Posts tagged neuroscience
Articles and news from the latest research reports.
Smoking during pregnancy may increase risk of bipolar disorder in offspring
A study published today in the American Journal of Psychiatry suggests an association between smoking during pregnancy and increased risk for developing bipolar disorder (BD) in adult children. Researchers at the New York State Psychiatric Institute and the Department of Epidemiology at the Mailman School of Public Health at Columbia University, in collaboration with scientists at the Kaiser Permanente Division of Research in Oakland, California, evaluated offspring from a large cohort of pregnant women who participated in the Child Health and Development Study (CHDS) from 1959-1966. The study was based on 79 cases and 654 comparison subjects. Maternal smoking during pregnancy was associated with a twofold increased risk of BD in their offspring.
Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and attentional difficulties. This is the first study to suggest an association between prenatal tobacco exposure and BD, a serious psychiatric illness marked by significant shifts in mood that alternate between periods of depression and mania. Symptoms typically become noticeable in the late teens or early adulthood.
"These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time," said Alan Brown, MD, MPH, senior author and Professor of Clinical Psychiatry and Epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health.
The authors wrote: “Much of the psychopathology associated with prenatal tobacco exposure clusters around the ‘externalizing’ spectrum, which includes attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and substance abuse disorders. Although not diagnostically classified along the externalizing spectrum, BD shares a number of clinical characteristics with these disorders, including inattention, irritability, loss of self-control, and proclivity to drug/alcohol use.” In effect, children who were exposed to tobacco smoke in utero may exhibit some symptoms and behaviors that are found in BD.
A previous study by Dr. Brown and colleagues found that flu virus in pregnant mothers was associated with a fourfold increased risk that their child would develop BD.
(Image: istockphoto)
The green spots above are clumps of protein inside yeast cells that are deficient in both zinc and a protein that prevents clumping. Research by Colin MacDiarmid and David Eide is exploring how a shortage of zinc can contribute to diseases. Photo: Colin MacDiarmid and David Eide/Journal of Biological Chemistry
Zinc discovery may shed light on Parkinson’s, Alzheimer’s
Scientists at UW-Madison have made a discovery that, if replicated in humans, suggests a shortage of zinc may contribute to diseases like Alzheimer’s and Parkinson’s, which have been linked to defective proteins clumping together in the brain.
With proteins, shape is everything. The correct shape allows some proteins to ferry atoms or molecules about a cell, others to provide essential cellular scaffolding or identify invading bacteria for attack. When proteins lose their shape due to high temperature or chemical damage, they stop working and can clump together — a hallmark of Parkinson’s and Alzheimer’s.
The UW researchers have discovered another stress that decreases protein stability and causes clumping: a shortage of zinc, an essential metal nutrient.
Zinc ions play a key role in creating and holding proteins in the correct shape. In a study just published in the online Journal of Biological Chemistry, Colin MacDiarmid and David Eide show that the gene Tsa1 creates “protein chaperones” that prevent clumping of proteins in cells with a zinc shortage. By holding proteins in solution, Tsa1 prevents damage that can otherwise lead to cell death.
For simplicity, the researchers studied the system in yeast — a single-celled fungus. Yeast can adapt to both shortages and excesses of zinc, says MacDiarmid, an associate scientist. “Zinc is an essential nutrient but if there’s too much, it’s toxic. The issue for the cell is to find enough zinc to grow and support all its functions, while at the same time not accumulating so much that it kills the cell.”
Cells that are low in zinc also produce proteins that counter the resulting stress, including one called Tsa1.
The researchers already knew that Tsa1 could reduce the level of harmful oxidants in cells that are short of zinc. Tsa1, MacDiarmid says, “is really a two-part protein. It can get rid of dangerous reactive oxygen species that damage proteins, but it also has this totally distinct chaperone function that protects proteins from aggregating. We found that the chaperone function was the more important of the two.”
"In yeast, if a cell is deficient in zinc, the proteins can mis-fold, and Tsa1 is needed to keep the proteins intact so they can function," says Eide, a professor of nutritional science. "If you don’t have zinc, and you don’t have Tsa1, the proteins will glom together into big aggregations that are either toxic by themselves, or toxic because the proteins are not doing what they are supposed to do. Either way, you end up killing the cell."
