Posts tagged neuroscience

ScienceDaily (June 19, 2012) — Fish cannot display symptoms of autism, schizophrenia, or other human brain disorders. However, a team of Whitehead Institute and MIT scientists has shown that zebrafish can be a useful tool for studying the genes that contribute to such disorders.

Zebrafish with certain genes turned off during embryonic development (center and right images) showed abnormalities of brain formation (top row) and axon wiring (bottom row). At left is a normally developing zebrafish embryo. (Credit: Sive Lab)

Led by Whitehead Member Hazel Sive, the researchers set out to explore a group of about two dozen genes known to be either missing or duplicated in about 1 percent of autistic patients. Most of the genes’ functions were unknown, but a new study by Sive and Whitehead postdocs Alicia Blaker-Lee, Sunny Gupta and, Jasmine McCammon, revealed that nearly all of them produced brain abnormalities when deleted in zebrafish embryos.

The findings, published online recently in the journal Disease Models & Mechanisms, should help researchers pinpoint genes for further study in mammals, says Sive, who is also professor of biology and associate dean of MIT’s School of Science. Autism is thought to arise from a variety of genetic defects; this research is part of a broad effort to identify culprit genes and develop treatments that target them.

"That’s really the goal — to go from an animal that shares molecular pathways, but doesn’t get autistic behaviors, into humans who have the same pathways and do show these behaviors," Sive says.

Sive recalls that some of her colleagues chuckled when she first proposed studying human brain disorders in fish, but it is actually a logical starting point, she says. Brain disorders are difficult to study because most of the symptoms are behavioral, and the biological mechanisms behind those behaviors are not well understood, she says.

"We thought that since we really know so little, that a good place to start would be with the genes that confer risk in humans to various mental health disorders, and to study these various genes in a system where they can readily be studied," she says.

Those genes tend to be the same across species — conserved throughout evolution, from fish to mice to humans — though they may control somewhat different outcomes in each species.

In the latest study, Sive and her colleagues focused on a genetic region known as 16p11.2, first identified by Mark Daly, a former Whitehead Fellow who discovered a type of genetic defect known as a copy number variant. A typical genome includes two copies of every gene, one from each parent; copy number variants occur when one of those copies is deleted or duplicated, and this can be associated with pathology.

The central “core” 16p11.2 region includes 25 genes. Both deletions and duplications in this region have been associated with autism, but it was unclear which of the genes might actually produce symptoms of the disease. “At the time, there was an inkling about some of them, but very few,” Sive says.

Sive and her postdocs began by identifying zebrafish genes analogous to the human genes found in this region. (In zebrafish, these genes are not clustered in a single genetic chunk, but are scattered across many chromosomes.) The researchers studied one gene at a time, silencing each with short strands of nucleic acids that target a particular gene and prevent its protein from being produced.

For 21 of the genes, silencing led to abnormal development. Most produced brain deficits, including improper development of the brain or eyes, thinning of the brain, or inflation of the brain ventricles, cavities that contain cerebrospinal fluid. The researchers also found abnormalities in the wiring of axons, the long neural projections that carry messages to other neurons, and in simple behaviors of the fish. The results show that the 16p11.2 genes are very important during brain development, helping to explain the connection between this region and brain disorders.

Furthermore, the researchers were able to restore normal development by treating the fish with the human equivalents of the genes that had been repressed. “That allows you to deduce that what you’re learning in fish corresponds to what that gene is doing in humans. The human gene and the fish gene are very similar,” Sive says.

To figure out which of these genes might have a strong effect in autism or other disorders, the researchers set out to identify genes that produce abnormal development when their activity is reduced by 50 percent, which would happen in someone who is missing one copy of the gene. (This correlation is not seen for most genes, because there are many other checks and balances that regulate how much of a particular protein is made.)

The researchers identified two such genes in the 16p11.2 region. One, called kif22, codes for a protein involved in the separation of chromosomes during cell division, and one, aldolase a, is involved in glycolysis — the process of breaking down sugar to generate energy for the cell.

