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.''

Monday, November 19, 2012

Four-Year-Old Brain Cancer Patient

Cancer claimed the life of medical marijuana poster child Cash “Cashy” Hyde after access to cannabis-based medication was cut off by a sweeping medical marijuana crackdown in Montana last summer

MISSOULA, MT — Cash “Cashy” Hyde passed away in his father’s arms this week. The four-year-old Montana boy—whose malignant brain cancer had been in remission while he received consistent medical cannabis treatments—is the latest casualty in the federal government’s war on voter-approved medical marijuana, says John Malanca, a close friend of the Hyde family.

Malanca recounts the Hyde family’s ordeal:
Desperate to find anything to keep their young child Cash alive, after traditional treatments and medications failed to slow the growth of the malignant tumor in his brain, Mike and Kalli Hyde turned to high-CBD cannabis oil. Cash’s cancer immediately went into remission, and he started to live a more normal life.
Cash was comfortable, started eating again, and recovered his desire to play.

Then, last summer, law enforcement officials in Montana came down hard on the medical marijuana industry.
Rather than face the risk of being stormed by armed agents and subjected to steep fines or jail time, many legally-compliant medical cannabis dispensaries in Montana closed down.

The federal crackdown resulted in the closure of most of the medical marijuana dispensaries in Montana, and cut off the Hyde’s access to the therapeutic cannabis oil that was keeping Cash’s cancer at bay. Once Cash’s medication was cut off, his cancer came back out of remission.

“We put out a call to action, asking people to donate cannabis oil for Cash’s health—and there was a heart-warming outpouring of donors and support,” said Malanca. “Unfortunately, by the time we got Cash the medication he needed, his cancer could no longer be controlled.”

The Hyde Family has established the Cash Hyde Foundation to help prevent unnecessary loss of health and life through advocacy of progressive and responsible medical marijuana policies, law enforcement, and legislation: “Cashy’s Law.”

The foundation also supports increased medical marijuana research, cannabis health education, and pediatric cancer research.

“Cannabis oil extended Cash’s life; he beat cancer twice,” said Malanca. “He brought so much love to this world and so many people together. He educated people.”

Effect Of Trance-like States On The Brain Studied Using Brazilian Mediums

In this week’s online open source journal PLOS ONE, a new study details how brain activity affects individuals who engage in psychography. Psychography, or automatic writing, is a technique used by mediums in an effort to free-write messages from the deceased or from spirits.

Researchers from Thomas Jefferson University and the University of Sao Paulo in Brazil embarked on this study, analyzing the cerebral blood flow (CBF) of Brazilian mediums during this mystical practice. What the team was able to determine was that the brain activity of the mediums underwent a significant decrease in activity when they would enter this mediumistic dissociative state.

To collect the data, researchers selected 10 mediums and injected them with a radioactive tracer that would allow them to visualize their brain activity during both normal writing and also during the practice of psychography. Of the 10 mediums observed in the study, five were considered as experienced while the other five were less expert. To observe the brain activity, researchers employed the use of SPECT (single photon emission computed tomography), allowing them to conclusively view the brain and the areas within it that were active and inactive at different times during the experiment.

“Spiritual experiences affect cerebral activity, this is known. But, the cerebral response to mediumship, the practice of supposedly being in communication with, or under the control of the spirit of a deceased person, has received little scientific attention, and from now on new studies should be conducted,” says Andrew Newberg, MD, director of Research at the Jefferson-Myrna Brind Center of Integrative Medicine and a nationally-known expert on spirituality and the brain, who collaborated with Julio F. P. Peres, Clinical Psychologist, PhD in Neuroscience and Behavior, Institute of Psychology at the University of Sao Paulo in Brazil, and colleagues on the research.

With between 15 and 47 years of automatic writing experience, and having performed the act as many as 18 times a month, each of the mediums was also right-handed, found to be in satisfactory mental health and not currently using any type of psychiatric drugs. Each medium was able to report that during the study, the trance-like state associated with psychography was achieved and that during the normal writing control task each was in a regular state of consciousness.

The data collected from both the experienced and non-expert mediums showed two different outcomes. The researchers noted that while the experienced psychographers showed a lowered level of activity, the less-expert psychographers showed an increase in CBF in the same observed area. The area that the SPECT focused on was the left hippocampus (limbic system), right superior temporal gyrus, and the frontal lobe regions of the left anterior cingulated and right precentral gyrus during both the act of psychography as compared to their normal, non-trance writing. This region has been deemed to be important due to its association with reasoning, planning, generating language, movement and problem solving. The lowered activity for the experienced mediums suggests, according to researchers, an absence of focus, self-awareness and consciousness during psychography.

As mentioned, the less expert psychographers presented data that showed the opposite from their more experienced counterparts. Their increased levels of CBF in the same frontal areas may be related to their more purposeful attempt at performing psychography.

The team pointed out that as none of the mediums had current mental disorders, their data supports currently held evidence that dissociative experiences are not uncommon in the general population and are not necessarily indicative of a mental disorder, especially when experienced in a religious or spiritual context. 
They do believe that additional research should be conducted to specifically address criteria for distinguishing between both healthy and pathological dissociative expression as it relates to mediumship.

The team also performed a detailed analysis of the writing samples that were collected. What they determined was that the complexity scores for the trance-induced writing was much higher than the control writing was. The more experienced mediums showed the highest complexity scores, which one would think would actually require more CBF activity in the frontal and temporal lobes. The writings composed during psychography typically involved ethical principles, the importance of spirituality, and bringing together the fields of science and spirituality.

Researchers have developed a few different hypotheses for why they think their data showed what it did. The first states that as frontal lobe activity decreases, the areas of the brain that support mediumistic writing are further disinhibited so that the overall complexity can increase. This process is similar to what is seen during alcohol and drug use. According to Newberg, “While the exact reason is at this point elusive, our study suggests there are neurophysiological correlates of this state.”

“This first-ever neuroscientific evaluation of mediumistic trance states reveals some exciting data to improve our understanding of the mind and its relationship with the brain. These findings deserve further investigation both in terms of replication and explanatory hypotheses,” states Newberg.

