Posts tagged memory

July 12, 2012

(HealthDay) — A supplement mixture (Souvenaid) containing dietary precursors and specific nutrients can improve memory in drug-naive patients with mild Alzheimer’s disease (AD), according to a study published in the July issue of the Journal of Alzheimer’s Disease.

Philip Scheltens, M.D., from the VU University Medical Center in Amsterdam, and colleagues conducted a 24-week, randomized, controlled trial in which drug-naive patients with mild AD were randomized in a 1:1 ratio to receive Souvenaid or an iso-caloric control product once daily. Memory function was assessed using the domain z-score of the Neuropsychological Test Battery (NTB).

The researchers found that, over the intervention period, the NTB memory domain z-score was significantly increased in patients taking Souvenaid versus the control group (P = 0.023), with a trend toward improvement in the NTB total composite z- score (P = 0.053). Functional connectivity in the delta band, as measured by an electroencephalography, was significantly different between the study groups in favor of the active group. There was very high adherence to the intervention (96.6 percent for the control and 97.1 percent for the active group). Both products were well tolerated and there was no between-group difference in the occurrence of serious adverse events.

"In conclusion, this study confirms that Souvenaid is well tolerated and improves memory performance,” the authors write. “Our results warrant further investigation of the clinical potential of Souvenaid in preclinical or clinical conditions characterized by synaptic loss, in particular AD.”

Several authors disclosed financial ties to Danone Research BV and Nutricia Advanced Medical Nutrition, which sponsored the study and manufacture Souvenaid.

Source: medicalxpress.com

ScienceDaily (July 11, 2012) — When humans learn, their brains relate new information with past experiences to derive new knowledge, according to psychology research from The University of Texas at Austin.

The study, led by Alison Preston, assistant professor of psychology and neurobiology, shows this memory-binding process allows people to better understand new concepts and make future decisions. The findings could lead to better teaching methods, as well as treatment of degenerative neurological disorders, such as dementia, Preston says.

"Memories are not just for reflecting on the past; they help us make the best decisions for the future," says Preston, a research affiliate in the Center for Learning and Memory, which is part of the university’s College of Natural Sciences. "Here, we provide a direct link between these derived memories and the ability to make novel inferences."

The paper was published online in July in the journal Neuron. The authors include University of Texas at Austin researchers Dagmar Zeithamova and April Dominick.

In the study, 34 subjects were shown a series of paired images composed of different elements (for example, an object and an outdoor scene). Each of the paired images would then reappear in more presentations. A backpack, paired with a horse in the first presentation, would appear alongside a field in a later presentation. The overlap between the backpack and outdoor scenery (horse and field) would cause the viewer to associate the backpack with the horse and field. The researchers used this strategy to see how respondents would delve back to a recent memory while processing new information.

Using functional Magnetic Resonance Imaging (fMRI) equipment, the researchers were able to look at the subjects’ brain activity as they looked at image presentations. Using this technique, Preston and her team were able to see how the respondents thought about past images while looking at overlapping images. For example, they studied how the respondents thought about a past image (a horse) when looking at the backpack and the field. The researchers found the subjects who reactivated related memories while looking at overlapping image pairs were able to make associations between individual items (i.e. the horse and the field) despite the fact that they had never studied those images together.

To illustrate the ways in which this cognitive process works, Preston describes an everyday scenario.

Imagine you see a new neighbor walking a Great Dane down the street. At a different time and place, you may see a woman walking the same dog in the park. When experiencing the woman walking her dog, the brain conjures images of the recent memory of the neighbor and his Great Dane, causing an association between the dog walkers to be formed in memory. The derived relationship between the dog walkers would then allow you to infer the woman is also a new neighbor even though you have never seen her in your neighborhood.

"This is just a simple example of how our brains store information that goes beyond the exact events we experience," Preston says. "By combining past events with new information, we’re able to derive new knowledge and better anticipate what to expect in the future."

During the learning tasks, the researchers were able to pinpoint the brain regions that work in concert during the memory-binding process. They found the hippocampal-ventromedial prefrontal cortex (VMPFC) circuit is essential for binding reactivated memories with current experience.

Source: Science Daily

July 11, 2012

An inflated sense of memory function in people with dementia may influence their likelihood of seeking help, new Flinders University research shows.