In work that has just begun, Sive’s lab is working with Stanford University researchers to explore in mice predictions made from the zebrafish study. They are also conducting molecular studies in zebrafish of the pathways affected by these genes, to get a better idea of how defects in these might bring about neurological disorders.

Source: Science Daily

June 19, 2012 By Janice Wood

Why do some people excel in sports, music and managing companies? New research points to uniquely high mind-brain development in those who excel.

“What we have found is an astonishing integration of brain functioning in high performers compared to average-performing controls,” said Fred Travis, Ph.D., director of the Center for Brain, Consciousness, and Cognition at Maharishi University of Management in Fairfield, Iowa.

He claims this research is the “first in the world to show that there is a brain measure of effective leadership.”

In the study, published in the journal Cognitive Processing, researchers found that 20 top-level managers scored higher on three measures — the Brain Integration Scale, Gibbs’s Socio-moral Reasoning questionnaire, and an inventory of peak experiences — compared to 20 low-level managers who served as controls.

“The current understanding of high performance is fragmented,” said co-researcher Harald Harung, Ph.D., of the Oslo and Akershus University College of Applied Sciences in Norway.

“What we have done in our research is to use quantitative and neurophysiological research methods on topics that so far have been dominated by psychology.”

The researchers carried out four studies comparing world-class performers to average performers. This recent study and two others examined top performers in management, sports and classical music. A number of years ago Harung and his colleagues published a study on a variety of professions, such as public administration, management, sports, arts, and education.

The studies include using electroencephalography (EEG) to look at the extent of integration and development of several brain processes.

Read more …

ScienceDaily (June 19, 2012) — Human brains process large and small numbers of objects using two different mechanisms, but infants have not yet developed the ability to make those two processes work together, according to new research from the University of Missouri.

"This research was the first to show the inability of infants in a single age group to discriminate large and small sets in a single task," said Kristy vanMarle, assistant professor of psychological sciences in the College of Arts and Science. "Understanding how infants develop the ability to represent and compare numbers could be used to improve early education programs."

The MU study found that infants consistently chose the larger of two groups of food items when both sets were larger or smaller than four, just as an adult would. Unlike adults, the infants showed no preference for the larger group when choosing between one large and one small set. The results suggest that at age one infants have not yet integrated the two mental functions: one being the ability to estimate numbers of items at a glance and the other being the ability to visually track small sets of objects.

In vanMarle’s study, 10- to 12-month-old infants were presented with two opaque cups. Different numbers of pieces of breakfast cereal were hidden in each cup, while the infants observed, and then the infants were allowed to choose a cup. Four comparisons were tested between different combinations of large and small sets. Infants consistently chose two food items over one and eight items over four, but chose randomly when asked to compare two versus four and two versus eight.

"Being unable to determine that eight is larger than two would put an organism at a serious disadvantage," vanMarle said. "However, ongoing studies in my lab suggest that the capacity to compare small and large sets seems to develop before age two."

The ability to make judgments about the relative number of objects in a group has old evolutionary roots. Dozens of species, including some fish, monkeys and birds have shown the ability to recognize numerical differences in laboratory studies. VanMarle speculated that being unable to compare large and small sets early in infancy may not have been problematic during human evolution because young children probably received most of their food and protection from caregivers. Infants’ survival didn’t depend on determining which bush had the most berries or how many predators they just saw, she said.

"In the modern world there are educational programs that claim to give children an advantage by teaching them arithmetic at an early age," said vanMarle. "This research suggests that such programs may be ineffective simply because infants are unable to compare some numbers with others."

Source: Science Daily

ScienceDaily (June 19, 2012) — Double-stranded breaks in cellular DNA can trigger tumorigenesis. LMU researchers have now determined the structure of a protein involved in the repair and signaling of DNA double-strand breaks. The work throws new light on the origins of neurodegenerative diseases and certain tumor types.