Brain power

Taking the pill to ward off dementia is not advised, says Arlene Harris. THE contraceptive pill has been lambasted and heralded since its conception in the 1960s. Some studies have found it to be a possible cause of cancer, while others have claimed it helps to prevent it. But it hasn’t been linked to brain health — until now.

Scientists at the University of Wisconsin have suggested that women in their 50s who took the pill during their earlier years performed better in memory tests than those who had never taken it and, in fact, may be less likely to develop dementia in later life.

The American researchers believe that oestrogen — which is the main hormone found in the pill — prevents hardening of the arteries, which increases blood supply to the brain and in turn helps to stave off dementia.

Lead researcher Kelly Egan, whose study is published in the Journal of Women’s Health, said: "Our analysis indicated that hormonal contraceptive use may have a protective cognitive (memory) effect, even years after use is discontinued. This is especially true in subjects with a longer duration of use."

But the Irish Medicines Board says this research is not conclusive and people would be advised not to start taking the pill for the sole purpose of preventing dementia.

"The IMB is aware of this study carried out by the University of Wisconsin," says a spokeswoman. "The authors themselves acknowledge the many limitations of the study and advise caution against interpretation of their results.

"Much more research is necessary in larger more focussed clinical trials before any conclusions can be made on this hypothesis."

Dr Shirley McQuade of the Dublin Well Woman Clinic agrees: "The reasons for dementia are complex and multifactorial," she says. "There probably is a link to oestrogen because previous studies have shown women who go through an early surgical menopause due to removal of their ovaries are more likely to have some cognitive impairment such as increased levels of forgetfulness.

"There have also been a number of studies looking at the possible protective effect of HRT on the development of dementia. However, it’s a bit of a leap from there to saying the contraceptive pill might be protective against dementia in the vast majority of normal women."

Matthew Gibb, senior social worker at the Memory Clinic in St James’ Hospital, Dublin, says looking after our vascular health will help to prevent hardening of the arteries.

"We would always advise people that what is good for the heart is good for the brain," he says.

Clues to Cause of Kids' Brain Tumors

TEHRAN (FNA)- Insights from a genetic condition that causes brain cancer are helping scientists better understand the most common type of brain tumor in children.
In new research, scientists at Washington University School of Medicine in St. Louis have identified a cell growth pathway that is unusually active in pediatric brain tumors known as gliomas. They previously identified the same growth pathway as a critical contributor to brain tumor formation and growth in neurofibromatosis-1 (NF1), an inherited cancer predisposition syndrome.

"This suggests that the tools we've been developing to diagnose and treat NF1 may also be helpful for sporadic brain tumors," says senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology.

The findings appear Dec. 1 in Genes and Development.

NF1 is among the most common tumor predisposition syndromes, but it accounts for only about 15 percent of pediatric low-grade gliomas known as pilocytic astrocytomas. The majority of these brain tumors occur sporadically in people without NF1.

Earlier research showed that most sporadic pilocytic astrocytomas possess an abnormal form of a signaling protein known as BRAF. In tumor cells, a piece of another protein is erroneously fused to the business end of BRAF.

Scientists suspected that the odd protein fusion spurred cells to grow and divide more often, leading to tumors. However, when they gave mice the same aberrant form of BRAF, they observed a variety of results. Sometimes gliomas formed, but in other cases, there was no discernible effect or a brief period of increased growth and cell division. In other studies, the cells grew old and died prematurely.

Gutmann, director of the Washington University Neurofibromatosis Center, previously showed that mouse NF1-associated gliomas arise from certain brain cells.

According to Gutmann, the impact of abnormal NF1 gene function on particular cell types helps explain why gliomas are most often found in the optic nerves and brainstem of children with NF1 -- these areas are where the susceptible cell types reside.

With that in mind, Gutmann and his colleagues tested the effects of the unusual fusion BRAF protein in neural stem cells from the cerebellum, where sporadic pilocytic astrocytomas often form, and in cells from the cortex, where the tumors almost never develop.

"Abnormal BRAF only results in increased growth when it is placed in neural stem cells from the cerebellum, but not the cortex," Gutmann says. "We also found that putting fusion BRAF into mature glial cells from the cerebellum had no effect."

When fusion BRAF causes increased cell proliferation, postdoctoral fellows Aparna Kaul, PhD and Yi-Hsien Chen, PhD, showed that it activates the same cellular growth pathway, called mammalian target of rapamycin (mTOR), that is normally also controlled by the NF1 protein. An extensive body of research into the mTOR pathway already exists, including potential treatments to suppress its function in other forms of cancer.

"We may be able to leverage these insights and our previous work in NF1 to improve the treatment of these common pediatric brain tumors, and that's very exciting," Gutmann says.

Gutmann and his colleagues are now working to identify more of the factors that make particular brain cells vulnerable to the tumor-promoting effects of the NF1 gene mutation and fusion BRAF. They are also developing animal models of sporadic pilocytic astrocytoma for drug discovery and testing.

Now, `molecular tweezer` drug can help treat Alzheimer`s

Now, `molecular tweezer` drug can help treat Alzheimer`sWashington: Researchers have developed a molecular compound CLR01 dubbed “molecular tweezers,” which prevents toxic proteins from aggregating or clumping together and killing brain cells in Alzheimer’s disease.

Researchers at UCLA demonstrated that the compound safely crossed the blood–brain barrier, cleared the existing amyloid-beta and tau aggregates, and also proved to be protective to the neurons’ synapses — another target of the disease — which allow cells to communicate with one another.

“This is the first demonstration that molecular tweezers work in a mammalian animal model,” Gal Bitan, an associate professor of neurology at UCLA and the senior author of the study, said.

“Importantly, no signs of toxicity were observed in the treated mice. The efficacy and toxicity results support the mechanism of this molecular tweezer and suggest these are promising compounds for developing disease-modifying therapies for Alzheimer’s disease, Parkinson’s and other disorders,” he said.

Bitan and his colleagues, including Aida Attar, first author of the study and a graduate student in Bitan’s lab, have been working with a particular molecular tweezer called CLR01.

In collaboration with scientists at the Universit√† Cattolica in Rome, the researchers, working first in cell cultures, found that CLR01 effectively inhibited a process known as synaptotoxicity, in which clumps of toxic amyloid damage or destroy a neuron’s synapses.