As part of her PhD, Flinders research associate Dr. Chris Materne studied the disparity between memory perception and performance in people with dementia.

In the first stage of the project, Dr. Materne analysed data from the Australian Longitudinal Study of Aging which showed that most survey participants believed their memory had remained stable over the 11-year assessment, despite tests showing a decline in memory performance.

She then conducted an intervention with 13 individuals, from a larger group of 23 people with dementia, using spaced retrieval memory training to help them achieve a specific task or activity, such as remembering to lock the front door or keep their glasses in the same spot.

“Spaced retrieval works by helping people remember specific information or tasks by getting them to respond to a prompt question over progressively increasing intervals of time,” Dr. Materne said.

“In one case we helped a man remember to put his glasses in the same place because he was always losing them which made both him and his wife quite distressed,” she said.

“We think the training taps into procedural memory so it becomes habitual rather than explicit memory, such as memory for facts, which tends to decline before procedural memory when you have dementia.”

The technique was conducted once a week for six weeks, with seven out of the 13 participants still able to perform their nominated activity or task after six months.

The 23 participants were also asked to rate their performance based on a specific question, such as how many people they could name in a photo with 10 faces.

While most respondents were initially over-confident in their abilities, with some claiming to be able to name all 10 faces, their perceptions did change over time to more accurately reflect their cognitive function.

About one third of family carers, however, initially considered their loved ones memory to be better than what the person with dementia actually reported.

“In the longitudinal sample people didn’t feel their memory had changed over time because the questions were more general but when we asked specific, detailed questions about memory in the smaller study, the respondents came to recognise their declining performance.”

Dr. Materne said the research highlighted the need for more comprehensive assessments when diagnosing dementia to increase the accuracy of peoples’ perceptions, and therefore their likelihood of seeking help.

Provided by Flinders University

Source: medicalxpress.com

ScienceDaily (July 9, 2012) — “Attentional blink” is the term psychologists use to describe our inability to recognize a second important object if we see it less than half a second after a first one. It always seemed impossible to overcome, but in a new paper in the Proceedings of the National Academy of Sciences, Brown University psychologists report they’ve found a way.

So far it has seemed an irreparable limitation of human perception that we strain to perceive things in the very rapid succession of, say, less than half a second. Psychologists call this deficit “attentional blink.” We’ll notice that first car spinning out in our path, but maybe not register the one immediately beyond it. It turns out, we can learn to do better after all. In a new study researchers now based at Brown University overcame the blink with just a little bit of training that was never been tried before.

"A color change can be very conspicuous. If all items are black and white and all of a sudden a color item is shown, you pay attention to that." Credit: Mike Cohea/Brown University"Attention is a very important component of visual perception," said Takeo Watanabe, professor of cognitive, linguistic and psychological sciences at Brown. "One of the best ways to enhance our visual ability is to improve our attentional function."

Watanabe and his team were at Boston University when they performed experiments described in a paper published the week of July 9 in the Proceedings of the National Academy of Sciences. The bottom line of the research is that making the second target object a distinct color is enough to train people to switch their attention more quickly than they could before. After that, they can perceive a second target object presented as quickly as a fifth of a second later, even when it isn’t distinctly colored.

Read more …

July 10, 2012 by Anne Trafton

A clinical trial of an Alzheimer’s disease treatment developed at MIT has found that the nutrient cocktail can improve memory in patients with early Alzheimer’s. The results confirm and expand the findings of an earlier trial of the nutritional supplement, which is designed to promote new connections between brain cells.

A graphic depicting a synapse, a connection between brain cells. Graphic: Christine Daniloff

Alzheimer’s patients gradually lose those connections, known as synapses, leading to memory loss and other cognitive impairments. The supplement mixture, known as Souvenaid, appears to stimulate growth of new synapses, says Richard Wurtman, a professor emeritus of brain and cognitive sciences at MIT who invented the nutrient mixture.

“You want to improve the numbers of synapses, not by slowing their degradation — though of course you’d love to do that too — but rather by increasing the formation of the synapses,” Wurtman says.

To do that, Wurtman came up with a mixture of three naturally occurring dietary compounds: choline, uridine and the omega-3 fatty acid DHA. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine is produced by the liver and kidney, and is present in some foods as a component of RNA.