Agents such as radiation or environmental toxins can cause double-stranded breaks in genomic DNA, which facilitate the development of tumors or the neurodegenerative disorders ataxia telangiectasia (AT) and AT-like disease (ATLD). Hence efficient repair mechanisms are essential for cell survival and function. The so-called MRN complex is an important component of one such system, and its structure has just been elucidated by a team led by Professor Karl-Peter Hopfner of LMU’s Gene Center.

Malignant mutations

The MRN complex consists of the nuclease Mre11, the ATPase Rad50 and the protein Nbs1. Nbs1 is responsible for recruiting the protein ATM, which plays a central role in early stages of the cellular response to DNA damage, to the site of damage. “How the MRN complex actually recognizes double-stranded breaks is still not clear,” says Hopfner. He and his colleagues therefore set out to clarify the issue by analyzing the structures of mutant, functionally defective versions of the complex.

"We found that pairs of Mre11 molecules form a flexible dimer, which is stabilized by Nbs1." Mutations in different subunits of the complex are associated with distinct syndromes, marked by a predisposition to certain cancers, sensitivity to radiation or neurodegeneration. Hopfner’s results help to explain these differences. For instance, the mutation linked to ATLD lies within the zone of contact between Mre11 and Nbs1, and may inhibit activation of ATM by weakening their interaction.

Source: Science Daily

June 19, 2012

Pathological rage can be blocked in mice, researchers have found, suggesting potential new treatments for severe aggression, a widespread trait characterized by sudden violence, explosive outbursts and hostile overreactions to stress.

In a study appearing today in the Journal of Neuroscience, researchers from the University of Southern California and Italy identify a critical neurological factor in aggression: a brain receptor that malfunctions in overly hostile mice. When the researchers shut down the brain receptor, which also exists in humans, the excess aggression completely disappeared.

The findings are a significant breakthrough in developing drug targets for pathological aggression, a component in many common psychological disorders including Alzheimer’s disease, autism, bipolar disorder and schizophrenia.

"From a clinical and social point of view, reactive aggression is absolutely a major problem," said Marco Bortolato, lead author of the study and research assistant professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy. “We want to find the tools that might reduce impulsive violence.”

A large body of independent research, including past work by Bortolato and senior author Jean Shih, USC University Professor and Boyd & Elsie Welin Professor in Pharmacology and Pharmaceutical Sciences at USC, has identified a specific genetic predisposition to pathological aggression: low levels of the enzyme monoamine oxidase A (MAO A). Both male humans and mice with congenital deficiency of the enzyme respond violently in response to stress.

"The same type of mutation that we study in mice is associated with criminal, very violent behavior in humans. But we really didn’t understand why that it is," Bortolato said.

Bortolato and Shih worked backwards to replicate elements of human pathological aggression in mice, including not just low enzyme levels but also the interaction of genetics with early stressful events such as trauma and neglect during childhood.

"Low levels of MAO A are one basis of the predisposition to aggression in humans. The other is an encounter with maltreatment, and the combination of the two factors appears to be deadly: it results consistently in violence in adults," Bortolato said.

The researchers show that in excessively aggressive rodents that lack MAO A, high levels of electrical stimulus are required to activate a specific brain receptor in the pre-frontal cortex. Even when this brain receptor does work, it stays active only for a short period of time.

"The fact that blocking this receptor moderates aggression is why this discovery has so much potential. It may have important applications in therapy," Bortolato said. "Whatever the ways environment can persistently affect behavior — and even personality over the long term — behavior is ultimately supported by biological mechanisms."

Importantly, the aggression receptor, known as NMDA, is also thought to play a key role in helping us make sense of multiple, coinciding streams of sensory information, according to Bortolato.

The researchers are now studying the potential side effects of drugs that reduce the activity of this receptor.

"Aggressive behaviors have a profound socio-economic impact, yet current strategies to reduce these staggering behaviors are extremely unsatisfactory," Bortolato said. "Our challenge now is to understand what pharmacological tools and what therapeutic regimens should be administered to stabilize the deficits of this receptor. If we can manage that, this could truly be an important finding."

