Posts tagged brain

March 28, 2012 by Stuart Mason Dambrot

(Medical Xpress) — College and cramming – often where’s there’s one, the other is not far behind. That said, however, it has been recognized since the late 1800s that repeated periodic exposure to the same material leads to better retention than does a single en masse session. Nevertheless, the phenomenon’s neurobiological processes have remained poorly understood, although activity-dependent synaptic plasticity – notably long-term potentiation (LTP) of glutamatergic transmission – is believed to enable rapid storage of new information. Recently, researchers at the University of California in Irvine and the Scripps Research Institute in Jupiter, Florida determined that hippocampal activity can enhance LTP through theta burst stimulation (TBS) – but only when the affected synapses receive, after a long delay, a secondary TBS. The researchers describe mechanisms that maximize synaptic changes that optimally encode new memory by requiring long delays learning-related TBS activity.

A second theta burst train expands the pool of F-actin-enriched spines. (A) Fluorescent phalloidin labeling in CA1 stratum radiatum. (Scale bar = 10 μm). (B) Counts of densely phalloidin-positive spines in slices collected 15 or 75 min after TBS1 (gray bars) or 15 min after TBS2 delayed by 60 min (black bar). (C) Traces show responses to two successive bursts separated by 200 ms (red for second response). (D) Counts of TBS1-induced phalloidin labeling for vehicle (gray) and CX614-treated (blue) slices. (E) Pretreatment with CX614 (blue line) caused a 70% increase in the magnitude of LTP induced by TBS1; this was accompanied by a loss of TBS2-induced potentiation. Image Copyright © 2012 PNAS, doi: 10.1073/pnas.1120700109

Gavin Rumbaugh (Scripps Research Institute) discussed the challenges he, Gary Lynch (University of California) and their team encountered in the study. “The field is trying to understand the neurobiology of new learning, and in particular, how learning induces an even more complex biology to keep new information in our neural circuits,” Rumbaugh tells Medical Xpress. “Over the recent decade, it has become clear that plasticity at individual synapses is a way that neural circuits store information. However, it remains unclear how properties of synapses influence key aspects of learning and memory.”

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March 28, 2012

(Medical Xpress) — While stimulants may improve unengaged workers’ performance, a new University of British Columbia study suggests that for others, caffeine and amphetamines can have the opposite effect, causing workers with higher motivation levels to slack off.

The study – published online today by Nature’s Neuropsychopharmacology – explored the impacts of stimulants on “slacker” rats and “worker” rats, and sheds important light on why stimulants might affect people differently, a question that has long been unclear. It also suggests that patients being treated with stimulants for a range of illnesses may benefit from more personalized treatment programs.

“Every day, millions of people use stimulants to wake up, stay alert and increase their productivity – from truckers driving all night to students cramming for exams,” says Jay Hosking, a PhD candidate in UBC’s Dept. of Psychology, who led the study. “These findings suggest that some stimulants may actually have an opposite effect for people who naturally favour the difficult tasks of life that come with greater rewards.”

Hosking says some individuals are more willing to concentrate and exert effort to achieve their goals than others. However, little is known about the brain mechanisms determining how much cognitive effort one will expend in decision-making for accomplishing tasks.

Hosking and study co-author Catharine Winstanley, a professor in UBC’s Dept. of Psychology, found that rats – like humans – show varying levels of willingness to expend high or low degrees of mental effort to obtain food rewards. When presented with stimulants, the “slacker” rats that typically avoided challenges worked significantly harder when given amphetamines, while “worker” rats that typically embraced challenges were less motivated by caffeine or amphetamine.

While more research is needed to understand the brain mechanisms at work, the study suggests that the amount of mental attention people devote to achieving their goals may play a role in determining how stimulants drugs affect them, Hosking says.

