Thursday, November 22, 2012

Glowing Vulcan ears reveal brain's lost neurons

These glowing shapes aren't the ears of a rave-happy Vulcan - they're slices from a mouse's brain.
The slice on the right is from a mouse that lacks a gene called Arl13b - the same gene whose mutation causes Joubert syndrome in humans. This is a rare neurological condition that is linked with autism-spectrum disorders and brain structure malformations.

Without Arl13b, the nerve cells known as interneurons can't find the right destination in the cerebral cortex during the brain's development. Since the interneurons don't end up in the right places, they can't be wired up properly later on. This causes the disrupted brain development, typical of Joubert syndrome, visible in the image on the right.

The researchers hope that their findings will lead to better treatments for people who have the syndrome.
"Ultimately, if you're going to come up with therapeutic solutions, it's important to understand the biology of the disease," says Eva Anton of the University of North Carolina in Chapel Hill,

Mysterious Substance In Brain Could Explain Why You're Always Sleepy

Most of us have suffered from a few nights of bad sleep, making it difficult to stay awake during the day. But for a select group of people, extreme daytime sleepiness cannot be remedied by getting more shut-eye.

This group has what's called primary hypersomnia. It's a rare condition in which patients are continuously tired, despite sleeping, on average, nearly 11 hours a day, or up to 75 hours per week.

Until now, the cause of hypersomnia was not known, but researchers at Emory University think they've found a lead. They've identified a mysterious chemical that acts like a sedative in the brains of people who can't seem to stay awake.

The new findings were published online Wednesday, Nov. 21, in the journal Science Translational Medicine

Mystery chemical
In the human brain, a chemical called gamma-amino butyric acid, or GABA, works to calm us down when it binds to its receptor. But in individuals with primary hypersomia, researchers believe this mystery substance in the cerebrospinal fluid (a clear fluid that "bathes" the brain and spinal cord) binds to the receptor and "changes its biophysical properties so that it becomes more sensitive to GABA when it sees GABA," lead author David Rye, a professor of neurology at Emory University School of Medicine, explained to us in an email.

This, in turn, enhances the effects of GABA, the brains natural "shut down" neurtransmitter.

The result?
People who suffer from hypersominsia say they "take a coma," rather than a nap, Rye tells us. That's because naps are generally refreshing. These people take long, deep nighttime and daytime sleeps that are not refreshing.

"They typically resort to elaborate means to get themselves to wake-up — for example, multiple alarm clocks — some that fly, some that walk and that need to be physically 'caught' in order to turn them off," Rye wrote.

Studying sleep
For the study, researchers gave seven hyper-sleepy patients a drug called flumazenil, which is typically used to treat people who overdose on sleep-inducing medications like Valium or Ambien. The treatment improved reaction times and alertness in some patients. This suggested there was some kind of substance mimicking the effects of sleeping pills in hypersomnia patients, though researchers are still not sure what that substance is.

According to a press release from Emory University, "based on its size and sensitivity to certain enzymes, it could be a peptide."

Currently, there are no approved treatments for hypersomnia. Doctors typically prescribe stimulant medications like Adderall, but there is little data to support their use, Rye said.

The new knowledge will help doctors find more effective treatments for a disorder that could affect at least 1 in 800 Americans, but is not well studied.

Symptoms of Autism Linked to Brain Protein in Mouse Study

Abnormalities in proteins that help connect neurons produced autism-like symptoms in mice, which may focus the search for drugs to treat people, researchers said.

The genetically altered mice had difficulty communicating, weren’t good at social interaction and showed repetitive behaviors, according to a paper published today in the journal Nature.

Some scientists are studying whether autism is the result of wrongly connected spaces between brain cells. Today’s data bolster that theory because the mutant mice had too many brain connections, making it impossible for the cells to communicate, said Daniel Smith, senior director of discovery neuroscience for Autism Speaks, an advocacy group based in New York.

“The bottom line is it’s still a long way from treating patients, but it’s exactly what we need from early discovery,” Smith, who didn’t participate in today’s study, said in a phone interview. “It gives us something more to hang our hat on.”

The U.S. Centers for Disease Control and Prevention reported in March that 1 in 88 children in the U.S. had autism or a related disorder in 2008, the latest period for which data is available. That was a 23 percent rise from 2006, the agency’s researchers reported, saying it was unclear how much of the increase was due to greater awareness of the disease.

The scientists in today’s study, led by Nahum Sonenberg, of McGill University in Montreal, research how proteins are made to look for clues to cancer. When they knocked out a gene called 4E-BP2, more proteins called neuroligins were produced in the mice.