Provided by University of Southern California

Source: medicalxpress.com

June 19, 2012

Researchers at the University of Iowa, together with colleagues from the California Institute of Technology and New York University, have discovered how a part of the brain helps predict future events from past experiences. The work sheds light on the function of the front-most part of the frontal lobe, known as the frontopolar cortex, an area of the cortex uniquely well developed in humans in comparison with apes and other primates.

The image shows the overlap of lesions for eight subjects superimposed on a template brain — red indicates maximum overlap (seven subjects) and dark blue is minimum overlap (one subject). The patient group was selected for lesions that include frontopolar cortex, but the lesions almost invariably extended outside to other parts of anterior prefrontal cortex. Credit: Christopher Kovach, University of Iowa

Making the best possible decisions in a changing and unpredictable environment is an enormous challenge. Not only does it require learning from past experience, but it also demands anticipating what might happen under previously unencountered circumstances. Past research from the UI Department of Neurology was among the first to show that damage to certain parts of the frontal lobe can cause severe deficits in decision making in rapidly changing environments. The new study from the same department on a rare group of patients with damage to the very frontal part of their brains reveals a critical aspect of how this area contributes to decision making. The findings were published June 19 in the Journal of Neuroscience.

"We gave the patients four slot machines from which to pick in order to win money. Unbeknownst to the patients, the probability of getting money from a particular slot machine gradually and unpredictably changed during the experiment. Finding the strategy that pays the most in the long run is a surprisingly difficult problem to solve, and one we hypothesized would require the frontopolar cortex,” explains Christopher Kovach, Ph.D., a UI post-doctoral fellow in neurosurgery and first author of the study.

Contrary to the authors’ initial expectation, the patients actually did quite well on the task, winning as much money, on average, as healthy control participants.

"But when we compared their behavior to that of subjects with intact frontal lobe, we found they used a different set of assumptions about how the payoffs changed over time,” Kovach says. “Both groups based their decisions on how much they had recently won from each slot machine, but healthy comparison subjects pursued a more elaborate strategy, which involved predicting the direction that payoffs were moving based on recent trends. This points towards a specific role for the frontopolar cortex in extrapolating recent trends.”

Kovach’s colleague and study author Ralph Adolphs, Ph.D., professor of neuroscience and psychology at the California Institute of Technology, adds that the study results “argue that the frontopolar cortex helps us to make short-term predictions about what will happen next, a strategy particularly useful in environments that change rapidly — such as the stock market or most social settings.”

Adolphs also hold an adjunct appointment in the UI Department of Neurology.

The study’s innovative approach to understanding the function of this part of the brain uses model-based analyses of behavior of patients with specific and precisely characterized areas of brain damage. These patients are members of the UI’s world-renowned Iowa Neurological Patient Registry, which was established in 1982 and has more than 500 active members with selective forms of damage, or lesions, to one or two defined regions in the brain.

"The University of Iowa is one of the few places in the world where you could carry out this kind of study, since it requires carefully assessed patients with damage to specific parts of their brain," says study author Daniel Tranel, Ph.D., UI professor of neurology and psychology and director of the UI Division of Behavioral Neurology and Cognitive Neuroscience.

In a final twist to the finding, the strategy taken by lesion patients was actually slightly better than the one used by comparison subjects. It happened that the task was designed so that the trends in the payoffs were, in fact, random and uninformative.

"The healthy comparison subjects seemed to perceive trends in what was just random noise," Kovach says.

This implies that the functions of the frontopolar cortex, which support more complex and detailed models of the environment, at times come with a downside: setting up mistaken assumptions.

"To the best of my knowledge this is the first study which links a normal tendency to see a nonexistent pattern in random noise, a type of cognitive bias, to a particular brain region," Kovach notes.

The researchers next want to investigate other parts of the frontal cortex in the brain, and have also begun to record activity directly from the brains of neurosurgical patients to see how single cells respond while making decisions. The work is also important to understand difficulties in decision making seen in disorders such as addiction.

Provided by University of Iowa

Source: medicalxpress.com

June 19, 2012

Four generations of a single family have been found to possess an abnormality within a specific brain region which appears to affect their ability to recall verbal material, a new study by researchers at the University of Bristol and University College London has found.