These nutrients are precursors to the lipid molecules that, along with specific proteins, make up brain-cell membranes, which form synapses. To be effective, all three precursors must be administered together.

Results of the clinical trial, conducted in Europe, appear in the July 10 online edition of the Journal of Alzheimer’s Disease. The new findings are encouraging because very few clinical trials have produced consistent improvement in Alzheimer’s patients, says Jeffrey Cummings, director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health.

“Memory loss is the central characteristic of Alzheimer’s, so something that improves memory would be of great interest,” says Cummings, who was not part of the research team.

Plans for commercial release of the supplement are not finalized, according to Nutricia, the company testing and marketing Souvenaid, but it will likely be available in Europe first. Nutricia is the specialized health care division of the food company Danone, known as Dannon in the United States.

Making connections

Wurtman first came up with the idea of targeting synapse loss to combat Alzheimer’s about 10 years ago. In animal studies, he showed that his dietary cocktail boosted the number of dendritic spines, or small outcroppings of neural membranes, found in brain cells. These spines are necessary to form new synapses between neurons.

Following the successful animal studies, Philip Scheltens, director of the Alzheimer Center at VU University Medical Center in Amsterdam, led a clinical trial in Europe involving 225 patients with mild Alzheimer’s. The patients drank Souvenaid or a control beverage daily for three months.

That study, first reported in 2008, found that 40 percent of patients who consumed the drink improved in a test of verbal memory, while 24 percent of patients who received the control drink improved their performance.

The new study, performed in several European countries and overseen by Scheltens as principal investigator, followed 259 patients for six months. Patients, whether taking Souvenaid or a placebo, improved their verbal-memory performance for the first three months, but the placebo patients deteriorated during the following three months, while the Souvenaid patients continued to improve. For this trial, the researchers used more comprehensive memory tests taken from the neuropsychological test battery, often used to assess Alzheimer’s patients in clinical research.

Patients showed a very high compliance rate: About 97 percent of the patients followed the regimen throughout the study, and no serious side effects were seen.

Both clinical trials were sponsored by Nutricia. MIT has patented the mixture of nutrients used in the study, and Nutricia holds the exclusive license on the patent.

Brain patterns

In the new study, the researchers used electroencephalography (EEG) to measure how patients’ brain-activity patterns changed throughout the study. They found that as the trial went on, the brains of patients receiving the supplements started to shift from patterns typical of dementia to more normal patterns. Because EEG patterns reflect synaptic activity, this suggests that synaptic function increased following treatment, the researchers say.

Patients entering this study were in the early stages of Alzheimer’s disease, averaging around 25 on a scale of dementia that ranges from 1 to 30, with 30 being normal. A previous trial found that the supplement cocktail does not work in patients with Alzheimer’s at a more advanced stage. This makes sense, Wurtman says, because patients with more advanced dementia have probably already lost many neurons, so they can’t form new synapses.

A two-year trial involving patients who don’t have Alzheimer’s, but who are starting to show mild cognitive impairment, is now underway. If the drink seems to help, it could be used in people who test positive for very early signs of Alzheimer’s, before symptoms appear, Wurtman says. Such tests, which include PET scanning of the hippocampus, are now rarely done because there are no good Alzheimer’s treatments available.

Provided by Massachusetts Institute of Technology

Source: medicalxpress.com

By Sabrina Richards | July 2, 2012

Scientists find that declining DNA methylation in mouse neurons may cause age-related memory deficits.

An elderly man
Flickr, BLEU MAN

Research is increasingly connecting changes in epigenetic regulation of gene expression  to the aging process. Many studies demonstrate that DNA methylation declines with age. Now, new research published yesterday (July 1) in Nature Neuroscience links DNA methylation with brain aging. Researchers show that levels of an enzyme that attaches methyl groups to cytosine nucleotides throughout the genome is linked to cognitive decline, and that its overexpression can restore performance of aging mice on memory-related tasks.

“We already know normal aging is associated with cognitive decline, but this paper links that with expression a specific DNA methyltransferase,” said Yuan Gao, an epigeneticist at the Lieber Institute for Brain Development in Maryland, who did not participate in the study. The current work also builds on other studies demonstrating that proper regulation of methylation in brain cells is critical to memory formation. Previous studies have suggested a connection between loss of DNA methylation and Alzheimer’s disease, said Gao, suggesting that if researchers could “restore [methyltransferase] activity and cure or delay dementia, it would make a nice model” for developing drugs to tackle age-related cognitive diseases.