Brain Function

Brain cells, called neurons, are connected through junctions called synapses. Neuroligins are on the receiving end of a synapse and too many of them increase the number of synapses. That isn’t necessarily good, though, Sonenberg said in a telephone interview.

“Neuroligins make contact, like a handshake,” Sonenberg said. “But with this mutation, the handshake becomes more like a tackle. It’s too much.”

To see if the changes caused by the gene mutation were reversible, the scientists gave the mice an experimental cancer drug to cut some of the synapse formation. After the now-adult mice received the medicine, many of their social deficits attenuated.

The drug isn’t safe for people because it’s too toxic, Sonenberg said. However, its demonstration in mice may spur scientists to explore similar compounds as treatments for the symptoms of autism, he said. Because the pathway has been well- studied in cancer, there may already be treatments available, said co-author Christos Gkogkas, a post-doctoral fellow at McGill.

The study was supported by grants from the Canadian Institutes of Health Research and Autism Speaks, among others.

Brain waves encode rules for behavior

Fluctuations in electrical activity may also allow the brain to form thoughts and memories.

Brain waves stock image
 One of the biggest puzzles in neuroscience is how our brains encode thoughts, such as perceptions and memories, at the cellular level. Some evidence suggests that ensembles of neurons represent each unique piece of information, but no one knows just what these ensembles look like, or how they form.

A new study from researchers at MIT and Boston University (BU) sheds light on how neural ensembles form thoughts and support the flexibility to change one’s mind. The research team, led by Earl Miller, the Picower Professor of Neuroscience at MIT, identified groups of neurons that encode specific behavioral rules by oscillating in synchrony with each other.

The results suggest that the nature of conscious thought may be rhythmic, according to the researchers, who published their findings in the Nov. 21 issue of Neuron.

“As we talk, thoughts float in and out of our heads. Those are all ensembles forming and then reconfiguring to something else. It’s been a mystery how the brain does this,” says Miller, who is also a member of MIT’s Picower Institute for Learning and Memory. “That’s the fundamental problem that we’re talking about — the very nature of thought itself.”

Rules for behavior

The researchers identified two neural ensembles in the brains of monkeys trained to respond to objects based on either their color or orientation. This task requires cognitive flexibility — the ability to switch between two distinct sets of rules for behavior.

“Effectively what they’re doing is focusing on some parts of information in the world and ignoring others. Which behavior they’re doing depends on the context,” says Tim Buschman, an MIT postdoc and one of the lead authors of the paper.

As the animals switched between tasks, the researchers measured the brain waves produced in different locations throughout the prefrontal cortex, where most planning and thought takes place. Those waves are generated by rhythmic fluctuations of neurons’ electrical activity.

When the animals responded to objects based on orientation, the researchers found that certain neurons oscillated at high frequencies that produce so-called beta waves. When color was the required rule, a different ensemble of neurons oscillated in the beta frequency. Some neurons overlapped, belonging to more than one group, but each ensemble had its own distinctive pattern.

Interestingly, the researchers also saw oscillations in the low-frequency alpha range among neurons that make up the orientation rule ensemble, but only when the color rule was being applied. The researchers believe that the alpha waves, which have been associated with suppression of brain activity, help to quiet the neurons that trigger the orientation rule.

“What this suggests is that orientation was dominant, and color was weaker. The brain was throwing this blast of alpha at the orientation ensemble to shut it up, so the animal could use the weaker ensemble,” Miller says.

The findings could explain how the brain can create any appropriate behavioral response to the countless possible combinations of stimuli, rules and required actions, says Pascal Fries, director of the Ernst Strungmann Institute for Neuroscience in Frankfurt, Germany.

“We likely compose the appropriate neuronal assembly on the fly through synchronization,” says Fries, who was not part of the research team. “The number of combinatorial possibilities is enormous, just like the number of possible 10-digit telephone numbers is.”

Eric Denovellis, a graduate student at Boston University, is also a lead author of the paper. Other authors are Cinira Diogo, a former Picower Institute postdoc, and Daniel Bullock, a professor of cognitive and neural systems at BU.

Oscillation as consciousness

The researchers are now trying to figure out how these neural ensembles coordinate their activity as the brain switches back and forth between different rules, or thoughts. Some neuroscientists have theorized that deeper brain structures, such as the thalamus, handle this coordination, but no one knows for sure, Miller says. “It’s one of the biggest mysteries of cognition, what controls your thoughts,” he says.

This work could also help unravel the neural basis of consciousness.