While the medical implications remain to be explored, there are clear similarities between yeast and human cells. “Zinc is needed by all cells, all organisms, it’s not just for steel roofs, nails and trashcans,” Eide says. “The global extent of zinc deficiency is debated, but diets that are high in whole grains and low in meat could lead to deficiency.”
If low zinc supply has the same effect on human cells as on yeast, zinc deficiency might contribute to human diseases that are associated with a build-up of “junked” proteins, such as Parkinson’s and Alzheimer’s. Eide says a similar protective system to Tsa1 also exists in animals, and the research group plans to move ahead by studying that system in human cell culture.
Genetic Influences on Cognition Increase with Age
About 70 percent of a person’s intelligence can be explained by their DNA — and those genetic influences only get stronger with age, according to new research from The University of Texas at Austin.
The study, authored by psychology researchers Elliot Tucker-Drob, Daniel Briley and Paige Harden, shows how genes can be stimulated or suppressed depending on the child’s environment and could help bridge the achievement gap between rich and poor students. The findings are published online in Current Directions in Psychological Science.
To investigate the underlying mechanisms at work, Tucker-Drob and his colleagues analyzed data from several studies tracking the cognitive ability and environmental circumstances of twin and sibling pairs. According to the findings, genetic factors account for 80 percent of cognition for children in economically advantaged households. Yet disadvantaged children – who rank lower in cognitive performance across the board – show almost no progress attributable to their genetic makeup.
This doesn’t mean disadvantaged children are genetically inferior. Instead, they have less high-quality opportunities, such as learning resources and parental involvement, to reach their genetic potential, Tucker-Drob says.
“Genetic influences on cognitive ability are maximized when people are free to select their own learning experiences,” says Tucker-Drob, who is an assistant professor of psychology. “We were born with blueprints; the question is how are we using our experiences to build upon our genetic makeup?”
In a related study, Daniel Briley, a psychology doctoral student, examined how genetic and environmental influences on cognition change over time. Using meta-analytic procedures — the statistical methods used to analyze and combine results from previous, related literature — Briley examined genetic and environmental influences on cognition in twin and sibling pairs from infancy to adolescence.
According to his findings, published in the July issue of Psychological Science, genes influencing cognition become activated during the first decade of life and accelerate over time. The results emphasize the importance of early literacy and education during the first decade of life.
“As children get older, their parents and teachers give them increasing autonomy to do their homework to the best of their ability, pay attention in class, and choose their peer group,” says Briley. “Each of these behaviors likely influences their academic development. If these types of behaviors are influenced by genes, then it would explain why the heritability of cognitive ability increases as children age.”
Tucker-Drob says this research highlights the possibilities for bridging the achievement gap between the rich and poor.
“The conventional view is that genes place an upper limit on the effects of social intervention on cognitive development,” says Tucker-Drob. “This research suggests the opposite. As social, educational and economic opportunities increase in a society, more children will have access to the resources they need to maximize their genetic potentials.”
(Source: utexas.edu)
Fattah Introduces House Resolution Recognizing World Alzheimer’s Month
Congressman Chaka Fattah (PA-02), a Congressional champion of research and funding for brain-related diseases, introduced a resolution Friday in the U.S. House of Representatives recognizing September as World Alzheimer’s Month. Worldwide, more than 35 million people suffer from Alzheimer’s, and in the United States more than five million individuals live with the debilitating disease.
“The impact of Alzheimer’s is too great for us not to pour more energy and funding into finding a cure for this debilitating disease,” Fattah said. “Beyond the millions worldwide and here at home who suffer from the disease, it puts a significant toll on the millions more family and friends who care for loved ones living with Alzheimer’s and dementia. We must continue to rally stakeholders around the world in the effort to prevent and treat Alzheimer’s.”
The resolution, H. Res. 364 supports the goals of World Alzheimer’s Month: to increase awareness about the disease, its impact on the lives of those affected by it, and the efforts of those seeking to cure Alzheimer’s. It also acknowledges the progress and improvements neurological research has made in the diagnosis and treatment of Alzheimer’s and other forms of dementia.
"As World Alzheimer’s Awareness Month comes to an end, it’s worth remembering that for millions of families across the country, every month is Alzheimer’s month," said George Vradenburg, chairman and co-founder of USAgainstAlzheimer’s. "However, with continued leadership from members of Congress like Rep. Chaka Fattah (PA-02) and others, we can secure the funding resources necessary to stop this disease by 2025."