DNA methylation, wherein a methyl group is attached to a cytosine next to a guanosine, is one form of epigenetic regulation that can modulate how available genes are to the cell’s transcription machinery, and thus how highly expressed they are. Scientists already appreciate how differences in epigenetic regulation can affect development of diseases like cancer, without need for gene mutations. Studies are also accumulating that correlate declining methylation with aging, although the mechanism remains unclear.

Classically, DNA methylation is considered a repressive modification, but that view is beginning to change, suggesting a more nuanced role for methylation in gene regulation, explained senior author Hilmar Bading of the University of Heidelberg. The twist in Bading’s current research is that the methyltransferase his group focuses on, Dnmt3a2, may be working to enable gene transcription, rather than repress it.

This gene-activating role may stem from methylation that blocks repressors, rather than activators, explained Trygve Tollesfbol, who investigates the role of epigenetics in cancer and aging at the University of Alabama, who did not participate in the research. Whether methylation is located in the promoter or body of the gene can also determine whether it inhibits or enhances transcription, explained Guoping Fan, who studies epigenetic regulation of neuron development at the University of California, Los Angeles.

Bading’s group identified Dnmt3a2 when looking for genes that are upregulated by neuronal activity. Knowing that DNA methylation decreases with age, first author Ana Oliviera compared Dnmt3a2 expression in 3-month-old and 18-month-old mice, and found lower levels of Dnmt3a2 in the older mice. Furthermore, learning tasks designed to stimulate hippocampus neurons failed to upregulate Dnmt3a2 expression in old mice as robustly as in young mice.

Theorizing that reduced Dnmt3a2-dependent DNA methylation contributed to older mice’s poorer performance on learning and memory tasks, the scientists used an adeno-associated virus to supplement Dnmt3a2 expression in their hippocampal neurons. Boosting its expression enhanced both brain methylation in the older mice, and their ability to learn. Conversely, when the researchers used short hairpin RNA to knockdown Dnmt3a2 expression in young mice, their performance on learning and memory tests worsened.

“I think Dnmt3a2 has a basic gating function,” said Bading. Neurons need to turn genes on and off quickly in response to changing stimulation. Bading hypothesizes that Dnmt3a2-dependent methylation helps keep genes—like brain-derived neurotrophic factor (BDNF) and Arc, both regulated by Dnmt3a2 and both involved in responses to signaling changes—receptive to changing stimulation, putting “the genome in the right state for being inducible,” Bading said. Genes like BDNF shouldn’t be transcribed all the time, but it may be that without Dnmt3a2-dependent methylation, “the door is closed” neurons can’t express them when they need to.

This could set up a vicious cycle, Bading explained, because Dnmt3a2 is also induced by neuronal activity. Less Dnmt3a2 would result in less expression of methylation-dependent genes, possibly including Dnmt3a2 itself, and the effect would worsen over time. “It would take many years to add up, but aging takes years,” Bading noted.

Methylation is unlikely to be the only epigenetic factor in aging, said Tollefsbol, who anticipates similar investigations into other DNA and histone modifications. BDNF itself has already been linked to histone acetylation and brain aging. “A good paper like this raises more questions than it answers,” Tollefsbol noted. “DNA methylation is probably only about a half or third of the [epigenetics and aging] equation.”

Source: TheScientist

ScienceDaily (June 28, 2012) — We’ve all heard that eating fish is good for our brains and memory. But what is it about DHA, an omega-3 fatty acid found in fish, that makes our memory sharper?

Researchers with the Faculty of Medicine & Dentistry discovered a possible explanation and just published their findings in the peer-reviewed journal Applied Physiology, Nutrition, and Metabolism.

Principal investigator Yves Sauve and his team discovered lab models fed a high-DHA diet had 30 per cent higher levels of DHA in the memory section of the brain, known as the hippocampus, when compared to animal models on a regular, healthy diet.

"We wanted to find out how fish intake improves memory," says Sauve, a medical researcher at the University of Alberta who works in the department of physiology, the department of ophthalmology and the Centre for Neuroscience.