Winstanley, a Michael Smith Foundation for Health Research scholar, says people with psychiatric illnesses, brain injuries and Attention Deficit Hyperactivity Disorder (ADHD) may benefit from treatment programs with greater personalization, noting that patients often use stimulants to counter drowsiness and fatigue from their conditions and treatments, with mixed results.

Provided by University of British Columbia

Source: medicalxpress.com

ScienceDaily (Mar. 27, 2012) — Just as the familiar sugar in food can be bad for the teeth and waistline, another sugar has been implicated as a health menace and blocking its action may have benefits that include improving long-term memory in older people and treating cancer.

Blocking the action of a sugar could boost memory and even fight cancer. The neuron on the left has CREB with O-GlcNAc and is short. The neuron on the right does not have that form of CREB and is long. (Credit: Linda Hsieh-Wilson, Ph.D.)

Progress toward finding such a blocker for the sugar — with the appropriately malicious-sounding name “oh-glick-nack” — was the topic of a report presented at the 243rd National Meeting & Exposition of the American Chemical Society (ACS) in San Diego on March 27.

Linda Hsieh-Wilson, Ph.D., explained that the sugar is not table sugar (sucrose), but one of many other substances produced in the body’s cells that qualify as sugars from a chemical standpoint. Named O-linked beta-N-acetylglucosamine — or “O-GlcNAc” — it helps in orchestrating health and disease at their origins, inside the billions of cells that make up the body. O-GlcNAc does so by attaching to proteins that allow substances to pass in and out of the nucleus of cells, for instance, and helping decide whether certain genes are turned on or off. In doing so, O-GlcNAc sends signals that may be at the basis of cancer, diabetes, Alzheimer’s disease and other disorders. Research suggests, for instance, that proteins loaded up with too much O-GlcNAc can’t function normally.

At the ACS meeting, Hsieh-Wilson described how research in her lab at the California Institute of Technology and Howard Hughes Medical Institute implicate O-GlcNAc in memory loss and cancer. The research emerged from Hsieh-Wilson’s use of advanced lab tools for probing a body process that involves attachment of sugars like O-GlcNAc to proteins. Called protein glycosylation, it helps nerves and other cells communicate with each other in ways that keep the body coordinated and healthy. When O-GlcNAc is attached to a protein, that binding process is known as O-GlcNAc glycosylation.

Hsieh-Wilson’s team screened the entire mammalian brain for all O-GlcNAc-glycosylated proteins, using a new process that her laboratory developed. They identified more than 200 proteins bearing O-GlcNAc attachments or tags, many for the first time. The research was done in mice, stand-ins for humans in research that cannot be done on people. Some of the proteins carrying O-GlcNAc were involved in regulating processes like drug addiction and securing long-term storage of memories.

O-GlcNAc’s effects on one particular protein, CREB, got the scientists’ attention. CREB is a key substance that turns on and regulates the activity of genes. Many of the genes in cells are inactive at any given moment. Substances like CREB, termed transcription factors, turn genes on. Hsieh-Wilson found that when O-GlcNAc attached to CREB, CREB’s ability to turn on genes was impaired. When the researchers blocked O-GlcNAc from binding CREB, the mice developed long-term memories faster than normal mice.

Could blocking O-GlcNAc boost long-term memory in humans?

"We’re far from understanding what happens in humans," Hsieh-Wilson emphasized. "Completely blocking O-GlcNAc might not be desirable. Do you really want to sustain all memories long-term, even of events that are best forgotten? How would blocking the sugar from binding to other proteins affect other body processes? There are a lot of unanswered questions. Nevertheless, this research could eventually lead to ways to improve memory."

In a related study, Hsieh-Wilson found that O-GlcNAc interacted with another protein in ways that encourage the growth of cancer cells, suggesting that blocking its attachment might protect against cancer or slow the growth of cancer. And indeed, in mouse experiments, blocking O-GlcNAc resulted in much smaller tumors.

Again, a treatment for humans based on this discovery is far in the future, but the study singles out O-GlcNAc as a potential new target for developing anti-cancer drugs.