Even though synapses in transgenic mice with Alzheimer’s may shut down and the mice may lose their memory, upon treatment, they form new synapses and regain their learning and memory abilities. “For humans, unfortunately, the situation is more problematic because the neurons gradually die in Alzheimer’s disease,” Bitan said.

“That’s why we must start treating as early as possible. The good news is that the molecular tweezers appear to have a high safety margin, so they may be suitable for prophylactic treatment starting long before the onset of the disease,” he said.

The report has been published in the journal Brain.

Questions Are Great Brain Boosters

Questions are great brain boosters. They can energize us to start a new behavior, or to break free and let go of an old one. That’s because questions can stimulate powerful emotions, such as curiosity or wonder, which put our brains in first gear, raring to go and learn. Some questions, that is.

A ground-breaking study by Swiss researchers published in Nature revealed that, though the neurons of the amygdala play a key part in processing fear, other areas, more specifically, the higher cortex can also play a key role in regulating the fear response and modulating new emotional learning. Thus fear does not have to debilitate our capacity to make better choices.

And, when it comes to dealing with fears, a good question can empower us to muster the courage to face challenges and fears, and perhaps discover new possibilities in the process!

Not all questions, however, energize optimal processes and our brain’s amazing capacity to learn and create new understanding in the process. Some questions achieve the opposite, and some of these aren’t ‘real’ questions.

‘Real’ versus rhetorical-why-loop questions?
Whereas most questions likely fall in low to high average range in terms of their potential for positive or negative impact on our brain’s otherwise amazing ability to change, heal and grow, arguably, all brains may be better off without the type of questions in the category of rhetorical-why loops.

The rhetorical-why-loop is not a question at all, and more like an indictment.

Whereas ‘real’ questions open space for some level of conversational exchange or possibility thinking, rhetorical-why-loops can hold a person’s mind (and body) hostage to rigid perceptions that cause them to treat losses, mistakes or failures as if they have power to permanently taint the value of a person or situation.

This position casually casts aside the possibility of restoring balance (via some level of acceptance that necessitates engaging higher cortex functions, such as reflective thinking), and automatically (subconsciously) demands harsh treatment instead, perhaps even infinite punishment – and the expectation that all concerned agree.

Examples of rhetorical-why loops include:
“Why me?”
“Why did this happen?”
“Why did this happen to me?”
“Why did you do this to me?”
Often these questions involve the use of absolute adverbs, such as always and never, for example:
“Why does this always happen?”
“Why does this only happen to me?”
“Why do you/they never listen to me?”
“Why do you/they always ignore me?”
In some cases, the questions may indict a relationship or target an idea or institution, in many cases God or Life itself. The body operating with fear in charge can act in desperate and irrational ways.
“Why, God?”
“Why would God let this happen?”
An important clarification: The above questions in and of themselves are not the problem per se.
It is quite natural to ask some or all of the above in some phases of dealing with information that pains or shocks us. And of course it is also possible to verbalize the questions in a light-hearted probing or joking way, and so on.

So what makes rhetorical-why-loops distinct? Their driving intent.

As a survival response, the intent of rhetorical-why loops seems to be to banish or attack the value, adequacy or worth of one or more human beings or life — and not to learn anything of value, discover new resources, choices or useful insights on one’s life journey.

Arguably, whether conscious or subconscious, it is the intent that either:
  • Produces emotional-physiological states in the direction of love- or fear-based emotions.
  • Decides whether the autonomic nervous system will remain in parasympathetic or activate sympathetic state.
  • Overall enriches or blocks optimal brain processes (depending on the intensity).
To be fair, there is a more “benevolent” underlying intent to keep in mind. Absent the skill or know-how to more effectively deal with or lower the intensity of painful emotions (which the body regards as a most pressing need), as protective or defensive strategies, this helps us avoid and redirect them. It also explains why we may use extreme measures (that defy logic) to distance and not feel or deal with painful emotions directly (which is not helpful in the long term!).

Regardless how benevolent, the overall effect of rhetorical-why-loops can result in a coup d’√©tat of a person’s mind and body to where they may come to totally believe that if only they could get an answer to the ‘why’ question they ask, things would change or go back to a pervious time when the pain was not present. 
In sum, whereas rhetorical-why-loop questions can block the brain’s natural ‘learning’ mode and keep us stuck in ‘protection’ mode, real questions empower us to break this hold and find the way out of toxic loops.
The intent of a question seems to be a driving factor.

A good question can energize us to more effectively deal with fears, sustain optimal states of mind and body, courageously face challenges and fears, inquire in new directions, probe more deeply for understanding – and even create new possibilities, seemingly out of thin air!

In Part 2, how rhetorical-why-loop questions can trip us up, and what empowering questions to ask instead.

The brain man

SOME people collect stamps, others vintage cars. As a young PhD student at the University of Cambridge in the 1980s, Claude Wischik was on a mission to collect brains. wasn't easy. At the time, few organ banks kept entire brains. But Wischik, an Australian who was in his early 30s at the time, was trying to answer a riddle still puzzling the scientific community: what causes Alzheimer's disease?

To do that, he needed to examine brain tissue from Alzheimer's patients soon after death. That meant getting families' approval and enlisting mortuary technicians to extract the brains, he says, "no matter the time of day or night". And it wasn't just a few brains: he collected more than 300 across about a dozen years.
In his lifelong investigation, Wischik has backed a minority scientific view

that a protein called tau - which forms twisted fibres known as tangles inside the brain cells of Alzheimer's patients - is largely responsible for driving the disease.

For 20 years much of the scientific community, with billions of dollars of pharmaceutical investment, has supported a different theory that places chief blame on a different protein, beta amyloid, which forms sticky plaques in the brains of sufferers.

But a string of experimental drugs designed to attack beta amyloid has failed recently in clinical trials, and after years on the sidelines Wischik sees this as tau's big moment.

In the early 90s he and his colleagues compared the brains of Alzheimer's sufferers with those of people who died without dementia, to see how their levels of amyloid and tau differed.

They found healthy and Alzheimer's brains could be filled with amyloid plaque but only Alzheimer's brains contained aggregated tau.

What's more, as the levels of aggregated tau in a brain increased, so did the severity of dementia.
"We decided that amyloid isn't what is making people demented," Wischik says.