"What we discovered is that memory cells in the hippocampus could communicate better with each other and better relay messages when DHA levels in that region of the brain were higher. This could explain why memory improves on a high-DHA diet."

Sauve noted it is a key finding that when a diet is supplemented with DHA, that additional stores of the omega-3 fatty acid are deposited in the brain. His team confirmed this finding, a discovery other labs have noted as well.

Supplementing your diet with DHA, such as increasing fish intake or taking supplements, could prevent declining DHA levels in the brain as we age, says Sauve.

This research was funded by Alberta Innovates — Health Solutions.

Earlier this year, Sauve and other colleagues discovered DHA prevents the accumulation of a toxic molecule at the back of the eye that causes age-related vision loss. He is continuing his research in this area.

Source: Science Daily

ScienceDaily (June 26, 2012) — Researchers have long been interested in discovering the ways that human brains represent thoughts through a complex interplay of electrical signals. Recent improvements in brain recording and statistical methods have given researchers unprecedented insight into the physical processes under-lying thoughts. For example, researchers have begun to show that it is possible to use brain recordings to reconstruct aspects of an image or movie clip someone is viewing, a sound someone is hearing or even the text someone is reading.

Researchers have long been interested in discovering the ways that human brains represent thoughts through a complex interplay of electrical signals. (Credit: © James Steidl / Fotolia)

A new study by University of Pennsylvania and Thomas Jefferson University scientists brings this work one step closer to actual mind reading by using brain recordings to infer the way people organize associations between words in their memories.

The research was conducted by professor Michael J. Kahana of the Department of Psychology in Penn’s School of Arts and Sciences and graduate student Jere-my R. Manning, then a member of the Neuroscience Graduate Group in Penn’s Perelman School of Medicine. They collaborated with other members of Kahana’s laboratory, as well as with research faculty at Thomas Jefferson University Hospital.

Their study was published in The Journal of Neuroscience.

The brain recordings necessary for the study were made possible by the fact that the participants were epilepsy patients who volunteered for the study while awaiting brain surgery. These participants had tiny electrodes implanted in their brains, which allowed researchers to precisely observe electrical signals that would not have been possible to measure outside the skull. While recording these electrical signals, the researchers asked the participants to study lists of 15 randomly chosen words and, a minute later, to repeat the words back in which-ever order they came to mind.

The researchers examined the brain recordings as the participants studied each word to home in on signals in the participant’ brains that reflected the meanings of the words. About a second before the participants recalled each word, these same “meaning signals” that were identified during the study phase were spontaneously reactivated in the participants’ brains.

Because the participants were not seeing, hearing or speaking any words at the times these patterns were reactivated, the researchers could be sure they were observing the neural signatures of the participants’ self-generated, internal thoughts.

Critically, differences across participants in the way these meaning signals were reactivated predicted the order in which the participants would recall the words. In particular, the degree to which the meaning signals were reactivated before recalling each word reflected each participant’s tendency to group similar words (like “duck” and “goose”) together in their recall sequence. Since the participants were instructed to say the words in the order they came to mind, the specific se-quence of recalls a participant makes provides insights into how the words were organized in that participant’s memory.

In an earlier study, Manning and Kahana used a similar technique to predict participants’ tendencies to organize learned information according to the time in which it was learned. Their new study adds to this research by elucidating the neural signature of organizing learned information by meaning.

"Each person’s brain patterns form a sort of ‘neural fingerprint’ that can be used to read out the ways they organize their memories through associations between words," Manning said.

The techniques the researchers developed in this study could also be adapted to analyze many different ways of mentally organizing studied information.

"In addition to looking at memories organized by time, as in our previous study, or by meaning, as in our current study, one could use our technique to identify neural signatures of how individuals organize learned information according to appearance, size, texture, sound, taste, location or any other measurable property," Manning said.

Such studies would paint a more complete picture of a fundamental aspect of human behavior.

"Spontaneous verbal recall is a form of memory that is both pervasive in our lives and unique to the human species," Kahana said. "Yet, this aspect of human memory is the least well understood in terms of brain mechanisms. Our data show a direct correspondence between patterns of brain activity and the meanings of individual words and show how this neural representation of meaning predicts the way in which one item cues another during spontaneous recall.