“The most fundamental characteristic of consciousness is its limited capacity. You only can hold a very few thoughts in mind simultaneously,” Miller says. These oscillations may explain why that is: Previous studies have shown that when an animal is holding two thoughts in mind, two different ensembles oscillate in beta frequencies, out of phase with one another.

“That immediately suggests why there’s a limited capacity to consciousness: Only so many balls can be kept in the air at the same time, only a limited amount of information can fit into one oscillatory cycle,” Miller says. Disruptions of these oscillations may be involved in neurological disorders such as schizophrenia; studies have shown that patients with schizophrenia have reduced beta oscillations.

The research was funded by the National Science Foundation and the National Institute of Mental Health.

Scans Spot Brain Changes in Patients With Concussion Syndrome

Findings could lead to improved detection methods, researchers say

Researchers who identified brain changes in people with post-concussion syndrome say their findings may lead to improved detection and treatment of the disorder.

Symptoms of post-concussion syndrome, which occurs in 20 percent to 30 percent of people who suffer mild traumatic brain injury, include headache and memory and concentration problems.

In this study, published online Nov. 21 in the journal Radiology, researchers conducted MRI brain scans of 18 healthy people and 23 people who had symptoms of post-concussion syndrome two months after suffering a mild-traumatic brain injury.

The MRI scans were done when the participants' brains were in a resting state, such as when the mind wanders or while daydreaming. It is believed that the resting state involves connections among a number of brain regions and that the default-mode network plays a major role, study author Dr. Yulin Ge, an associate professor in the radiology department at the NYU School of Medicine in New York City, said in a journal news release.
Previous research has shown that the default-mode network is altered in people with brain disorders such as Alzheimer's disease, autism and schizophrenia.

This study found that communications and information integration in the brains of the people with post-concussion syndrome were disrupted among key default-mode network structures, and that the brain had to tap into different areas to compensate for this impaired function.

Through their ongoing research, Ge and colleagues hope to identify a biological feature, or biomarker, that can be used to monitor post-concussion syndrome progression and recovery, and to assess the effects of treatment.

Treatment for brain injury disappoints in study

694940094001_1409784734001_640-brain.jpg The hunt for brain injury treatments has suffered a big disappointment in a major study that found zero benefits from a supplement that the U.S. military had hoped would help wounded troops.

The supplement is marketed as a memory booster online and in over-the-counter powders and drinks. It is also widely used by doctors in dozens of countries to treat traumatic brain injuries and strokes, although evidence on whether it works has been mixed.

U.S. scientists had high hopes that in large doses it would help speed recovery in patients with brain injuries from car crashes, falls, sports accidents and other causes. But in the most rigorous test yet, citicoline (see-tee-KOH'-leen) worked no better than dummy treatments at reducing forgetfulness, attention problems, difficulty concentrating and other symptoms.

"We very much were disappointed," said Dr. Ross Zafonte, the lead author and a traumatic brain injury expert at Harvard Medical School. "We took a therapy that is utilized worldwide and we found that at least its present use should be called into question."

The study involved 1,213 patients aged 18 and older hospitalized at eight U.S. trauma centers. They had mild to severe traumatic brain injuries — blows to the head resulting in symptoms ranging from dizziness to loss of consciousness and with complications including brain bleeding or other damage.

Half of the patients received citicoline — also known as CDP choline — in pills or in liquid within 24 hours of being injured. The dose of 2,000 milligrams was much higher than used in over-the-counter products and it was given daily for three months. The rest got a dummy treatment, and all were followed for six months.

Most patients improved on measures of memory, learning and other mental functions, but those on the supplement fared no better than those given dummy treatment. That suggests their improvement was due to the normal healing process.

A total of 73 patients died during the study, about equal numbers in both groups.

Zafonte noted that citicoline patients with the mildest injuries did slightly worse than those who'd been given dummy treatments. Those results could have been due to chance, but he said they only reinforce the conclusion that the supplement should not be used for traumatic brain injuries.

The study appears in Wednesday's Journal of the American Medical Association.

More than 1 million Americans suffer traumatic brain injuries each year and 53,000 die. Military data show more than 250,000 cases have occurred in service members since 2000, many during the wars in Iraq and Afghanistan.

There is no effective treatment for these injuries.

"The military would have been overjoyed if this had been the one," said Dr. Robert Ruff, co-author of a journal editorial and neurology chief at the Cleveland Veterans Affairs Medical Center. The study results imply that a single drug alone won't be sufficient to help these patients improve, he said.

Citicoline is a naturally occurring brain compound made of choline, a chemical needed to build brain cells. Choline is found in some foods including beef liver, eggs and wheat germ. Commercial versions of choline and citicoline are both sold as diet supplements.