Fattah added: “This month and every month we must continue to work to elevate the issue, seek new early prevention and treatment strategies, and work towards ultimately finding a cure. We know that neurological research advances this progress, and brings us ever closer to a cure.”
Throughout September, Congressman Fattah continued his work heightening awareness of Alzheimer’s and other neurological diseases. On Saturday, Fattah addressed a day-long conference on Traumatic Brain Injury (TBI) at the University of Pennsylvania. Earlier in the month, Fattah spoke at a California Mental Health Symposium that helped raised more than $2.8 million for research and education.
Fattah is the Ranking Democrat on the House Appropriations Committee’s Subcommittee on Commerce, Justice, Science and Related Agencies, which oversees funding for a significant amount of government-sponsored research. In 2011, Fattah created the Fattah Neuroscience Initiative (FNI) to expand the dialogue around brain diseases and foster cross-sector collaboration for research and funding opportunities.
Researchers Ferret Out Function Of Autism Gene
Findings in bacteria, yeast, mice show how flawed transport gene contributes to the condition
Researchers say it’s clear that some cases of autism are hereditary, but have struggled to draw direct links between the condition and particular genes. Now a team at the Johns Hopkins University School of Medicine, Tel Aviv University and Technion-Israel Institute of Technology has devised a process for connecting a suspect gene to its function in autism.
In a report in the Sept. 25 issue of Nature Communications, the scientists say mutations in one such autism-linked gene, dubbed NHE9, which is involved in transporting substances in and out of structures within the cell, causes communication problems among brain cells that likely contribute to autism.
“Autism is considered one of the most inheritable neurological disorders, but it is also the most complex,” says Rajini Rao, Ph.D., a professor of physiology in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine. “There are hundreds of candidate genes to sort through, and a single genetic variant may have different effects even within the same family. This makes it difficult to separate the chaff from the grain, to distinguish harmless variations from disease-causing mutations. We were able to use a new process to screen variants in one candidate gene that has been linked to autism, and figure out how they might contribute to the disorder.”
An estimated one in 88 children in the United States is affected by autism spectrum disorders, a group of neurological development conditions marked by varying degrees of social, communication and behavioral problems. Scientists for years have looked for the biological roots of the problem using tools such as genome-wide association studies and gene-linkage analysis, which crunch genetic and health data from thousands of people in an effort to pinpoint disease-causing genetic variants. But while such techniques have turned up a number of gene mutations that may be linked to autism, none of them appear in more than 1 percent of people with the condition. With numbers that low, researchers need a way to screen variants in order to make a definitive link, Rao says.
For the new study, Rao and her collaborators focused on NHE9, which other researchers had flagged as a suspect in attention-deficit hyperactivity disorder, addiction and epilepsy as well as autism spectrum disorders. The gene was already known to be involved in transporting hydrogen, sodium and potassium ions in and out of cellular compartments called endosomes, and the team wondered how this function might be related to neurological conditions.
Rao’s collaborators at Tel Aviv University and Technion-Israel Institute of Technology constructed a computer model of the NHE9 protein based on previous research on a distant relative in bacteria. They then used the model to predict how autism-linked variants in the NHE9 gene would affect the protein’s shape and function. Some of them were predicted to cause dramatic changes, while other changes appeared to be more subtle.
Rao’s team next tested how these variant forms of NHE9 would affect a relatively simple organism often used in genetic studies: yeast. “Using yeast to screen the function of variants was a quick, easy and inexpensive way of figuring out which were worth further study, and which we could ignore because they didn’t have any effect,” Rao says. To do that, the team engineered the yeast form of NHE9 to have the variants seen in autistic people.
For those mutations that did have a detectable effect on the yeast, the team moved on to a third and more challenging step, in mouse brains. They homed in on astrocytes, a type of brain cell that clears the signaling molecule glutamate out of the way after it has performed its job of delivering a message across a synapse between two nerve cells. Using lab-grown mouse astrocytes with variant forms of NHE9, the researchers found a change in the pH (acidity) inside cellular compartments called endosomes, which in turn altered the ability of cells to take up glutamate. Because endosomes are the vehicles that deliver cargo essential for communication between brain cells, changing their pH alters traffic to and from the cell surface, which could affect learning and memory, Rao says. “Elevated glutamate levels are known to trigger seizures, perhaps explaining why autistic patients with mutations in NHE9 and related genes also have seizures,” she notes.
