Research team discovers: brain does not process sensory information sufficiently

The reason why some people are worse at learning than others has been revealed by a research team from Berlin, Bochum, and Leipzig, operating within the framework of the Germany-wide network “Bernstein Focus State Dependencies of Learning”. They have discovered that the main problem is not that learning processes are inefficient per se, but that the brain insufficiently processes the information to be learned. The scientists trained the subjects’ sense of touch to be more sensitive. In subjects who responded well to the training, the EEG revealed characteristic changes in brain activity, more specifically in the alpha waves. These alpha waves show, among other things, how effectively the brain exploits the sensory information needed for learning. “An exciting question now is to what extent the alpha activity can be deliberately influenced with biofeedback”, says PD Dr. Hubert Dinse from the Neural Plasticity Lab of the Ruhr-Universität Bochum. “This could have enormous implications for therapy after brain injury or, quite generally, for the understanding of learning processes.” The research team from the Ruhr-Universität, the Humboldt Universität zu Berlin, Charité – Universitätsmedizin Berlin and the Max Planck Institute (MPI) for Human Cognitive and Brain Sciences reported their findings in the Journal of Neuroscience.

Learning without attention: passive training of the sense of touch

How well we learn depends on genetic aspects, the individual brain anatomy, and, not least, on attention. “In recent years we have established a procedure with which we trigger learning processes in people that do not require attention”, says Hubert Dinse. The researchers were, therefore, able to exclude attention as a factor. They repeatedly stimulated the participants’ sense of touch for 30 minutes by electrically stimulating the skin of the hand. Before and after this passive training, they tested the so-called “two-point discrimination threshold”, a measure of the sensitivity of touch. For this, they applied gentle pressure to the hand with two needles and determined the smallest distance between the needles at which the patient still perceived them as separate stimuli. On average, the passive training improved the discrimination threshold by twelve percent—but not in all of the 26 participants. Using EEG, the team studied why some people learned better than others.

Imaging the brain state using EEG: the alpha waves are decisive

The cooperation partners from Berlin and Leipzig, PD Dr. Petra Ritter, Dr. Frank Freyer, and Dr. Robert Becker recorded the subjects’ spontaneous EEG before and during passive training. They then identified the components of the brain activity related to improvement in the discrimination test. The alpha activity was decisive, i.e., the brain activity was in the frequency range 8 to 12 hertz. The higher the alpha activity before the passive training, the better the people learned. In addition, the more the alpha activity decreased during passive training, the more easily they learned. These effects occurred in the somatosensory cortex, that is, where the sense of touch is located in the brain.

Researchers seek new methods for therapy

“How the alpha rhythm manages to affect learning is something we investigate with computer models”, says PD Dr. Petra Ritter, Head of the Working Group “Brain Modes” at the MPI Leipzig and the Berlin Charité. “Only when we understand the complex information processing in the brain, can we intervene specifically in the processes to help disorders”, adds Petra Ritter. New therapies are the aim of the cooperation network, which Ritter coordinates, the international “Virtual Brain” project, which her team collaborates on, and the “Neural Plasticity Lab”, chaired by Hubert Dinse at the RUB.

Learning is dependent on access to sensory information

A high level of alpha activity counts as a marker of the readiness of the brain to exploit new incoming information. Conversely, a strong decrease of alpha activity during sensory stimulation counts as an indicator that the brain processes stimuli particularly efficiently. The results, therefore, suggest that perception-based learning is highly dependent on how accessible the sensory information is. The alpha activity, as a marker of constantly changing brain states, modulates this accessibility.

Brain imaging research shows how unconscious processing improves decision-making

When faced with a difficult decision, it is often suggested to “sleep on it” or take a break from thinking about the decision in order to gain clarity.

But new brain imaging research from Carnegie Mellon University, published in the journal “Social Cognitive and Affective Neuroscience,” finds that the brain regions responsible for making decisions continue to be active even when the conscious brain is distracted with a different task. The research provides some of the first evidence showing how the brain unconsciously processes decision information in ways that lead to improved decision-making.