In the mid-90s he discovered that a drug sometimes used to treat psychosis dissolved tangles in a test tube.
He tried to set up a company to develop the drug as a treatment for Alzheimer's but found American and British venture capitalists wanted to invest in amyloid projects, not tau.

By 2002 he had scraped together $5 million from Asian investors with the help of a Singapore physician who was the father of a classmate of Wischik's son at Cambridge.

The company Wischik co-founded 10 years ago, TauRx Pharmaceuticals, is based in Singapore but conducts most of its research in Scotland, where he now lives. As his tau effort was launched, early tests of drugs designed to attack amyloid plaques were disappointing.

A vaccine developed by Athena Neurosciences failed to improve patients' cognitive function in a trial that ended in 2002.

To better understand these results, a team of British scientists largely unaffiliated with Athena or the failed clinical trial decided to examine the brains of patients who had taken part in the study. They waited for the patients to die, then, after probing the brains, concluded that the vaccine had indeed cleared amyloid plaque but had not prevented further neuro-degeneration.

In 2004 TauRx began a clinical trial of its drug, called methylene blue, in 332 Alzheimer's patients.
About the same time, a drug maker called Elan Corp, which had bought Athena Neurosciences, began a trial of an amyloid-targeted drug called bapineuzumab in 234 patients.

A key moment came in 2008 when Wischik and Elan presented results of their studies at an Alzheimer's conference in Chicago.

The Elan drug failed to improve cognition any more than a placebo pill did and Elan shares plummeted by more than 60 per cent across the next few days.

The TauRx results Wischik presented were more positive, though not unequivocal. The study showed that after 50 weeks of treatment Alzheimer's patients taking a placebo had lost 7.8 points in a test of cognitive function, while people taking 60mg of TauRx's drug three times a day had lost only one. This amounted to an 87 per cent reduction in the rate of decline for people taking the TauRx drug.

But TauRx did not publish a full set of data from the trial and this led to some scepticism among researchers. (Wischik says it didn't protect the company's commercial interests.)

What's more, a higher, 100mg dose of the drug didn't produce the same positive effects in patients. Wischik blames this on the way the 100mg dose was formulated and says the company is testing a tweaked version of the drug in its new clinical trials, which will begin enrolling patients this year.

With its new clinical trial program under way, TauRx is the first company to test a tau-targeted drug against Alzheimer's in a large human study, known in the industry as a phase 3 trial.

Wischik admits he may be just as much a zealot about tau as he accuses others of being about beta amyloid. "I may be," he says. "In the end ... it's down to the phase three trial."

Albert Einstein’s brain may provide clues to his genius

Called the “embodiment of pure intellect,” Albert Einstein has long been considered one of the most brilliant men who ever lived. During his life and since his death, people everywhere have wondered how one man could have possessed such genius. Now, scientists may have uncovered a clue within the physicist’s unusual brain. The images of Einstein’s brain are published in Falk, Lepore & Noe 2012, (The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs, “Brain”) and are reproduced here with permission from the National Museum of Health and Medicine, Silver Spring, Md.

According to a new study led by Florida State University evolutionary anthropologist Dean Falk, “portions of Einstein’s brain have been found to be unlike those of most people and could be related to his extraordinary cognitive abilities.”

“Certain things are normal,” Falk told The Huffington Post in a phone interview. “Brain size is normal. Overall shape is asymmetrical, and that is normal. What is unusual is the complexity and convolution in the various parts of the brain.”

According to a written statement issued by the university, the study, published Nov. 16 in the journal “Brain,” reveals the description of Einstein’s entire cerebral cortex. To do this, Falk and her colleagues examined 14 recently uncovered photographs of Einstein’s brain — photos that, Falk said, were difficult to obtain.

When Einstein died in 1955, his brain was removed by Thomas Harvey, a doctor at the hospital where the physicist died, NPR notes. It is likely that Harvey never got permission to remove the brain, but as author Brian Burrell writes in “Postcards from the Brain Museum,” the doctor got a posthumous stamp of approval from Einstein’s son. Harvey had said that he intended to study the brain, or at the very least, to find other scientists to do so — something that was never satisfactorily achieved in the doctor’s lifetime.

Still, scientists are now able to study Einstein’s brain thanks to a number of photos and specimen slides that Harvey had prepared of the organ. The brain, which was photographed from multiple angles, also has been sectioned into 240 blocks from which histological slides were made.

As the FSU statement notes, most of the photographs, blocks and slides were lost from public sight for more than 55 years; fortunately, a number of them have been recently rediscovered and some can now be found at the National Museum of Health and Medicine. It was with a few of these images, 14 to be exact, that Falk and her colleagues were able to take a closer look at Einstein’s brain.

What they discovered was astonishing.

“Although the overall size and asymmetrical shape of Einstein’s brain were normal, the prefrontal, somatosensory, primary motor, parietal, temporal and occipital cortices were extraordinary,” said Falk, who compared the organ to 85 other human brains already described in the scientific literature. “These may have provided the neurological underpinnings for some of his visuospatial and mathematical abilities.”

Optogenetics illuminates pathways of motivation through brain, Stanford study shows

STANFORD, Calif. — Whether you are an apple tree or an antelope, survival depends on using your energy efficiently. In a difficult or dangerous situation, the key question is whether exerting effort — sending out roots in search of nutrients in a drought or running at top speed from a predator — will be worth the energy. a paper to be published online Nov. 18 in Nature, Karl Deisseroth, MD, PhD, a professor of bioengineering and of psychiatry and behavioral sciences at Stanford University, and postdoctoral scholar Melissa Warden, PhD, describe how they have isolated the neurons that carry these split-second decisions to act from the higher brain to the brain stem. In doing so, they have provided insight into the causes of severe brain disorders such as depression.
In organisms as complex as humans, the neural mechanisms that help answer the question, "Is it worth my effort?" can fail, leading to debilitating mental illnesses. Major depressive disorder, for instance, which affects nearly 20 percent of people at some point in life, is correlated with underperformance in the parts of the brain involved in motivation. But researchers have struggled to work out the exact cause and effect.

"It's challenging because we do not have a fundamental understanding of the circuitry that controls this sort of behavioral pattern selection. We don't understand what the brain is doing wrong when these behaviors become dysfunctional, or even what the brain is supposed to be doing when things are working right," Deisseroth said. "This is the level of the mystery we face in this field."

