By monitoring the behavior of a class of cells in the brains of living mice, neuroscientists at Johns Hopkins discovered that these cells remain highly dynamic in the adult brain, where they transform into cells that insulate nerve fibers and help form scars that aid in tissue repair.

Published online April 28 in the journal Nature Neuroscience, their work sheds light on how these multipurpose cells communicate with each other to maintain a highly regular, grid-like distribution throughout the brain and spinal cord. The disappearance of one of these so-called progenitor cells causes a neighbor to quickly divide to form a replacement, ensuring that cell loss and cell addition are kept in balance.

“There is a widely held misconception that the adult nervous system is static or fixed, and has a limited capacity for repair and regeneration,” says Dwight Bergles, Ph.D., professor of neuroscience and otolaryngology at the Johns Hopkins University School of Medicine. “But we found that these progenitor cells, called oligodendrocyte precursor cells (OPCs), are remarkably dynamic. Unlike most other adult brain cells, they are able to respond to the repair needs around them while maintaining their numbers.”

OPCs can mature to become oligodendrocytes — support cells in the brain and spinal cord responsible for wrapping nerve fibers to create insulation known as myelin. Without myelin, the electrical signals sent by neurons travel poorly and some cells die due to the lack of metabolic support from oligodendrocytes. It is the death of oligodendrocytes and the subsequent loss of myelin that leads to neurological disability in diseases such as multiple sclerosis.

During brain development, OPCs spread throughout the central nervous system and make large numbers of oligodendrocytes. Scientists know that few new oligodendrocytes are born in the healthy adult brain, yet the brain is flush with OPCs. However, the function of OPCs in the adult brain wasn’t clear.

To find out, Bergles and his team genetically modified mice so that their OPCs contained a fluorescent protein along their edges, giving crisp definition to their many fine branches that extend in every direction. Using special microscopes that allow imaging deep inside the brain, the team watched the activity of individual cells in living mice for over a month.

The researchers discovered that, far from being static, the OPCs were continuously moving through the brain tissue, extending their “tentacles” and repositioning themselves. Even though these progenitors are dynamic, each cell maintains its own area by repelling other OPCs when they come in contact.

“The cells seem to sense each other’s presence and know how to control the number of cells in their population,” says Bergles. “It looks like this process goes wrong in multiple sclerosis lesions, where there are reduced numbers of OPCs, a loss that may impair the cells’ ability to sense whether demyelination has occurred. We don’t yet know what molecules are involved in this process, but it’s something we’re actively working on.”

To see if OPCs do more than form new oligodendrocytes in the adult brain, the team tested their response to injury by using a laser to create a small wound in the brain. Surprisingly, OPCs migrated to the injury site and contributed to scar formation, a previously unsuspected role. The empty space in the OPC grid, created by the loss of the scar-forming OPCs, was then filled by cell division of neighboring OPCs, providing an explanation for why brain injury is often accompanied by proliferation of these cells.

“Scar cells are not oligodendrocytes, so the term ‘oligodendrocyte precursor cell’ may now be outdated,” says Bergles. “These cells are likely to have a broader role in tissue regeneration and repair than we thought. Because traumatic brain injuries, multiple sclerosis and other neurodegenerative diseases require tissue regeneration, we are eager to learn more about the functions of these enigmatic cells.”

Research opens door to new drug therapies for Parkinson’s disease

McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson’s disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The Neuro, and Dr. Kalle Gehring  in the Department of Biochemistry at the Faculty of Medicine, have discovered the three-dimensional structure of the protein Parkin. Mutations in Parkin cause a rare hereditary form of Parkinson’s disease and are likely to also be involved in more commonly occurring forms of Parkinson’s disease. The Parkin protein protects neurons from cell death due to an accumulation of defective mitochondria. Mitochondria are the batteries in cells, providing the power for cell functions. This new knowledge of Parkin’s structure has allowed the scientists to design mutations in Parkin that make it better at recognizing damaged mitochondria and therefore possibly provide better protection for nerve cells. The research will be published online May 9 in the leading journal Science.

VIDEO: Parkin protein

“The majority of Parkinson’s patients suffer from a sporadic form of the disease that occurs from a complex interplay of genetic and environmental factors which are still not fully understood, explains Dr. Fon, neurologist at The Neuro and head of the McGill Parkinson Program, a National Parkinson Foundation Centre of Excellence. “A minority of patients have genetic mutations in genes such as Parkin that cause the disease. Although there are differences between the genetic and sporadic forms, there is good reason to believe that understanding one will inform us about the other. It’s known that toxins that poison mitochondria can lead to Parkinson’s-like symptoms in humans and animals. Recently, Parkin was shown to be a key player in the cell’s system for identifying and removing damaged mitochondria.”