"This research begins to chip away at the mystery of our unconscious brains and decision-making," said J. David Creswell, assistant professor of psychology in CMU’s Dietrich College of Humanities and Social Sciences and director of the Health and Human Performance Laboratory. "It shows that brain regions important for decision-making remain active even while our brains may be simultaneously engaged in unrelated tasks, such as thinking about a math problem. What’s most intriguing about this finding is that participants did not have any awareness that their brains were still working on the decision problem while they were engaged in an unrelated task."

Scientists Discover How Animals Taste, and Avoid, High Salt Concentrations

For consumers of the typical Western diet—laden with levels of salt detrimental to long-term health—it may be hard to believe that there is such a thing as an innate aversion to very high concentrations of salt.

But Charles Zuker, PhD, and colleagues at Columbia University Medical Center have discovered how the tongue detects high concentrations of salt (think seawater levels, not potato chips), the first step in a salt-avoiding behavior common to most mammals.

The findings, which were published online in the journal Nature, could serve as a springboard for the development of taste modulators to help control the appetite for a high-salt diet and reduce the ill effects of too much sodium.

The sensation of saltiness is unique among the five basic tastes. Whereas mammals are always attracted to the tastes of sweet and umami, and repelled by sour and bitter, their behavioral response to salt dramatically changes with concentration.

“Salt taste in mammals can trigger two opposing behaviors,” said Dr. Zuker, professor in the Departments of Biochemistry & Molecular Biophysics and of Neuroscience at Columbia University College of Physicians & Surgeons. “Mammals are attracted to low concentrations of salt; they will choose a salty solution over a salt-free one. But they will reject highly concentrated salt solutions, even when salt-deprived.”

Over the past 15 years, the receptors and other cells on the tongue responsible for detecting sweet, sour, bitter, and umami tastes—as well as low concentrations of salt—have been uncovered largely through the efforts of Dr. Zuker and his collaborator Nicholas Ryba from the National Institute of Dental and Craniofacial Research.

“But we didn’t understand what was behind the aversion to high concentrations of salt,” said Yuki Oka, a postdoctoral fellow in Dr. Zuker’s laboratory and the lead author of the study.

The researchers expected high-salt receptors to reside in cells committed only to detecting high salt. “Over the years our studies have shown that each taste quality—sweet, bitter, sour, umami, and low-salt—is mediated by different cells,” Dr. Ryba said. “So we thought there must be different taste receptor cells for high-salt. But unexpectedly, Dr. Oka found high salt is mediated by cells we already knew.”

Rewiring the serotonin system

An interdisciplinary team of researchers from the University of Texas Medical Branch at Galveston and the University of Houston has found a new way to influence the vital serotonin signaling system — possibly leading to more effective medications with fewer side effects.

Scientists have linked malfunctions in serotonin signaling to a wide range of health issues, everything from depression and addictions to epilepsy and obesity and eating disorders. Much of their attention has focused on complex proteins called serotonin receptors, which are located in the cell membrane. Each receptor has a so-called “active site” specially suited to bond with a serotonin molecule; when that bond is formed, the receptor changes shape, transmitting a signal to the cell’s interior.

Traditional drug discovery efforts target interactions that take place at such active sites. But a receptor’s behavior can also be changed by additional proteins that bind to the receptor at locations quite distant (in molecular terms) from the active site, in a process called “allosteric regulation” — the mechanism examined by the UTMB-UH team for one specific and highly significant kind of serotonin receptor, designated the 5-HT2C.

“This is a whole new way of thinking about this system, targeting these interactions,” said UTMB professor Kathryn Cunningham, senior author of a paper on the research now online in the Journal of Neuroscience. “Basically, we’ve created a new series of molecules and validated that we can use them to change the way the receptor functions both in vitro and in vivo, through an allosteric effect.”

(Image: thedea.org)

Blood May Hold Clues to Risk of Memory Problems After Menopause

New Mayo Clinic research suggests that blood may hold clues to whether post-menopausal women may be at an increased risk for areas of brain damage that can lead to memory problems and possibly increased risk of stroke. The study shows that blood’s tendency to clot may contribute to areas of brain damage called white matter hyperintensities. The findings are published in the Feb. 13 online issue of Neurology, the medical journal of the American Academy of Neurology.

The study involved 95 women with an average age of 53 who recently went through menopause. The women had magnetic resonance imaging, or MRIs, taken of their brains at the start of the study. They then received a placebo, oral hormone therapy or the hormone skin patch. They had MRIs periodically over the next four years.

