(Image caption: The complex shape of individual oligodendrocytes (OLs) and myelin in adult mice injected with tamoxifen. Credit: Sarah Jolly)

Myelin vital for learning new practical skills

New evidence of myelin’s essential role in learning and retaining new practical skills, such as playing a musical instrument, has been uncovered by UCL research. Myelin is a fatty substance that insulates the brain’s wiring and is a major constituent of ‘white matter’. It is produced by the brain and spinal cord into early adulthood as it is needed for many developmental processes, and although earlier studies of human white matter hinted at its involvement in skill learning, this is the first time it has been confirmed experimentally.

The study in mice, published in Science today, shows that new myelin must be made each time a skill is learned later in life and the structure of the brain’s white matter changes during new practical activities by increasing the number of myelin-producing cells. Furthermore, the team say once a new skill has been learnt, it is retained even after myelin production stops. These discoveries could prove important in finding ways to stimulate and improve learning, and in understanding myelin’s involvement in other brain processes, such as in cognition.

For a child to learn to walk or an adult to master a new skill such as juggling, new brain circuit activity is needed and new connections are made across large distances and at high speeds between different parts of the brain and spinal cord. For this, electrical signals fire between neurons connected by “axons” – thread-like extensions of their outer surfaces which can be viewed as the ‘wire’ in the electric circuit. When new signals fire repeatedly along axons, the connections between the neurons strengthen, making them easier to fire in the same pattern in future. Neighbouring myelin-producing cells called oligodendrocytes (OLs) recognise the repeating signal and wrap myelin around the active circuit wiring. It is this activity-driven insulation that the team identified as essential for learning.

The team demonstrated that young adult mice need to make myelin to learn new motor skills but that new myelin does not need to be produced to recall and perform a pre-learned skill. They tested the ability of mice to learn to run on a complex wheel with irregularly spaced rungs. The study looked at thirty-six normal mice and thirty-two mice with a drug-controlled genetic switch to prevent new OLs and myelin from being made. They found the mice that were prevented from producing new myelin could not master the complex wheel, whereas those that could produce myelin did learn, with differences between the two groups’ abilities seen after only two hours of practice.

A second experiment looked at mice that were first allowed to learn to run on the complex wheel before being treated with the drug to prevent further myelin production. When the mice were later re-introduced to the complex wheel, they were immediately able to run at top speed without having to spend time re-learning. This shows that the inability to make new myelin did not affect the mouse’s running ability and that new myelin is not required to remember and perform a skill once learned; it is required only during the initial learning phase.

Lead researcher, Professor Bill Richardson, Director of the UCL Wolfson Institute for Biomedical Research, said: “From earlier studies of human white matter using advanced MRI technology, we thought OLs and myelin might be involved in some way in skill learning, so we decided to attack this idea experimentally. We were surprised how quickly we saw differences in the ability of mice from each group to learn how to run on complex wheel, which shows just how fast the brain can respond to wrap newly-activated circuits in myelin and how this improves learning. This rapid response suggests that a number of alternative axon pathways might already exist in the brain that could be used to drive a particular sequence of movements, but it quickly works out which of those circuits is most efficient and both selects and protects its chosen route with myelin.

“We think these findings are really exciting as they open up opportunities to investigate the role of OLs and myelin in other brain processes, such as cognitive activities (like navigating through a maze), to see if the requirement for new myelin is general or specific to motor activity. I’m keen to find out the precise sequence of changes to OLs and myelin during learning and whether these changes are needed more in some parts of the brain than others, which might shed light on some of the mysteries still surrounding how the brain adapts and learns throughout life.”

Scientists find ‘hidden brain signatures’ of consciousness in vegetative state patients

There has been a great deal of interest recently in how much patients in a vegetative state following severe brain injury are aware of their surroundings. Although unable to move and respond, some of these patients are able to carry out tasks such as imagining playing a game of tennis. Using a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, researchers have previously been able to record activity in the pre-motor cortex, the part of the brain which deals with movement, in apparently unconscious patients asked to imagine playing tennis.