Lab studies in animals had suggested that high doses of citicoline could help speed recovery from brain injuries, with almost no side effects.

Several studies in humans examined citicoline as a possible treatment for strokes but had mixed results. Still, it is widely used in Europe and Japan to treat strokes and brain injuries. The product used in the study is made by the Spanish pharmaceutical company Ferrer Grupo, which makes prescription-grade citicoline.

Dr. Steven Zeisel, a choline scientist and director of the University of North Carolina's Nutrition Research Institute, said it's still possible citicoline would work if used in combination with other potential treatments, but to determine that would require another rigorous and costly study. He was not involved in the research.

The National Institute of Child Health and Human Development helped pay for the study, along with grants from several universities. The government institute has spent nearly $30 million since 2002 to fund a research network seeking treatments for traumatic brain injuries.

The citicoline results were eagerly anticipated in a military-commissioned Institute of Medicine report last year on potential nutritional treatments for traumatic brain injury. Besides citicoline, the report said other nutrients being studied held some promise, including fatty acids and zinc.

Zafonte, the study's lead author, was on the committee that wrote the report.

"It's back to the drawing board," he said. "We all had such hope this would make some difference."

Brain photos reveal clues to Einstein's genius

a Brainiac under the microscope … Albert Einstein's brain had extra convolutions and folds.

Albert Einstein is widely regarded as a genius, but how did he get that way? Many researchers have assumed it took a special brain to come up with the theory of relativity and other stunning insights that form the foundation of modern physics. A study of 14 newly discovered photographs of Einstein's brain, which was preserved for study after his death, concludes it was indeed unusual in many ways. But researchers still do not know exactly how the brain's extra folds and convolutions translated into Einstein's amazing abilities.

The story of Einstein's brain began in 1955 when the Nobel prize-winning physicist died in New Jersey, at 76. His son Hans Albert and executor, Otto Nathan, gave the examining pathologist Thomas Harvey, permission to preserve the brain for scientific study.

Harvey photographed and then cut it into 240 blocks, which were embedded in a resin-like substance. He cut the blocks into as many as 2000 thin sections for microscopic study, and in subsequent years distributed microscopic slides and photographs of the brain to at least 18 researchers around the world. Excepting the slides he kept for himself, no one is sure where the specimens are now.

Only six peer-reviewed publications resulted from these scattered materials. Some of these studies did find interesting features in Einstein's brain, including a greater density of neurons in some parts and a higher than usual ratio of glia (cells that help neurons to transmit nerve impulses) to neurons. Two studies of the brain's gross anatomy, including one published in 2009 by anthropologist Dean Falk of Florida State University, found that Einstein's parietal lobes - possibly linked to his remarkable ability to conceptualise physics problems - had an unusual pattern of grooves and ridges.

But the Falk study was based on only a handful of photographs that had been previously made available by Harvey, who died in 2007. In 2010, Harvey's heirs agreed to transfer all of his materials to the US Army's National Museum of Health and Medicine in Maryland. For a new study, published in the journal Brain, Falk teamed with neurologist Frederick Lepore of the Robert Wood Johnson Medical School, in New Jersey, and Adrianne Noe, director of the museum, to analyse 14 photographs of the whole brain that have never been made public.

The team compared Einstein's brain with those of 85 other humans already described in the scientific literature, and found that the great physicist did have something special between his ears. Although the brain, weighing 1230 grams, is average in size, several regions feature additional convolutions and folds. The regions on the left side of the brain that facilitate sensory inputs into, and motor control of, the face and tongue are much larger than normal, and his prefrontal cortex - linked to planning, focused attention and perseverance in the face of challenges - is also greatly expanded.

A neuroscientist at Harvard Medical School in Boston, Albert Galaburda, says that ''what's great about this paper is that it puts down … the entire anatomy of Einstein's brain in great detail''. Even so, Galaburda adds, the study raises ''very important questions for which we don't have an answer". Among them are whether Einstein started off with a special brain that predisposed him to be a great physicist, or whether doing great physics caused certain parts of his brain to expand. Einstein's genius, Galaburda says, was probably due to ''some combination of a special brain and the environment he lived in''.

Falk agrees that both nature and nurture were probably involved, pointing out that Einstein's parents were ''very nurturing'' and encouraged him to be independent and creative, not only in science but also in music, paying for piano and violin lessons. (Falk's 2009 study found that a brain region linked to musical talent was highly developed in Einstein's brain.)

''Einstein programmed his own brain,'' Falk says, adding that when the field of physics was ripe for new insights, ''he had the right brain in the right place at the right time.''