Source: Science Daily

March 27, 2012

A hallmark of human intelligence is the ability to efficiently adapt to uncertain, changing and open-ended environments. In such environments, efficient adaptive behavior often requires considering multiple alternative behavioral strategies, adjusting them, and possibly inventing new ones. These reasoning, learning and creative abilities involve the frontal lobes, which are especially well developed in humans compared to other primates. However, how the frontal function decides to create new strategies and how multiple strategies can be monitored concurrently remain largely unknown.

In a new study, published March 27 in the online, open-access journal PLoS Biology, Anne Collins and Etienne Koechlin of Ecole Normale Supérieure and Institut National de la Santé et de la Recherche Médicale, France, examine frontal lobe function using behavioral experiments and computational models of human decision-making. They find that human frontal function concurrently monitors no more than three/four strategies but favors creativity, i.e. the exploration and creation of new strategies whenever no monitored strategies appear to be reliable enough.

The researchers asked one hundred participants to find “3-digit pin codes” by a method of trial and error, under a variety of conditions. They then developed a computational model that predicted the responses produced by participants, which also revealed that participants made their choices by mentally constructing and concurrently monitoring up to three distinct behavioral strategies; flexibly associating digits, motor responses and expected auditory feedbacks.

"This is a remarkable result, because the actual number of correct codes varied across sessions. This suggests that this capacity limit is a hard constraint of human higher cognition," said Dr. Koechlin. Consistently, the performance was significantly better in sessions including no more than three repeated codes.

Furthermore, the researchers found that the pattern of participants’ responses derived from a decision system that strongly favors the exploration of new behavioral strategies: “The results provide evidence that the human executive system favors creativity for compensating its limited monitoring capacity” explained Dr. Koechlin. “It favors the exploration of new strategies but restrains the monitoring and storage of uncompetitive ones. Interestingly, this ability to regulate creativity varied across participants and critically explains individual variations in performances. We believe our study may also help to understand the biological foundations of individual differences in decision-making and adaptive behavior”.

Provided by Public Library of Science

Source: medicalxpress.com

ScienceDaily (Mar. 27, 2012) — Cognitive training including puzzles, handicrafts and life skills are known to reduce the risk, and help slow down the progress, of dementia amongst the elderly. A new study published in BioMed Central’s open access journal BMC Medicine showed that cognitive training was able to improve reasoning, memory, language and hand eye co-ordination of healthy, older adults.

It is estimated that by 2050 the number of people over 65 years old will have increased to 1.1 billion worldwide, and that 37 million of these will suffer from dementia. Research has already shown that mental activity can reduce a person’s risk of dementia but the effect of mental training on healthy people is less well understood. To address this researchers from China have investigated the use of cognitive training as a defence against mental decline for healthy older adults who live independently.

To be recruited onto the trial participants had to be between 65 and 75 years old, and have good enough eyesight, hearing, and communication skills, to be able to complete all parts of the training. The hour long training sessions occurred twice a week, for 12 weeks, and the subjects were provided with homework. Training included a multi-approach system tackling memory, reasoning, problem solving, map reading, handicrafts, health education and exercise, or focussing on reasoning only. The effect of booster training, provided six months later, was also tested.

The results of the study were positive. Profs Chunbo Li and Wenyuan Wu who led the research explained, “Compared to the control group, who received no training, both levels of cognitive training improved mental ability, although the multifaceted training had more of a long term effect. The more detailed training also improved memory, even when measured a year later and booster training had an additional improvement on mental ability scores.”

This study shows that cognitive training therapy may prevent mental decline amongst healthy older people and help them to continue independent living longer in their advancing years.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Individuals with major depressive disorder (MDD) often undergo multiple courses of antidepressant treatment during their lives. This is because the disorder can recur despite treatment and because finding the right medication for a specific individual can take time.

