion that walking hinders one’s ability to think.
University of Michigan researchers at the School of Kinesiology and the College of Engineering examined how well study participants performed a very complex spatial cognitive task while walking versus standing still.
"We’re saying that at least for this task, which is fairly complicated, walking and thinking does not compromise your thinking ability at all," said Julia Kline, a U-M doctoral candidate in biomedical engineering and first author on the study, which appears online in Frontiers in Human Neuroscience.
The finding surprised researchers, who expected to see decreased thinking performance with increased walking speed, Kline said. The 2011 best-selling book “Thinking Fast and Slow” suggests that because walking requires mental effort, walking may hinder our ability to think when compared to standing still.
"Past studies that have compared mental performance at a slow walking speed and standing have not found any differences, but our study is the first to show that the walking speed doesn’t matter," said Daniel Ferris, professor of kinesiology and biomedical engineering and senior author of the paper.
"Given the health benefits of walking, we should not discourage people from walking and thinking when they want."
Ferris offered one caveat: previous research has shown that walking performance can be impaired in the elderly when they dual-task during gait.
Ferris, Kline and Katherine Poggensee of U-M’s Human Neuromechanics Laboratory measured the ability of young, healthy participants to memorize numbers and their placement on a grid, and then enter those numbers correctly with a keypad while walking different speeds and standing still.
"Think of filling numbers one through nine on a tic-tac-toe grid and then remembering where they all are," Ferris said. "At every walking speed and standing still, participants entered about half the numbers correctly."
While speed didn’t change task performance, people took wider steps when performing the task than when they were only walking, which may be to compensate and stay balanced while concentrating, Kline said.
All participants showed increased activity in areas of the brain associated with spatial relationships and short-term memory during the cognitive task. In keeping with the U-M findings, a recent Stanford study suggested that walking fueled creativity.
In addition to good news for treadmill-desk users or people who like to think on the move, the study provides a useful scientific tool by demonstrating that it’s possible to collect accurate EEG data on moving subjects, Kline said.
This is important to researchers who study the brain and are concerned about getting accurate results when the subjects aren’t perfectly still. U-M researchers achieved their EEG results by applying different signal-processing techniques to eliminate the movement “noise” from the EEG signal.
Molecular Switches for Age-Related Memory Decline? A Genetic Variant Protects Against Brain Aging
Even among the healthiest individuals, memory and cognitive abilities decline with age. This aspect of normal aging can affect an individual’s quality of life and capability to live independently but the rate of decline is variable across individuals. There are many factors that can influence this trajectory, but perhaps none more importantly than genetics.
Scientists are seeking to identify key molecular switches that control age-related memory impairment. When new molecules are identified as critical to the process of memory consolidation, they are then tested to determine whether they contribute to the memory problems of the elderly.
One of these proteins is called KIBRA and the gene responsible for its production is WWC1. KIBRA is known to play a role in human memory and so researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health, led by senior author Dr. Venkata Mattay, conducted a study to determine the effects of genetic variants in WWC1 on memory. Their findings are published in the current issue of Biological Psychiatry.
“Identifying these genetic factors, while helping us better understand the neurobiology of cognitive aging, will also aid in identifying mechanisms that confer individuals with resilience to withstand the inevitable age-related changes in neural architecture and function,” explained Mattay.
Using imaging genetics, a method that combines genetics with brain imaging technology, the team explored the effect of a variant in the WWC1 gene on age-related changes in memory function. The particular WWC1 variant under investigation has three potential forms – CC, TT, or CT.
They recruited 233 healthy volunteers, who ranged in age from 18-89 years. The volunteers completed a battery of cognitive tests, underwent genotyping, and completed a memory task during a brain imaging scan.
They found that individuals who carry the T allele, as either CT or TT, performed better on the memory task and showed more active engagement in the hippocampus, a vital brain region for memory, with increasing age.
“Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” said Mattay. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”
Dr. John Krystal, Editor of Biological Psychiatry, commented, “The risk mechanisms for age-related memory impairment that we identify today may become the targets for the prevention and treatment of this problem in the future.”
Simple technique may help older adults better remember written information
University of Florida researchers have advice for older adults who need to remember detailed written information: Don’t just read it, tell someone about it.
That recommendation comes from a new UF study that showed that older adults who read a text and then described what they had read to someone else remembered more details of the text than older adults who simply re-read the passage multiple times.
The findings appear in the April issue of the journal Aphasiology.
Older adults are better able than younger adults to recall the gist of information they learn, but they have more difficulty remembering details, said lead investigator Yvonne Rogalski, who conducted the research as part of her doctoral dissertation work at the UF College of Public Health and Health Professions.
“Older adults can rely on things they’ve learned in the past and they can build on that vast wealth of semantic information that they’ve collected over the years. That works as long as the information is familiar, but where it breaks down is when they have to read something that is unfamiliar and has a lot of details,” said Rogalski, now an assistant professor in the department of speech-language pathology and audiology at Ithaca College.