Rao and her team hope that pinpointing the importance of this trafficking mechanism in autism spectrum disorders may lead to the development of new drugs for autism that alter endosomal pH. As the use of genomic data becomes increasingly commonplace in the future, the step-wise strategy devised by her team can be used to screen gene variants and identify at-risk patients, she says.
(Source: hopkinsmedicine.org)
Pulse propagation and signal transduction in the hydraulic brain
When Descartes turned his critical eye to the nervous system, he reasoned that the nerves must transduce hydraulic power to control the musculature. In the circulatory system, blood is pushed comparatively slowly through the aorta, perhaps around 0.3 meters per second. Superimposed on that flow, however, is an arterial pulse wave which propagates much faster, both through the blood and the walls of the vessel. For compliant and healthy vessels that speed might be around 10 meters per second, while for more hardened arteries, it could be 15 or higher. Modern day electrophysiologists have since replaced the hydraulic model with the idea that nerves really only transmit information—electrical information no less. Yet when looking at the power supply to the leg, for example, it is still hard to ignore the fact that the main femoral artery, at a diameter scarcely a half of an inch, looks rather meager next to the “information-supplying” sciatic nerve, which may actually be more like three-quarters of an inch. A conflux of ideas from a variety of disciplines has recently led to a critical re-emergence of the more mechanical side of the nervous system. To that point, two German scientists have just published a paper in the journal, Medical Hypotheses, where they suggest that the pulse wave is the main event in nervous conduction, while the electrical show is mere epiphenomenon.
We recently discussed the increasingly popular idea that action potentials may actually be soliton waves which propagate in the membranes of axons as phase transitions with minimal loss in energy. Convincing biologists that these subtle creatures could exist in the chaotic and varied conditions inside neurons has been a challenge. However, it is harder to argue against the fact that any kind of electrochemical spike based on the rapid influx of ions will be accompanied by a significant pressure pulse. The idea that the German researchers have supported, is that these as the pressure pulses naturally decay in the viscoelastic medium of the nerve, they are refreshed by ionic input at the nodes between myelinated axon segments, or continuously in unmyelinated axons.
If you have ever been absent-minded enough to grab a live wire, or even brush up strongly against one, the sensation is unforgettable. It is not such a stretch to acknowledge that when you slam your funny bone, or more precisely the Ulnar nerve (largest unprotected nerve in your body), the resultant vibe and decay feels almost identical to a real electrical assault. Similarly, the so-called “stingers” that run down the limbs after a sharp blow to the head are familiar to most footballers, and can give one quite a shock. Unfortunately these (albeit very simplistic) macroscopic intuitions don’t hold up so well when extended to the microscopic domain. Granted, when the electrochemical mechanisms that are assumed to underlie nervous conduction are looked at in detail, it becomes more difficult to disentangle the mechanical from the electric. However, as the authors observe, at some point, an attentive electrophysiologist must ask his or herself, “why are so many ion channels mechanosensitive” ?
One unexpected finding of the patch clamp recording technique was that the dilation of the membrane caused by local tension leads to considerable increase in transmembrane ion flow. Impulse waves causing short extensions in the membrane can directly induce opening and closing of both voltage and ligand gated channels. The idea that the pore in these channels is a rigid tube isolated from larger membrane events is difficult to support in this context. According to the authors, it is quite likely that common mechanoreceptor devices, like the pressure- or vibration-sensitive Vater-Pacinian corpuscles of the skin, conduct signals to initiate high-speed polysynaptic muscle reflex circuits without any classical intermediary electrical conversion.
The exact conduction velocity of mechanical impulses in nerve fibers remains unknown. It is estimated that under physiologic conditions, an unamplified axoplasmic pressure pulse would decay over roughly 1 mm due to viscosity, depending on the distensibility of the axon wall. When compared to the theoretical case of an absolutely rigid wall, a typical myelin sheath may be rigid enough to support pulse speeds up to one-fifth of the estimated maximum. That speed is not to shabby when compared with some rough estimates from previous authors, which put the maximum pulse velocity under an indistensible membrane somewhere upwards of 1500 meters per second. Suddenly, the quicker than life eyeblink response, or speed of the tenderfoot stepping on a sharp shard, become a little more comprehensible.