Clinicians refer to this slowing down of motivation in depressed patients as "psychomotor retardation." According to Deisseroth, who is also a practicing psychiatrist, patients may experience this symptom mentally, finding it hard to envision the positive results of an action, or, he said, they may feel physically heavy, like their limbs just do not want to move.

"This is one of the most debilitating aspects of depression, and motivation to take action is something that we can model in animals. That's the exciting opportunity for us as researchers," said Deisseroth, who also holds the D.H. Chen Professorship.

Light coercion
Psychiatrists, Deisseroth included, believe the will to act may be born in the prefrontal cortex — the foremost part of the brain that helps plan and coordinate action. It then zips through the brain as a series of electrical signals, passing from neuron to neuron along countless branching pathways until it reaches the nerves that directly implement movement. Until this study, however, it was not clear which of these pathways might control the willingness to meet challenges, or the anticipation that action might be worthwhile in a difficult situation.

To isolate these pathways relevant to depression, Deisseroth's team needed to stimulate specific brain cells in rodents and observe changes in their behavior. They used optogenetics, a technique Deisseroth developed at Stanford in 2005, which has since revolutionized the fields of bioengineering and neuroscience.

The secret is as old as green algae. These single-celled organisms produce a protein called channelrhodopsin that makes them sensitive to sunlight. Borrowing and engineering the gene for this protein, Deisseroth has been able to create neurons that respond to light delivered from fiber-optic cables. He can turn the neurons on and off by sending bursts of light to activate different areas of the brain and then observe the effects on behavior.

Working backward
Surprisingly, the researchers found that simply stimulating the prefrontal cortices of rodents didn't motivate them to try any harder in a laboratory challenge. It turns out that motivation is not as simple as stimulating a region of the brain. Instead of one switch in the prefrontal cortex that turns motivation on, multiple switches work in concert. Some neurons excite motivated activity and others inhibit it. Broadly stimulating the executive part of the brain will not generate a simple effect on behavior.

"It's one step more subtle" said Deisseroth, "but this is something that optogenetics was very well-suited to resolve."

An optogenetic method called projection targeting allowed the scientists to work backward from the brain stem and find the exact pathway from neurons in the prefrontal cortex that signal motivation.

The researchers first introduced their light-sensitive protein into cells in the prefrontal cortex. The light sensitivity then spread out like the branches of a tree through all the outgoing connections and eventually made its way to the brain stem, making those regions light sensitive, too.

Then, illuminating the newly light-sensitive regions of the brain stem thought to control motivational movement, Deisseroth and Warden watched the behavioral effects as a subgroup of neurons in the prefrontal cortex that sent connections to brain stem were activated. They could see not only which cells are possibly involved in motivation, but the way motivation moves from one brain region to another.

Mapping motivation
The researchers suspected that one part of the brain stem in particular, the dorsal raphe nucleus, might be crucial to behaviors that control effort. This cluster of cells is a production hub for serotonin — a chemical messenger that changes the firing behavior of other cells. Serotonin is associated with mood modulation; many antidepressant drugs, for instance, may act by increasing serotonin concentration in the brain.

When the pathway between the prefrontal cortex and the dorsal raphe nucleus was stimulated, rodents facing a challenge in the lab showed an immediate and dramatic surge in motivation.

Curiously, however, when the rodents were relaxing in their home environment, the same stimulation had no effect. The pathway was not merely linked to any action, or to agitation; it was, more specifically, helping to "set the effort that the organism was willing to put forth to meet a challenge," Deisseroth said.

Researchers were also able to produce the opposite effect — reduced effort in response to challenge — by stimulating prefrontal neurons that project to the lateral habenula, a region perched atop the brain stem that is thought to play a role in depression. When this region was getting signals driven optogenetically from the prefrontal cortex, rodents put forward less effort.

Larger puzzles
These findings are part of a larger puzzle that Deisseroth and his team have pieced together by using optogenetics to model human behavior in animal subjects. The work has already helped clinicians and researchers to better understand what is going on in a patient's brain.

Connecting depressive symptoms with brain pathways may be helpful in the development of drugs, but according to Deisseroth, the most important part of this research is its insight into how motivation works in both depressed and healthy people.

He has observed that this insight alone can be helpful to those dealing with mental illness and seeking an explanation for troubling symptoms that feel deeply personal. For those patients, he said, simply knowing that a biological reality underlies their experience can be a motivational force in itself.

Brain on Fire

‘A relatively treatable autoimmune illness, Anti-NDMA-receptor encephalitis, a brain lobe swell detected by brain biopsy.’
A Manilan spending summers with relatives in the rural, I remember hearing of a young man “whose body and mind were demon-possessed, had turned deranged and unmanageable that his impoverished family had to take him to the deepest forest; left him there to live and die by himself.”   Filipinos read and hear too often of catatonic people of all ages, believed to have been turned that way by mangkukulam; possessed by witches; made fun of by middle-earth creatures called dwende;  and all sorts of frightening superstitions accepted by  many as realities.
A new memoir,  ‘Brain on Fire: My Month of Madness’ piece together Susannah Cahalan’s physical and mental breakdown, her lost terrifying one month in the hospital, and the grueling year it took to recover.
Sarah B. Weir,  a Yahoo! blogger  tells us the story:   That before Susannah Cahalan, 24, mysteriously contracted the disease, she was a bright, outgoing, and ambitious reporter of the New York Post.

Weir continues with her narration about Cahalan:    After exhibiting flu-like symptoms that were initially diagnosed as mono, the victim suddenly began experiencing delusions and behaving erratically. Within a few weeks, she became increasingly abusive, moody, and paranoid. Her doctors brushed off her condition as a result of too much partying and stress, but her first violent seizure signaled there was something critically askew.

Late one night, Cahalan’s guttural moans and grating squeaks woke up her boyfriend, Stephen. “My arms suddenly whipped out in front of me like, like a mummy, as my eyes rolled back and my body stiffened,” Cahalan writes. “I was gasping for air. My body continued to stiffen as I inhaled repeatedly, with no exhale. Blood and foam began to spurt through clenched teeth. Terrified, [he] stifled a panicked cry and for a second he stared, frozen, at my shaking body.”   Cahalan now describes her seizures as eerily similar to the character Regan’s outbursts in ‘The Exorcist.’