During the study, women with higher levels of thrombogenic microvesicles, the platelets more likely to cause blood to clot, were likelier to have higher increases in the amount of white matter hyperintensities (shown as concentrated white areas on an MRI scan), which may lead to memory loss.

"This study suggests that the tendency of the blood to clot may contribute to a cascade of events leading to the development of brain damage in women who have recently gone through menopause," says study author Kejal Kantarci, M.D., of Mayo Clinic. "Preventing the platelets from developing these microvesicles could be a way to stop the progression of white matter hyperintensities in the brain."

All of the women had white matter hyperintensities at the start of the study. The amount increased by an average volume of 63 cubic millimeters at 18 months, 122 cubic millimeters at three years and 155 cubic millimeters at four years.

(Image: Shutterstock)

The party in your brain

A team of political scientists and neuroscientists has shown that liberals and conservatives use different parts of the brain when they make risky decisions, and these regions can be used to predict which political party a person prefers. The new study suggests that while genetics or parental influence may play a significant role, being a Republican or Democrat changes how the brain functions.

Dr. Darren Schreiber, a researcher in neuropolitics at the University of Exeter, has been working in collaboration with colleagues at the University of California, San Diego on research that explores the differences in the way the brain functions in American liberals and conservatives. The findings are published in the journal PLOS ONE on 13 February.

In a prior experiment, participants had their brain activity measured as they played a simple gambling game. Dr. Schreiber and his UC San Diego collaborators were able to look up the political party registration of the participants in public records. Using this new analysis of 82 people who performed the gambling task, the academics showed that Republicans and Democrats do not differ in the risks they take. However, there were striking differences in the participants’ brain activity during the risk-taking task.

Democrats showed significantly greater activity in the left insula, a region associated with social and self-awareness. Meanwhile Republicans showed significantly greater activity in the right amygdala, a region involved in the body’s fight-or-flight system. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk.

In fact, brain activity in these two regions alone can be used to predict whether a person is a Democrat or Republican with 82.9% accuracy. By comparison, the longstanding traditional model in political science, which uses the party affiliation of a person’s mother and father to predict the child’s affiliation, is only accurate about 69.5% of the time. And another model based on the differences in brain structure distinguishes liberals from conservatives with only 71.6% accuracy.

The model also outperforms models based on differences in genes. Dr. Schreiber said: “Although genetics have been shown to contribute to differences in political ideology and strength of party politics, the portion of variation in political affiliation explained by activity in the amygdala and insula is significantly larger, suggesting that affiliating with a political party and engaging in a partisan environment may alter the brain, above and beyond the effect of heredity.”

These results may pave the way for new research on voter behaviour, yielding better understanding of the differences in how liberals and conservatives think. According to Dr. Schreiber: “The ability to accurately predict party politics using only brain activity while gambling suggests that investigating basic neural differences between voters may provide us with more powerful insights than the traditional tools of political science.”

Gene thought to be linked to Alzheimer’s is marker for only mild impairment

Defying the widely held belief that a specific gene is the biggest risk factor for Alzheimer’s disease, two Cornell developmental psychologists and their colleagues report that people with that gene are more likely to develop mild cognitive impairment — but not Alzheimer’s.

The study suggests that older adults with healthy brain function can get genetic tests to predict increased risk of future mild cognitive impairment. However, once they are impaired cognitively, the tests won’t predict their likelihood of developing Alzheimer’s.

"Right now, genetic tests are used in exactly the opposite way. That is, healthy people don’t get the tests to predict their risk of mild cognitive impairment, but impaired people get them to predict their risk of Alzheimer’s disease," said Charles Brainerd, professor of human development and the study’s lead co-author with Valerie Reyna, professor of human development. "So, impaired people think that tests will tell them if they are at increased risk of Alzheimer’s, which they won’t. And healthy people think that tests won’t tell them whether they are at increased risk of cognitive impairment, which they will."

The researchers describe their findings in the January issue of Neuropsychology (27:1).

The work builds on previous research by Brainerd and associates that suggested the ε4 allele of the APOE genotype increases the risk of mild cognitive impairment as well as Alzheimer’s.