The theory as it stands is incomplete and needs to be adapted for specific cases with real biology in mind. In different animals, and in different regions of their brains, conduction in neurons goes by different names. For example, in the cerebellum, the unmyelinated parallel fibers pack to extreme densities in a regular crystalline lattice whose reason to be defies physiologic explanation to this day. Just as we currently have no good explanation for how signals could be properly isolated in nerve bundles where seemingly random nodes of Ranvier overlap in extent and influence, it is hard to imagine parallel fibers could maintain their electrochemical, or even mechanical, autonomy within this geometry.
The pressure wave theory wields considerable predictive power when it comes to explaining some of the unique synaptic specializations found throughout the brain. When considered only from an electrochemical point of view, the huge structural synaptic investments, like those found at the neuromuscular junction (NMJ), can hardly be imagined to be driven by local, and weak, current or field effects. One might need look no further than simple-to-recreate Chaldni patterns set up in two dimensions on the surface of a taunt drum, to make the imaginative leap to a three dimensional system, with multiple vibrating players, where more extreme patterns might easily be set up to provide authorship to repeatable complex structure. For the NMJ in particular, the case has been made that at the end-plate, the comparatively enormous efflux of acetylcholine to the deeply-guttered cleft, and propagation of excitation through the transverse tubule system, are all components of a continuous mechanical amplifier.
The apparent ease with which evolving organisms manage to cobble together all manner of sensitive hearing devices becomes infinitely more explicable once we see that nature has apparently been doing this kind of thing all alone inside of neurons. The amplification and transduction through liquid channels, of barely noticeable vibrations against a background of thermal noise much greater in magnitude, is in this light, no evolutionary stumble-upon, but rather the bread and butter of neural systems, and perhaps many aspects of life in general.
When Cells ‘Eat’ Their Own Power Plants; Pitt Scientists Solve Mystery of Basic Cellular Process
A mix of serendipity and dogged laboratory work allowed a diverse team of University of Pittsburgh scientists to report in the Oct. 1 issue of Nature Cell Biology that they had solved the mystery of a basic biological function essential to cellular health.
By discovering a mechanism by which mitochondria – tiny structures inside cells often described as “power plants” – signal that they are damaged and need to be eliminated, the Pitt team has opened the door to potential research into cures for disorders such as Parkinson’s disease that are believed to be caused by dysfunctional mitochondria in neurons.
"It’s a survival process. Cells activate to get rid of bad mitochondria and consolidate good mitochondria. If this process succeeds, then the good ones can proliferate and the cells thrive," said Valerian Kagan, Ph.D., D.Sc., a senior author on the paper and professor and vice chair of the Pitt Graduate School of Public Health’s Department of Environmental and Occupational Health. "It’s a beautiful, efficient mechanism that we will seek to target and model in developing new drugs and treatments."
Dr. Kagan, who, as a recipient of a Fulbright Scholar grant, currently is serving as visiting research chair in science and the environment at McMaster University in Ontario, Canada, likened the process to cooking a Thanksgiving turkey.
"You put the turkey in the oven and the outside becomes golden, but you can’t just look at it to know it’s ready. So you put a thermometer in, and when it pops up, you know you can eat it," he said. "Mitochondria give out a similar ‘eat me’ signal to cells when they are done functioning properly."
Cardiolipins, named because they were first found in heart tissue, are a component on the inner membrane of mitochondria. When a mitochondrion is damaged, the cardiolipins move from its inner membrane to its outer membrane, where they encourage the cell to destroy the entire mitochondrion.
However, that is only part of the process, says Charleen T. Chu, M.D., Ph.D., professor and the A. Julio Martinez Chair in Neuropathology in the Pitt School of Medicine’s Department of Pathology, another senior author of the study. “It’s not just the turkey timer going off; it’s a question of who’s holding the hot mitt to bring it to the dining room?” That turns out to be a protein called LC3. One part of LC3 binds to cardiolipin, and LC3 causes a specialized structure to form around the mitochondrion to carry it to the digestive centers of the cell.
The research arose nearly a decade ago when Dr. Kagan had a conversation with Dr. Chu at a research conference. Dr. Chu, who studies autophagy, or “self-eating,” in Parkinson’s disease, was seeking a change on the mitochondrial surface that could signal to LC3 to bring in the damaged organelle for recycling. It turned out they were working on different sides of the same puzzle.