"Given the critical role of language in human thought and communication, identifying a neural representation that reflects the meanings of words as they are spontaneously recalled brings us one step closer to the elusive goal of mapping thoughts in the human brain."

Source: Science Daily

June 22nd, 2012

New research suggests that it is possible to suppress emotional autobiographical memories. The study published this month by psychologists at the University of St Andrews reveals that individuals can be trained to forget particular details associated with emotional memories.

The important findings may offer exciting new potential for therapeutic interventions for individuals suffering from emotional disorders, such as depression and post-traumatic stress disorder.

The research showed that although individuals could still accurately recall the cause of the event, they could be trained to forget the consequences and personal meaning associated with the memory.

The work was carried out by researchers Dr Saima Noreen and Professor Malcolm MacLeod of the University’s School of Psychology. Lead author Dr Noreen explained, “The ability to remember and interpret emotional events from our personal past forms the basic foundation of who we are as individuals.

Research is starting to show that autobiographical memories may be forgotten. This image is adapted from a photograph of a painting. Both are in the public domain. The original painting is translated as The Break-Up Letter and was painted by Alfred Émile Léopold Stevens (ca 1867).

“These novel findings show that individuals can be trained to not think about memories that have personal relevance and significance to them and provide the most direct evidence to date that we possess some kind of control over autobiographical memory.”

The research involved participants generating emotional memories in response to generic cue words, such as theatre, barbecue, wildlife etc. Participants were asked to recall the cause of the event, the consequence of the event and the personal meaning they derived from the event.

Subjects were then asked to provide a single word that was personal to them which reminded them of the memory. In a subsequent session, participants were shown the cue and personal word pairings and were asked to either recall the memory associated with the word pair or to not think about the associated memory.

Interestingly, the findings revealed that whilst the entire autobiographical episode was not forgotten, the details associated with the memory were. Specifically, individuals could remember what caused the event, but were able to forget what happened and how it made them feel.

Co-author Professor MacLeod commented, “The capacity to engage in this kind of intentional forgetting may be critical to our ability to maintain coherent images about who we are and what we are like”.

Source: Neuroscience News

June 18, 2012

Fear conditioning using sound and taste aversion, as applied to mice, have revealed interesting information on the basis of memory allocation.

Credit: Thinkstock

European ‘Cellular mechanisms underlying formation of the fear memory trace in the mouse amygdala’ (FEAR Memory TRACE) project is investigating memory allocation and the recruitment of certain neurons to encode a memory. By studying conditioned fear memory in response to an auditory stimulus, the researchers have delved into pathological emotional states and neural mechanisms involved in memory allocation, retrieval and extinction.

Prior research has revealed that the conditioned fear response in mice is located in a specific bundle of neurons in the amygdala. Memory allocation modulation is due to expression of the transcription factor, cyclic adenosine 3’, 5’-monophosphate response element binding protein (CREB) and possibly neuronal excitability.

FEAR Memory TRACE focused on the electrophysiological properties of neurons encoding the same memory. The project also aimed to ascertain the biophysical mechanisms in the plasticity changes recorded in the specific set of neurons in the fear memory trace.

Recording information on auditory fear conditioning and conditioned taste aversion, the scientists used intra-amygdala surgery using viral vectors and electrophysiological experiments to detect neuronal excitability.

Transfected by virus, CREB tagged with green fluorescent protein together with the gene for channelrhodopsin2 were used in neural control experiments. Combined, these two elements caused neuron firing in specific nerve cells. Molecular techniques included western blot for protein detection, genotyping and viral DNA preparation.

Behavioural tests on long- and short-term memory of mice involving fear conditioning and taste aversion showed increased memory performance at the three-hour point rather than the five-hour point. The intrinsic excitability of the mice receiving both shock and the tone was increased at three hours, not five, compared to mice that only received the tone.

As the project continues to its close in two years, the aim is to identify biophysical mechanisms involved in recruiting neurons that compete with each other for a specific memory. FEAR Memory TRACE will also develop computational models to assess the role of these mechanisms in memory performance.

Information on biochemical processes in neural mechanisms has wide application in many clinical situations including patients suffering memory loss, such as stroke victims. Fear response manipulation can be applied in treatment of neuroses and phobias.

Provided by CORDIS

Source: medicalxpress.com