Cahalan was  plunged into a nightmare world of paranoia, psychosis, and ultimately, catatonia.  In another era, it’s likely she would have been permanently institutionalized or given a lobotomy.  In another culture, she might have been exorcised for demonic possession.  [In back of beyond locations in the Philippines, the local priest would have been called to do exorcism with a Cross and holy water to get the devil out of her body.
 That failing, the undiagnosed victim  may have been left in the jungle to fare for herself.  In Manila, she may have been confined at the National Psychopatic Hospital chained to her bed.]

Cahalan was admitted to the New York University Medical Center, and spent a month that was forever erased from her memory as her brain short-circuited. Only later, by cobbling  physicians’ notes and her father’s journal, and viewing chilling hospital videos would she fully understand the extent of her disintegration. Her frontal lobe function was almost at zero and the medical staff couldn’t be sure the right hemisphere of her brain would be salvageable. Although $1 million worth of medical tests provided few clues to her illness, her parents never gave up. “They were completely focused on finding an answer.”

Her savior, who she lovingly refers to as Dr. House, was Souhel Najjar, a Syrian immigrant.  While her other doctors had all but given up on finding a diagnosis, Dr.  Najjar swiftly ordered a brain biopsy that would confirm his hunch that she was suffering from an autoimmune disease that had been identified only two years earlier.

“[Dr. Najjar]  life’s experience shaped who he is as a doctor, and he also happens to be brilliant,” says Cahalan. “He’s so adamant about getting the full sense of you as a person…he was told that he was too slow for his elementary school. He’s made it his life’s mission to not let people fall through the cracks.”
Cahalan was the 217th person in the world to be diagnosed with anti-NDMA-receptor encephalitis, a relatively treatable illness that causes swelling in the right lobe of the brain. Untreated, she may have sunk into coma and eventually died.

Najjar also provided the title to her book. “At a pivotal moment in my disease, he pulled my parents out of the hospital room and literally said to them, ‘Her brain is on fire,’” Cahalan tells Shine. “At that point, they felt it was a relief to hear that. Describing it in layman’s terms gave them some hope.”

Cahalan wants her story to help people who might “otherwise get lost in the system.” She tells Shine [a publishing institution in the USA].   “We don’t understand how neurological autoimmune disorders work. They are so under diagnosed. About 75 percent occur in women who may get told they are just stressed. Or they are hysterical.  My disease was only discovered in 2007—how many more diseases haven’t been identified yet?”

Freestyle rapping is good for the brain


Freestyle rapping – the art of spontaneously improvising lyrics in real time - doesn't just inspire awe in fans. It apparently does wonders for the brains of those who make up lyrics on the spot.

After using functional magnetic resonance imaging to study the brain activity of rappers when they are freestyling, researchers at the U.S.-based National Institute of Health concluded that the process is similar to that of other spontaneous creative acts, including jazz improvisation.

The team, led by Dr. Siyuan Liu, scanned the brains of 12 freestyle rap artists who had at least five years of rapping experience while they performed two tasks using an identical 8-bar musical track. For the first task, they improvised rhyming lyrics and rhythmic patterns guided only by the beat. In the second task, they performed a well-rehearsed set of lyrics.

When the rappers freestyled, the researchers observed increases in brain activity in the medial prefrontal cortex, a brain region responsible for motivation of thought and action.

Vocal improvisation also increased brain activity in the perisylvian system (involved in language production) and in the amygdala (an area of the brain linked to emotion), suggesting that improvisation engages a brain network that links motivation, language, mood, and action.

The findings were published online in the Nov. 15 issue of Scientific Reports.

Drug offers brain cancer victims extra weeks of normal life

Patients with incurable brain tumours could be given new hope thanks to a drug currently used on bowel cancer, a study suggests.

Glioblastoma multiforme (GBM) kills more people under 40 than any other cancer. Each year in the UK, around 3,000 are diagnosed with the disease, the most common and most dangerous of brain tumours.

Unlike other cancers, which are more likely to strike as patients get older, GBM is just as prevalent in patients  who are young and healthy.

Unfortunately, the average sufferer will only survive for 14 months after diagnosis and 2,500 die from their tumours annually. New hope: A new trial has found Avastin may help slow the affects of brain cancer
New hope: A new trial has found Avastin may help slow the affects of brain cancer for patients

However, a new trial published yesterday shows patients can be given an extra four-and-a-half months without their condition worsening if they also receive the drug Avastin.

The trial on 911 men and women suggests Avastin can slow the growth of the tumour, giving patients a few more months of relatively normal life before the tumour grows so big that it starts to destroy their ability to speak, their behaviour, their memory and their movement.

Normally, a patient with GBM will have around six months between diagnosis and treatment, and when they relapse and their condition deteriorates. The new trial suggests Avastin could boost that to around ten months.

Dr Kirsten Hopkins, a consultant clinical oncologist at the Bristol Oncology Centre who was in charge of the UK branch of the trial, said that although the benefit might sound small, a few weeks would be extremely important for patients.

‘These patients are often young and this disease is devastating. Everyone I speak to in the medical world feels that if they were the ones diagnosed, they would want to be themselves for as long as possible,’ she says. 

‘This is a time when patients need to be able to talk to their family, do things with loved ones, discuss the future and what their wishes are for when they have passed away. 
Fast killer: Glioblastoma multiforme (GBM) - the most common and dangerous type of brain tumours - kills 2,500 every year
Fast killer: Glioblastoma multiforme (GBM) - the most common and dangerous type of brain tumours - kills 2,500 every year 
‘Giving them a few extra months to do that before they deteriorate and cannot speak is important. This is an endpoint in itself, even if this drug does not improve overall survival rates.’

The results of the AvAglio trial, presented at the Society for Neuro-Oncology annual meeting in Washington, do not reveal whether patients who took Avastin also survived for longer, but this set of data is due to be published early next year.

At the moment, patients diagnosed with GBM are usually offered surgery to remove the tumour, followed by cycles of chemotherapy and radiotherapy. For most, however, relapse is inevitable and half will have died from the disease within  14 months. Around 25 per cent will manage to survive for two years, while fewer than ten per cent live for five years.