This is the first suggestion of a heritable abnormality in otherwise healthy humans, and this has important implications for our understanding of the genetic basis of cognition.

Dr Josie Briscoe of Bristol’s School of Experimental Psychology and colleagues at the Institute of Child Health in London studied eight members of a single family (aged 8 years), who despite all having high levels of intelligence have since childhood, experienced profound difficulties in recalling sentences and prose, and language difficulties in listening comprehension and naming less common objects .

While their conversation is articulate and engaging, they can experience the inability to ‘find’ a particular word or topic – a phenomenon similar to the ‘tip-of-the-tongue’ problem experienced by many people. They also report associated problems such as struggling to follow a narrative thread while reading or watching television drama.

Dr Briscoe said: “With their consent, we conducted a number of standard memory and language tests on the affected members of the family. These showed they had difficulty repeating longer sentences correctly and learning words in lists and pairs. This suggests their difficulties lie in semantic cognition: the way people construct and generate meaning from words, objects and ideas.”

"Given the very wide variation in age, the coherence of their difficulties in semantic cognition was remarkable."

The researchers also used Magnetic Resonance Imaging (MRI) to study the brains of the affected family members and found they had reduced grey matter in the posterior inferior portion of the temporal lobe, a brain area known to be involved in semantic cognition.

Dr Briscoe said: “These brain abnormalities were surprising to find in healthy people, particularly in the same family, although similar brain regions have been implicated in research with older adults with neurological problems that are linked to semantic cognition”

"Our findings have uncovered a potential causal link between anomalous neuroanatomy and semantic cognition in a single family. Importantly, the pattern of inheritance appears as a potentially dominant trait. This may well prove to be the first example of a heritable, highly specific abnormality affecting semantic cognition in humans.”

Provided by University of Bristol

Source: medicalxpress.com

June 18, 2012 By Bill Steele

(Phys.org) — If you hire a robot to help you move into your new apartment, you won’t have to send out for pizza. But you will have to give the robot a system for figuring out where things go. The best approach, according to Cornell researchers, is to ask “How will humans use this?”

A robot populates a room with imaginary human stick figures in order to decide where objects should go to suit the needs of humans.

Researchers in the Personal Robotics Lab of Ashutosh Saxena, assistant professor of computer science, have already taught robots to identify common objects, pick them up and place them stably in appropriate locations. Now they’ve added the human element by teaching robots to “hallucinate” where and how humans might stand, sit or work in a room, and place objects in their usual relationship to those imaginary people.

Their work will be reported at the International Symposium on Experimental Robotics, June 21 in Quebec, and the International Conference of Machine Learning, June 29 in Edinburgh, Scotland.

Previous work on robotic placement, the researchers note, has relied on modeling relationships between objects. A keyboard goes in front of a monitor, and a mouse goes next to the keyboard. But that doesn’t help if the robot puts the monitor, keyboard and mouse at the back of the desk, facing the wall.

Above left, random placing of objects in a scene puts food on the floor, shoes on the desk and a laptop teetering on the top of the fridge. Considering the relationships between objects (upper right) is better, but he laptop is facing away from a potential user and the food higher than most humans would like. Adding human context (lower left) makes things more accessible. Lower right: how an actual robot carried it out. (Personal Robotics Lab)

Relating objects to humans not only avoids such mistakes but also makes computation easier, the researchers said, because each object is described in terms of its relationship to a small set of human poses, rather than to the long list of other objects in a scene. A computer learns these relationships by observing 3-D images of rooms with objects in them, in which it imagines human figures, placing them in practical relationships with objects and furniture. You don’t don’t put a sitting person where there is no chair. You can put a sitting person on top of a bookcase, but there are no objects there for the person to use, so that”s ignored. It The computer calculates the distance of objects from various parts of the imagined human figures, and notes the orientation of the objects.