Now, a team of researchers led by scientists at the University of Cambridge and the MRC Cognition and Brain Sciences Unit, Cambridge, have used high-density electroencephalographs (EEG) and a branch of mathematics known as ‘graph theory’ to study networks of activity in the brains of 32 patients diagnosed as vegetative and minimally conscious and compare them to healthy adults. The findings of the research are published today in the journal PLOS Computational Biology. The study was funded mainly by the Wellcome Trust, the National Institute of Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC).

The researchers showed that the rich and diversely connected networks that support awareness in the healthy brain are typically – but importantly, not always – impaired in patients in a vegetative state. Some vegetative patients had well-preserved brain networks that look similar to those of healthy adults – these patients were those who had shown signs of hidden awareness by following commands such as imagining playing tennis.

Dr Srivas Chennu from the Department of Clinical Neurosciences at the University of Cambridge says: “Understanding how consciousness arises from the interactions between networks of brain regions is an elusive but fascinating scientific question. But for patients diagnosed as vegetative and minimally conscious, and their families, this is far more than just an academic question – it takes on a very real significance. Our research could improve clinical assessment and help identify patients who might be covertly aware despite being uncommunicative.”

The findings could help researchers develop a relatively simple way of identifying which patients might be aware whilst in a vegetative state. Unlike the ‘tennis test’, which can be a difficult task for patients and requires expensive and often unavailable fMRI scanners, this new technique uses EEG and could therefore be administered at a patient’s bedside. However, the tennis test is stronger evidence that the patient is indeed conscious, to the extent that they can follow commands using their thoughts. The researchers believe that a combination of such tests could help improve accuracy in the prognosis for a patient.

Dr Tristan Bekinschtein from the MRC Cognition and Brain Sciences Unit and the Department of Psychology, University of Cambridge, adds: “Although there are limitations to how predictive our test would be used in isolation, combined with other tests it could help in the clinical assessment of patients. If a patient’s ‘awareness’ networks are intact, then we know that they are likely to be aware of what is going on around them. But unfortunately, they also suggest that vegetative patients with severely impaired networks at rest are unlikely to show any signs of consciousness.”

The Neuroscience of Holding It

Wherever you are right now: squeeze your glutes. Feel that? You just also contracted your pelvic floor too, whether you wanted to or not.

Scientists studying the source of chronic abdominal and pelvic floor pain found an unexpected connection in the brain between the pelvic floor – the muscle responsible for, among other things, keeping you from peeing your pants – and various muscles throughout the body. They’ve found some evidence for a link as far away as the toes (try tapping a toe and see if you feel the clench), but the strongest link so far is with the glutes.

“We knew that pelvic floor muscles contract involuntarily in healthy people to make sure they don’t accidently urinate, but we didn’t know what part of the nervous system was doing this,” said Jason Kutch, corresponding author on a study about the research and an assistant professor in the Division of Biokinesiology & Physical Therapy at the USC Ostrow School of Dentistry. “Now we know that there are specific brain regions controlling involuntary pelvic floor contraction.”

Kutch collaborated with colleagues at USC Ostrow, the Keck School of Medicine of USC, and Loma Linda University on the research. Their findings were published on October 8 in the Journal of Neuroscience.

The team used electromyographic recordings – which measure the activation of muscle tissue – to show that pelvic floor activation occurred in conjunction with the activation of certain muscles (like the glutes), but not others (like fingers).

They then used functional magnetic image resonance (fMRI) imaging to show that a specific part of the brain (the medial wall of the precentral gyrus – a part of the primary motor cortex) activates both when the pelvic floor contracts and when the glutes are squeezed – but not when fingers move.

“We hope that this vein of research will help us to find the causes of chronic pelvic floor pain, which disproportionately affect women, and may even yield information that could help people struggling with incontinence,” Kutch said.