Avastin, which is made by the pharmaceutical giant Roche, works by reducing blood supply to the tumour and slowing its growth. It is already used to treat colorectal, breast and ovarian cancers.

Some patients in the UK already receive Avastin to treat recurrent forms of brain cancer, but most have had to apply through the Cancer Drugs Fund because it is not yet approved for this use on the NHS.

Charities welcomed the  news but said they wanted to know more about any possible side-effects of taking Avastin,  as well as ensure it was given  to patients before they deteriorated. They pointed  out that at the moment only  0.7 per cent of total NHS  cancer funding is spent on  brain tumours.

Colin Speirs, founder of the charity Headcase, lost his wife Becky to GBM when she was only 40. She was diagnosed in 2009 and died 14 months later, leaving three young children.

‘In principle, anything that slows the progression of GBM has to be a good thing,’ he said.

‘But this disease is such a minefield and it’s important to remember different patients are affected differently, depending on which side of the brain the tumour is found. 

‘My wife was climbing mountains after she was diagnosed but then the tumour progressed and it was on the  left of her brain, so it affected movement, personality  and memory. 

‘I would want any new drug to ensure it gives patients four more months when they can climb mountains and not four more when the disease has already robbed them of their speech and memory.’

It currently takes the average GP three months to diagnose GBM. 

This is because symptoms include severe headaches, vomiting and blurred vision, which can be attributed to other conditions such as migraine. Sufferers may also experience an itchy head and feel as if something is running across their scalp.

Figures suggest that in the next few years, about 20,000 Britons will be diagnosed with brain tumours. 

Three in every four will be  the result of cancers in other parts of the body spreading to the brain.

Saturday, November 10, 2012

ADHD Drugs Impact The Brain's Reward System
Two to three percent of children in denmark meet the standards to be diagnosed with ADHD, making it extremely important to understand how ADHD drugs work. Now, University of Copenhagen researchers are gathering new information about the impact of ADHD medicine by utilizing a new mathematical reconstruction of a small part of a particular brain region which processes reward and punishment, which always involves the chemical dopamine.

Jakob Kisbye Dreyer, postdoctoral candidate at the Department of Neuroscience and Pharmacology, Faculty of Medical and Health Sciences, University of Copenhagen, said:
"It had been discussed for years whether treating ADHD with Ritalin and similar drugs affects the reward system to any significant degree, simply because the dosage given to patients is so low. We are the first to show that some components of the dopamine signaling pathways are extremely sensitive to drugs like Ritalin. We have also developed a unified theory to describe the effect of such drugs on the dopamine signal."
Dreyer stresses in the new study, which was published in the Journal of Neurophysiology, the significance of understanding what happens during treatments with ADHD medications, such as Ritalin, because knowledge helps to develop more advanced drugs, and also to comprehend the psychology behind ADHD.

Human behavior is driven by unconscious assessment of the cost to gain ratio. The new findings demonstrate that ADHD drugs lessen the signals regarding expected consequence or punishment.

Dopamine, a chemical found in the brain, assists in several processes which alter human behaviors. Certain activities, such as having sex, taking narcotics, winning a competition, and eating, boost levels of dopamine being released. The researchers believe that dopamine plays a part in urging us to repeat behaviors that had, in the past, been linked to reward.

Dreyer explained:
"Control mechanisms in the brain help keep the dopamine signal in balance so we can register the tiny deviations that signal reward and punishment. We discovered while trying to describe these control mechanisms that our model can be used to examine the influence of Ritalin, for example, on the signal. Suddenly we could see that different pathways of the reward system are affected to different degrees by the medicine, and we could calculate at what dosage different parts of the signal would be changed or destroyed."
Ritalin and other ADHD medications have been seen to have inconsistent results, because high dosage increases activity and low dosage decreases it, often making it difficult to find the right dosage for each individual patient.

"We can explain this double effect using our theory. The dopamine signal in the part of the brain that controls our motor behavior is only affected at a higher dose that the dose usually prescribed for treatment. Also, our model shows that the threshold between a clinically effective dose and too high a dose is very low. That may explain why the small individual differences between patients have a big impact on treatment," concluded Dreyer.

Ties between brain, better buildings examined

Can the buildings we inhabit make us well sooner? Can they make prisoners calmer? Can they impact an autistic child?
Scientists and architects will come together today at Scottsdale's Taliesin West to explore the connection between the brain and buildings.

The "Minding Design: Neuroscience, Design Education, and the Imagination" conference is sold out at 250 participants.

Taliesin West officials see the conference as an opportunity to broaden its reach by connecting experts from around the nation. 

Sean Malone, chief executive officer of the Frank Lloyd Wright Foundation, said the scholarly conference embodies the foundation's vision of transforming people's lives through Wright's principles.

 "We believe we have an opportunity and responsibility to help shape architecture and design at the highest level," Malone said, adding that Taliesin West, Wright's winter home and studio campus that now offers tours and houses the Frank Lloyd Wright School of Architecture, is the ideal place to host. "There was nobody more innovative and engaged than Frank Lloyd Wright." 

Cathedrals, theaters and museums are believed to inspire and heighten creativity, but this conference will delve into what is happening in the brain when we're inside buildings and how architects can better serve certain populations and humanity. 

The symposium brings in neuroscientists and architects from around the country to discuss how environment shapes the human experience through brain research and theories while impacting imagination, health and other areas. 

Tricia Anderson, an interior designer in South Bend, Ind., spotted the conference on Taliesin West's Facebook page and decided it was the perfect complement to her pursuit of advanced degrees in psychology and interior design.

"I've always felt that a person's environment not only reflects your personality, but it also has a strong effect on your creativity and inspiration and your overall well-being," she said.

Michael Arbib, director of the University of Southern California Brain Project, charted ways in which designing a building can use knowledge of brain function. He is a speaker at the symposium.

Also a member of the Academy of Neuroscience for Architecture (, Arbib said that it may be years before designing a building with a knowledge of brain function becomes widely practiced. But the connection between the two could result in more fruitful lives.

Studies of Alzheimer's patients may help influence the design of buildings, which could make it easier for them to find their way around. Hospitals may acquire lighting that does not disrupt the body's circadian rhythms at night.

"I'll be making every effort to make it clear to the architects why they should care about the brain and how it relates to design," he said.