Dr. Gehring, head of McGill’s structural biology centre, GRASP, likens Parkin to a watchdog for damaged mitochondria. “Our structural studies show that Parkin is normally kept in check by a part of the protein that acts as a leash to restrict Parkin activity. When we made mutations in this specific ‘leash’ region in the protein, we found that Parkin recognized damaged mitochondria more quickly. If we can reproduce this response with a drug rather than mutations, we might be able to slow the progression of disease in Parkinson’s patients.”

Parkin is an enzyme in cells that attaches a small protein, ubiquitin, to other proteins to mark them for degradation. For example, when mitochondria are damaged, Parkin is switched on which leads to the clearing of the dysfunctional mitochondria. This is an important process because damaged mitochondria are a major source of cellular stress and thought to play a central role in the death of neurons in neurodegenerative diseases.

Husband and wife team, Drs. Jean-François Trempe and Véronique Sauvé, are lead authors on the paper. Dr. Sauvé led the Gehring team that used X-ray crystallography to determine the structure of Parkin. Dr. Trempe in the Fon laboratory directed the functional studies of Parkin.

(Source: mcgill.ca)

Scientists have identified a set of tests that could help identify whether and how Huntington’s disease (HD) is progressing in groups of people who are not yet showing symptoms. The latest findings from the TRACK-HD study*, published Online First in The Lancet Neurology, could be used to assess whether potential new treatments are slowing the disease up to 10 years before the development of noticeable symptoms.

“Currently, the effectiveness of a new drug is decided by its ability to treat symptoms. These new tests could be used in future preventative drug trials in individuals who are gene positive for HD but are not yet showing overt motor symptoms. These people have the most to gain by initiating treatment early to delay the start of these overt symptoms and give them a high quality of life for a longer period of time”, explains lead author Sarah Tabrizi from University College London’s Institute of Neurology.

The TRACK-HD investigators have previously reported a range of tests that could be used in clinical trials to assess the effectiveness of potential disease-modifying drugs in people who already show signs of the disease. But in individuals without noticeable symptoms there was little evidence of a decline in function over two years, limiting the ability to test new drugs early in the disease course.

HD is caused by the mutation of a single gene on chromosome 4, which causes a part of the DNA (known as a CAG motif) to repeat many more times than it is supposed to. The length of the CAG repeat is known to be a major determinant of the age at which symptoms of the disease are likely to start, but its contribution to progression is unclear.

Here the TRACK-HD investigators extend the study to a third year with the aim of identifying some of the earliest biological changes in individuals with presymptomatic HD, giving additional power to predict how the disease may progress beyond that already expected from age and CAG length.

Over 3 years, baseline measures derived from brain imaging were the clearest markers of disease progression and future diagnosis, above and beyond the effect of age and CAG count, in gene carriers up to 20 years before they were expected to show symptoms.

In particular, the investigators suggest that measuring volume change in white matter and the caudate and putamen regions might be future endpoints for treatment trials.

In individuals up to 10 years away from developing symptoms, there was also significant deterioration in performance on a number of motor (movement) and cognitive (intellectual function) tasks compared with controls, and the frequency of apathy increased. Finger tapping was the most sensitive of the motor assessments, while the symbol digit modality test proved to be the most sensitive of the cognitive measures.

According to Tabrizi, “A new generation of drugs will be ready for human trials in the very near future. Diagnosis in HD is something of an artificial construct at onset of motor symptoms, and this study now gives us a number of other, more well-defined parameters that correlate with disease progression. Something that suggests we’re moving towards a more biological, as opposed to physical, definition of disease progression that reduces the importance of an ‘onset event’ is great news. By extending the reach of clinical trials to include individuals who are currently free of overt symptoms there is a realistic future possibility that treatments in the pipeline can significantly improve the quality of life for patients and families.”**

Writing in a linked Comment, Francis O. Walker, M.D., from Wake Forest School of Medicine in the USA says that the TRACK-HD investigators have set the standard for observational studies in other neurodegenerative diseases, adding that, “Virtual roadmaps of disease in the minds of practitioners are good for care in the framework of the traditional patient encounter, but it takes substantial effort, teamwork, and genius to turn them into rigorous, quantifiable timelines that can be used to test efficacy in future therapeutic trials.”

* The Track-HD study was established to identify differences between people carrying the HD mutation at different stages and healthy controls that could be used to accurately predict the progression of HD using a variety of techniques to assess changes in brain function, motor function, behaviour, and cognition. 366 individuals from Canada, France, the Netherlands and the UK were enrolled: 120 presymptomatic carriers of the HD gene mutation, 123 patients with early symptomatic HD, and 123 healthy controls.