Broadly, the finding speaks to the interconnected nature of our bodies and brains, and all of the hard work going on in the pelvic floor muscles – without us even know it.

Chemical Derived from Broccoli Sprouts Shows Promise in Treating Autism

Results of a small clinical trial suggest that a chemical derived from broccoli sprouts — and best known for claims that it can help prevent certain cancers — may ease classic behavioral symptoms in those with autism spectrum disorders (ASDs).

The study, a joint effort by scientists at MassGeneral Hospital for Children and the Johns Hopkins University School of Medicine, involved 40 teenage boys and young men, ages 13 to 27, with moderate to severe autism.

In a report published online in the journal Proceedings of the National Academy of Sciences during the week of Oct. 13, the researchers say that many of those who received a daily dose of the chemical sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared to those who received a placebo.

“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” says Paul Talalay, M.D., professor of pharmacology and molecular sciences, who has researched these vegetable compounds for the past 25 years.

“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” says co-investigator Andrew Zimmerman, M.D., now a professor of pediatric neurology at UMass Memorial Medical Center.

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New Information about Neurons Could Lead to Advancements in Understanding Brain and Neurological Disorders

Neurons are electrically charged cells, located in the nervous system, that interpret and transmit information using electrical and chemical signals. Now, researchers at the University of Missouri have determined that individual neurons can react differently to electrical signals at the molecular level and in different ways—even among neurons of the same type. This variability may be important in discovering underlying problems associated with brain disorders and neural diseases such as epilepsy.

“Genetic mutations found in neurological disorders create imbalances in the inward and outward flow of electrical current through cells,” said David Schulz, associate professor in the Division of Biological Sciences in the College of Arts and Science and a researcher in the Interdisciplinary Neuroscience Program at MU. “Often, neurons react to electrical signals, or voltage, and compensate by altering their own electrical outputs. The variability in these imbalances, even among multiple cells of the same kind within the brain, is one of the major problems scientists face when trying to design therapeutics for disorders like epilepsy. Seizures in individuals can be caused by different imbalances—therefore getting to the root of how neurons act individually makes our studies important.”

Schulz and his team previously proved that two identical neurons can reach the same electrical activity in different ways. In his new study, Schulz hypothesized that neurons might use the cell’s genetic code, or its messenger RNA (mRNA), to “fine tune” the production of proteins, helping individual cells react accordingly.

Using clusters of neurons obtained from Jonah crabs, Schulz and his team experimentally altered electrical input and output in the neurons and measured the messenger RNA (mRNA) levels found within the cells. Invertebrates like crabs are useful in neuroscience research because their neurons are simple enough to observe and study, but advanced enough that they can be “scaled up” to apply to higher organisms, Schulz said.

They found that when normal patterns of stimulation were maintained, cells engaged the correct ratios of mRNA to produce the proteins needed to help keep electrical impulses in order; however, when normal patterns of activity were not maintained, this fundamentally changed the cells at the molecular level.

“We were the first to show that the correct ratios of mRNAs are actively maintained by the actual activity or voltage of the cell, and not chemical feedback,” Schulz said. “These results represent a novel aspect of regulation that might be useful for developing therapeutics for neuronal disorders later.”

Schulz’ study, “Activity-dependent feedback regulates correlated ion channel mRNA levels in single identified motor neurons,” was published in the August 18^th edition of Current Biology.

Funding for better understanding of neural stem cells

(Image caption: This image shows the brain’s default mode network, where memory and sensory information are stored. Credit: Marcus Raichle, Washington University)

What happens to your brain when your mind is at rest?

For many years, the focus of brain mapping was to examine changes in the brain that occur when people are attentively engaged in an activity. No one spent much time thinking about what happens to the brain when people are doing very little.

But Marcus Raichle, a professor of radiology, neurology, neurobiology and biomedical engineering at Washington University in St. Louis, has done just that. In the 1990s, he and his colleagues made a pivotal discovery by revealing how a specific area of the brain responds to down time.