While the relationship between prior treatment and the brain’s response to subsequent treatment is unknown, a new study by UCLA researchers suggests that how the brain responds to antidepressant medication may be influenced by its remembering of past antidepressant exposure.

Interestingly, the researchers used a harmless placebo as the key to tracking the footprints of prior antidepressant use.

Aimee Hunter, the study’s lead author and an assistant professor of psychiatry at UCLA’s Semel Institute for Neuroscience and Human Behavior, and colleagues showed that a simple placebo pill, made to look like actual medication for depression, can “trick” the brain into responding in the same manner as the actual medication.

The report was published online March 23 in the journal European Neuropsychopharmacology.

The investigators examined changes in brain function in 89 depressed persons during eight weeks of treatment, using either an antidepressant medication or a similar-looking placebo pill. They set out to compare the two treatments — medication versus placebo — but they also added a twist: They separately examined the data for subjects who had never previously taken an antidepressant and those who had.

The researchers focused on the prefrontal cortex, an area of the brain thought to be involved in planning complex cognitive behavior, personality expression, decision-making and moderating social behavior, all things depressed people wrestle with.

Brain changes were assessed using electroencephalograph (EEG) measures developed at UCLA by study co-authors Dr. Ian Cook, UCLA’s Miller Family Professor of Psychiatry, and Dr. Andrew Leuchter, a professor of psychiatry and director of the Laboratory of Brain, Behavior and Pharmacology at UCLA’s Semel Institute. The EEG measure, recorded from scalp electrodes, is linked to blood flow in the cerebral cortex, which suggests the level of brain activity.

The antidepressant medication given during the study appeared to produce slight decreases in prefrontal brain activity, regardless of whether subjects had received prior antidepressant treatment during their lifetime or not. (A decrease in brain activity is not necessarily a bad thing, the researchers note; with depression, too much activity in the brain can be as bad as too little.)

However, the researchers observed striking differences in the power of placebo, depending on subjects’ prior antidepressant use. Subjects who had never been treated with an antidepressant exhibited large increases in prefrontal brain activity during placebo treatment. But those who had used antidepressant medication in the past showed slight decreases in prefrontal activity — brain changes that were indistinguishable from those produced by the actual drug.

"The brain’s response to the placebo pill seems to depend on what happened previously — on whether or not the brain has ever ‘seen’ antidepressant medication before," said Hunter, who is a member of the placebo research team at the Laboratory of Brain, Behavior and Pharmacology. "If it has seen it before, then the brain’s signature ‘antidepressant-exposure’ response shows up."

According to Hunter, the effect looks conspicuously like a classical conditioning phenomenon, wherein prior exposure to the actual drug may have produced the specific prefrontal brain response and subsequent exposure to the cues surrounding drug administration — the relationship with the doctor or nurse, the medical treatment setting, the act of taking a prescribed pill and so forth — came to elicit a similar brain response through ‘conditioning’ or ‘associative learning.’

While medication can have a powerful effect on our physiology, said Hunter, “the behaviors and cues in the environment that are associated with taking medication can come to elicit their own effects. One’s personal treatment history is one of the many factors that influence the overall effects of treatment.”

Still, she noted, there are other possible explanations, and further research is needed to tease out changes in brain function that are related to antidepressant exposure, compared with brain changes that are related to clinical improvement during treatment.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Smoking alters the impact of a schizophrenia risk gene. Scientists from the universities of Zurich and Cologne demonstrate that healthy people who carry this risk gene and smoke process acoustic stimuli in a similarly deficient way as patients with schizophrenia. Furthermore, the impact is all the stronger the more the person smokes.

Schizophrenia has long been known to be hereditary. However, as a melting pot of disorders with different genetic causes is concealed behind manifestations of schizophrenia, research has still not been able to identify the main gene responsible to this day.