Together with Hülya Bayır, M.D., research director of pediatric critical care medicine, Children’s Hospital of Pittsburgh of UPMC and professor, Pitt’s Department of Critical Care Medicine, and a team of nearly two dozen scientists, the three senior authors worked out how the pieces of the mitochondria signaling problem fit together.
Now that they’ve worked out the basic mechanism, Dr. Chu indicates that many more research directions will likely follow.
"There are so many follow-up questions," she said. "What is the process that triggers the cardiolipin to move outside the mitochondria? How does this pathway fit in with other pathways that affect onset of diseases like Parkinson’s? Interestingly, two familial Parkinson’s disease genes also are linked to mitochondrial removal."
Dr. Bayir explained that while this process may happen in all cells with mitochondria, it is particularly important that it functions correctly in neuronal cells because these cells do not divide and regenerate as readily as cells in other parts of the body.
"I think these findings have huge implications for brain injury patients," she said. "The mitochondrial ‘eat me’ signaling process could be a therapeutic target in the sense that you need a certain level of clearance of damaged mitochondria. But, on the other hand, you don’t want the clearing process to go on unchecked. You must have a level of balance, which is something we could seek to achieve with medications or therapy if the body is not able to find that balance itself."
(Source: upmc.com)
Finding the place where the brain creates illusory shapes and surfaces
The logo of the 1984 Los Angeles Olympics includes red, white and blue stars, but the white star is not really there: It is an illusion. Similarly, the “S” in the USA Network logo is wholly illusory.
Both of these logos take advantage of a common perceptual illusion where the brain, when viewing a fragmented background, frequently sees shapes and surfaces that don’t really exist.
“It’s hallucinating without taking drugs,” said Alexander Maier, assistant professor of psychology at Vanderbilt University, who headed a team of neuroscientists who has pinpointed the area of the brain that is responsible for these “illusory contours.”
In the Sept. 30 online early edition of the Proceedings of the National Academy of Sciences, Maier’s team reported that they have discovered groups of neurons in a region of the visual cortex called V4 that fire when an individual is viewing a pattern that produces such an illusion and remain quiescent when viewing an almost identical pattern that doesn’t.
Studies have shown that a diverse range of species, including monkeys, cats, owls, goldfish and even honeybees perceive these illusory contours. This has led scientists to propose that they are the byproduct of methods that the brain has evolved to spot predators or prey hiding in the bushes, a capability with considerable survival value.
Although scientists discovered illusory contours more than a century ago, it is only in the last 30 years that they have begun studying them because they reveal the internal mechanisms that the brain uses to interpret sensory input.
The gold square marks the location in the V4 region of a macaque’s visual cortex, where the neurons respond to visual contours. (Alex Maier, Donna Pritchett / Vanderbilt)
In mammals, visual stimuli is processed in the back of the brain in an area called the visual cortex. Efforts to map this area have found that it is made up of five different regions at the back of brain (labeled V1 to V5.)
The primary visual cortex, V1, takes the stimuli coming from the eyes and sorts it by a variety of basic properties, including orientation, color and spatial variation. It also splits the information into two pathways, called the dorsal and ventral streams.
From V1, both streams are routed to the second major area of the visual cortex. V2 performs many of the same functions as V1 but adds some more complex processing, such as recognizing the disparities in the signals coming from the two eyes that produce binocular vision.
From V2, one pathway, sometimes called the “Where Pathway,” goes to V5 and is associated with object location and motion detection. The other pathway, sometimes called the “What Pathway,” goes to V4 and is associated with object representation and form recognition.
“Studies have shown that V4 is involved in both object recognition and visual attention, so we thought it might also be involved with illusory contours,” said Michele Cox, the Vanderbilt graduate student who is first author on the study.
A Kanizsa square (Courtesy of D. Alan Stubbs, University of Maine)
First, the researchers searched for the neurons in V4 that were associated with different locations in the retinas of macaque monkeys. Once these maps were complete, they rewarded the monkeys for staring at a screen containing an example of an illusory contour called a Kanizsa square. This consists of four “Pac-Man” figures with their “mouths” oriented to form the corners of a square. When black Pac-Men are placed on a white background, the brain creates a bright white square connecting them.
While the monkeys were looking at the Kanizsa square, the researchers discovered that the neurons that represented the area in the middle of the Pac-Men, the area covered by the illusory square, began firing. However, when the monkeys viewed the same four Pac-Men with their mouths facing outward – an orientation that doesn’t produce the illusion – these central neurons remained silent.