"A great deal of meaningful activity is occurring in the brain when a person is sitting back and doing nothing at all," says Raichle, who has been funded by the National Science Foundation (NSF) Division of Behavioral and Cognitive Sciences in the Directorate for Social, Behavioral and Economic Sciences. "It turns out that when your mind is at rest, dispersed brain areas are chattering away to one another."

The results of these discoveries now are integral to studies of brain function in health and disease worldwide. In fact, Raichle and his colleagues have found that these areas of rest in the brain—the ones that ultimately became the focus of their work—often are among the first affected by Alzheimer’s disease, a finding that ultimately could help in early detection of this disorder and a much greater understanding of the nature of the disease itself.

For his pioneering research, Raichle this year was among those chosen to receive the prestigious Kavli Prize, awarded by The Norwegian Academy of Science and Letters. It consists of a cash award of $1 million, which he will share with two other Kavli recipients in the field of neuroscience.

His discovery was a near accident, actually what he calls “pure serendipity.” Raichle, like others in the field at the time, was involved in brain imaging, looking for increases in brain activity associated with different tasks, for example language response.

In order to conduct such tests, scientists first needed to establish a baseline for comparison purposes which typically complements the task under study by including all aspects of the task, other than just the one of interest.

"For example, a control task for reading words aloud might be simply viewing them passively," he says.

In the Raichle laboratory, they routinely required subjects to look at a blank screen. When comparing this simple baseline to the task state, Raichle noticed something.

"We didn’t specify that you clear your mind, we just asked subjects to rest quietly and don’t fall asleep," he recalls. "I don’t remember the day I bothered to look at what was happening in the brain when subjects moved from this simple resting state to engagement in an attention demanding task that might be more involved than simply increases in brain activity associated with the task.

"When I did so, I observed that while brain activity in some parts of the brain increased as expected, there were other areas that actually decreased their activity as if they had been more active in the ‘resting state,"’ he adds. "Because these decreases in brain activity were so dramatic and unexpected, I got into the habit of looking for them in all of our experiments. Their consistency both in terms of where they occurred and the frequency of their occurrence—that is, almost always—really got my attention. I wasn’t sure what was going on at first but it was just too consistent to not be real."

These observations ultimately produced ground-breaking work that led to the concept of a default mode of brain function, including the discovery of a unique fronto-parietal network in the brain. It has come to be known as the default mode network, whose regions are more active when the brain is not actively engaged in a novel, attention-demanding task.

"Basically we described a core system of the brain never seen before," he says. "This core system within the brain’s two great hemispheres increasingly appears to be playing a central role in how the brain organizes its ongoing activities"

The discovery of the brain’s default mode caused Raichle and his colleagues to reconsider the idea that the brain uses more energy when engaged in an attention-demanding task. Measurements of brain metabolism with PET (positron emission tomography) and data culled from the literature led them to conclude that the brain is a very expensive organ, accounting for about 20 percent of the body’s energy consumption in an adult human, yet accounting for only 2 percent of the body weight.

"The changes in activity associated with the performance of virtually any type of task add little to the overall cost of brain function," he continues. "This has initiated a paradigm shift in brain research that has moved increasingly to studies of the brain’s intrinsic activity, that is, its default mode of functioning."

Raichle, whose work on the role of this intrinsic brain activity on facets of consciousness was supported by NSF, is also known for his research in developing and using imaging techniques, such as positron emission tomography, to identify specific areas of the brain involved in seeing, hearing, reading, memory and emotion.

In addition, his team studied chemical receptors in the brain, the physiology of major depression and anxiety, and has evaluated patients at risk for stroke. Currently, he is completing research studying what happens to the brain under anesthesia.

"The brain is capable of so many things, even when you are not conscious," Raichle says. "If you are unconscious, the organization of the brain is maintained, but it is not the same as being awake."