Gene mutation behind brain defects identifiedl

Gene mutation behind brain defects identifiedWashington: Mutations in a single gene – that causes intellectual disability and increases the risk of developing autism spectrum disorder - severely disrupts the organization of developing brain circuits during early childhood, a new study has revealed.

This study by scientists from the Florida campus of The Scripps Research Institute helps explain how genetic mutations can cause profound cognitive and behavioural problems.

“In this study, we did something no one else had done before,” Gavin Rumbaugh, a TSRI associate professor who led the new research, said.

“Using an animal model, we looked at a mutation known to cause intellectual disability and showed for the first time a causative link between abnormal synapse maturation during brain development and life-long cognitive disruptions commonly seen in adults with a neurodevelopmental disorder,” he said.

The study focused on a critical synaptic protein known as SynGAP1.

Mutations in the gene that encodes this protein cause disabilities in an estimated one million people worldwide, according to the paper.

“You might think this accelerated development of brain circuits would make you smarter,” Rumbaugh said.

“But the increased excitability actually disorganizes brain development. We think that early maturation of these excitatory synapses disrupts the timing of later developmental milestones. It rains down chaos on this complex process, preventing normal intellectual and behavioural development,” he said.

Brain Has Distinct Activity Pattern When Losing Consciousness During Anesthesia

A new study from the US reveals for the first time, that the brain has a distinct pattern of electrical activity as patients lose consciousness during anesthesia. The pattern shows very slow oscillations, reflecting a breakdown of communication between the different regions of the brain, each of which shows shorts bursts of activity alternating with longer silences.
The researchers write about their findings in a paper published online first on 5 November in the Proceedings of the National Academy of Sciences.

They hope that by improving understanding of what happens in the brain as it loses consciousness, the study will help anesthesiologists better maintain the right balance between too little and too much anesthetic.

Senior author Patrick Purdon, an instructor of anesthesia at Massachusetts General Hospital (MGH) and Harvard Medical School, says in a statement, clinicians will now know what to look for on the electroencephalograph (EEG) when putting a patient under anesthesia:

"We now finally have an objective physiological signal for measuring when someone's unconscious under anesthesia."
EEG Patterns in Epileptic Patients An EEG is a machine that records electrical activity of the brain through electrodes on the scalp. It measures changes in voltage resulting from the various currents flowing between neurons or brain cells.

For their study, Purdon and colleagues studied epileptic patients who had electrodes implanted in their brains to monitor seizures and were having an operation to remove them.

The patients received a common anesthetic known as propofol and had their brain activity monitored by EEG.

Propofol activates receptors on neurons, in a way that makes the brain cells less active, although exactly how this happens is not clear.

The researchers noticed the EEG showed a distinct pattern at the point where consciousness was lost. This was about 40 seconds after receiving the anesthetic, and was defined by the moment when patients stopped responding to sounds played to them every four seconds.

Distinct Pattern of Overall and Local Brain Activity
To record brain activity, Purdon and colleagues used two different sized of electrode, each size taking a different reading of brain activity. The larger electrodes, about the size of a large coin, were placed about 1 cm apart and recorded the overall EEG or brain wave pattern.

The smaller, more localized, electrodes were concentrated in a group of rows about 4 mm wide. Between 50 and 100 of these were implanted in each patient, in different brain regions.

These smaller electrodes recorded activity from individual neurons, and this study is thought to be the first to record neuron activity in patients as they lose consciousness.

The large electrodes showed that within one or two seconds of patients losing consciousness, the EEG pattern suddenly turned to low frequency oscillations, at about 1 cycle per second (about 1 Hz).

This coincided with the small electrodes showing a "flickering" pattern at individual neuron level. Individual neurons within localized brain regions were active for a few hundred milliseconds, then became quiet for a few hundred milliseconds. This created the oscillating pattern seen on the EEG, say the researchers.

"We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (< 1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space," they write.

Periodic Silencing Prevents Communication in Brain One of the lead authors, Laura Lewis, a graduate student in the Department of Brain and Cognitive Sciences (BCS) at Massachusetts Institute of Technology (MIT), says:

"Within a small area, things can look pretty normal, but because of this periodic silencing, everything gets interrupted every few hundred milliseconds, and that prevents any communication."

"When one area was active, it was likely that another brain area that it was trying to communicate with was not active. Even when the neurons were on, they still couldn't send information to other brain regions," she explains.
Loss of Consciousness Could Be "Failure of Information Integration"
Michael Avidan is a professor of anesthesiology at Washington University School of Medicine, and was not involved in the study. He describes the findings as "exciting" and suggests they offer neurobiological evidence for the "information integration theory" of consciousness. This theory suggests large-scale brain networks integrate information from the senses to generate our overall impression of the world around us.

When we lose consciousness, there could still be information "coming into the brain, but that information is remaining localized and doesn't get integrated into a coherent picture," he explains.

Another lead author, Emery Brown, professor of brain and cognitive sciences and health sciences and technology at MIT and an anesthesiologist at MGH, says this mechanism of "failure of information integration" has been put forward before as a possible explanation for loss of consciousness, but it was not clear how it worked.

"This finding really narrows it down quite a bit. It really does, in a very fundamental way, constrain the possibilities of what the mechanisms could be," he adds.

Successful Anesthesia: Maintaing a Delicate Balance
The researchers hope the pattern will help anesthesiologists improve monitoring of patients as they receive anesthesia, thus preventing rare cases where patients wake up during operations or where too much anesthetic stops them breathing.

At present, anesthesiologists monitor patients under anesthetic with recordings that calculate an index from the EEG. But that index can hide the underlying physiology that can be seen directly in the slow waves.

Brown says their findings suggest they should be looking at and interpreting the oscillations in the raw EEG readings.

"If you do that, you have a physiologically linked way to know when someone is unconscious. We can take this into the operating room today and give better patient care," he adds.

The team is now going to look at what happens in the brain as it regains consciousness. They have already started looking at the effects of other anesthesia drugs, to see if they generate the same brain patterns.

Purdon says based on EEG studies there appear to be many other drugs producing the same slow oscillations. But there are also a number that are "doing something totally different," he adds.

Funds from the Nationa Institutes of Health (NIH), the Canadian Research Foundation, and the National Institute of Neurological Disorders and Stroke, helped finance the study.