“Basically, the brain is acting like a detective,” said Maier. “It is responding to cues in the environment and making its best guesses about how they fit together. In the case of these illusions, however, it comes to an incorrect conclusion.”
Two graphs show the activity of neurons in V4 associated with the position of the illusory Kanizsa square. The percentage of neurons firing more than doubles when the monkey views pac-men with their mouths facing inward to produce the illusion (top) compared to their activity level when the monkey is viewing pac-men with their mouths facing outward (bottom). (Michelle Cox and Alex Maier / Vanderbilt)
(Source: news.vanderbilt.edu)
Bionic leg is controlled by brain power
A team of specialists has designed a bionic prosthetic leg that can reproduce a full range of ambulatory movements by communicating with the brain of the person wearing it.
The act of walking may not seem like a feat of agility, balance, strength and brainpower. But lose a leg, as Zac Vawter did after a motorcycle accident in 2009, and you will appreciate the myriad calculations that go into putting one foot in front of the other.
Taking on the challenge, a team of software and biomedical engineers, neuroscientists, surgeons and prosthetists has designed a prosthetic limb that can reproduce a full repertoire of ambulatory tricks by communicating seamlessly with Vawter’s brain.
A report published Wednesday in the New England Journal of Medicine describes how the team fit Vawter with a prosthetic leg that has learned — with the help of a computer and some electrodes — to read his intentions from a bundle of nerves that end above his missing knee.
For the roughly 1 million Americans who have lost a leg or part of one due to injury or disease, Vawter and his robotic leg offer the hope that future prosthetics might return the feel of a natural gait, kicking a soccer ball or climbing into a car without hoisting an inert artificial limb into the vehicle.
Vawter’s prosthetic is a marvel of 21st century engineering. But it is Vawter’s ability to control the prosthetic with his thoughts that makes the latest case remarkable. If he wants his artificial toes to curl toward him, or his artificial ankle to shift so he can walk down a ramp, all he has to do is imagine such movements.
The work was done at the Rehabilitation Institute of Chicago under an $8-million grant from the Army. The armed forces hope to apply findings from such studies to the care of about 1,200 service personnel who have lost a lower limb in Iraq and Afghanistan.
"We want to restore full capabilities" to people who’ve lost a lower limb, said Levi J. Hargrove, lead author of the new report. "While we’re focused and committed to developing this system for our wounded warriors, we’re very much thinking of this other, much larger population that could benefit as well."
The report describes advances across a wide range of disciplines: in orthopedic and peripheral nerve surgery, neuroscience, and the application of pattern-recognition software to the field of prosthetics.
Weighing just over 10 pounds, the leg has two independent engines powering movement in the ankle and knee. And it bristles with sensors, including an accelerometer and gyroscope, each capable of detecting and measuring movement in three dimensions.
Most prosthetics in use today require the physical turn of a key to transition from one movement to another. But with the robotic leg, those transitions are effortless, Vawter said.
"With this leg, it just flows," said the 32-year-old software engineer, who spends most of his days using a typical prosthetic but travels to Chicago several times a year from his home in Yelm, Wash. "The control system is very intuitive. There isn’t anything special I have to do to make it work right."
Before Vawter could strap on the bionic lower limb, engineers in Chicago had to “teach” the prosthetic how to read his motor intentions from tiny muscle contractions in his right thigh.
At the institute’s Center for Bionic Medicine, Vawter spent countless hours with his thigh wired up with electrodes, imagining making certain movements on command with his missing knee, ankle and foot.
Using pattern-recognition software, engineers discerned, distilled and digitized those recorded electrical signals to catalog an entire repertoire of movements. The prosthetic could thus be programmed to recognize the subtlest contraction of a muscle in Vawter’s thigh as a specific motor command.
Given surgical practices still in wide use, the prospects for such a connection between a patient’s prosthetic and his or her peripheral nerves are generally dim. In most amputations, the nerves in the thigh are left to languish or die.
Dr. Todd Kuiken, a neurosurgeon at the rehabilitation institute, pioneered a practice called “reinervation” of nerves severed by amputation, and Vawter’s orthopedic surgeon at the University of Washington Medical Center was trained to conduct the delicate operation. Dr. Douglas Smith rewired the severed nerves to control some of the muscles in Vawter’s thigh that would be used less frequently in the absence of his lower leg.