The researchers analyzed data from the only nationally representative dataset of its kind, the National Institute on Aging’s Aging, Demographics and Memory Study. They looked at data from 418 people over age 70 to see if those who carried the allele were more likely to develop mild cognitive impairment compared with those who did not have the allele. They also looked at whether ε4 carriers with mild cognitive impairment were more likely to develop Alzheimer’s disease compared with non-carriers with mild cognitive impairment.

They found that healthy ε4 carriers were nearly three times — 58 percent — more likely to develop mild cognitive impairment compared with non-carriers. However, ε4 carriers with mild cognitive impairment developed Alzheimer’s at the same rate as non-carriers.

Scientists advance the art of magic with a study of Penn and Teller’s ‘cups and balls’ illusion

Cognitive brain researchers have studied a magic trick filmed in magician duo Penn & Teller’s theater in Las Vegas, to illuminate the neuroscience of illusion. Their results advance our understanding of how observers can be misdirected and will aid magicians as they work to improve their art.

The research team was led by Dr. Stephen Macknik, Director of the Laboratory of Behavioral Neurophysiology at Barrow Neurological Institute, in collaboration with fellow Barrow researchers Hector Rieiro and Dr. Susana Martinez-Conde, Director of the Laboratory of Visual Neuroscience. The study, titled “Perceptual elements in Penn and Teller’s “Cups and Balls” magic trick” was published today, Feb 12th 2013, as part of the launch of PeerJ, a new peer reviewed open access journal in which all articles are freely available to everyone. “Cups and Balls,” a magic illusion in which balls appear and disappear under the cover of cups, is one of the oldest magic tricks in history, with documented descriptions going back to Roman conjurors in 3 B.C. “But we still don’t know how it really works in the brain,” says Macknik, “because this is the first, long overdue, neuroscientific study of the trick.”

The discovery concerns the way magicians manipulate human cognition and perception. The “Cups and Balls” trick has many variations, but the most common one uses three balls and three cups. The magician makes the balls pass through the bottom of cups, jump from cup to cup, disappear from a cup and turn up elsewhere, turn into other objects, and so on. The cups are usually opaque and the balls brightly colored. Penn & Teller’s variant is performed with three opaque and then with three transparent cups. “The transparent cups mean that visual information about the loading of the balls is readily available to the brain, yet still the spectators cannot see how the trick is done!” said Martinez-Conde.

Magicians have performed and systematically developed the art and theory of this illusion for thousands of years, but each new generation of conjurers offers new insights and hypotheses about how and why it works for the audience. Here the scientists turned the power of the scientific method to the illusion. The experiments tracked when and where observers looked during video clips portraying specific element of the performance, filmed by a NOVA scienceNOW TV crew. By quantifying how well observers tracked the loading and unloading of balls with and without transparent cups, the scientists determined that some aspects of the illusion were even more powerful at controlling attention than aspects originally predicted by the magician.

The end result is that cognitive scientists now have an improved understanding of how (and by how much) observers can be misdirected. In addition, this knowledge can help magicians further hone their art.

In Some Dystonia Cases, Deep Brain Therapy Benefits May Linger After Device Turned Off

Two patients freed from severe to disabling effects of dystonia through deep brain stimulation therapy continued to have symptom relief for months after their devices accidentally were fully or partly turned off, according to a report published online Feb. 11 in the journal Movement Disorders.

“Current thought is that symptoms will worsen within hours or days of device shut-off, but these two young men continued to have clinical benefit despite interruption of DBS therapy for several months. To our knowledge, these two cases represent the longest duration of retained benefit in primary generalized dystonia. Moreover, when these patients’ symptoms did return, severity was far milder than it was before DBS,” said senior author Michele Tagliati, MD, director of the Movement Disorders Program at Cedars-Sinai’s Department of Neurology.

Dystonia causes muscles to contract, with the affected body part twisting involuntarily and symptoms ranging from mild to crippling. If drugs – which often have undesirable side effects, especially at higher doses – fail to give relief, neurosurgeons and neurologists may work together to supplement medications with deep brain stimulation, aimed at modulating abnormal nerve signals. Electrical leads are implanted in the brain – one on each side – and an electrical pulse generator is placed near the collarbone. The device is then programmed with a remote, hand-held controller. Tagliati is an expert in device programming, which fine-tunes stimulation for individual patients.