As a doctoral student Rogalski developed a training technique called Read Attentively, Summarise and Review, or RASR, which requires participants to read a passage aloud and then summarize from memory what they’ve read after each paragraph. The training is designed to help people “encode” information and commit it to memory.
“In the reading aloud portion, attention is heightened because you know you’re going to have to recall something,” she said. “Then retrieving that information through the summaries has the ability to act as a secondary encoding. Reading and recalling the text paragraph by paragraph instead of the whole text is designed to reduce the information processing demands.”
For the UF study, 44 healthy adults ages 60 to 75 used one of two methods to recall details from texts on real — but unusual — animals. Participants who used a technique called Read and Reread Attentively read the entire passage aloud once, and then re-read each paragraph three times aloud in succession. Those in the RASR group read the whole text aloud once, then for each paragraph they read it aloud, summarized it from memory and then re-read it aloud again. Participants in both groups were tested immediately after studying and 24 hours later.
The researchers found that participants who summarized the information aloud remembered more details about the texts than those who just re-read the material. In addition, combining the summarization method with an immediate post-test showed the most benefit for remembering text details after a 24-hour delay.
“We think it is effective because by reading the information and then putting it into your own words you have to do quite a bit of processing of not only the information, but also the relationships among bits of information,” said Lori Altmann, an associate professor in the UF department of speech, language, and hearing sciences, and a study co-author along with John Rosenbek, also a professor in the department. “Picking out the relationships that are important to you as you see them can help to order the information in your own memory.”
Older adults can put the principles of the summarization technique to work for themselves whenever they want or need to learn detailed information, such as a magazine article or medication plan, the researchers say. They suggest that people read the information and then describe it from memory to a partner who can check for accuracy.
“The RASR method is a very functional treatment and it’s something that healthy older adults or even people with mild dementias could use on their own to try and improve their memory,” Altmann said. “It doesn’t involve anything high-tech, and that’s the beauty of it.”
(Source: news.ufl.edu)
Investigators Discover How Key Protein Enhances Memory and Learning
Case Western Reserve researchers have discovered that a protein previously implicated in disease plays such a positive role in learning and memory that it may someday contribute to cures of cognitive impairments. The findings regarding the potential virtues of fatty acid binding protein 5 (FABP5) — usually associated with cancer and psoriasis — appear in the May 2 edition of The Journal of Biological Chemistry.
“Overall, our data show that FABP5 enhances cognitive function and that FABP5 deficiency impairs learning and memory functions in the brain hippocampus region,” said senior author Noa Noy, PhD, a professor of pharmacology at the School of Medicine. “We believe if we could find a way to upregulate the expression of FABP5 in the brain, we might have a therapeutic handle on cognitive dysfunction or memory impairment in some human diseases.”
FABP5 resides in many tissues and is especially highly expressed in the brain. Noy and her Case Western Reserve School of Medicine and National Institute on Alcohol Abuse and Alcoholism colleagues particularly wanted to understand how this protein functioned in neurons. They performed imaging studies comparing the activation of a key transcription factor in the brain tissue of normal mice and in FABP5-deficient mice. (Transcription factor is a protein the controls the flow of genetic information). The investigations revealed that FABP5 performs two different functions in neurons. First, it facilitates the degradation of endocannabinoids, which are neurological modulators controlling appetite, pain sensation, mood and memory. Second, FABP5 regulates gene expression, a process that essentially gives cells their marching orders on structure, appearance and function.
“FABP5 improves learning and memory both because it delivers endocannabinoids to cellular machinery that breaks them down and because it shuttles compounds to a transcription factor that increases the expression of cognition-associated genes,” Noy said.
Even though endocannabinoids affect essential physiological processes from appetite to memory, the “cannabinoid” part of the word signifies that these natural biological compounds act similarly to drugs such as marijuana and hashish. Too much endocannabinoid can lead to impaired learning and memory.
In simple terms, FABP5 transports endocannabinoids for processing. FABP5 functions like a bus and carries the brain’s endocannabinoids and their biological products to two stations within the neuron cell. FABP5 captures endocannabinoids entering the neuron and delivers them to an enzyme that degrades them (station 1). Then, that degraded product is picked up by the same protein (FABP5) and shuttled to the cell nucleus — specifically, to a transcription factor within it (station 2). Binding of the degraded product activates the transcription factor and allows it to induce expression of multiple genes. The genes that are induced in this case tell the cells to take steps that promote learning and memory.
Noy and associates also compared memory and learning in FABP5-deficient mice and in normal ones. In one test, both sets of mice repeatedly swam in mazes that had a platform in one established location where they could climb out of the water. During subsequent swims, the wild-type mice reached the platform quickly because they had learned — and remembered — its location. Their FABP5-deficient counterparts took much longer, typically finding the platform’s location by chance.
“In addition to regulating cell growth as in skin and in cancer cells, for example, FABP5 also plays a key role in neurons of the brain,” Noy said. “FABP5 controls the biological actions of small compounds that affect memory and learning and that activate a transcription factor, which regulates neuronal function.”
(Source: casemed.case.edu)