(Source: newswise.com)

How does San Francisco Giants slugger Pablo Sandoval swat a 95 mph fastball, or tennis icon Venus Williams see the oncoming ball, let alone return her sister Serena’s 120 mph serves? For the first time, vision scientists at the University of California, Berkeley, have pinpointed how the brain tracks fast-moving objects.

The discovery advances our understanding of how humans predict the trajectory of moving objects when it can take one-tenth of a second for the brain to process what the eye sees.

That 100-millisecond holdup means that in real time, a tennis ball moving at 120 mph would have already advanced 15 feet before the brain registers the ball’s location. If our brains couldn’t make up for this visual processing delay, we’d be constantly hit by balls, cars and more.

Thankfully, the brain “pushes” forward moving objects so we perceive them as further along in their trajectory than the eye can see, researchers said.

“For the first time, we can see this sophisticated prediction mechanism at work in the human brain,” said Gerrit Maus, a postdoctoral fellow in psychology at UC Berkeley and lead author of the paper published today (May 8) in the journal, Neuron.

A clearer understanding of how the brain processes visual input – in this case life in motion – can eventually help in diagnosing and treating myriad disorders, including those that impair motion perception. People who cannot perceive motion cannot predict locations of objects and therefore cannot perform tasks as simple as pouring a cup of coffee or crossing a road, researchers said.

This study is also likely to have a major impact on other studies of the brain. Its findings come just as the Obama Administration initiates its push to create a Brain Activity Map Initiative, which will further pave the way for scientists to create a roadmap of human brain circuits, as was done for the Human Genome Project.

Using functional Magnetic Resonance Imaging (fMRI) Gerrit and fellow UC Berkeley researchers Jason Fischer and David Whitney located the part of the visual cortex that makes calculations to compensate for our sluggish visual processing abilities. They saw this prediction mechanism in action, and their findings suggest that the middle temporal region of the visual cortex known as V5 is computing where moving objects are most likely to end up.

For the experiment, six volunteers had their brains scanned, via fMRI, as they viewed the “flash-drag effect,”(a, b) a visual illusion in which we see brief flashes shifting in the direction of the motion.

“The brain interprets the flashes as part of the moving background, and therefore engages its prediction mechanism to compensate for processing delays,” Maus said.

The researchers found that the illusion – flashes perceived in their predicted locations against a moving background and flashes actually shown in their predicted location against a still background – created the same neural activity patterns in the V5 region of the brain. This established that V5 is where this prediction mechanism takes place, they said.

In a study published earlier this year, Maus and his fellow researchers pinpointed the V5 region of the brain as the most likely location of this motion prediction process by successfully using transcranial magnetic stimulation, a non-invasive brain stimulation technique, to interfere with neural activity in the V5 region of the brain, and disrupt this visual position-shifting mechanism.

“Now not only can we see the outcome of prediction in area V5,” Maus said. “But we can also show that it is causally involved in enabling us to see objects accurately in predicted positions.”

On a more evolutionary level, the latest findings reinforce that it is actually advantageous not to see everything exactly as it is. In fact, it’s necessary to our survival:

“The image that hits the eye and then is processed by the brain is not in sync with the real world, but the brain is clever enough to compensate for that,” Maus said. “What we perceive doesn’t necessarily have that much to do with the real world, but it is what we need to know to interact with the real world.”

(Source: newscenter.berkeley.edu)

With a goal of helping patients with spinal cord injuries, Jason Gallivan and a team of researchers at Queen’s University’s Department of Psychology and Centre for Neuroscience Studies are probing deep into the human brain to learn how it manages basic daily tasks.

The team’s most recent research, in collaboration with a group at Western University, investigated how the human brain supports tool use. The researchers were especially interested in determining the extent to which brain regions involved in planning actions with the hand alone would also be involved in planning actions with a tool. They found that although some brain regions were involved in planning actions with either the hand or tool alone, the vast majority were involved in planning both hand- and tool-related movements. In a subset of these latter brain areas the researchers further determined that the tool was in fact being represented as an extension of the hand.

“Tool use represents a defining characteristic of high-level cognition and behaviour across the animal kingdom but studying how the brain – and the human brain in particular – supports tool use remains a significant challenge for neuroscientists” says Dr. Gallivan. “This work is a considerable step forward in our understanding of how tool-related actions are planned in humans.”

Over the course of one year, human participants had their brain activity scanned using functional magnetic resonance imaging (fMRI) as they reached towards and grasped objects using either their hand or a set of plastic tongs. The tongs had been designed so they opened whenever participants closed their grip, requiring the participants to perform a different set of movements to use the tongs as opposed to when using their hand alone.

The team found that mere seconds before the action began, that the neural activity in some brain regions was predictive of the type of action to be performed upon the object, regardless of whether the hand or tool was to be used (and despite the different movements being required). By contrast, the predictive neural activity in other brain regions was shown to represent hand and tool actions separately. Specifically, some brain regions only coded actions with the hand whereas others only coded actions with the tool.