In order to study the genetic background of schizophrenia, the frequency of particular risk genes between healthy and ill people has mostly been compared until now. Pharmacopyschologist Professor Boris Quednow from University Hospital of Psychiatry, Zurich, and Professor Georg Winterer’s workgroup at the University of Cologne have now adopted a novel approach. Using electroencephalography (EEG), the scientists studied the processing of simple acoustic stimuli (a sequence of similar clicks). When processing a particular stimulus, healthy people suppress the processing of other stimuli that are irrelevant to the task at hand. Patients with schizophrenia exhibit deficits in this kind of stimulus filtering and thus their brains are probably inundated with too much information. As psychiatrically healthy people also filter stimuli with varying degrees of efficiency, individual stimulus processing can be associated with particular genes.

Smokers process stimuli less effectively

In a large-scale study involving over 1,800 healthy participants from the general population, Boris Quednow and Georg Winterer examined how far acoustic stimulus filtering is connected with a known risk gene for schizophrenia: the so-called “transcription factor 4” gene (TCF4). TCF4 is a protein that plays a key role in early brain development. As patients with schizophrenia often smoke, the scientists also studied the smoking habits of the test subjects.

The data collected shows that psychiatrically healthy carriers of the TCF4 gene also filter stimuli less effectively — like people who suffer from schizophrenia. It turned out that primarily smokers who carry the risk gene display a less effective filtering of acoustic impressions. This effect was all the more pronounced the more the people smoked. Non-smoking carriers of the risk gene, however, did not process stimuli much worse. “Smoking alters the impact of the TCF4 gene on acoustic stimulus filtering,” says Boris Quednow, explaining this kind of gene-environment interaction. “Therefore, smoking might also increase the impact of particular genes on the risk of schizophrenia.”

The results could also be significant for predicting schizophrenic disorders and for new treatment approaches, says Quednow and concludes: “Smoking should also be considered as an important cofactor for the risk of schizophrenia in future studies.” A combination of genetic (e.g. TCF4), electrophysiological (stimulus filtering) and demographic (smoking) factors could help diagnose the disorder more rapidly or also define new, genetically more uniform patient subgroups.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Though autism is often not diagnosed until the age of three, some children begin to show signs of developmental delay before they turn a year old. While not all infants and toddlers with delays will develop autism spectrum disorders (ASD), experts point to early detection of these signs as key to capitalizing on early diagnosis and intervention, which is believed to improve developmental outcomes.

According to Dr. Rebecca Landa, director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, Md., parents need to be empowered to identify the warning signs of ASD and other communication delays.

"We want to encourage parents to become good observers of their children’s development so that they can see the earliest indicators of delays in a baby’s communication, social and motor skills," says Dr. Landa, who also cautions that some children who develop ASD don’t show signs until after the second birthday or regress after appearing to develop typically.

For the past decade, Dr. Landa has followed infant siblings of children with autism to identify red flags of the disorder in their earliest form. Her research has shown that diagnosis is possible in some children as young as 14 months and sparked the development of early intervention models that have been shown to improve outcomes for toddlers showing signs of ASD as young as one and two years old.

Dr. Landa recommends that as parents play with their infant (6 — 12 months), they look for the following signs that have been linked to later diagnosis of ASD or other communication disorders:

1. Rarely smiles when approached by caregivers 2. Rarely tries to imitate sounds and movements others make, such as smiling and laughing, during simple social exchanges 3. Delayed or infrequent babbling 4. Does not respond to his or her name with increasing consistency from 6 — 12 months 5. Does not gesture to communicate by 10 months 6. Poor eye contact 7. Seeks your attention infrequently 8. Repeatedly stiffens arms, hands, legs or displays unusual body movements such as rotating the hands on the wrists, uncommon postures or other repetitive behaviors 9. Does not reach up toward you when you reach to pick him or her up 10. Delays in motor development, including delayed rolling over, pushing up and crawling

"If parents suspect something is wrong with their child’s development, or that their child is losing skills, they should talk to their pediatrician or another developmental expert," says Dr. Landa. "Don’t adopt a ‘wait and see’ perspective. We want to identify delays early in development so that intervention can begin when children’s brains are more malleable and still developing their circuitry."