Eventually it learns commonalities: There are lots of imaginary people sitting on the sofa facing the TV, and the TV is always facing them. The remote is usually near a human’s reaching arm, seldom near a standing person’s feet. “It is more important for a robot to figure out how an object is to be used by humans, rather than what the object is. One key achievement in this work is using unlabeled data to figure out how humans use a space,” Saxena said.

In a new situation the a robot places human figures in a 3-D image of a room, locating them in relation to objects and furniture already there. “It puts a sample of human poses in the environment, then figures out which ones are relevant and ignores the others,” Saxena explained. It decides where new objects should be placed in relation to the human figures, and carries out the action.

The researchers tested their method using images of living rooms, kitchens and offices from the Google 3-D Warehouse, and later, images of local offices and apartments. Finally, they programmed a robot to carry out the predicted placements in local settings. Volunteers who were not associated with the project rated the placement of each object for correctness on a scale of 1 to 5.

Comparing various algorithms, the researchers found that placements based on human context were more accurate than those based solely in relationships between objects, but the best results of all came from combining human context with object-to-object relationships, with an average score of 4.3. Some tests were done in rooms with furniture and some objects, others in rooms where only a major piece of furniture was present. The object-only method performed significantly worse in the latter case because there was no context to use. “The difference between previous works and our [human to object] method was significantly higher in the case of empty rooms,” Saxena reported.

Provided by Cornell University

Source: phys.org

June 18th, 2012

Robots equipped with tactile sensor able to identify materials through touch, paving the way for more useful prostheses.

What does a robot feel when it touches something? Little or nothing until now. But with the right sensors, actuators and software, robots can be given the sense of feel, or at least the ability to identify different materials by touch.

Researchers at the University of Southern California’s Viterbi School of Engineering published a study today in Frontiers in Neurorobotics showing that a specially designed robot can outperform humans in identifying a wide range of natural materials according to their textures, paving the way for advancements in prostheses, personal assistive robots and consumer product testing.

The robot was equipped with a new type of tactile sensor built to mimic the human fingertip. It also used a newly designed algorithm to make decisions about how to explore the outside world by imitating human strategies. Capable of other human sensations, the sensor can also tell where and in which direction forces are applied to the fingertip and even the thermal properties of an object being touched.

Like the human finger, the group’s BioTac® sensor has a soft, flexible skin over a liquid filling. The skin even has fingerprints on its surface, greatly enhancing its sensitivity to vibration. As the finger slides over a textured surface, the skin vibrates in characteristic ways. These vibrations are detected by a hydrophone inside the bone-like core of the finger. The human finger uses similar vibrations to identify textures, but the robot finger is even more sensitive.

[Video: Robots Get a Feel for the World]
What does a robot feel when it touches something? Little or nothing until now. Researchers at the USC Viterbi School of Engineering publish a study in Frontiers in Neurorobotics showing that specially designed robots can be taught to feel even more than humans. Vimeo video by USC Viterbi. USC Viterbi.

When humans try to identify an object by touch, they use a wide range of exploratory movements based on their prior experience with similar objects. A famous theorem by 18th century mathematician Thomas Bayes describes how decisions might be made from the information obtained during these movements. Until now, however, there was no way to decide which exploratory movement to make next. The article, authored by Professor of Biomedical Engineering Gerald Loeb and recently graduated doctoral student Jeremy Fishel, describes their new theorem for solving this general problem as “Bayesian Exploration.”

Built by Fishel, the specialized robot was trained on 117 common materials gathered from fabric, stationery and hardware stores. When confronted with one material at random, the robot could correctly identify the material 95% of the time, after intelligently selecting and making an average of five exploratory movements. It was only rarely confused by pairs of similar textures that human subjects making their own exploratory movements could not distinguish at all.

Tactile sensors which mimic finger tips enables robots to identify materials through touch better than humans. Image from press release by USC Viterbi School of Engineering.

So, is touch another task that humans will outsource to robots? Fishel and Loeb point out that while their robot is very good at identifying which textures are similar to each other, it has no way to tell what textures people will prefer. Instead, they say this robot touch technology could be used in human prostheses or to assist companies who employ experts to assess the feel of consumer products and even human skin.

Source: Neuroscience News