Few studies have looked at the consequences of interrupted DBS therapy, although one found “fairly rapid worsening of dystonia in 14 patients after interruption of stimulation for 48 hours, with symptom severity at times becoming worse than the pre-operative baseline.” In another study of 10 patients with generalized dystonia, however, symptoms did not return in four patients when stimulation was discontinued for 48 hours.

Findings from the 10-patient study correlate well with these two cases, Tagliati said.

“It appears that several factors – age, duration of disease, length of time the patient has received DBS treatment and stimulation parameters – determine which patients may retain symptom relief after prolonged DBS interruption. Our two patients were young, 20 years old. They both began DBS therapy a relatively short time after disease onset; one at four years and the other at seven years. One had received continuous stimulation for five years and the other for 18 months before stimulation was interrupted,” Tagliati said.

“We can’t say for certain why these factors make the difference,” he added, “But we theorize that a younger brain with shorter exposure to the negative effects of dystonia may be more responsive to therapy and have greater ‘plasticity’ to adapt back to normal. Both of our patients received DBS therapy at a lower energy than most patients experience, suggesting the possibility that low-frequency stimulation over an extended time may help retrain the brain’s low-frequency electrical activity.”

Both instances of device shut-off were accidental and were discovered during doctor visits after mild symptoms returned. The patient who had undergone five years of DBS therapy had only one stimulator turned off for about three months; the one stimulating the left side of his brain remained active. In the other patient, the left device had been off for about seven months and the right one for two months, Tagliati said.

Tagliati was senior author of a 2011 Journal of Neurology article on a study showing that for patients suffering from dystonia, deep brain therapy tends to get better, quicker results when started earlier rather than later.

“We knew from earlier work that younger patients with shorter disease duration had better clinical outcomes in the short term. In our 2011 article, we reported that they fare best in the long term, as well. That study uniquely showed that age and disease duration play complementary roles in predicting long-term clinical outcomes. The good news for older patients is that while they may not see the rapid gains of younger patients, their symptoms may gradually improve over several years,” Tagliati said.

Identification of abnormal protein may help diagnose, treat ALS and frontotemporal dementia

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, and frontotemporal dementia (FTD) are devastating neurodegenerative diseases with no effective treatment. Researchers are beginning to recognize ALS and FTD as part of a spectrum disorder with overlapping symptoms. Now investigators reporting online February 12 in the Cell Press journal Neuron have discovered an abnormal protein that first forms as a result of genetic abnormalities and later builds up in the brains of many patients with either disease.

"In identifying the novel protein that abnormally accumulates in the brains of affected patients, we have uncovered a potentially new therapeutic target and biomarker that would allow clinicians to confirm diagnosis of the diseases," says senior author Dr. Leonard Petrucelli, Chair of Neuroscience at Mayo Clinic in Florida.

By analyzing brain tissue from patients with ALS or FTD, Dr. Petrucelli and his team discovered that the abnormal protein, which they call C9RANT, is generated as a result of repeat expansions of nucleotides in the noncoding region of the C9ORF72 gene. These expansions are the most common cause of ALS and FTD. “Simply put, an error in the highly regulated cellular process through which proteins are generated causes the abnormal production of C9RANT,” explains Dr. Petrucelli.

The researchers discovered the protein C9RANT after creating a novel antibody to specifically detect it. The ability to detect C9RANT in individuals’ cerebrospinal fluid may provide a valuable diagnostic and prognostic tool for identifying patients carrying the C9ORF72 repeat expansion and for then tracking the progression of the disease in these at-risk individuals.

"Although it remains to be shown whether C9RANT is causing the cell death or toxicity associated with disease symptoms, our discovery offers a potential target to prevent neuronal loss in patients carrying the C9ORF72 repeat expansion," says Dr. Petrucelli.

The concept that abnormal proteins accumulate and can be toxic to cells is not new. In fact, tau protein forms tangles in Alzheimer’s disease and alpha-synuclein forms clumps in Parkinson’s disease. Just as new therapies are being developed to break down the protein aggregates associated with these diseases, developing a therapeutic strategy to target C9RANT aggregates may also prove beneficial.