Within a few months of the amputation, those nerves had recovered from the shock of the injury and begun to regenerate and carry electrical impulses. When Vawter thought about flexing his right foot in a particular way, the rerouted nerve endings would consistently cause a distinctive contraction in his hamstring. When he pondered how he would position his foot on a stair step and ready it for the weight of his body, the muscle contraction would be elsewhere — but equally consistent.
Compared with prosthetics that were not able to “read” the intent of their wearers, the robotic leg programmed to follow Vawter’s commands reduced the kinds of errors that cause unnatural movements, discomfort and falls by as much as 44%, according to the New England Journal of Medicine report.
Vawter said he had “fallen down a whole bunch of times” while wearing his everyday prosthetic, but not once while moving around on his bionic leg.
He said he could move a lot faster too — which would be helpful for keeping up with his 5-year-old son and 3-year-old daughter. But first, Vawter added, he needs to persuade Hargrove’s team to let him wear it home.
Hitting the perfect tennis serve requires hours and hours of practice, but for scientists who study complex motor behaviors, there always has been a large unanswered question — what is the brain learning from those hours spent on the court? Is it simply the timing required to hit the perfect serve, or is it the precise path along which to move the hand?
The answer, Harvard researchers say, is both — but in separate circuits.
Bence Ölveczky, the John L. Loeb Associate Professor of the Natural Sciences, has found that the brain uses two largely independent neural circuits to learn the temporal and spatial aspects of a motor skill. The study is described in a Sept. 26 paper in Neuron.
“What we’re studying is the structure of motor-skill learning,” Ölveczky said. “What we were able to show is that the brain divides something that’s complex into modules — in this case for timing and for motor implementation — as a way to take advantage of the hierarchical structure of the motor system, and it imprints learning at the different levels independently.”
To tease out how those independent circuits operate, Ölveczky and his colleagues turned to a creature well-known for its ability to learn — the zebra finch. The tiny birds are regularly used in studies of learning because each male learns to sing a unique song from its father.
In a series of experiments, Ölveczky’s team used traditional conditioning techniques to change the timing of a bird’s song by speeding up or slowing down certain “syllables” in the song. They could also change which vocal muscles were activated and have the bird sing at a higher or lower pitch.
“But when you change the pitch of a syllable, the duration doesn’t change, and when you change the duration the pitch doesn’t change,” Ölveczky said. “It appears the neural circuits for the two features are separate.”
Additional evidence that the circuits for learning motor implementation and timing are distinct came when researchers lesioned the basal ganglia of the birds — the region of the brain long thought to play a critical role in song learning.
“The thinking had been that there was one circuit for song-learning in general,” Ölveczky said. “We found that if we lesioned the basal ganglia and repeated the pitch-shift experiment, the bird could no longer use the information it got from our feedback to change its behavior — in other words, it couldn’t learn.”
Experiments aimed at changing the birds’ timing, however, were just as effective, suggesting two separate learning circuits — with only one involving the basal ganglia.
Such independence and modularity is critical, Ölveczky said, because it allows different features of a behavior to be modified independently if circumstances change. Parallel learning of different features can also speed up the learning process and enable the flexibility we see in birdsong and many human motor skills.
“If you learn something — it could be your tennis serve, or it could be any behavior — and you need to slow it down or speed it up to fit some new contingency, you don’t have to completely re-learn the whole thing, you can just change the timing, and everything else will remain exactly the same.
“In fact, ‘slow practice,’ a technique used by many piano and dance teachers, makes good use of this modularity,” Ölveczky said. “Students are first taught to perform the movements of a piece slowly. Once they have learned it, all they need to do is get the timing right. The technique works because the two processes — motor implementation and timing — do not interfere with each other.”
The hope among researchers, Ölveczky said, is that a better understanding of how birds learn complex motor tasks such as singing unique songs will help shed new light on the neural underpinnings of learning in humans.
“For us, this is inspiration to look at similar types of questions in mammals,” he said. “The flexibility with which we can alter the spatial and temporal structure of our motor output is similar to songbirds, but our understanding of how the mammalian brain implements the underlying learning process is not anywhere near as advanced as for songbirds. The intriguing parallels in both circuitry and behavior, however, suggest a general principle of how the brain parses the motor skill learning process.”