“Being able to decode desired tool use behaviours from brain signals takes us one step closer to using those signals to control those same types of actions with prosthetic limbs,” says Dr. Gallivan. “This work uncovers the brain organization underlying the planning of movements with the hand and hand-operated tools and this knowledge could help people suffering from spinal cord injuries.”

The research was recently published in eLife.

(Source: queensu.ca)

Adding captivating visuals to a textbook lesson to attract children’s interest may sometimes make it harder for them to learn, a new study suggests.

Researchers found that 6- to 8-year-old children best learned how to read simple bar graphs when the graphs were plain and a single color.

Children who were taught using graphs with images (like shoes or flowers) on the bars didn’t learn the lesson as well and sometimes tried counting the images rather than relying on the height of the bars.

“Graphs with pictures may be more visually appealing and engaging to children than those without pictures. However, engagement in the task does not guarantee that children are focusing their attention on the information and procedures they need to learn. Instead, they may be focusing on superficial features,” said Jennifer Kaminski, co-author of the study and research scientist in psychology at The Ohio State University.

Kaminski conducted the study with Vladimir Sloutsky, professor of psychology at Ohio State.

The problem of distracting visuals is not just an academic issue. In the study, the authors cite real-life examples of colorful, engaging – and possibly confusing - bar graphs in educational materials aimed at children, as well as in the popular media.

And when the authors asked 16 kindergarten and elementary school teachers whether they would use the visually appealing graphs featured in this study, all of them said they would. Intuitively, most of these teachers felt that the graphs with the pictures would be more effective for instruction than the graphs without, according to the researchers.

The findings apply beyond learning graphs and mathematics, the authors said.

“When designing instructional material, we need to consider children’s developing ability to focus their attention and make sure that the material helps them focus on the right things,” Kaminski said.

“Any unnecessary visual information may distract children from the very procedures we want them to learn.”

The study appears online in the Journal of Educational Psychology and will appear in a future print edition.

The main study involved 122 students in kindergarten, first and second grade. All were tested individually.

The experiment began with a training phase where a researcher showed each child a graph on a computer screen and taught him or her how to read it. The children were then tested on three graphs to see if they could accurately interpret them.

The graphs in the training phase involved how many shoes were in a lost and found for each of five weeks. Half the students were presented with graphs in which the bars were a solid color. The other students were shown graphs in which the bars contained pictures of shoes. The number of shoes in the bars was equal to the corresponding y-value on the graph. In other words, if there were five shoes in the lost and found, there were five shoes pictured in the bar.

After the training phase, the children were tested on new graphs in which the bars were either solid-colored or contained pictures of objects such as flowers. However, the number of objects pictured did not equal the correct y-value for the bar. In other words, the bar value could equal 14 flowers, but only seven flowers were pictured.

“This allowed us to clearly identify which students learned the correct way to read a bar graph from those who simply counted the number of objects in each bar,” Sloutsky said.

Sure enough, children who trained with the pictures on the graph were more likely than others to get the answers wrong by simply counting the objects in each bar.

All of the first- and second-graders and 75 percent of the kindergarten children who learned on the solid-bar graphs appropriately read the new graphs.

However, those who learned with the more visually appealing shoe graphs did not do nearly as well. In this case, 90 percent of kindergarteners and 72 percent of first-graders responded by counting the number of flowers pictured. Second-graders did better, but still about 30 percent responded by counting.

All the children were then tested again with graphs that featured patterned bars, with either stripes or polka dots within each bar.

Again, those who learned from the more visually appealing graphs did worse at interpreting these patterned graphs.

“To our surprise, some children tried to count all the tiny polka dots or stripes in the bars. They clearly didn’t learn the correct way to read the graphs,” Kaminski said.

The researchers conducted several other related experiments to confirm the results and make sure there weren’t other explanations for the findings. In one experiment, some children were trained on graphs with pictures of objects. But in this case, the number of objects pictured was not even close to the correct value of the bar, so the students could not use counting as a strategy.

Still, these children did not do as well on subsequent tests as did those who learned on the graphs with single-colored bars.

“When teaching children new math concepts, keeping material simple is very important,” Sloutsky said.

“Any extraneous information we provide, even with the best of intentions, to make the lesson more interesting may actually hurt learning because it may be misinterpreted,” he said.

The researchers said these results don’t mean that textbook authors or others can never use interesting visuals or other techniques to capture the interest of students.

“But they need to study how such material will affect students’ attention. You can’t assume that it is beneficial just because it is colorful; in can affect learning by distracting attention from what is relevant,” Sloutsky said.

(Source: researchnews.osu.edu)