Source: Science Daily

March 26, 2012

A meta-analysis of previously published studies found that the ratio of blood plasma amyloid-β (Aβ) peptides Aβ42:Aβ40 was significantly associated with development of Alzheimer disease and dementia, according to a report published Online First by Archives of Neurology.

"Plasma levels of amyloid-β (Aβ) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data," the authors write as background in the study.

Alain Koyama, S.M., then of Harvard School of Public Health and Brigham and Women’s Hospital, Boston, now with the University of California, San Francisco, and colleagues conducted a meta-analysis of 13 previously published studies to examine the association between plasma amyloid-β and development of dementia, Alzheimer disease (AD) and cognitive decline.

The 13 studies included in the analysis had a total of 10,303 participants, and were published between 1995 and 2011. The studies also included measurement of at least one relevant plasma amyloid-β species (Aβ40, Aβ42, or Aβ42: Aβ40 ratio) and reported an effect estimate for dementia, AD or cognitive decline.

The authors found that lower Aβ42: Aβ40 ratios were significantly associated with development of Alzheimer disease and dementia, with most studies in the analysis reporting similar findings. Plasma levels of Aβ40 and Aβ42 alone, however, were not significantly associated with either outcome.

"In conclusion, despite the limitations of existing research and heterogeneity across the studies considered, this systematic review and meta-analysis suggests that the ratio of plasma Aβ42: Aβ40 may have value in predicting the risk for later development of dementia or AD and merits further investigation."

More information: Arch Neurol. Published online March 26, 2012. doi:10.1001/archneurol.2011.1841

Provided by JAMA and Archives Journals

Source: medicalxpress.com

ScienceDaily (Mar. 26, 2012) — A new study, using brain imaging technology, reveals structural adaptations in short-track speed skaters’ brains which are likely to explain their extraordinary balance and co-ordination skills.

Short track speed skaters. (Credit: © sarah besson / Fotolia)

The work by Im Joo Rhyu from the Korea University College of Medicine, and colleagues, is published online in Springer’s journal Cerebellum.

The cerebellum in the brain plays an essential role in balance control, coordinated movement, and visually guided movement, which are key abilities required for short-track speed skaters as they glide on perfectly smooth ice, cornering and passing at high speeds. Previous studies have shown that damage to the cerebellum results in impaired balance and coordination. In addition, structural changes in the brain have been documented following training of complex motor skills, in both jugglers and basketball players for instance. Are these changes sports-specific?

To assess the effect of short-track speed skating training on the relative structure and size of the two brain hemispheres, the authors analyzed brain MRI scans of 16 male professional short-track speed skaters. They compared them to scans of 18 non-skaters, who did not engage in regular exercise.

They found that skaters had larger right hemispheres of the cerebellum and vermian lobules VI-VII (the lobes connecting the left and right parts of the cerebellum) than non-skaters. These results suggest that the specialized abilities of balance and coordination in skaters are associated with a certain amount of flexibility in the structure of the right hemisphere of the cerebellum and vermian VI-VII.

Why do the structural changes occur to the right side of the cerebellum? Gliding on smooth ice requires specialized abilities to control dynamic balance and coordination. During cornering at high speed, short-track speed skaters turn only to the left while maintaining balance on their right foot. Standing on the right foot activates the right lobes of the cerebellum.

In addition, learning a visually guided task is thought to occur in the right side of the brain. Therefore the larger volume of the right hemisphere of the cerebellum in these skaters is likely to be associated with the type of movements which the sport requires, for strong visual guidance while cornering and passing.

The authors conclude: “Short-track speed skaters’ specialized abilities of balance and coordination stimulate specific structural changes in the cerebellum, following extensive training. These changes reflect the effects of extraordinary abilities of balance and coordination on the right region of the brain.”

Source: Science Daily